Low-Risk Intraductal Papillary Mucinous Neoplasms Research Articles

Small cyst size and lack of growth as negative predictors of malignant transformation in low-risk intraductal papillary mucinous neoplasms of the pancreas: A systematic review and meta-analysis.

For branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) without worrisome features (WFs) or high-risk stigmata (HRS), current guidelines recommend surveillance. However, these intraductal papillary mucinous neoplasm (IPMNs), especially the small and stable-sized ones, carry a low risk of malignant transformation. Our aim was to assess whether small cyst size and absence of rapid growth provide reassurance against the development of WFs/HRS and malignancy (high-grade dysplasia (HGD) or pancreatic cancer (PC)). PubMed/Medline, Embase, the Cochrane Library and the Web of Science Core Collection were systematically searched from inception to May 2023 to identify studies investigating surveillance outcomes of low-risk BD-IPMNs. Studies assessing baseline cyst size and/or growth in relation to WFs/HRS and/or HGD/PC were included. The Newcastle-Ottawa scale tool was used to assess study quality. Of the 1937 identified manuscripts, 21 studies were eligible for inclusion. The quality of these studies was considered reasonable. A negative association between cyst size and WFs/HRS development was found in 11 out of 13 relevant studies, but only one out of nine studies reported a negative association between size and malignancy. Regarding cyst growth, four out of six studies described a negative association with the development of WFs/HRS, and all six reported a negative association with malignancy. The pooled relative risk (RR) of developing WFs/HRS or malignancy for cysts ≤15mm was 0.37 (95% CI 0.25-0.57) and the RR of developing malignancy for cyst growth <2-2.5mm/year was 0.04 (95% CI 0.02-0.09)). This systematic review and meta-analysis shows that small and stable-sized low-risk BD-IPMNs are associated with a markedly low progression rate, with stable cyst size being the most reassuring feature. Because of substantial heterogeneity in definitions and reported outcome measures, prospective studies are needed to confirm that surveillance of small and stable sized cyst can be de-intensified or even discontinued.

Optimal age to discontinue long-term surveillance of intraductal papillary mucinous neoplasms: comparative cost-effectiveness of surveillance by age

ObjectiveCurrent guidelines recommend long-term image-based surveillance for patients with low-risk intraductal papillary mucinous neoplasms (IPMNs). This simulation study aimed to examine the comparative cost-effectiveness of continued versus discontinued surveillance at...

Intraductal Papillary Mucinous Neoplasm Surveillance Leads to Early Diagnosis and Better Outcomes of Concomitant Cancer.

To examine whether long-term surveillance of intraductal papillary mucinous neoplasms (IPMNs) leads to early diagnosis and better clinical outcomes of pancreatic ductal adenocarcinomas (PDACs) developing concomitantly with IPMNs. Long-term image-based surveillance is recommended for patients with low-risk IPMNs. However, it is unknown whether the surveillance can improve surgical and survival outcomes of patients with concomitant PDACs. Using a prospective single-institutional cohort of 4,620 patients with pancreatic cysts including 3,638 IPMN patients, we identified 63 patients who developed concomitant PDAC during long-term surveillance. We compared overall survival (OS) of 46 cases with concomitant PDAC to that of 460 matched cases diagnosed with non-IPMN-associated PDAC at the same institution. Multivariable hazard ratios and 95% confidence intervals (CIs) for overall mortality were computed using the Cox regression model with adjustment for potential confounders. Concomitant PDACs were identified at an earlier cancer stage compared to non-IPMN-associated PDACs with 67% and 38% cases identified at stage 2 or earlier, respectively (P<0.001) and 57% and 21% cases with R0 resection, respectively (P<0.001). Compared to non-IPMN-associated PDACs, concomitant PDACs were associated with longer OS (P=0.034) with a multivariable hazard ratio of 0.61 (95% CI, 0.39-0.96). The 5-year survival rate of patients with concomitant PDAC was higher compared to patients with non-IPMN-associated PDAC (34% vs. 18%, respectively; P=0.018). The surveillance for patients with IPMNs was associated with early identification of concomitant PDACs and longer survival of patients diagnosed with this malignancy.

Abdominal ultrasound in the characterization of branch-duct intraductal papillary mucinous neoplasms: A new tool for surveillance of low-risk patients?

BackgroundMagnetic resonance imaging (MRI) is regarded as gold-standard for intraductal papillary mucinous neoplasms (IPMNs) follow-up. Given the low risk of transformation and the increasing population under surveillance, there is growing interest in identifying optimal follow-up strategies. AimTo evaluate reliability of abdominal ultrasound (US) for characterization of low-risk IPMN, compared to MRI. MethodsProspective monocentric study among 79 consecutive patients with a suspected BD-IPMN on US. Each patient underwent confirmatory MRI. We evaluated Cohen's kappa statistic and concordance rate (CR) between MRI and US. ResultsOf 79 suspected IPMNs on US, MRI confirmed 71 BD-IPMNs. There was high agreement for cyst location and number (CR and kappa of 77.5 % and 81.7 % and 0.66±0.08 and 0.62±0.11 respectively). We found high agreement for cyst size (CR=96.5 %, kappa=0.93±0.05) and main pancreatic duct (MPD) dilatation (CR=100 %, kappa=1). There was a good agreement for thickened septa (CR=80.3 %, kappa=0.38±0.12). US seems inferior to MRI for the identification of mural nodules < 5 mm (CR=97.2 %, kappa=0). ConclusionsIn a cohort of low-risk BD-IPMN, US presented high agreement rate with MRI regarding location, number, and size. There was a good agreement for MPD dilatation and thickened septa, while US underperform for detection of mural nodules < 5 mm.

Dynamics and costs of patients with appropriate, Уtoo earlyФ and Уtoo lateФ surgery in low-risk Intraductal Papillary Mucinous Neoplasms

Dynamics and costs of patients with appropriate, Уtoo earlyФ and Уtoo lateФ surgery in low-risk Intraductal Papillary Mucinous Neoplasms

Multiinstitutional Validation Study of Cyst Fluid Protein Biomarkers in Patients With Cystic Lesions of the Pancreas.

Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas. Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4). This multiinstitutional study enrolled patients who underwent EUS-FNA for a cystic lesion of the pancreas. Treatment recommendations regarding resection were based on standard clinical, radiographic, and endoscopic features. Predicted probabilities of high-risk IPMN (high-grade dysplasia/invasive cancer) were calculated using the previously developed clinical-molecular nomograms. Cyst fluid was obtained from 100 patients who underwent diagnostic EUS-FNA. Within this group there were 35 patients who underwent resection, and 65 were monitored radiographically. Within the group that underwent resection, 26 had low-risk IPMN or benign non-IPMN lesions, and 9 had high-risk IPMN. Within the surveillance group, no patient progressed to resection or developed cancer after a median follow-up of 12months (range: 0.5-38). Using the clinical/radiographic nomogram alone, 2 out of 9 patients with high-risk IPMN had a predicted probability >0.5. In the clinical-molecular models, 6 of 9 patients in model 1, and 6 of 9 in model 2, had scores >0.5. This prospective study of patients with unknown cyst pathology further demonstrates the importance of cyst fluid protein analysis in the preoperative identification of patients with high-risk IPMN. Longer follow-up is necessary to determine if this model will be useful in clinical practice.

Bioinformatic Analysis and Integration of Transcriptome and Proteome Results Identify Key Coding and Noncoding Genes Predicting Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas.

Background Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). IPMNs are generally associated with high risk of developing malignancy and therefore need to be diagnosed and assessed accurately, once detected. Existing diagnostic methods are inadequate, and identification of efficient biomarker capable of detecting high-risk IPMNs is necessitated. Moreover, the mechanism of development of malignancy in IPMNs is also elusive. Methods Gene expression meta-analysis conducted using 12 low-risk IPMN and 23 high-risk IPMN tissue samples. We have also listed all the altered miRNAs and long noncoding RNAs (lncRNAs), identified their target genes, and performed pathway analysis. We further enlisted cyst fluid proteins detected to be altered in high-risk or malignant IPMNs and compared them with fraction of differentially expressed genes secreted into cyst fluid. Results Our meta-analysis identified 270 upregulated and 161 downregulated genes characteristically altered in high-risk IPMNs. We further identified 61 miRNAs and 14 lncRNAs and their target genes and key pathways contributing towards understanding of the gene regulation during the progression of the disease. Most importantly, we have detected 12 genes altered significantly both in cystic lesions and cyst fluid. Conclusion Our study reports, for the first time, a meta-analysis identifying key changes in gene expression between low-risk and high-risk IPMNs and also explains the regulatory aspect through construction of a miRNA-lncRNA-mRNA interaction network. The 12-gene-signature could function as potential biomarker in cyst fluid for detection of IPMN with a high risk of developing malignancy.

Circulating and Salivary Antibodies to Fusobacterium nucleatum Are Associated With Cystic Pancreatic Neoplasm Malignancy.

ObjectivesIntraductal papillary mucinous neoplasms (IPMNs) are cystic precursor lesions to pancreatic cancer. The presence of oral microbes in pancreatic tissue or cyst fluid has been associated with high-grade dysplasia (HGD) and cancer. The present study aims at investigating if humoral immunity to pancreas-associated oral microbes reflects IPMN severity.DesignPaired plasma (n = 109) and saliva (n = 65) samples were obtained from IPMN pancreatic cystic tumor cases and controls, for anti-bacterial antibody analysis and DNA quantification by enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. Tumor severity was graded by histopathology, laboratory, and clinical data. Circulating plasma and salivary antibody reactivity to a pancreas-associated oral microbe panel were measured by ELISA and correlated to tumor severity.ResultsThe patient group with high-risk cystic tumors (HGD and/or associated invasive cancer) shows ample circulating IgG reactivity to Fusobacterium nucleatum (F. nucleatum) but not to Granulicatella adiacens (G. adiacens), which is independent of the salivary bacteria DNA levels. This group also shows higher salivary IgA reactivity to F. nucleatum, Fap2 of F. nucleatum, and Streptococcus gordonii (S. gordonii) compared to low-risk IPMN and controls. The salivary antibody reactivity to F. nucleatum and Fap2 are found to be highly correlated, and cross-competition assays further confirm that these antibodies appear cross-reactive.ConclusionOur findings indicate that humoral reactivity against pancreas-associated oral microbes may reflect IPMN severity. These findings are beneficial for biomarker development.

The diagnosis and management of intraductal papillary mucinous neoplasms of the pancreas: has progress been made?

Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are premalignant mucin-producing epithelial tumors that arise from the pancreatic ductal system. These cystic tumors represent 15-30% of cystic lesions of the pancreas [Basturk et al. in Am J Surg Pathol 39(12):1730-1741, 1; Ferrone et al. in Arch Surg (Chicago, Ill: 1960) 144(5):448-454, 2, Kosmahl et al. in Virchows Arch Int J Pathol 445(2):168-178, 3; Spinelli et al. in Ann Surg. 239(5):651-657, 4]. It is believed that IPMN can progress from low-grade dysplasia to high-grade dysplasia to invasive cancer, and this pathway of progression accounts for 20-30% of pancreatic cancer [Adsay et al. in Am J Surg Pathol 28(7):839-848, 5; Tanaka et al. in J Gastroenterol 40(7):669-675, 6; Wu et al. in Sci Transl Med 3(92):92ra66, 7]. Furthermore, it is also widely believed that IPMN represent a field defect of the pancreas in which the entire ductal system is at risk of developing invasive carcinoma, not only in the area of radiographically detectable IPMN, and thus the remaining gland should undergo surveillance after partial pancreatectomy [Salvia et al. in Ann Surg 239(5):678-685, 8; Izawa et al. in Cancer 92(7):1807-1817, 9; Yamaguchi and Tanaka in Jpn J Clin Oncol 41(7):836-840, 10]. Increasingly, surgeons are faced with the dilemma between recommending highly complex resections-that have significant morbidity and mortality-in patients who may have low-risk IPMN (low-grade dysplasia), or alternatively, recommending observation for those who could possibly be harboring a radiographically occult malignancy. Given the complexity of the management decisions for patients with IPMN, the purpose of this paper is to review the current literature and to provide a summary of how accurate we are currently with the identification of high-grade dysplasia or progression to carcinoma in patients who present with IPMN.

Cyst Fluid Biosignature to Predict Intraductal Papillary Mucinous Neoplasms of the Pancreas with High Malignant Potential

Current standard-of-care technologies, such as imaging and cyst fluid analysis, are unable to consistently distinguish intraductal papillary mucinous neoplasms (IPMNs) of the pancreas at high risk of pancreatic cancer from low-risk IPMNs. The objective was to create a single-platform assay to identify IPMNs that are at high risk for malignant progression. Building on the Verona International Consensus Conference branch duct IPMN biomarker review, additional protein, cytokine, mucin, DNA, and microRNA cyst fluid targets were identified for creation of a quantitative polymerase chain reaction-based assay. This included messenger RNA markers: ERBB2, GNAS, interleukin 1β, KRAS, MUCs1, 2, 4, 5AC, 7, prostaglandin E2R, PTGER2, prostaglandin E synthase 2, prostaglandin E synthase 1, TP63; microRNA targets: miRs 101, 106b, 10a, 142, 155, 17, 18a, 21, 217, 24, 30a, 342, 532, 92a, and 99b; and GNAS and KRAS mutational analysis. A multi-institutional international collaborative contributed IPMN cyst fluid samples to validate this platform. Cyst fluid gene expression levels were normalized, z-transformed, and used in classification and regression analysis by a support vector machine training algorithm. From cyst fluids of 59 IPMN patients, principal component analysis confirmed no institutional bias/clustering. Lasso (least absolute shrinkage and selection operator)-penalized logistic regression with binary classification and 5-fold cross-validation used area under the curve as the evaluation criterion to create the optimal signature to discriminate IPMNs as low risk (low/moderate dysplasia) or high risk (high-grade dysplasia/invasive cancer). The most predictive signature was achieved with interleukin 1β, MUC4, and prostaglandin E synthase 2 to accurately discriminate high-risk cysts from low-risk cysts with an area under the curve of up to 0.86 (p= 0.002). We have identified a single-platform polymerase chain reaction-based assay of cyst fluid to accurately predict IPMNs with high malignant potential for additional studies.

CT radiomics to predict high-risk intraductal papillary mucinous neoplasms of the pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) are radiographically visible precursor lesions of pancreatic cancer. Despite standard criteria for assessing risk, only 18% of cysts are malignant at resection. Thus, a large number of patients undergo unnecessary invasive surgery for benign disease. The ability to identify IPMNs with low or high risk of transforming into invasive cancer would optimize patient selection and improve surgical decision-making. The purpose of this study was to investigate quantitative CT imaging features as markers for objective assessment of IPMN risk. This retrospective study analyzed pancreatic cyst and parenchyma regions extracted from CT scans in 103 patients to predict IPMN risk. Patients who underwent resection between 2005 and 2015 with pathologically proven branch duct (BD)-IPMN and a preoperative CT scan were included in the study. Expert pathologists categorized IPMNs as low or high risk following resection as part of routine clinical care. We extracted new radiographically inspired features as well as standard texture features and designed prediction models for the categorization of high- and low-risk IPMNs. Five clinical variables were also combined with imaging features to design prediction models. Using images from 103 patients and tenfold cross-validation technique, the novel radiographically inspired imaging features achieved an area under the receiver operating characteristic curve (AUC) of 0.77, demonstrating their predictive power. The combination of these features with clinical variables obtained the best performance (AUC=0.81). The present study demonstrates that features extracted from pretreatment CT images can predict the risk of IPMN. Development of a preoperative model to discriminate between low-risk and high-risk IPMN will improve surgical decision-making.

Pancreatic cystic neoplasms: What is the most cost-effective follow-up strategy?

Pancreatic cystic neoplasms are one of the most frequent incidental findings in the field of pancreatic diseases, estimated to be present in up to 45% of the general population. They represent an heterogeneous group of tumors with different biological behavior and variable risk of progression to malignancy. While serous cystadenomas (SCAs) have no risk of malignant progression, mucinous cyst adenoma are malignant in 20% of cases and this risk is higher in intraductal papillary mucinous neoplasms (IPMN). Nonsurgical management could be applied in patients with a SCA and in low-risk IPMN and these patients could be managed with follow-up strategies. While follow-up could be interrupted in patients unfit for surgery due to comorbidities or age, and in SCA stable over time, recent evidences do not support surveillance discontinuation in patients with IPMNs fit for surgery.

Progression of Unresected Intraductal Papillary Mucinous Neoplasms of the Pancreas to Cancer: A Systematic Review and Meta-analysis

It is not clear how best to manage patients with low-risk intraductal papillary mucinous neoplasms (IPMNs) of the pancreas because little is known about IPMN progression to cancer. We sought to determine the cumulative incidence of development of pancreatic cancer in persons with unresected IPMNs (particularly low-risk IPMNs). We performed a systematic search of the MEDLINE and Embase databases through November 30, 2016 for studies reporting the cumulative incidence of pancreatic cancer in patients with unresected IPMNs or studies that provided data in sufficient detail for us to calculate cumulative incidence values. We categorized patient series as studies on low-risk IPMNs (lesions without main pancreatic duct involvement or mural nodules) or non-low-risk IPMNs. Wecalculated meta-analytic cumulative incidence values for pancreatic cancer at 1, 3, 5, and 10 years of follow-up by using the inverse variance method and random-effects model. Among 1514 articles screened, we identified 10 studies of low-risk IPMNs (n= 2411) and 9studies of non-low-risk IPMNs (n= 825). In studies of low-risk IPMNs, the meta-analytic cumulative incidence values for pancreatic cancer were 0.02% at 1 year (95% confidence interval [CI], 0.0%-0.23%; I2= 0.0%), 1.40% at 3 years (95% CI, 0.58%-2.48%; I2= 58.5%), 3.12% at 5 years (95% CI, 1.12%-5.90%; I2= 88.0%), and 7.77% at 10 years (95% CI, 4.09%-12.39%; I2= 79.8%). These values were much higher in studies of non-low-risk IPMNs; cumulative incidence values for pancreatic cancer were 1.95% at 1 year (95% CI, 0.0%-5.99%; I2= 84.2%), 5.69% at 3 years (95% CI, 1.10%-12.77%; I2= 89.9%), 9.77% at 5 years (95% CI, 3.04%-19.27%; I2= 92.0%), and 24.68% at 10 years (95% CI, 14.87%-35.90%; I2= 74.3%). The pooled cumulative incidence steadily increased linearly as the follow-up duration increased. In a systematic review and meta-analysis, we found that low-risk IPMNs have almost 8% chance of progressing to pancreatic cancer within 10 years, and higher-risk IPMNs have almost 25% chance of progressing to cancer in 10 years; incidence values increase linearly with time. Continued long-term surveillance is therefore vital for patients with low-risk IPMNs.

Endoscopic Ultrasound for Risk Stratification of Pancreatic Cystic Neoplasms

Introduction: Endoscopic Ultrasound (EUS) plays a large role in the workup and evaluation of both incidental and symptomatic pancreatic cysts. EUS can aid in risk stratification of pancreatic cystic neoplasms (PCNs). A subset of PCN, intraductal papillary mucinous neoplasms (IPMNs) have the potential for malignant transformation and risk is stratified from high to low. EUS can aid in differentiation between benign and malignant IPMNs and is used in current guidelines used to direct patients to observation or resection. Methods: A total of 80 patients were identified who underwent both endoscopic ultrasound and surgical resection of a cystic pancreatic lesion between the dates of January 2008 to January 2014. A total of 36 were found to have IPMNs. A retrospective chart analysis was conducted on patients with diagnosis of IPMN to identify features seen at the time of EUS and to collect data such as age, gender and CEA value. Descriptive statistics, including counts and percentages and means and standard deviations, were calculated and reported for patient specific demographics and cyst characteristics including cyst pathology, mural nodules, wall and duct characteristics, CEA level and cyst size. Low risk IPMNs were identified on surgical pathology by the presence of low grade dysplasia or no dysplasia. High risk IPMNs were identified on surgical pathology as high grade dysplasia or invasive adenocarcinoma. The two groups were compared. For data measured on an interval scale, student's t-test was used. If the data were ordinal or not normally distributed, the Wilcoxon rank-sum test was employed. For nominal data, the chi-square test or Fisher's exact test was performed. SAS Enterprise Guide®, version 5.1, was used for all analyses. A two-tailed p-value of less than 0.05 was considered statistically significant. Results: A comparison of high and low risk IPMNs showed a statistically significant difference in main ductal dilatation and in cytology obtained during EUS. gender, presence of mural nodule, tortuosity of the pancreatic duct, wall thickness, age, CEA level and cyst size were not found to be significantly different between the two groups. Conclusion: For IPMNs, measurement of main ductal dilatation and results of cytology observed and obtained during EUS were statistically significant differences between low and high risk IPMNsTable 1: Results

Pancreatic cyst fluid concentration of high-mobility group A2 protein acts as a differential biomarker of dysplasia in intraductal papillary mucinous neoplasm

No reliable cyst fluid biomarkers exist that allow preoperative identification of patients with intraductal papillary mucinous neoplasms (IPMNs) and high-risk pathology. High-mobility group (HMG) A2protein has been demonstrated to be a biomarker of dysplasia in IPMNs. It is unknown whether HMGA2 protein is present in the cyst fluid from IPMNs. The aims of this study were to determine whether HMGA2 protein is present in the cyst fluid of IPMNs and demonstrate whether HMGA2 protein concentration correlates with the degree of dysplasia. Patients with surgically resected IPMNs and banked pancreatic cyst fluid were identified. Low-risk IPMNs (low-grade [LGD] or moderate dysplasia [MD]) and high-risk IPMNs (high-grade dysplasia [HGD] or invasive cancer) were identified. Pancreatic cyst fluid concentrations of HMGA2 protein were measured via enzyme-linked immunosorbent assay. Samples from 31 patients were analyzed. HMGA2 protein was detected in the cyst fluid of 30 of 31 specimens (97%). Median cyst fluid HMGA2 protein concentration (ng/mL) was as follows: LGD, 0.6 (interquartile range [IQR] 0.35-0.6); MD, 1.55 (IQR 0.65-2.7); HGD, 4.2 (IQR 1.7-9.2) (P< .05). The median HMGA2 protein concentration was significantly higher in the HGD group (4.2 ng/mL, IQR 1.7-9.2) compared with the concentration in the low-risk group (1.1 ng/mL, IQR 0.6-2.7, P= .03). HMGA2 protein is present in IPMN cyst fluid. Significantly higher concentrations of cyst fluid HMGA2 protein are found in IPMNs with HGD compared with lesions with LGD or MD. Cyst fluid concentrations of HMGA2 protein may thus serve as a biomarker to differentiate patients with high-risk IPMNs from those with low-risk IPMNs.

A genome-wide investigation of microRNA expression identifies biologically-meaningful microRNAs that distinguish between high-risk and low-risk intraductal papillary mucinous neoplasms of the pancreas.

BackgroundIntraductal papillary mucinous neoplasms (IPMNs) are pancreatic ductal adenocarcinoma (PDAC) precursors. Differentiating between high-risk IPMNs that warrant surgical resection and low-risk IPMNs that can be monitored is a significant clinical problem, and we sought to discover a panel of mi(cro)RNAs that accurately classify IPMN risk status.Methodology/Principal FindingsIn a discovery phase, genome-wide miRNA expression profiling was performed on 28 surgically-resected, pathologically-confirmed IPMNs (19 high-risk, 9 low-risk) using Taqman MicroRNA Arrays. A validation phase was performed in 21 independent IPMNs (13 high-risk, 8 low-risk). We also explored associations between miRNA expression level and various clinical and pathological factors and examined genes and pathways regulated by the identified miRNAs by integrating data from bioinformatic analyses and microarray analysis of miRNA gene targets. Six miRNAs (miR-100, miR-99b, miR-99a, miR-342-3p, miR-126, miR-130a) were down-regulated in high-risk versus low-risk IPMNs and distinguished between groups (P<10−3, area underneath the curve (AUC) = 87%). The same trend was observed in the validation phase (AUC = 74%). Low miR-99b expression was associated with main pancreatic duct involvement (P = 0.021), and serum albumin levels were positively correlated with miR-99a (r = 0.52, P = 0.004) and miR-100 expression (r = 0.49, P = 0.008). Literature, validated miRNA:target gene interactions, and pathway enrichment analysis supported the candidate miRNAs as tumor suppressors and regulators of PDAC development. Microarray analysis revealed that oncogenic targets of miR-130a (ATG2B, MEOX2), miR-342-3p (DNMT1), and miR-126 (IRS-1) were up-regulated in high- versus low-risk IPMNs (P<0.10).ConclusionsThis pilot study highlights miRNAs that may aid in preoperative risk stratification of IPMNs and provides novel insights into miRNA-mediated progression to pancreatic malignancy. The miRNAs identified here and in other recent investigations warrant evaluation in biofluids in a well-powered prospective cohort of individuals newly-diagnosed with IPMNs and other pancreatic cysts and those at increased genetic risk for these lesions.

EUS 2008 Working Group document: evaluation of EUS-guided pancreatic-cyst ablation

Pancreatic cysts encompass a wide spectrum of morphologic and histopathologic types. 1 Broadly, they are classified into 2 main types, mucinous and nonmucinous, which differ natural history and clinical characteristics. The nonmucinous lesions include serous cystadenomas and cystic endocrine tumors. Mucinous cystic lesions may be benign, borderline, or malignant nature and include benign mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMN). Mucinous cysts are unique their predisposition toward malignant transformation. The traditional therapy of cystic neoplasms, particularly mucinous lesions, has been surgical resection. There is now evidence to support clinical monitoring of low-risk mucinous lesions, such as side-branch IPMN lesions or those patients who are poor surgical candidates. Although small, incidental simple pancreatic cysts 2 cm or smaller may enlarge over a prolonged time. Morbidity or mortality because of these small simple cysts is extremely unlikely, and observation appears to be a safe management option. 2 Sahani et al 3 reported on 86 patients with cystic lesions less than 3 cm diameter that were resected after EUS-guided FNA. The majority (n = 75) of small pancreatic cysts were benign. Thirty-six cysts were unilocular, and virtually all of these (n = 35) were benign. The presence of septa was associated with borderline or in situ malignancy 20% of cases (10 of 50). Low-risk IPMNs the elderly are probably best managed with periodic imaging. 4 A report of a recent task force also recommended periodic imaging for cysts less than 3 cm diameter.5 A general schema for management of pancreatic-cyst neoplasm is shown Table 1. As an alternative to surgical resection or monitoring, EUS-guided ethanol ablation of pancreatic-cystic lesions may have a role carefully selected patients. This section of the EUS 2008 Working Group Proceedings will evaluate the current role of EUS-guided ethanol ablation the management of pancreatic cyst neoplasms and provide recommendations for future research this area.