Despite the increasing rate of detection of incidental pancreatic cystic lesions (PCLs), current standard-of-care methods for their diagnosis and risk stratification remain inadequate. Intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent PCLs. The existing modalities, including endoscopic ultrasound and cyst fluid analysis, only achieve accuracy rates of 65-75% in identifying carcinoma or high-grade dysplasia in IPMNs. Furthermore, surgical resection of PCLs reveals that up to half exhibit only low-grade dysplastic changes or benign neoplasms. To reduce unnecessary and high-risk pancreatic surgeries, more precise diagnostic techniques are necessary. A promising approach involves integrating existing data, such as clinical features, cyst morphology, and data from cyst fluid analysis, with confocal endomicroscopy and radiomics to enhance the prediction of advanced neoplasms in PCLs. Artificial intelligence and machine learning modalities can play a crucial role in achieving this goal. In this review, we explore current and future techniques to leverage these advanced technologies to improve diagnostic accuracy in the context of PCLs.

Pancreatic ductal adenocarcinoma has a very high mortality rate which has been only minimally improved in the last 30 years. This high mortality is closely related to late diagnosis, which is usually made when the tumor is large and has extensively infiltrated neighboring tissues or distant metastases are already present. This is a paradoxical situation for a tumor that requires nearly 15 years to develop since the first founding mutation. Response to chemotherapy under such late circumstances is poor, resistance is frequent, and prolongation of survival is almost negligible. Early surgery has been, and still is, the only approach with a slightly better outcome. Unfortunately, the relapse percentage after surgery is still very high. In fact, early surgery clearly requires early diagnosis. Despite all the advances in diagnostic methods, the available tools for improving these results are scarce. Serum tumor markers permit a late diagnosis, but their contribution to an improved therapeutic result is very limited. On the other hand, effective screening methods for high-risk populations have not been fully developed as yet. This paper discusses the difficulties of early diagnosis, evaluates whether the available diagnostic tools are adequate, and proposes some simple and not-so-simple measures to improve it.

Pancreatic cyst fluid analysis can help diagnose pancreatic cyst type and the risk of high-grade dysplasia and cancer. Recent evidence from molecular analysis of cyst fluid has revolutionized the field with multiple markers showing promise in accurate diagnosis and prognostication of pancreatic cysts. The availability of multi-analyte panels has great potential for more accurate prediction of cancer.

Mucinous Cystic Neoplasms (MCN) of the pancreas are premalignant cysts for which current guidelines support pancreatic resection. The primary aim of this systematic review and meta-analysis is to define the pooled rate of malignancy for MCN.

A systematic review of eligible studies published between 2000 and 2021 was performed on PubMed and Embase. Primary outcome was rate of malignancy. Data regarding high-risk features, including cyst size and mural nodules, were collected and analyzed.

A total of 40 studies and 3292 patients with resected MCN were included in the final analysis. The pooled rate of malignancy was 16.1% (95%CI 13.1-19.0). The rate of malignant MCN in studies published before 2012 was significantly higher than that of studies published after recent guidelines were published (21.0% vs 14.9%, p < 0.001). Malignant MCN were larger than benign (mean difference 25.9 mm 95%CI 14.50-37.43, p < 0.001) with a direct correlation between size and presence of malignant MCN (R2 = 0.28, p = 0.020). A SROC identified a threshold of 65 mm to be associated with the diagnosis of malignant MCN. Presence of mural nodules was associated with the diagnosis of a malignant MCN (OR = 4.34, 95%CI 3.00-6.29, p < 0.001).

Whereas guidelines recommend resection of all MCN, the rate of malignancy in resected MCN is 16%, implying that surveillance has a role in most cases, and that surgical selection criteria are warranted. Size and presence of mural nodules are significantly associated with an increased risk of malignant degeneration, small MCN and without mural nodules can be considered for surveillance.

To determine whether uncinate duct dilatation (UDD) increases the risk of high-grade dysplasia or invasive carcinoma (HGD/IC) in Fukuoka-positive intraductal papillary mucinous neoplasms (IPMNs).

Though classified as a branch duct, the uncinate duct is the primary duct of the pancreatic ventral anlage. We hypothesized that UDD, like main duct dilatation, confers additional risk for HGD/IC.

A total of 467 patients met inclusion criteria in a retrospective cohort study of surgically resected IPMNs at the Massachusetts General Hospital. We used multivariable logistic regression to analyze the association between UDD (defined as ≥4 mm) and HGD/IC, controlling for Fukuoka risk criteria. In a secondary analysis, the modeling was repeated in the 194 patients with dorsal branch duct IPMNs (BD-IPMNs) in the pancreatic neck, body, or tail.

Mean age at surgery was 70, and 229 (49%) patients were female. In total, 267 (57%) patients had only worrisome features and 200 (43%) had at least 1 high-risk feature. UDD was present in 164 (35%) patients, of whom 118 (73%) had HGD/IC. On multivariable analysis, UDD increased the odds of HGD/IC by 2.8-fold, even while controlling for Fukuoka risk factors (95% CI: 1.8-4.4, P <0.001). Prevalence of HGD/IC in all patients with UDD was 73%, compared with 74% in patients with high-risk stigmata and 73% in patients with main duct IPMNs. In the secondary analysis, UDD increased the odds of HGD/IC by 3.2-fold in patients with dorsal BD-IPMNs (95% CI: 1.3-7.7, P =0.010).

UDD confers additional risk for HGD/IC unaccounted for by current Fukuoka criteria. Further research can extend this study to Fukuoka-negative patients, including unresected patients.

Intraductal papillary mucinous neoplasms (IPMNs), a type of cystic pancreatic cancer (PC) precursors, are increasingly identified on cross-sectional imaging and present a significant diagnostic challenge. While surgical resection of IPMN-related advanced neoplasia, i.e., IPMN-related high-grade dysplasia or PC, is an essential early PC detection strategy, resection is not recommended for IPMN-low-grade dysplasia (LGD) due to minimal risk of carcinogenesis, and significant procedural risks. Based on their promising results in prior validation studies targeting early detection of classical PC, DNA hypermethylation-based markers may serve as a biomarker for malignant risk stratification of IPMNs. This study investigates our DNA methylation-based PC biomarker panel (ADAMTS1, BNC1, and CACNA1G genes) in differentiating IPMN-advanced neoplasia from IPMN-LGDs.

Our previously described genome-wide pharmaco-epigenetic method identified multiple genes as potential targets for PC detection. The combination was further optimized and validated for early detection of classical PC in previous case-control studies. These promising genes were evaluated among micro-dissected IPMN tissue (IPMN-LGD: 35, IPMN-advanced neoplasia: 35) through Methylation-Specific PCR. The discriminant capacity of individual and combination of genes were delineated through Receiver Operating Characteristics curve analysis.

As compared to IPMN-LGDs, IPMN-advanced neoplasia had higher hypermethylation frequency of candidate genes: ADAMTS1 (60% vs. 14%), BNC1 (66% vs. 3%), and CACGNA1G (25% vs. 0%). We observed Area Under Curve (AUC) values of 0.73 for ADAMTS1, 0.81 for BNC1, and 0.63 for CACNA1G genes. The combination of the BNC1/ CACNA1G genes resulted in an AUC of 0.84, sensitivity of 71%, and specificity of 97%. Combining the methylation status of the BNC1/CACNA1G genes, blood-based CA19-9, and IPMN lesion size enhanced the AUC to 0.92.

DNA-methylation based biomarkers have shown a high diagnostic specificity and moderate sensitivity for differentiating IPMN-advanced neoplasia from LGDs. Addition of specific methylation targets can improve the accuracy of the methylation biomarker panel and enable the development of noninvasive IPMN stratification biomarkers.

The rate of incidentally detected pancreatic cystic lesions (PCLs) has increased over the past decade and was recently reported at 8%. These lesions pose a unique challenge, as each subtype of PCL carries a different risk of malignant transformation, ranging from 0% (pancreatic pseudocyst) to 34-68% (main duct intraductal papillary mucinous neoplasm). It is imperative to correctly risk-stratify the malignant potential of these lesions in order to provide the correct care course for the patient, ranging from monitoring to surgical intervention. Even with the multiplicity of guidelines (i.e., the American Gastroenterology Association guidelines and Fukuoka/International Consensus guidelines) and multitude of diagnostic information, risk stratification of PCLs falls short. Studies have reported that 25-64% of patients undergoing PCL resection have pancreatic cysts with no malignant potential, and up to 78% of mucin-producing cysts resected harbor no malignant potential on pathological evaluation. Clinicians are now incorporating artificial intelligence technology to aid in the management of these difficult lesions. This review article focuses on advancements in artificial intelligence within digital pathomics, radiomics, and genomics as they apply to the diagnosis and risk stratification of PCLs.

There is growing evidence to indicate that inflammatory reactions are involved in cancer progression. The aim of this study is to assess the significance of systemic inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the ratio of C-reactive protein to albumin ratio (CAR), the prognostic nutritional index (PNI) and the modified Glasgow prognostic score (mGps) in the diagnosis and prognosis of malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Data were obtained from a retrospective analysis of patients who underwent pancreatic resection for IPMNs from January 2005 to December 2015. Univariate and multivariate analyses were performed, considering preoperative inflammatory biomarkers, clinicopathological variables, and imaging features. Eighty-three patients with histologically proven IPMNs of the pancreas were included in the study, 37 cases of low-grade or intermediate dysplasia and 46 cases of high-grade dysplasia (HGD) or invasive carcinoma. Univariate analysis showed that obstructive jaundice (p = 0.02) and a CAR of >0.083 (p = 0.001) were predictors of malignancy. On multivariate analysis, only the CAR was a statistically significant independent predictor of HGD or invasive carcinoma in pancreatic IPMNs, identifying a subgroup of patients with a poor prognosis. Combining the CAR with patients' imaging findings, clinical features and tumor markers can be useful in the clinical management of IPMNs. Their value should be tested in prospective studies.

Objectives: Pancreatic cysts are frequently detected in high-risk individuals (HRI) undergoing surveillance for pancreatic cancer. The International Cancer of the Pancreas Screening (CAPS) Consortium developed consensus recommendations for surgical resection of pancreatic cysts in HRI that are similar to the Fukuoka guidelines used for the management of sporadic cysts. We compared the performance characteristics of CAPS criteria for pancreatic cyst management in HRI with the Fukuoka guidelines originally designed for the management of cysts in non-HRI.

Using prospectively collected data from CAPS studies, we determined for each patient with resected screen-detected cyst(s) whether Fukuoka guidelines or CAPS consensus statements would have recommended surgery. We compared sensitivity, specificity, PPV, NPV, and Receiver Operator Characteristics (ROC) curves of these guidelines at predicting the presence of high-grade dysplasia or invasive cancer in pancreatic cysts.

356/732 HRI had ≥ one pancreatic cyst detected; 24 had surgery for concerning cystic lesions. The sensitivity, specificity, PPV, and NPV for the Fukuoka criteria were 40%, 85%, 40%, and 85%, while those of the CAPS criteria were 60%, 85%, 50%, 89%, respectively. ROC curve analyses showed no significant difference between the Fukuoka and CAPS criteria.

In HRI, the CAPS and Fukuoka criteria are moderately specific, but not sufficiently sensitive for detecting advanced neoplasia in cystic lesions. New approaches are needed to guide the surgical management of cystic lesions in HRI.

To evaluate the significance of UDD in IPMNs.

The uncinate process of the pancreas has an independent ductal drainage system. International consensus guidelines of IPMNs still consider it as a branch-duct, even though it is the main drainage system for the uncinate process.

A retrospective review of all surgically treated IPMNs at our institution after 2008 was performed. Preoperative radiological studies were reviewed by an abdominal radiologist who was blinded to the pathological results. In addition to the Fukuoka criteria, presence of UDD was recorded. Using multivariate analysis, the pathological significance of UDD in predicting advanced neoplasia [high grade dysplasia or invasive carcinoma (HGD/IC)] was determined.

Two hundred sixty patients were identified (mean age at diagnosis was 68 years and 49% were females): 122 (47%) had HGD/IC. UDD was noted in 59 (23%), of which 36 (61%) had HGD/IC (P < 0.003). On multivariate analysis, UDD was an independent predictor of HGD/IC (odds ratio = 2.99, P < 0.04). Subgroup analysis on patients with IPMNs confined to the dorsal portion of the gland (n = 161), also demonstrated UDD to be a significant predictor of HGD/IC in those remote lesions (odds ratio: 4.41, P = 0.039).

This is the largest study to evaluate the significance of UDD in IPMNs and shows it to be a high-risk feature. This association persisted for remote IPMNs limited to the dorsal pancreas, suggesting UDD may be associated with an aggressive phenotype even in remote IPMN lesions.

Over the years, several guidelines have been introduced to guide management of mucinous pancreatic cystic neoplasms (mPCN). In this study, we aimed to evaluate and compare the clinically utility of the Sendai-06, Fukuoka-12, Fukuoka-17 and European-18 guidelines in predicting malignancy of mPCN.

One hundred and eighty-eight patients with mucinous cystic neoplasms (MCN) or intraductal papillary mucinous neoplasm (IPMN) who underwent surgery were retrospectively reviewed and classified under the 4 guidelines. Malignancy was defined as high grade dysplasia and invasive carcinoma.

Raised CA19-9>37U/ml, enhancing mural nodule≥5 mm and main pancreatic duct≥10 mm were significantly associated with malignancy on multivariate analysis. Increasing number of high risk features, absolute indications (European-18), worrisome risk or relative indications (European-18) were significantly associated with an increased likelihood of malignancy. The positive predictive values (PPV) of high risk features for Sendai-06, Fukuoka-12, Fukuoka-17 and absolute indications (European-18) for malignancy were 53%, 76%, 78% and 78% respectively. The negative predictive values (NPV) of the Sendai-06, Fukuoka-12 and Fukuoka-17 were 100%, while that of the European-18 was 92%. Risk of malignancy for patients with ≥4 worrisome features (Fukuoka-17) and ≥3 relative indications (European-18) was 66.7% and 75.0% respectively.

All 4 guidelines studied were useful in the initial triage of mPCN for the risk stratification of malignancy. The Fukuoka-17 had the highest PPV and NPV.

Society consensus guidelines are commonly used to guide management of pancreatic cystic neoplasms (PCNs). However, downsides of these guidelines include unnecessary surgery and missed malignancy. The aim of this study was to use computed tomography (CT)-guided deep learning techniques to predict malignancy of PCNs.

Patients with PCNs who underwent resection were retrospectively reviewed. Axial images of the mucinous cystic neoplasms were collected and based on final pathology were assigned a binary outcome of advanced neoplasia or benign. Advanced neoplasia was defined as adenocarcinoma or intraductal papillary mucinous neoplasm with high-grade dysplasia. A convolutional neural network (CNN) deep learning model was trained on 66% of images, and this trained model was used to test 33% of images. Predictions from the deep learning model were compared to Fukuoka guidelines.

Twenty-seven patients met the inclusion criteria, with 18 used for training and 9 for model testing. The trained deep learning model correctly predicted 3 of 3 malignant lesions and 5 of 6 benign lesions. Fukuoka guidelines correctly classified 2 of 3 malignant lesions as high risk and 4 of 6 benign lesions as worrisome. Following deep learning model predictions would have avoided 1 missed malignancy and 1 unnecessary operation.

In this pilot study, a deep learning model correctly classified 8 of 9 PCNs and performed better than consensus guidelines. Deep learning can be used to predict malignancy of PCNs; however, further model improvements are necessary before clinical use.

This article outlines the principles behind the management of pancreatic cystic lesions. We outline what the general surgeon needs to know in managing and triaging these patients. It is our feeling that the general surgeon is often the first line of evaluation of these complex patients and a working knowledge of the different types of cysts is critical to safe care of the patient.

Incidental pancreatic cysts are common, and management strategies continue to evolve. This review summarizes diagnostic and management recommendations in older patients with these lesions based on guidelines and best clinical evidence.

Diagnosis of cyst type has been enhanced with improved imaging and cyst fluid analysis and visualization. Recent outcome studies indicate that certain cyst types should be followed independent of patient age as long as certain criteria which are reviewed are met. Differentiation of pancreatic cyst type is important as this dictates the need for long-term follow-up. Because most cyst-related neoplasia occurs in older patients, surveillance should continue within certain guidelines.

A differential diagnosis of advanced pancreatic cystic neoplasms (PCNs) is critical to determine optimal treatment. The Fukuoka and American Gastroenterological Association (AGA) guidelines are the most widely accepted criteria for the management of PCNs.

This study aimed to evaluate the diagnostic value of these guidelines in predicting advanced neoplasia (AN).

A comprehensive electronic search of the PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases was conducted to identify all relevant studies evaluating the Fukuoka and AGA guidelines in surgically resected and histologically confirmed PCNs. Pooled sensitivity, specificity, and diagnostic odds ratios (DORs) were calculated as compound measures of diagnostic accuracy using the random-effects model. Summary of receiver operating characteristic (SROC) curves and the area under the curve (AUC) were also performed.

A total of 21 studies with 3723 patients were included in this meta-analysis. Of these studies, 15, 4, and 2 evaluated the Fukuoka guidelines, the AGA guidelines, and both guidelines, respectively. For AN prediction, the Fukuoka guidelines had a pooled sensitivity of 0.67 (95% confidence interval [CI] 0.64-0.70), pooled specificity of 0.64 (95% CI 0.62-0.66), and pooled DOR of 6.28 (95% CI 4.38-9.01), with an AUC of the SROC of 0.78. AGA guidelines showed a pooled sensitivity of 0.59 (95% CI 0.52-0.65), pooled specificity of 0.77 (95% CI 0.74-0.80), and pooled DOR of 5.84 (95% CI 2.60-13.15), with an AUC of 0.79 (95% CI 0.70-0.88).

When used alone, the Fukuoka and AGA guidelines showed similar but unsatisfactory diagnostic accuracy in the risk stratification of malignant potential of PCN. Thus, we recommend that they be applied only as a broad framework in clinical practice.

Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cyst fluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND).

From an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs.

Of 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs (TBX15, BMP3) achieved sensitivity and specificity above 90%. Discrimination was significantly better by this CF-MDM panel than by mutant KRAS or carcinoembryonic antigen, with areas under the receiver operating characteristic curve of 0.93 (95% confidence interval: 0.86-0.99), 0.71 (0.57-0.85), and 0.72 (0.60-0.84), respectively. Cutoffs for the MDM panel applied to an independent CF validation set (31 cases, 56 controls) yielded similarly high discrimination, areas under the receiver operating characteristic curve = 0.86 (95% confidence interval: 0.77-0.94, P = 0.2).

Novel MDMs discovered and validated in tissue accurately identify PCLs harboring HGD/PC. A panel of 2 MDMs assayed in CF yielded results with potential to enhance current risk prediction algorithms. Prospective studies are indicated to optimize and further evaluate CF-MDMs for clinical use.

DNA-based testing of pancreatic cyst fluid (PCF) is a useful adjunct to the evaluation of pancreatic cysts (PCs). Mutations in KRAS/GNAS are highly specific for intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), while TP53/PIK3CA/PTEN alterations are associated with advanced neoplasia. A prospective study was performed to evaluate preoperative PCF DNA testing.

Over 43-months, 626 PCF specimens from 595 patients were obtained by endoscopic ultrasound (EUS)-fine needle aspiration and assessed by targeted next-generation sequencing (NGS). Molecular results were correlated with EUS findings, ancillary studies and follow-up. A separate cohort of 159 PCF specimens was also evaluated for KRAS/GNAS mutations by Sanger sequencing.

KRAS/GNAS mutations were identified in 308 (49%) PCs, while alterations in TP53/PIK3CA/PTEN were present in 35 (6%) cases. Based on 102 (17%) patients with surgical follow-up, KRAS/GNAS mutations were detected in 56 (100%) IPMNs and 3 (30%) MCNs, and associated with 89% sensitivity and 100% specificity for a mucinous PC. In comparison, KRAS/GNAS mutations by Sanger sequencing had a 65% sensitivity and 100% specificity. By NGS, the combination of KRAS/GNAS mutations and alterations in TP53/PIK3CA/PTEN had an 89% sensitivity and 100% specificity for advanced neoplasia. Ductal dilatation, a mural nodule and malignant cytopathology had lower sensitivities (42%, 32% and 32%, respectively) and specificities (74%, 94% and 98%, respectively).

In contrast to Sanger sequencing, preoperative NGS of PCF for KRAS/GNAS mutations is highly sensitive for IPMNs and specific for mucinous PCs. In addition, the combination of TP53/PIK3CA/PTEN alterations is a useful preoperative marker for advanced neoplasia.

Pancreatic cystic lesions are a common clinical entity. The majority are neoplastic and have the potential for malignant transformation. To assist with patient management, a number of clinical guidelines have been developed over the past decade. However, controversies exist in regards to the various guidelines and treatment strategies they offer. This article will review the various clinical guidelines for management of pancreatic cysts, describe the limitations of these guidelines, and present future directions for improvement in clinical decision making for patients diagnosed with a pancreatic cystic neoplasm.

For patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs, cysts), it is a challenge to identify those at high risk for malignant lesions. We sought to identify factors associated with development of pancreatic cancer, focusing on neoplasm growth rate.

We performed a retrospective study of 189 patients with BD-IPMNs who underwent at least 2 contrast-enhanced cross-sectional imaging studies, 1 year or more apart, at a tertiary referral center from January 2003 through 2013. Patients with cysts that had Fukuoka worrisome or high-risk features were excluded. Two radiologists reviewed all images. Cyst size was recorded at the initial and final imaging studies and growth rate was calculated. We collected patient demographic data, cyst characteristics, and clinical outcomes; univariate logistic regression models were used to determine the odds of developing worrisome features. The primary outcomes were to determine growth rate of low-risk BD-IPMNs and to assess whether cyst growth rate correlates high-risk features of IPMNs.

Based on image analyses, cysts were initially a median 11 mm (range, 3-31 mm) and their final size was 12.5 mm (range, 3-42 mm). After a median follow-up time of 56 months (range, 12-163 months), the median cyst growth rate was 0.29 mm/year. Twelve patients developed worrisome features, no patients developed high-risk features, 4 patients had surgical resection, and no cancers developed. The rate of BD-IPMN growth was greater in patients who developed worrisome features than those who did not (2.84 mm/year vs 0.23 mm/year; P < .001). The odds of developing worrisome features increased for each unit (mm) increase in cyst size (odds ratio, 1.149; 95% CI, 1.035-1.276, P = .009).

In a retrospective analysis of images from patients with BD-IPMN, we found low-risk BD-IPMNs to grow at an extremely low rate (less than 0.3 mm/year). BD-IPMNs in only about 6% of patients developed worrisome features, and none developed high-risk features or invasive cancers. BD-IPMNs that developed worrisome features were associated with a significantly higher rate of growth than lesions with low-risk features. Low risk BD-IPMNs that grow more than 2.5 mm/year might require surveillance.

The sudden prevalence increase of pancreatic cystic neoplasms (PCN) related to the use of cross-sectional imaging has raised several concerns. Even if there is a tangible risk of progression towards pancreatic cancer (PC), surgical resection cannot be offered to all patients due to the high risk of morbidity and mortality. Available guidelines are useful tools to identify patients at higher risk for harboring cancer thanks to their sensitivity. Because of their low specificity, however, such a risk is often overestimated. Recent evidence deriving from large observational series of surveilled patients suggests that the overall risk of PC is low. A large proportion of patients affected by PCN can be safely observed over time. Several follow-up schedules have been proposed in guidelines but none of them proved to be the most cost-effective. Moreover, it must still be demonstrated that any surveillance protocol can be associated with a reduction in PC-related mortality. By now, with most studies reporting a lifelong risk of malignancy, the only evidence-based recommendation regarding surveillance is that follow-up should never be discontinued as repeated observations are crucial for PC risk stratification.

The risk of invasive cancer in resected intraductal papillary mucinous neoplasm with main pancreatic duct involvement is 33%-60%. Most guidelines, therefore, advise resection of main duct intraductal papillary mucinous neoplasm and mixed type intraductal papillary mucinous neoplasm in surgically fit patients, although advice on the surgical strategy (partial or total pancreatectomy) differs. We performed a survey amongst international experts to guide the design of future studies and help to prepare for a single international set of guidelines.

An online survey including case vignettes was sent to 221 international experts who had published on main duct/mixed type intraductal papillary mucinous neoplasm in the previous decade and to all surgeon and gastroenterologist members of the pancreatic cyst guideline committees of the European Study Group and the International Association of Pancreatology.

Overall, 97 experts (67 surgeons, 30 gastroenterologists) from 19 countries replied (44% response rate). Most (93%) worked in an academic hospital, with a median of 15 years' experience with intraductal papillary mucinous neoplasm treatment. In main duct/mixed type intraductal papillary mucinous neoplasm patients with pancreatic duct dilation (>5 mm) in the entire pancreas, 41% (n = 37) advised nonoperative surveillance every 3-6 months, whereas 59% (n = 54) advised operative intervention. Of those who advised operative intervention, 46% (n = 25) would perform a total pancreatectomy and 31% (n = 17) pancreatoduodenectomy with follow-up. No structural differences in advice were seen between surgeons and gastroenterologists, between continents where the respondents lived, and based on years of experience.

This international survey identified a clinically relevant lack of consensus in the treatment strategy in main duct/mixed type intraductal papillary mucinous neoplasm among experts. Studies with long-term follow-up including quality of life after partial and total pancreatectomy for main duct/mixed type intraductal papillary mucinous neoplasm are required.

Pancreatic cancer is a highly lethal disease with a dismal 5-year prognosis. Knowledge of its genetics may help in identifying new methods for patient screening, and cancer treatment. In this review, we will describe the most common mutations responsible for the genesis of pancreatic cancer and their impact on screening, patterns of disease progression, and therapy.

Increases in the quality as well as utilization of cross-sectional imaging have led to rising diagnoses of pancreatic cystic lesions (PCL). Accurate presurgical diagnosis enables appropriate triage of PCLs. Unfortunately, current diagnostic approaches have suboptimal accuracy and may lead to unnecessary surgical resections or missed diagnoses of advanced neoplasia. Additionally, early detection represents an opportunity for intervention to prevent the progression to pancreatic adenocarcinoma. Our aim for this review is to systematically review the current literature on confocal endomicroscopy and molecular biomarkers in the evaluation of PCLs. Confocal laser endomicroscopy is a novel technology that allows for real-time in vivo microscopic imaging with multiple clinical trials identifying characteristic endomicroscopy findings of various pancreatic cystic lesions. DNA-based molecular markers have also emerged as another diagnostic modality as the pattern of genetic alternations present in cyst fluid can provide both diagnostic and prognostic data. We propose that both techniques can be utilized to improve patient outcomes.

To evaluate the correlation between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values, and the presence of invasive carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN).

NLR and (PLR) are inflammatory markers that have been associated with overall survival in patients with invasive malignancies, including pancreatic cancer.

We retrospectively reviewed 272 patients who underwent surgical resection for histologically confirmed IPMN from January 1997 to July 2015. NLR and PLR were calculated and coevaluated with additional demographic, clinical, and imaging data for possible correlation with IPMN-associated carcinoma in the form of a predictive nomogram.

NLR and PLR were significantly elevated in patients with IPMN-associated invasive carcinoma (P < 0.001). In the multivariate analysis, NLR value higher than 4 (P < 0.001), IPMN cyst of size more than 3 cm (P < 0.001), presence of enhanced solid component (P = 0.014), main pancreatic duct dilatation of more than 5 mm (P < 0.001), and jaundice (P < 0.001) were statistically significant variables. The developed statistical model has a c-index of 0.895. Implementation of the statistically significant variables in a predictive nomogram provided a reliable point system for estimating the presence of IPMN-associated invasive carcinoma.

NLR is an independent predictive marker for the presence of IPMN-associated invasive carcinoma. Further prospective studies are needed to assess the predictive ability of NLR and how it can be applied in the clinical setting.

Within the past few decades, there has been a dramatic increase in the detection of incidental pancreatic cysts. It is reported a pancreatic cyst is identified in up to 2.6% of abdominal scans. Many of these cysts, including serous cystadenomas and pseudocysts, are benign and can be monitored clinically. In contrast, mucinous cysts, which include intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, have the potential to progress to pancreatic adenocarcinoma. In this review, we discuss the current management guidelines for pancreatic cysts, their underlying genetics, and the integration of molecular testing in cyst classification and prognostication.

The management of intraductal papillary mucinous neoplasm (IPMN) continues to evolve. In particular, the indications for resection of branch duct IPMN have changed from early resection to more deliberate observation as proposed by the international consensus guidelines of 2006 and 2012. Another guideline proposed by the American Gastroenterological Association in 2015 restricted indications for surgery more stringently and recommended physicians to stop surveillance if no significant change had occurred in a pancreatic cyst after five years of surveillance, or if a patient underwent resection and a non-malignant IPMN was found. Whether or not it is safe to do so, as well as the method and interval of surveillance, has generated substantial debate. Based on a consensus symposium held during the meeting of the International Association of Pancreatology in Sendai, Japan, in 2016, the working group has revised the guidelines regarding prediction of invasive carcinoma and high-grade dysplasia, surveillance, and postoperative follow-up of IPMN. As the working group did not recognize the need for major revisions of the guidelines, we made only minor revisions and added most recent articles where appropriate. The present guidelines include updated information and recommendations based on our current understanding, and highlight issues that remain controversial or where further research is required.

With increased utilization and ongoing advancements in cross-sectional abdominal imaging, the identification of a pancreatic cyst has become a frequent finding. While many pancreatic cysts are associated with a benign clinical course, others may transform into pancreatic ductal adenocarcinoma. However, distinguishing a benign from a malignant pancreatic cyst or pancreatic cyst with malignant potential on the basis of standard clinical findings, imaging parameters and ancillary studies can be challenging. Hence, a significant interest within the past decade has been the identification of novel biomarkers to accurately classify and prognosticate a pancreatic cyst. Within this review, we discuss novel DNA, miRNA, protein and metabolite biomarkers, and their relevance in clinical practice. In addition, we focus on future areas of research that have the potential to change pancreatic cyst management.

CT and MRI are the imaging modalities of choice to guide the clinical management of incidentally discovered pancreatic cysts. Most of these lesions are mucinous cysts with varying degrees of malignant potential. This article reviews the CT and MRI findings that help differentiate a potentially aggressive lesion that requires EUS or surgery from a lesion of low malignant potential that is appropriate for imaging surveillance. The imaging-based societal guidelines for these cysts are reviewed.

Pancreatic cysts, especially incidental asymptomatic ones seen on noninvasive imaging such as CT or MR imaging, remain a clinical challenge. The etiology of such cysts may range from benign cysts without any malignant potential such as pancreatic pseudocysts and serous cystadenomas to premalignant or frankly malignant cysts such as mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, cystic degeneration associated with solid tumors such as pancreatic ductal adenocarcinoma or pancreatic endocrine neoplasms, and solid pseudopapillary neoplasms. The clinical challenge in 2017 is to accurately preoperatively diagnose them and their malignant potential before deciding about surgery, surveillance or doing nothing. This review will focus on the currently available clinical guidelines for doing so.

Pancreatic cysts are commonly found on cross-sectional imaging. The question arises in determining which lesions are premalignant or malignant and may require further testing, intervention, or follow-up. In pancreatic cysts without obvious malignancy on imaging, we approach them using the Four "S" Criteria. These are (1) symptoms that may be originating from the pancreatic cyst; (2) size of the cyst 2 cm or larger and/or main pancreatic duct greater than 5 mm; (3) survival of the patient, based on comorbidity index to determine surgical fitness; and then endoscopic ultrasound with fine needle aspiration (FNA) recommended to determine (4) solid component presence in the cyst, namely, nodule or thick walls, as well as to perform FNA to obtain cyst content. Current cyst fluid analysis options include use of cytology to determine presence of malignancy and carcinoembryonic antigen and fluid genetics to identify potentially premalignant lesions. The aims of this article are to explore current management guidelines for pancreatic cysts, present a comprehensive approach to pancreatic cysts, and explain the advantages and disadvantages of each option for evaluation of pancreatic cysts including endoscopic ultrasound with FNA with cyst fluid analysis using an evidence-based approach.

Currently, 3 guidelines are available for the management of pancreatic cysts. These guidelines vary in their indication for resection of high-risk cysts. We retrospectively compared the final pathologic outcome of surgically removed pancreatic cysts with the indications for resection according to 3 different guidelines.

Patients who underwent pancreatic resection were extracted from our prospective pancreatic cyst database (2006-present). The final histopathologic diagnosis was compared with the initial indication for surgery stated by the guidelines of the International Association of Pancreatology (IAP), European Study Group on Cystic tumors of the Pancreas and American Gastroenterological Association (AGA). We considered surgery in retrospect justified for malignancy, high-grade dysplasia, solid pseudopapillary neoplasms, neuroendocrine tumors or symptom improvement. Furthermore, we evaluated the patients with suspected intraductal papillary mucinous neoplasm (IPMN) separately.

Overall, 115 patients underwent pancreatic resection. The preoperative diagnosis was correct in 83 of 115 patients (72%) and differentiation between benign and premalignant in 99 of 115 patients (86%). In retrospect, surgery was justified according to the aforementioned criteria in 52 of 115 patients (45%). For patients with suspected IPMN (n = 75) resection was justified in 36 of 67 (54%), 36 of 68 (53%), and 32 of 54 (59%) of patients who would have had surgery based on the IAP, European, or AGA guidelines, respectively. The AGA guideline would have avoided resection in 21 of 75 (28%) patients, versus 8 of 75 (11%) and 7 of 75 (9%) when the IAP or European guideline would have been applied strictly. Nevertheless, 4 of 33 patients (12%) with high-grade dysplasia or malignancy would have been missed with the AGA guidelines, compared with none with the IAP or European guidelines.

Although fewer patients undergo unnecessary surgery based on the AGA guidelines, the risk of missing malignancy or high-grade dysplasia with this guideline seems considerably high.

Increasing numbers of incidental pancreatic lesions are being detected each year. Accurate characterisation of pancreatic lesions into benign, precancerous, and cancer masses is crucial in deciding whether to use treatment or surveillance. Distinguishing benign lesions from precancerous and cancerous lesions can prevent patients from undergoing unnecessary major surgery. Despite the importance of accurately classifying pancreatic lesions, there is no clear algorithm for management of focal pancreatic lesions.

To determine and compare the diagnostic accuracy of various imaging modalities in detecting cancerous and precancerous lesions in people with focal pancreatic lesions.

We searched the CENTRAL, MEDLINE, Embase, and Science Citation Index until 19 July 2016. We searched the references of included studies to identify further studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively.

We planned to include studies reporting cross-sectional information on the index test (CT (computed tomography), MRI (magnetic resonance imaging), PET (positron emission tomography), EUS (endoscopic ultrasound), EUS elastography, and EUS-guided biopsy or FNA (fine-needle aspiration)) and reference standard (confirmation of the nature of the lesion was obtained by histopathological examination of the entire lesion by surgical excision, or histopathological examination for confirmation of precancer or cancer by biopsy and clinical follow-up of at least six months in people with negative index tests) in people with pancreatic lesions irrespective of language or publication status or whether the data were collected prospectively or retrospectively.

Two review authors independently searched the references to identify relevant studies and extracted the data. We planned to use the bivariate analysis to calculate the summary sensitivity and specificity with their 95% confidence intervals and the hierarchical summary receiver operating characteristic (HSROC) to compare the tests and assess heterogeneity, but used simpler models (such as univariate random-effects model and univariate fixed-effect model) for combining studies when appropriate because of the sparse data. We were unable to compare the diagnostic performance of the tests using formal statistical methods because of sparse data.

We included 54 studies involving a total of 3,196 participants evaluating the diagnostic accuracy of various index tests. In these 54 studies, eight different target conditions were identified with different final diagnoses constituting benign, precancerous, and cancerous lesions. None of the studies was of high methodological quality. None of the comparisons in which single studies were included was of sufficiently high methodological quality to warrant highlighting of the results. For differentiation of cancerous lesions from benign or precancerous lesions, we identified only one study per index test. The second analysis, of studies differentiating cancerous versus benign lesions, provided three tests in which meta-analysis could be performed. The sensitivities and specificities for diagnosing cancer were: EUS-FNA: sensitivity 0.79 (95% confidence interval (CI) 0.07 to 1.00), specificity 1.00 (95% CI 0.91 to 1.00); EUS: sensitivity 0.95 (95% CI 0.84 to 0.99), specificity 0.53 (95% CI 0.31 to 0.74); PET: sensitivity 0.92 (95% CI 0.80 to 0.97), specificity 0.65 (95% CI 0.39 to 0.84). The third analysis, of studies differentiating precancerous or cancerous lesions from benign lesions, only provided one test (EUS-FNA) in which meta-analysis was performed. EUS-FNA had moderate sensitivity for diagnosing precancerous or cancerous lesions (sensitivity 0.73 (95% CI 0.01 to 1.00) and high specificity 0.94 (95% CI 0.15 to 1.00), the extremely wide confidence intervals reflecting the heterogeneity between the studies). The fourth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (dysplasia) provided three tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing invasive carcinoma were: CT: sensitivity 0.72 (95% CI 0.50 to 0.87), specificity 0.92 (95% CI 0.81 to 0.97); EUS: sensitivity 0.78 (95% CI 0.44 to 0.94), specificity 0.91 (95% CI 0.61 to 0.98); EUS-FNA: sensitivity 0.66 (95% CI 0.03 to 0.99), specificity 0.92 (95% CI 0.73 to 0.98). The fifth analysis, of studies differentiating cancerous (high-grade dysplasia or invasive carcinoma) versus precancerous (low- or intermediate-grade dysplasia) provided six tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing cancer (high-grade dysplasia or invasive carcinoma) were: CT: sensitivity 0.87 (95% CI 0.00 to 1.00), specificity 0.96 (95% CI 0.00 to 1.00); EUS: sensitivity 0.86 (95% CI 0.74 to 0.92), specificity 0.91 (95% CI 0.83 to 0.96); EUS-FNA: sensitivity 0.47 (95% CI 0.24 to 0.70), specificity 0.91 (95% CI 0.32 to 1.00); EUS-FNA carcinoembryonic antigen 200 ng/mL: sensitivity 0.58 (95% CI 0.28 to 0.83), specificity 0.51 (95% CI 0.19 to 0.81); MRI: sensitivity 0.69 (95% CI 0.44 to 0.86), specificity 0.93 (95% CI 0.43 to 1.00); PET: sensitivity 0.90 (95% CI 0.79 to 0.96), specificity 0.94 (95% CI 0.81 to 0.99). The sixth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (low-grade dysplasia) provided no tests in which meta-analysis was performed. The seventh analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) provided two tests in which meta-analysis was performed. The sensitivity and specificity for diagnosing cancer were: CT: sensitivity 0.83 (95% CI 0.68 to 0.92), specificity 0.83 (95% CI 0.64 to 0.93) and MRI: sensitivity 0.80 (95% CI 0.58 to 0.92), specificity 0.81 (95% CI 0.53 to 0.95), respectively. The eighth analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) or benign lesions provided no test in which meta-analysis was performed.There were no major alterations in the subgroup analysis of cystic pancreatic focal lesions (42 studies; 2086 participants). None of the included studies evaluated EUS elastography or sequential testing.

We were unable to arrive at any firm conclusions because of the differences in the way that study authors classified focal pancreatic lesions into cancerous, precancerous, and benign lesions; the inclusion of few studies with wide confidence intervals for each comparison; poor methodological quality in the studies; and heterogeneity in the estimates within comparisons.

The aim of this study was to compare the American Gastroenterological Association guidelines (AGA criteria), the 2012 (Fukuoka criteria), and 2006 (Sendai criteria) International Consensus Guidelines for the diagnosis of advanced pancreatic cystic neoplasms.

All patients who underwent surgical resection of a pancreatic cyst from August 2007 through January 2016 were retrospectively analyzed at a single tertiary academic center. Relevant clinical and imaging variables along with pathology results were collected to determine appropriate classification for each guideline. Advanced pancreatic cystic neoplasms were defined by the presence of either high-grade dysplasia or cystic adenocarcinoma. Diagnostic accuracy was measured by ROC analysis.

A total of 209 patients were included. Both the AGA and Fukuoka criteria had a higher diagnostic accuracy for advanced neoplastic cysts than the Sendai criteria: AGA ROC 0.76 (95% CI 0.69-0.81), Fukuoka ROC 0.78 (95% CI 0.74-0.82), and Sendai ROC 0.65 (95% CI 0.61-0.69) (p < 0.0001). There was no difference between the Fukuoka and the AGA criteria. While the sensitivity was higher in the Fukuoka criteria compared to the AGA criteria (97.7 vs. 88.6%), the specificity was higher in the AGA criteria compared to the Fukuoka criteria (62.4 vs. 58.2%).

In a surgical series of patients with pancreatic cysts, the AGA and Fukuoka criteria had superior diagnostic accuracy for advanced neoplastic cysts compared to the original Sendai criteria.

Background and study aims The American Gastroenterological Association (AGA) recently published guidelines for the management of asymptomatic pancreatic cystic neoplasms (PCNs). We aimed to evaluate the diagnostic characteristics of the AGA guidelines in appropriately recommending surgery for malignant PCNs. Patients and methods A retrospective multicenter study was performed of patients who underwent endoscopic ultrasound (EUS) for evaluation of PCNs who ultimately underwent surgical resection from 2004 - 2014. Demographics, EUS characteristics, fine-needle aspiration (FNA) results, type of resection, and final pathologic diagnosis were recorded. Patients were categorized into 2 groups (surgery or surveillance) based on what the AGA guidelines would have recommended. Performance characteristics for the diagnosis of cancer or high-grade dysplasia (HGD) on surgical pathology were calculated. Results Three hundred patients underwent surgical resection for PCNs, of whom the AGA guidelines would have recommended surgery in 121 (40.3 %) and surveillance in 179 (59.7 %) patients. Among patients recommended for surgery, 45 (37.2 %) had cancer, whereas 76 (62.8 %) had no cancer/HGD. Among patients recommended for surveillance, 170 (95.0 %) had no cancer/HGD; however, 9 (5.0 %) patients had cancer that would have been missed. For the finding of cancer/HGD on surgical pathology, the AGA guidelines had 83.3 % sensitivity (95 % CI 70.7 - 92.1), 69.1 % specificity (95 % CI 62.9 - 74.8), 37.2 % positive predictive value (95 % CI 28.6 - 46.4), 95.0 % negative predictive value (95 % CI 90.7 - 97.7), and 71.7 % accuracy (95 % CI 67.4 - 74.6). Conclusions The 2015 AGA guidelines would have resulted in 60 % fewer patients being referred for surgical resection, and accurately recommended surveillance in 95 % of patients with asymptomatic PCNs. Future prospective studies are required to validate these guidelines. Meeting presentations: Presented in part at Digestive Diseases Week 2016.

Objectives Management of asymptomatic pancreatic cysts is challenging. Guidelines by the American Gastroenterological Association (AGA) and International Association of Pancreatology (Fukuoka) seek to identify high-risk patients. We assessed performance of these guidelines in selecting patients for endoscopic ultrasound (EUS) and/or surgery. Methods PART I - We retrospectively studied 143 asymptomatic cysts with magnetic resonance imaging (MRI) followed by EUS. Appropriate selection for EUS was defined as: malignant cytology or surgical pathology, or development of concerning features on MRI as defined by the guidelines. PART II - We retrospectively studied 152 resected cysts to assess the performance of guidelines in selecting cysts for surgery using malignant histology as the outcome. Results PART I - Of 143 EUS, 43 (30.1 %) were male with median age 65.0 years (interquartile range [IQR] 58.0 - 73.0). AGA guideline demonstrated lower sensitivity (17.6 % versus 35.3 %, P = 0.03), higher specificity (94.5 % versus 66.1 %, p < 0.001), and higher accuracy (76.2 % versus 58.7 %, P = 0.002) than Fukuoka. There was no difference in positive predictive value (50.0 % versus 24.5 %, P = 0.15) and negative predictive value (78.6 % versus 76.6 %, p=0.75). PART II - Of 152 resected cysts, 45 (29.8 %) were male with median age 59.0 years (IQR 47.3 - 66.7). There was no difference in performance characteristics of the guidelines in selecting cysts for surgery. AGA and Fukuoka guidelines missed 25.0 % and 18.8 % of malignant cysts, respectively (P = 1.00). Conclusions For referral to EUS, the AGA guideline was highly specific compared to Fukuoka; both suffered from poor sensitivity, although the Fukuoka guideline was relatively more sensitive than AGA. For referral to surgery, both guidelines have modest sensitivity and specificity and miss a similar percentage of malignant lesions.

Pancreatic cysts are a clinical quandary in both diagnosis and management. Although many cysts, such as pseudocysts and serous cystadenomas, are benign and can be monitored clinically, mucinous cysts, such as intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, have the potential to progress to pancreatic cancer. Considering the poor prognosis of pancreatic cancer, the detection of a pancreatic cyst can be a source of anxiety for both the patient and physician. This diagnosis in turn can lead to expensive, invasive, and even harmful surveillance and treatment options. As a consequence, several national and international guidelines for the management of pancreatic cysts have been developed over the past decade. However, these guidelines rely on standard clinical assessment, radiographical imaging, and ancillary fluid studies that have insufficient sensitivity and specificity. The application of DNA-based molecular techniques has emerged as an adjunct to the assessment of pancreatic cysts. The cellular content of pancreatic cyst fluid aspirate is often suboptimal for analysis, but DNA isolated from lysed or exfoliated cells within the cyst can be analysed for genetic abnormalities. Moreover, whole exome sequencing and targeted sequencing of the major pancreatic cysts has identified unique mutational profiles for cyst type and genetic alterations that coincide with the development of pancreatic cancer. In this Review, we discuss the major cystic lesions of the pancreas and their underlying molecular pathology, current management guidelines for pancreatic cysts, and integration of DNA-based molecular testing within this field.

To determine if neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were predictive of malignancy in pancreatic cystic neoplasms (PCN) and if these improved the performance of the international consensus guidelines (ICG) in the initial triage of these patients.

318 patients with surgically-treated suspected PCN were retrospectively reviewed. Malignant neoplasms were defined as neoplasms harbouring invasive carcinoma. The optimal cut-off for NLR and PLR were determined by plotting the receiver operating characteristics (ROC) curves of NLR/PLR in predicting malignant PCN and utilizing the Youden index.

The optimal NLR and PLR cut-offs were determined to be 3.33 and 205, respectively. Univariate analyses demonstrated that symptomatic PCNs, age, obstructive jaundice, presence of solid component, dilatation of main pancreatic duct ≥10 mm, high NLR and high PLR were predictive of a malignant PCN. Multivariate analyses demonstrated that obstructive jaundice, presence of solid component, MPD ≥10 mm and high PLR but not NLR were independent predictors of a malignant PCN. A high PLR significantly predicted invasive carcinoma in patients classified within the ICG(HR) group. Comparison between the ROC curves of the ICG versus ICG plus high PLR in predicting malignant PCN demonstrated a significant improvement in the accuracy of the ICG when PLR was included [AUC 0.784 (95% CI: 0.740-0.829) vs AUC 0.822 (95% CI: 0.772-0.872) (p = 0.0032)].

High PLR is an independent predictor of malignancy in PCN. The addition of PLR as a criterion to the ICG improved the accuracy of these guidelines in detecting invasive neoplasms.

The American Gastroenterological Association (AGA) recently reported evidence-based guidelines for the management of asymptomatic neoplastic pancreatic cysts. These guidelines advocate a higher threshold for surgical resection than prior guidelines and imaging surveillance for a considerable number of patients with pancreatic cysts. The aims of this study were to assess the accuracy of the AGA guidelines in detecting advanced neoplasia and present an alternative approach to pancreatic cysts.

The study population consisted of 225 patients who underwent EUS-guided FNA for pancreatic cysts between January 2014 and May 2015. For each patient, clinical findings, EUS features, cytopathology results, carcinoembryonic antigen analysis, and molecular testing of pancreatic cyst fluid were reviewed. Molecular testing included the assessment of hotspot mutations and deletions for KRAS, GNAS, VHL, TP53, PIK3CA, and PTEN.

Diagnostic pathology results were available for 41 patients (18%), with 13 (6%) harboring advanced neoplasia. Among these cases, the AGA guidelines identified advanced neoplasia with 62% sensitivity, 79% specificity, 57% positive predictive value, and 82% negative predictive value. Moreover, the AGA guidelines missed 45% of intraductal papillary mucinous neoplasms with adenocarcinoma or high-grade dysplasia. For cases without confirmatory pathology, 27 of 184 patients (15%) with serous cystadenomas (SCAs) based on EUS findings and/or VHL alterations would continue magnetic resonance imaging (MRI) surveillance. In comparison, a novel algorithmic pathway using molecular testing of pancreatic cyst fluid detected advanced neoplasias with 100% sensitivity, 90% specificity, 79% positive predictive value, and 100% negative predictive value.

The AGA guidelines were inaccurate in detecting pancreatic cysts with advanced neoplasia. Furthermore, because the AGA guidelines manage all neoplastic cysts similarly, patients with SCAs will continue to undergo unnecessary MRI surveillance. The results of an alternative approach with integrative molecular testing are encouraging but require further validation.