The multidisciplinary pancreatic cyst clinic: A collaborative approach to streamlined management.

BACKGROUND: Pancreatic cysts are often incidentally detected on routine imaging studies. Of these, mucinous cysts have a malignant potential. Several guidelines propose different management strategies, and implementation in patient care is inconsistent in the absence of dedicated infrastructure. METHODS: To address the challenges of pancreatic cyst diagnosis and management, we established a multidisciplinary pancreas cyst clinic (PCC) within our health system. This clinic encompasses both tertiary care academic centers and community hospitals, with leadership from surgical oncology, gastroenterology, and radiology. Our PCC's primary goal is to provide accurate diagnosis and tailored management recommendations for all patients with pancreatic cysts. Additionally, we maintain a prospective database to study the disease's natural history and the outcomes of various treatment strategies. CLINIC INFRASTRUCTURE: The clinic meets once per week for 45 min virtually via Zoom in the mornings. Patients are referred via electronic medical record (EMR) order, telephone call, or email from patient or referring provider. A dedicated advanced practice provider reviews referrals several times per day, calls patients to gather clinical data, ensures imaging is uploaded, and coordinates logistical aspects of the meeting during the dedicated time. Conferences are attended by representatives from surgery, radiology, medical pancreatology, and interventional gastroenterology. Each patient case is reviewed in detail and recommendations are submitted to referring providers and patients via an EMR message and letter. For patients requiring imaging surveillance, patients are followed longitudinally by the referring provider, gastroenterology team, or surgical team. For patients requiring endoscopic ultrasound (EUS) or surgical consultation, expedited referral to these services is made with prompt subsequent evaluation. RESULTS: A total of 1052 patients from our health system were evaluated between 2020 and 2021. Of these, 196 (18.6 %) underwent EUS, 41 (3.9 %) underwent upfront surgical resection, and the remainder were referred to gastroenterology (141-13.4 %), surgery (314-29.8 %), or back to their referring provider (597-56.7 %) for ongoing surveillance in collaboration with their primary care provider (PCP). Of cysts under surveillance, 61.3 % remained stable, 13.2 % increased in size, and 2 % decreased in size. A total of 2.3 % of patients were recommended to discontinue surveillance. CONCLUSIONS: The PCC provides infrastructure that has served to provide multidisciplinary review and consensus recommendations to patients with pancreatic cysts. This has served to improve the application of guidelines while providing individualized recommendations to each patient, while aiding non-expert referring providers throughout the region.

Natural history and growth prediction model of pancreatic serous cystic neoplasms.

OBJECTIVE: Serous cystic neoplasms (SCN) are benign pancreatic cystic neoplasms that may require resection based on local complications and rate of growth. We aimed to develop a predictive model for the growth curve of SCNs to aid in the clinical decision making of determining need for surgical resection. METHODS: Utilizing a prospectively maintained pancreatic cyst database from a single institution, patients with SCNs were identified. Diagnosis confirmation included imaging, cyst aspiration, pathology, or expert opinion. Cyst size diameter was measured by radiology or surgery. Patients with interval imaging ≥3 months from diagnosis were included. Flexible restricted cubic splines were utilized for modeling of non-linearities in time and previous measurements. Model fitting and analysis were performed using R (V3.50, Vienna, Austria) with the rms package. RESULTS: Among 203 eligible patients from 1998 to 2021, the mean initial cyst size was 31 mm (range 5-160 mm), with a mean follow-up of 72 months (range 3-266 months). The model effectively captured the non-linear relationship between cyst size and time, with both time and previous cyst size (not initial cyst size) significantly predicting current cyst growth (p < 0.01). The root mean square error for overall prediction was 10.74. Validation through bootstrapping demonstrated consistent performance, particularly for shorter follow-up intervals. CONCLUSION: SCNs typically have a similar growth rate regardless of initial size. An accurate predictive model can be used to identify rapidly growing outliers that may warrant surgical intervention, and this free model (https://riskcalc.org/SerousCystadenomaSize/) can be incorporated in the electronic medical record.

Benefit of Extended Surveillance of Low-Risk Pancreatic Cysts After 5-Year Stability: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Low-risk branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) lacking worrisome features (WF) and high-risk stigmata (HRS) warrant surveillance. However, their optimal duration, especially among cysts with initial 5 years of size stability, warrants further investigation. We systematically reviewed the surveillance of low-risk BD-IPMNs and investigated the incidence of WF/HRS and advanced neoplasia, high-grade dysplasia, and pancreatic cancer during the initial (<5 years) and extended surveillance period (>5-years). METHODS: A systematic search (CRD42020117120) identified studies investigating long-term IPMN surveillance outcomes of low-risk IPMN among the Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until July 9, 2021. The outcomes included the incidence of WF/HRS and advanced neoplasia, disease-specific mortality, and surveillance-related harm (expressed as percentage per patient-years). The meta-analysis relied on time-to-event plots and used a random-effects model. RESULTS: Forty-one eligible studies underwent systematic review, and 18 studies were meta-analyzed. The pooled incidence of WF/HRS among low-risk BD-IPMNs during initial and extended surveillance was 2.2% (95% CI, 1.0%-3.7%) and 2.9% (95% CI, 1.0%-5.7%) patient-years, respectively, whereas the incidence of advanced neoplasia was 0.6% (95% CI, 0.2%-1.00%) and 1.0% (95% CI, 0.6%-1.5%) patient-years, respectively. The pooled incidence of disease-specific mortality during initial and extended surveillance was 0.3% (95% CI, 0.1%-0.6%) and 0.6% (95% CI, 0.0%-1.6%) patient-years, respectively. Among BD-IPMNs with initial size stability, extended surveillance had a WF/HRS and advanced neoplasia incidence of 1.9% (95% CI, 1.2%-2.8%) and 0.2% (95% CI, 0.1%-0.5%) patient-years, respectively. CONCLUSIONS: A lower incidence of advanced neoplasia during extended surveillance among low-risk, stable-sized BD-IPMNs was a key finding of this study. However, the survival benefit of surveillance among this population warrants further exploration through high-quality studies before recommending surveillance cessation with certainty.

Computed high-b-value high-resolution DWI improves solid lesion detection in IPMN of the pancreas.

OBJECTIVES: To examine the effect of high-b-value computed diffusion-weighted imaging (cDWI) on solid lesion detection and classification in pancreatic intraductal papillary mucinous neoplasm (IPMN), using endoscopic ultrasound (EUS) and histopathology as a standard of reference. METHODS: Eighty-two patients with known or suspected IPMN were retrospectively enrolled. Computed high-b-value images at b = 1000 s/mm2 were calculated from standard (b = 0, 50, 300, and 600 s/mm2) DWI images for conventional full field-of-view (fFOV, 3 × 3 × 4 mm3 voxel size) DWI. A subset of 39 patients received additional high-resolution reduced-field-of-view (rFOV, 2.5 × 2.5 × 3 mm3 voxel size) DWI. In this cohort, rFOV cDWI was compared against fFOV cDWI additionally. Two experienced radiologists evaluated (Likert scale 1-4) image quality (overall image quality, lesion detection and delineation, fluid suppression within the lesion). In addition, quantitative image parameters (apparent signal-to-noise ratio (aSNR), apparent contrast-to-noise ratio (aCNR), contrast ratio (CR)) were assessed. Diagnostic confidence regarding the presence/absence of diffusion-restricted solid nodules was assessed in an additional reader study. RESULTS: High-b-value cDWI at b = 1000 s/mm2 outperformed acquired DWI at b = 600 s/mm2 regarding lesion detection, fluid suppression, aCNR, CR, and lesion classification (p = < .001-.002). Comparing cDWI from fFOV and rFOV revealed higher image quality in high-resolution rFOV-DWI compared to conventional fFOV-DWI (p ≤ .001-.018). High-b-value cDWI images were rated non-inferior to directly acquired high-b-value DWI images (p = .095-.655). CONCLUSIONS: High-b-value cDWI may improve the detection and classification of solid lesions in IPMN. Combining high-resolution imaging and high-b-value cDWI may further increase diagnostic precision. CLINICAL RELEVANCE STATEMENT: This study shows the potential of computed high-resolution high-sensitivity diffusion-weighted magnetic resonance imaging for solid lesion detection in pancreatic intraductal papillary mucinous neoplasia (IPMN). The technique may enable early cancer detection in patients under surveillance. KEY POINTS: • Computed high-b-value diffusion-weighted imaging (cDWI) may improve the detection and classification of intraductal papillary mucinous neoplasms (IPMN) of the pancreas. • cDWI calculated from high-resolution imaging increases diagnostic precision compared to cDWI calculated from conventional-resolution imaging. • cDWI has the potential to strengthen the role of MRI for screening and surveillance of IPMN, particularly in view of the rising incidence of IPMNs combined with now more conservative therapeutic approaches.

Surgical treatment for pancreatic cystic lesions-implications from the multi-center and prospective German StuDoQ|Pancreas registry.

PURPOSE: The detection of pancreatic cystic lesions (PCL) causes uncertainty for physicians and patients, and international guidelines are based on low evidence. The extent and perioperative risk of resections of PCL in Germany needs comparison with these guidelines to highlight controversies and derive recommendations. METHODS: Clinical data of 1137 patients who underwent surgery for PCL between 2014 and 2019 were retrieved from the German StuDoQ|Pancreas registry. Relevant features for preoperative evaluation and predictive factors for adverse outcomes were statistically identified. RESULTS: Patients with intraductal papillary mucinous neoplasms (IPMN) represented the largest PCL subgroup (N = 689; 60.6%) while other entities (mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), neuroendocrine tumors, pseudocysts) were less frequently resected. Symptoms of pancreatitis were associated with IPMN (OR, 1.8; P = 0.012) and pseudocysts (OR, 4.78; P < 0.001), but likewise lowered the likelihood of MCN (OR, 0.49; P = 0.046) and SCN (OR, 0.15, P = 0.002). A total of 639 (57.2%) patients received endoscopic ultrasound before resection, as recommended by guidelines. Malignancy was histologically confirmed in 137 patients (12.0%), while jaundice (OR, 5.1; P < 0.001) and weight loss (OR, 2.0; P = 0.002) were independent predictors. Most resections were performed by open surgery (N = 847, 74.5%), while distal lesions were in majority treated using minimally invasive approaches (P < 0.001). Severe morbidity was 28.4% (N = 323) and 30d mortality was 2.6% (N = 29). Increased age (P = 0.004), higher BMI (P = 0.002), liver cirrhosis (P < 0.001), and esophageal varices (P = 0.002) were independent risk factors for 30d mortality. CONCLUSION: With respect to unclear findings frequently present in PCL, diagnostic means recommended in guidelines should always be considered in the preoperative phase. The therapy of PCL should be decided upon in the light of patient-specific factors, and the surgical strategy needs to be adapted accordingly.

Lymphoepithelial cyst of the pancreas: can common imaging features help to avoid resection?

BACKGROUND: Differentiation of cystic pancreatic neoplasms remains a challenging task for radiologists regarding the main aim of identifying malignant and premalignant lesions. PURPOSE: The study aimed to compare the radiological features of lymphoepithelial cysts (LEC) with other cystic pancreatic lesions, which could help to differentiate them in order to avoid unnecessary resection. MATERIAL AND METHODS: We retrospectively reviewed 10 cases of resected and histopathologically confirmed LECs during a 12-year period with available imaging studies; 20 patients with mucinous cystic neoplasms (MCN), 20 patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMN), and 20 patients with serous cystic neoplasms (SCN) were selected to serve as control groups. Imaging findings as well as clinical data were analyzed. RESULTS: The following imaging morphology of LEC was identified: simple cystic appearance (20%) and mixed cystic-solid appearance (80%) with either a diffuse subsolid component (30%) or mural nodule(s) (50%). All lesions revealed exophytic location with a strong male predominance (9:1). MCNs occurred exclusively in middle-aged women, IPMN in both sexes showed slight male predominance (13:7), and SCN showed female predominance (5:15). Median patient age in LEC (48.5, IQR 47-54.5) was significantly younger compared to IPMN (p < 0.001) and SCN (p = 0.02). Unenhanced CT attenuation of LEC was higher than MCNs (p = 0.025) and IPMNs (p = 0.021), showing no significant difference to SCN (p = 0.343). CONCLUSION: The present study provides key radiological features of LEC for the differentiation from other cystic pancreatic lesions such as increased CT attenuation in the unenhanced phase, absence of a connection to the main pancreatic duct (MPD), and exophytic location. In addition to these imaging features, clinical data, such as male predominance in LEC, must be considered for the differentiation of cystic pancreatic lesions.

Clinical Characteristics of Patients With Surgically Resected Pancreatic Cysts: A Retrospective Analysis of 136 Patients.

OBJECTIVES: To retrospectively analyze the characteristics of pancreatic cysts with respect to histopathological diagnosis and various diagnostic imaging tools. METHODS: The clinical features of 136 patients and characteristics of histopathologically diagnosed cysts were retrospectively assessed. The diagnostic accuracy of endoscopic ultrasound (EUS), computed tomography (CT), and magnetic resonance imaging (MRI) for pancreatic cysts was compared. Risk factors for high-grade dysplasia/invasive cancer in patients with intraductal papillary mucinous neoplasms (IPMNs) were also determined. RESULTS: The final analysis included 30 serous cystic neoplasms (SCNs) (21.6%), 13 mucinous cystic neoplasms (MCNs) (9.4%), 65 IPMNs (46.8%), and 13 solid pseudopapillary neoplasms (SPNs) (9.4%). The percentage of women with MCNs, SPNs, SCNs, and IPMNs was 100.0, 76.9, 73.3, and 47.7%, respectively (P < .001). The percentages of patients over 60 years of age with IPMNs, SCNs, MCNs, and SPNs were 73.9, 23.3, 0, and 0%, respectively (P < .001). The percentage of cysts located in the body and tail of the pancreas in MCNs, SCNs, SPNs, and IPMNs was 100, 70, 53.9, and 46.2%, respectively (P < .001). A unique honeycomb appearance was observed in 26.7% of SCNs. The overall diagnostic accuracy of EUS, CT, and MRI for pancreatic cysts was 82.6, 72.5, and 73.9%, respectively. Lesion size and presence of solid components were independent predictors of high-risk IPMNs. CONCLUSIONS: Patient characteristics and cyst features can help to differentiate pancreatic cyst types and identify high-risk IPMNs. The diagnostic accuracy of EUS for pancreatic cysts is superior to that of CT and MRI.

Limitations and prospects in the management of IPMN: a retrospective, single-center observational study.

BACKGROUND: With increasing use and enhanced accuracy of cross-sectional imaging, the diagnosis of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has increased over the last few decades. The extent to which malignant transformation occurs remains unclear, making the management of IPMNs controversial. The aim of this study was to evaluate the progression rate and outcome of follow-up in patients with IPMNs. METHODS: A database of all patients diagnosed with IPMN at the Cantonal Hospital HFR Fribourg, Switzerland, between January 2006 and December 2019 with a follow-up of at least 6 months was analyzed retrospectively. Descriptive statistics were performed on patient demographics, IPMN characteristics, and follow-up data. RESULTS: A total of 56 patients were included in this study. Ten patients underwent primary surgery, 46 were enrolled in a surveillance program.21.7% (n = 5) of patients under surveillance presented with worrisome features of IPMN; progression rates were significantly higher in these patients (p = 0.043). Most progression occurred in the early follow-up period. Five patients underwent surgery due to progression, of which 2 presented high-grade dysplasia and 2 malignancy on postoperative histology. CONCLUSIONS: The limited predictive value of current guidelines may lead to surgical overtreatment, and the decision to proceed with surgical resection should be made with caution. Further prospective analyses and the development of novel biomarkers are needed to better understand the natural history of IPMN and improve diagnostic precision.

Comorbidities Drive the Majority of Overall Mortality in Low-Risk Mucinous Pancreatic Cysts Under Surveillance.

BACKGROUND & AIMS: The Charlson Comorbidity Index (CACI) has been suggested as a tool to determine comorbidity burden and guide management for patients with mucinous pancreatic cysts (Intrapapillary Mucinous Neoplasms and Mucinous Cystic Neoplasms), but has not been studied well among "low-risk" mucinous pancreatic cysts i.e. without worrisome features (WF) and high-risk stigmata (HRS). This study sought to determine the comorbidity burden among surveillance population of low-risk pancreatic cysts and provide their follow-up mortality outcomes. METHODS: A single center study retrospectively reviewed a prospective pancreatic cyst database and included individuals with low-risk cysts undergoing serial imaging during 2016. Electronic medical records were reviewed to determine their baseline age-adjusted CACI (age-CACI). After 4 years, their progression to WF, disease specific (pancreatic malignancy-related, DSM), extra-pancreatic (EPM), and overall mortalities (OM) were determined using Kaplan-Meir Survival Analysis. RESULTS: 502 individuals underwent prospective surveillance. The study included 440 individuals with low-risk suspected or presumed mucinous cysts and excluded 50 and 12 individuals with WF and HRS respectively. Over a median follow-up of 56 months, 12 WF progressions, 2 DSMs, 42 EPMs, and 44 OMs were observed. Baseline age-CACI had good predictive capacity for 4-year EPM (Area-Under Curve: 0.87; p< .0001). The median age-CACI of 4 enabled cohort stratification into Low (age-CACI <4) and High CACI (age-CACI ≥4) groups. A significantly higher OM (p< .001) was observed among the High CACI group as compared to the Low CACI group. CONCLUSION: Through real-time application of CACI to patient outcomes, our analysis supports incorporation of this comorbidity assessment tool in making shared surveillance decisions among low-risk pancreatic cyst population.

Circulating CD8+CD122+ T cells as a prognostic indicator of pancreatic cancer.

PURPOSE: The distribution of tissue infiltrating lymphocytes has been shown to affect the prognosis of patients with pancreatic cancer in some previous studies. However, the role of peripheral lymphocytes in pancreatic cancer remains debated. The purpose of this study was to analyze the peripheral subtypes of T lymphocytes, and establish their association with the prognosis of patients with pancreatic cancer. METHODS: Blood and tissue samples were collected from patients with metastatic pancreatic cancer (n = 54), resectable pancreatic cancer (n = 12), and benign pancreatic cysts (n = 52) between April 2019 and January 2022 and analyzed. RESULTS: Patients with metastatic pancreatic cancer had a larger proportion of both tumor-suppressive and tumor-promoting cells than those with benign pancreatic cysts. In addition, the proportion of peripheral CD4+ T cells positively correlated with the survival of patients with metastatic pancreatic cancer, and the proportion of peripheral CD8+CD122+ T cells was associated with early mortality (< 90 days). After chemotherapy, CD8+CD122+ T cells decreased in patients who had a partial response or stable disease. Moreover, by analyzing resected specimens, we first proved that the existence of CD8+CD122+ T cells in a tumor microenvironment (TME) depends on their proportion in peripheral blood. CONCLUSION: Circulating CD8+CD122+ T cells can be a prognostic indicator in patients with pancreatic cancer.

Can we predict the progression of premalignant pancreatic cystic tumors to ductal adenocarcinoma?

Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent malignant pancreatic tumor. Few studies have shown how often PDACs arise from cystic precursor lesions. This special report aims to summarize the evidence on the progression of precancerous lesions to PDAC. A review of the literature found four studies that discussed pancreatic intraepithelial lesions (PanINs), three that discussed mucinous cystic neoplasms (MCN) and five that discussed intraductal papillary neoplasms (IPMNs). PanINs were the most common precursors lesion, with approximately 80% of PDACs originating from this lesion. The lack of evidence characterizing the features of PDAC precursor cystic lesions potentially leads to a subset of patients undergoing surgery unnecessarily. Advancements in molecular techniques could allow the study of cystic lesions at a genetic level, leading to more personalized management.

Cancer arising from the ducts within the pancreas is the most common type of pancreatic cancer. Some cancers develop from precancerous changes, but these are not currently well described. Therefore, we have summarized the existing knowledge on the precancerous changes causing pancreatic cancer. We found three main precancerous changes: pancreatic intraepithelial lesions; mucinous cystic neoplasms; and intraductal papillary neoplasms. Pancreatic intraepithelial lesions were the most common pancreatic precancerous lesion, leading to 80% of cancers of the pancreatic ducts. A few studies indicate that patients would benefit from surgery to remove precancerous lesions. We believe that, due to advances in genetic studies, personalized strategies for treating pancreatic cancers will emerge in the future.

A meta-analysis: incidental intraductal papillary mucinous neoplasm and extra-pancreatic malignancy.

INTRODUCTION: Meta-analysis aimed to quantify the relationship between intraductal papillary mucinous neoplasm (IPMN) and increased incidence of extra-pancreatic malignancy (EPM) previously reported in qualitative observational cohort studies. METHODS: Study protocol was registered with PROSPERO (CRD42020169614) and conducted to the Meta-analysis Of Observational Studies in Epidemiology and systematic review reported with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Assessing the Methodological Quality of Systematic Reviews guidelines. RESULTS: Sixteen studies (total of 8240 patients) were included in the pooled, and 7399 patients in the subgroup meta-analyses. The odds ratio (OR) for any EPM in the presence of IPMN was 57.9 (95% confidence interval 40.5-82.7), fixed effects, I2 = 59% (p < 0.0014). Subgroup analysis for any gastrointestinal EPM (i.e. oesophagus, stomach, colon and rectum) in the presence of an IPMN estimated an overall OR of 12.9 (95% confidence interval 8.8-19.0), fixed effects, I2 = 64% (p < 0.0004). CONCLUSION: Patients with an IPMN are categorically at increased risk for a higher incidence of EPM and particularly the odds of a gastrointestinal malignancy are also increased in comparison with the general population. We advocate that patients presenting with an IPMN should be considered for gastrointestinal screening including colonoscopy, upper gastrointestinal endoscopy or computed tomography.

Recommendations for the Management of Incidental Pancreatic Findings in Adults by the Canadian Association of Radiologists Incidental Findings Working Group.

The Canadian Association of Radiologists Incidental Findings Working Group consists of both academic subspecialty and general radiologists and is tasked with adapting and expanding upon the American College of Radiology incidental findings white papers to more closely apply to Canadian practice patterns, particularly more comprehensively dealing with the role of ultrasound and pursuing more cost-effective approaches to the workup of incidental findings without compromising patient care. Presented here are the 2021 Canadian guidelines for the management of pancreatic incidental findings. Topics covered include anatomic variants, fatty atrophy, pancreatic calcifications, ductal ectasia, and management of incidental pancreatic cysts.

Considerations in laparoscopic resection of giant pancreatic cystic neoplasms.

Background: Laparoscopic distal pancreatectomy (LDP) with (LDPS) or without splenectomy for cystic tumours in the body and tail has become the standard of care. Data on patients with large tumours of the body and tail of the pancreas are sparse. Patients and Methods: A retrospective analysis of a prospectively maintained database of patients who were managed with laparoscopic surgery for pancreatic cystic neoplasm since 2010 was done. Patients with cysts more than 8 cm were analysed. Clinical presentation, imaging, details of the surgical procedure and the outcomes were looked into. Results: Five patients of giant pancreatic cystic neoplasm (GPCN) were managed with LDPS. Four patients were female, mean age was 45 years (range 15-69 years). The mean cyst size was 11.2 cms (range 8-15 cm). The splenic vein was either stretched or thrombosed in all patients. Three patients had sinistral portal hypertension. All patients were operated with a modified five-port placement. None of the patients required conversion. Mean operative duration was 3½ h, blood loss was 80 ml approximately and none required a blood transfusion. One patient had a biochemical leak. All patients were discharged from the hospital by 3rd postoperative day. Drain removal was done before discharge except in the patient with biochemical leak (removed on day 6). On a median follow-up of 89 months (range 1-120 months), two patients developed diabetes. There has been no Overwhelming post-splenectomy infections (OPSI). Conclusion: Laparoscopic distal pancreatectomy is feasible in patients with GPCN and offers the all the short-term benefits, namely lesser pain, no wound infections, early return of bowel activity, early return to orals and early discharge and early return to work. Splenectomy was required in all patients because of splenic vein thrombosis and portal hypertension in three and for technical reasons in the rest.

Systematic review and meta-analysis of observational studies on BD-IPMNS progression to malignancy.

BACKGROUND: The vast majority of presumed branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas are referred to a surveillance program due to the relatively low risk of malignancy. We aim to evaluate all available data from observational studies focused on the risks of BD-IPMN progression and malignancy to provide vital insights into its management in clinical practice. METHODS: A comprehensive search was conducted at PubMed, Cochrane, Web of Science and Embase for observational studies published before January 1st, 2020. The progression of BD-IPMN was defined as the development of worrisome features (WFs) or high-risk stigmata (HRS) during surveillance. Overall malignancy was defined as all malignancies, such as malignant IPMN, concomitant pancreatic ductal adenocarcinoma (PDAC) and other malignancies, including BD-IPMN with high-grade sec. Baltimore consensus 2015 or BD-IPMN with high-grade dysplasia (carcinoma in situ) sec. WHO 2010. A meta-analysis was performed to investigate the presence of a mural nodule as a possible predictor of malignancy. RESULTS: Twenty-four studies were included, with a total of 8941 patients with a presumed BD-IPMN. The progression rate was 20.2%, and 11.8% underwent surgery, 29.5% of whom showed malignancy at the final pathology. Of those, 78% had malignant IPMNs, and 22% had concomitant pancreatic cancer. Overall, 0.5% had distant metastasis. The meta-analysis showed that the risk of malignancy in the presence of a mural nodule >5 mm had a RR of 5.457 (95% CI 1.404-21.353), while a nonenhancing mural nodule or an enhancing mural nodule < 5 mm had a RR of 5.286 (95% CI 1.805-15.481) of harboring malignancy. CONCLUSION: Most presumed BD-IPMNs entering surveillance do not become malignant. Of those submitted to surgery, concomitant PDAC adds to the overall risk of detecting malignancy.

Long-term follow-up of branch-duct intraductal papillary mucinous neoplasms with No change in first 5 Years of diagnosis.

BACKGROUND: Discontinuation of branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) surveillance after 5 years of no change remains controversial. Long-term outcomes of BD-IPMN without significant changes in the first 5 years were evaluated. METHODS: We performed a multi-center retrospective analysis of patients with BD-IPMN diagnosis from 2005 to 2011 (follow-up until 2017). Significant changes were defined as pancreatic cancer (PC), pancreatectomy, high-risk stigmata (HRS), worrisome features (WF) and worrisome EUS features (WEUS). RESULTS: Of 982 patients who had no significant changes, 5 (0.5%), 7 (0.7%), 99 (10.1%), 4 (0.4%) patients developed PC, HRS, WF, WEUS, respectively, post-5 years. PC and HRS/WF/WEUS incidences at 12 years were 1.0% and 29.0%, respectively. Patients that developed HRS/WF/WEUS had larger cyst size in first 5 years compared to those that did not [16 (12-23) vs. 12 (9-17) mm, p = 0.0001], cyst size of >15 mm having higher cumulative incidence of HRS/WF/WEUS. PC mortality was 0.8%; all-cause mortality was 32%. Incidence of mortality due to PC was higher in HRS/WF/WEUS group, p < 0.0001. The mortality rate at 12 years for ACCI (age-adjusted Charlson Comorbidity Index) of ≤3, 4-6, and ≥7 were 3.5%, 19.9%, and 57.6% (p < 0.0001), respectively. CONCLUSIONS: Incidence of PC in patients with BD-IPMN without significant changes in first 5 years of diagnosis remains low at 1.0%. Incidence of HRS/WF/WEUS was higher at 29.0%. PC-related mortality was higher in HRS/WF/WEUS group. These risks should be weighed against patients' overall mortality (utilizing scoring systems such as ACCI) when making surveillance decision of BD-IPMN beyond 5 years.

The utility of intracystic glucose levels in differentiating mucinous from non-mucinous pancreatic cysts.

BACKGROUND: Differentiating benign non-mucinous from potentially malignant mucinous pancreatic cysts is still a challenge. This study aims to improve this distinction with cyst fluid analysis. METHODS: A cohort study of pancreatic cyst undergoing EUS/FNA was performed from a prospectively maintained database between 2014 and 2018 was performed. RESULTS: 113 patients were analyzed (40 non-mucinous and 73 mucinous). For differentiating mucinous from non-mucinous cyst: intracyst glucose ≤41 mg/dl had a sensitivity of 92% and a specificity of 92%; positive predictive value (PPV) of 96 and negative predictive value (NPV) of 86. Glucose ≤21 mg/dl had a sensitivity of 88%, specificity of 97%, PPV of 98 and NPV of 81. CEA ≥192 ng/mL had a sensitivity of 50% and a specificity of 92%; PPV of 92 and NPV of 50. Glucose ≤21 mg/dl or CEA ≥192 ng/mL combined had a sensitivity of 93%, specificity of 92%, PPV of 96 and NPV of 87 (Fig. 1, Table 1). CONCLUSION: Intra-cyst glucose levels (≤41 mg/dl) outperforms classic CEA testing for differentiation of mucinous from non-mucinous pancreatic cysts. It was found to be an excellent diagnostic test with an AUC of 0.95 (95% CI: 0.81, 0.97).

Elevated hemoglobin A1c is associated with the presence of pancreatic cysts in a high-risk pancreatic surveillance program.

BACKGROUND: Emerging evidence demonstrates that surveillance of individuals at high-risk (HRIs) of developing pancreatic adenocarcinoma allows for identification and treatment of resectable tumors with improved survival. Population-based data suggest that hyperglycemia may be present up to three years before the development of pancreatic cancer. We investigated whether elevated hemoglobin A1c (HbA1c) is associated with the development of pancreatic cysts in a pancreatic surveillance program. METHODS: We performed a retrospective study of HRIs who underwent pancreatic surveillance at a single institution between May 2013 and March 2019, according to published criteria. We collected demographic information, clinical data including HbA1c, and imaging results. We compared data using univariable and multivariable analyses. Our primary outcome was the presence of pancreatic cysts on initial surveillance in patients with elevated HbA1c. RESULTS: Ninety-eight patients underwent surveillance imaging via EUS or MRCP and seventy-four patients met inclusion criteria. Thirty patients were found to have cysts on initial imaging. Older age (p < 0.01) and HbA1c in the prediabetic range or higher (p = 0.01) were associated with the presence of cysts or solid lesions on univariable analysis. After controlling for confounders, age (aOR 9.08, 95% CI 2.29-36.10), and HbA1c > 5.7% (aOR 5.82, 95% CI 1.50-22.54) remained associated with presence of cysts and solid lesions in HRIs. In patients with cysts or solid lesions there was a strong association between increased age and elevated HbA1c (p < 0.01). CONCLUSION: HRIs with elevated HbA1c were more likely to have pancreatic cysts compared to individuals with lower HbA1c on initial imaging in a pancreatic surveillance program. These findings may help tailor the surveillance protocols for those at increased risk of developing pancreatic adenocarcinoma.

Impact of needle-based confocal laser endomicroscopy on the therapeutic management of single pancreatic cystic lesions.

BACKGROUND AND AIM: The diagnosis and therapeutic management of large single pancreatic cystic lesions (PCLs) represent major issues for clinicians and essentially rely on endoscopic ultrasound fine-needle aspiration (EUS-FNA) findings. Needle-based confocal laser endomicroscopy (nCLE) has high diagnostic performance for PCLs. This study aimed to evaluate the impact of nCLE on the therapeutic management of patients with single PCLs. METHODS: Retrospective and comparative study. Five independent pancreatic disease experts from tertiary hospitals independently reviewed data from a prospective database of 206 patients with single PCL, larger than 2 cm and who underwent EUS-FNA and nCLE. Two evaluations were performed. The first one included the sequential review of clinical information, EUS report and FNA results. The second one included the same data + nCLE report. Participants had to propose a therapeutic management for each case. RESULTS: The addition of nCLE to EUS-FNA led to significant changes in therapeutic management for 28% of the patients (p < 0.001). nCLE significantly increased the interobserver agreement of 0.28 (p < 0.0001), from 0.36 (CI 95% 0.33-0.49) to 0.64 (CI 95% 0.61-0.67). nCLE improved the rates of full agreement among the five experts of 24% (p < 0.0001), from 30 to 54%. With nCLE, the surveillance rate of benign SCAs fell by 35%, from 40 (28/70) to 5% (4/76). CONCLUSION: The addition of nCLE to EUS-FNA significantly improves reliability of PCL diagnosis and could impact the therapeutic management of patients with single PCLs. ClinicalTrials.gov number, NCT01563133.

Cystic pancreatic neuroendocrine tumors: A more favorable lesion?

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are predominantly solid lesions with malignant potential. Cystic PNETs are a small subset in which data are scarce. The aim of this study was to compare clinical and biologic differences between cystic and solid PNETs. METHODS: Patients with PNETs undergoing pancreatectomy between 1988 and 2016 at a high-volume center were reviewed retrospectively. Demographic, clinical, and histopathologic data were collected and analyzed. RESULTS: 347 patients with PNETs were identified; 27% (n = 91) were cystic. Patients with cystic PNETs were generally older (59 vs. 55 years, p = 0.05). Cystic PNETs were more commonly non-functional (95% vs. 82%, p = 0.004), asymptomatic (44% vs. 28%, p = 0.009), and located in the pancreatic body/tail (81% vs. 60%, p < 0.001) than solid PNETs. Although cystic and solid PNETs had similar sizes and pathologic stage at the time of resection, Ki-67 proliferation index (Ki-67 ≤ 9%: 98% vs. 85%; p = 0.007), and histologic grade (grade I: 84% vs. 59%; p = 0.009) had less aggressive features in cystic PNETs. CONCLUSION: In addition to reporting a higher than previously published incidence of cystic PNET (27%), this study found significant differences in multiple clinicopathologic variables between cystic and solid PNETs. Cystic PNET may be a distinct and possibly less aggressive subtype of PNET yet have similar pathologic stage, recurrence, and survival to solid PNETs. Cystic PNETs require further attention to better understand the true natural history.