Diagnosis and management of pancreatic cystic lesions for the non-gastroenterologist.

Although most pancreatic cystic lesions do not progress to cancer, they create concern for patients and their primary care physicians. The lack of consensus guidelines on diagnosis and surveillance of these lesions can lead to a management conundrum. We review current guidelines on diagnosis and management.

The Use of Integrated Molecular Testing in the Assessment and Management of Pancreatic Cysts.

PURPOSE OF REVIEW: As abdominal imaging becomes more sensitive and regularly used, pancreatic cystic lesions (PCLs) are being diagnosed more frequently. A small but clinically significant minority of these lesions have a predisposition to either harbor malignancy or undergo malignant transformation. This review highlights the current state and performance of cystic fluid biomarkers and how they may be incorporated into management. RECENT FINDINGS: Among the major domains of molecular testing for PCLs, DNA based analyses have demonstrated the highest accuracy in identifying cyst type and have the most data to support their clinical use. However, epigenetic and protein biomarker based molecular assessments have emerged with the potential to complement DNA based approaches. In addition, recent studies have increasingly demonstrated the value associated with combinations of mutations and other biomarkers in identifying higher grade mucinous cystic lesions. We present the performance of individual biomarkers in cyst fluid analysis with an emphasis on an algorithmic approach to improve the accurate identification of both cyst type and risk of malignant transformation.

Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.

BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.

Lymphoepithelial cysts of the pancreas: case report and review of the literature.

BACKGROUND: Lymphoepithelial cysts (LECs) of the pancreas are a rare type of true pancreatic cysts and represent an estimated 0.5% of all pancreatic cystic lesions. They are benign lesions and have no malignant potential. However, they are hard to differentiate from malignant lesions because their imaging and clinical presentation vary greatly. Seeing as these are benign lesions which are increasingly found incidentally during imaging for other indications, correct diagnosis is important to prevent unnecessary intervention and morbidity. CASE REPORT: We report the case of a 41-year-old female who presented with abdominal discomfort, bloating and dyspepsia. An abdominal computed tomography (CT) showed a large mass in the left fossa. We describe the diagnostic and therapeutic measures taken in this case. METHODS: We reviewed the literature for common features of the LEC. We grouped common imaging and histological features of the LEC of the pancreas to provide easily identifiable characteristics to facilitate diagnosis. For the review, we focused on papers, mostly case reports, presenting these common characteristics. We also reviewed the literature for key topics that should be taken into account when considering therapeutic interventions in a patient with a possible diagnosis of a LEC. CONCLUSION: Cysts of the pancreas are increasingly identified due to widespread use and improved resolution of cross-sectional imaging. To obtain the correct diagnosis, it is sometimes necessary to combine advanced imaging, i.e. CT and MRI-imaging, and endoscopic ultrasound with fine needle aspiration (EUS/FNA), while CA 19-9 also has diagnostic value. We summarize all diagnostic characteristics in a table for ease of use. Furthermore we summarized possible therapeutic interventions.

[Management of a cystic lesion of the pancreas discovered incidentally]. / Prise en charge d'une lésion kystique du pancréas de découverte fortuite.

Pancreatic cysts (PC) are common and often discovered incidentally. The distinction between PC is essential, because of the potential malignancy of some lesions requiring surgical resection. The clinical orientation will depend on the clinical history and the radiological characteristics. Indeed, in front of all PCs, it is essential to characterize them using cross-sectional imaging (MRI) in order to highlight the worrisome features requiring further examinations by endoscopic ultrasonography and fine needle aspiration of the cysts to guide the diagnosis. Referral to an expert center will allow to propose to each patient an adequate approach: surgical resection, surveillance according to the recommendations or therapeutic abstention.

Les lésions kystiques du pancréas (LKP) sont fréquentes et souvent découvertes de manière fortuite. La distinction entre les différentes LKP est primordiale, en raison du potentiel dégénératif de certaines lésions. L'orientation clinique dépendra des antécédents personnels, du profil clinique et des caractéristiques radiologiques. Devant tout kyste du pancréas, il est primordial de caractériser les LKP à l'aide d'une imagerie en coupe (IRM) afin de mettre en évidence les signes péjoratifs nécessitant un complément d'examen par écho-endoscopie digestive (EED) avec ponction du liquide intrakystique afin de guider le diagnostic. L'orientation vers un centre expert permettra de proposer une attitude adaptée à la lésion et au patient : résection chirurgicale, surveillance selon les recommandations ou abstention thérapeutique.

Comparison of Society Guidelines for the Management and Surveillance of Pancreatic Cysts: A Review.

Importance: The identification of incidental pancreas cystic lesions (PCLs) has increased in recent decades with the expanded use and improved sensitivity of cross-sectional imaging. Because the overall risk of malignancy associated with PCLs is low, yet the relative morbidity of pancreatic surgery is high, evidence-based guidelines are necessary for appropriate surveillance and management. Therefore, this article provides a review of existing guidelines regarding surveillance and management of PCLs and highlights recent advances in the diagnostic evaluation of cysts and the postresection management of mucinous lesions. Observations: There are 5 main guidelines related to the management of PCLs: the American Gastrointestinal Association (AGA) guidelines, the American College of Gastroenterology (ACG) guidelines, the American College of Radiology (ACR) recommendations, the European evidence-based guidelines, and the International Association of Pancreatology (IAP)/Fukuoka guidelines. These guidelines are based on retrospective studies that do not account or control for most tumor- and patient-specific factors. These guidelines also vary in scope, recommendations for surgical resection vs surveillance, as well as duration and type of follow-up. Conclusions and Relevance: PCL guidelines should be viewed within the context of the data limitations on which they are based. PCL subtype-specific guidelines on surveillance and treatment are needed. In the future, the integration of cyst-specific genomic analysis, as well as evolutions in advanced diagnostic tools, such as cyst fluid next-generation sequencing and EUS-guided confocal laser endomicroscopy, may also better inform treatment guidelines. Owing to the current low-quality evidence on which many guidelines are based and the inherent morbidity of pancreas surgery, it is imperative that patients with PCLs are referred to institutions with advanced diagnostics and a multidisciplinary approach to patient surveillance and management.

Pancreatic cystic lesions. Differential diagnosis and treatment strategy.

The differential diagnosis of pancreatic cystic lesions (PCLs) includes non-neoplastic lesions and neoplastic epithelial lesions. Given that management is determined by the risk for malignant progression, associated symptoms, and other characteristics, an accurate diagnosis is imperative. The present review attempts to provide a critical path that facilitates the characterization and management of PCLs.

[Guidelines for Diagnosis and Treatment of Pancreatic Cystic Neoplasms Based on Radiology].

As the detection rate of pancreatic cystic neoplasms (PCN) increases,recommendations or guidelines for the diagnosis and treatment of PCN have been released from professional organizations.From the perspective of radiology,we compared seven guidelines in terms of general introduction,preoperative monitoring methods and strategies,stratification of risk factors,surgical indications,and postoperative follow-ups,aiming to provide references for the evaluation of images and the formulation of individualized approach for the treatment of PCN.

Management Algorithms for Pancreatic Cystic Neoplasms.

CONTEXT.­: The detection of pancreatic cystic neoplasms (PCNs) has increased owing to the advancement and widespread use of imaging modalities, resulting in differences between past and current management methods for PCNs, including intraductal papillary mucinous neoplasms (IPMNs). Therefore, clinicians should accurately diagnose and determine appropriate treatment strategies. However, previously published treatment guidelines for IPMNs present different indications for treatment. OBJECTIVE.­: To review the current status of PCNs, including epidemiologic change, malignancy risk, and factors for treatment, and to provide the optimal management algorithms for PCNs, including IPMNs, from the clinician's point of view. DATA SOURCES.­: Literature review of published studies and the authors' own work. CONCLUSIONS.­: The treatment of PCNs relies on the type of cyst that is present or suspected. Serous cystic neoplasms are usually benign, and observation is sufficient. However, surgical treatment is required for mucinous cystic neoplasms, and malignancy risk differs according to lesion size. Solid pseudopapillary neoplasms also require surgery. The detection of small IPMNs has been increasing, and most branch duct-type IPMNs are dormant. However, cysts 3 cm or larger or growing branch duct-type IPMNs must be carefully monitored because of the increasing risk of malignancy. Therefore, surveillance strategies should be different according to the size of the lesions. A tailored approach is needed for selecting surgery or surveillance, considering the malignancy potential of the lesion and patient-associated factors such as operative risks and life expectancy. Nomograms are valuable tools for selecting treatment methods as a customized approach for IPMNs.

Consenso chileno de diagnóstico y manejo de neoplasias quísticas pancreáticas. Club de páncreas Chile-SCHGE / Chilean consensus on diagnosis and management of pancreatic cystic neoplasms

Pancreatic cystic neoplasms (PCN) are frequently detected on abdominal images performed for non-pancreatic indications. Their prevalence in asymptomatic population ranges from 2.7 to 24.8%, and increases with age. There are several types of pancreatic cysts. Some may contain cancer or have malignant potential, such as mucinous cystic neoplasms, including mucinous cystadenoma (MCN) and intraductal papillary mucinous neoplasms (IPMN). In contrast, others are benign, such as serous cystadenoma (SCA). However, even those cysts with malignant potential rarely progress to cancer. Currently, the only treatment for pancreatic cysts is surgery, which is associated with high morbidity and occasional mortality. The Board of the Chilean Pancreas Club of the Chilean Gastroenterology Society developed the first Chilean multidisciplinary consensus for diagnosis, management, and surveillance of PCN. Thirty experts were invited and answered 21 statements with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree. A consensus was adopted when at least 80% of the sum of the answers "fully agree" and "partially agree" was reached. The consensus was approved by the Board of Directors of the Chilean Pancreas Club for publication.

Society of Abdominal Radiology Disease Focused Panel Survey on Clinical Utilization of Incidental Pancreatic Cyst Management Recommendations and Template Reporting.

OBJECTIVE: To assess current practice patterns with respect to protocols used for incidental pancreatic cyst follow-up, management guidelines, and template reporting. METHODS: The Society of Abdominal Radiology Disease Focused Panel on intraductal pancreatic neoplasms distributed an anonymous 14-question survey to its members in June 2018 that focused on current utilization of incidental pancreatic cyst guidelines, protocols, and template reporting. RESULTS: Among the 1,390 email invitations, 323 responded, and 94.7% (306 of 323) completed all questions. Respondents were mainly radiologists (93.8%, 303 of 323) from academic institutions (74.7%, 227 of 304) in North America (93.7%, 286 of 305). Of respondents, 42.5% (136 of 320) preferred 2017 ACR recommendations, 17.8% (57 of 320) homegrown systems, 15.0% (48 of 320) Fukuoka guidelines, and 7.8% (25 of 320) American Gastroenterological Association guidelines. The majority (68.7%, 222 of 323) agreed or strongly agreed that developing a single international consensus recommendation for management was important, and most radiologists preferred to include them in reports (231 of 322, 71.7%); yet only half included recommendations in >75% of reports (161 of 321). MR cholangiopancreatography was the modality of choice for follow-up of <2.5 cm cysts. Intravenous contrast was routinely used by 69.7% (212 of 304). Standardized reporting templates were rarely used in practice (12.8% 39 of 306). CONCLUSIONS: Nearly 7 of 10 radiologists desire a unified international consensus recommendation for management of incidental cystic pancreatic lesions; ACR 2017 recommendations are most commonly used, followed by homegrown systems and Fukuoka guidelines. The majority of radiologists routinely use MR cholangiopancreatography with intravenous contrast for follow-up of incidental cystic lesions, but template reporting is rarely used.

Pancreatic cystic neoplasms: a review of current recommendations for surveillance and management.

Pancreatic cystic neoplasms (PCN) comprise of a diverse array of pancreatic cysts, including intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), cystic neuroendocrine tumors (cNET), and many others. Increasing use of cross-sectional imaging has resulted in greater numbers of PCNs discovered incidentally. The overall risk of malignancy is low, but can vary considerably between different classes of PCNs. Furthermore, many pancreatic cysts are indeterminate on imaging, and the inability to reliably predict the course of disease remains a challenge for radiologists. Due to the variability in disease course and a lack of high-quality studies on PCNs, there is no universal consensus when it comes to balancing optimal surveillance while avoiding the risk for overtreatment. Currently, there are three widely accepted international guidelines outlining guidelines for surveillance and management of PCNs: the American Gastroenterological Association (AGA) in 2015, the International Association of Pancreatology (IAP) last revised in 2017, and the European Study Group on Cystic Tumours of the Pancreas (European) last revised in 2018. In 2017, the American College of Radiology released its own comprehensive set of recommendations for managing indeterminate pancreatic cysts that are detected incidentally on CT or MRI. The purpose of this paper is to describe the key differences between the ACR recommendations and the aforementioned three sets of guidelines regarding cyst management, imaging surveillance, performance, and cost-effectiveness.

[Management of Cystic Lesions of the Pancreas]. / Vorgehen bei Nachweis von zystischen Pankreasraumforderungen.

Cystic pancreatic lesions are a frequent incidental finding on ultrasound or cross sectional imaging. The incidence of pancreatic lesions experience a steady climb in recent years due to an increased number of cross sectional imaging and an increasing life expectancy. The clinical challenge is to identify individuals bearing lesions with potentially malignant or pre-malignant features. Indeed, by far most cystic pancreatic lesions are not associated with an increased risk for the development of cancer. Taking into account the increasing incidence rates of cystic pancreatic lesions a rational and economic use of diagnostics is warranted. This review provides an overview on the different types of cystic lesions, the appropriate use of diagnostics and a clinical management algorithm balancing intervention and surveillance.

[Chilean consensus on diagnosis and management of pancreatic cystic neoplasms]. / Consenso chileno de diagnóstico y manejo de neoplasias quísticas pancreáticas. Club de páncreas Chile-SCHGE.

Pancreatic cystic neoplasms (PCN) are frequently detected on abdominal images performed for non-pancreatic indications. Their prevalence in asymptomatic population ranges from 2.7 to 24.8%, and increases with age. There are several types of pancreatic cysts. Some may contain cancer or have malignant potential, such as mucinous cystic neoplasms, including mucinous cystadenoma (MCN) and intraductal papillary mucinous neoplasms (IPMN). In contrast, others are benign, such as serous cystadenoma (SCA). However, even those cysts with malignant potential rarely progress to cancer. Currently, the only treatment for pancreatic cysts is surgery, which is associated with high morbidity and occasional mortality. The Board of the Chilean Pancreas Club of the Chilean Gastroenterology Society developed the first Chilean multidisciplinary consensus for diagnosis, management, and surveillance of PCN. Thirty experts were invited and answered 21 statements with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree. A consensus was adopted when at least 80% of the sum of the answers "fully agree" and "partially agree" was reached. The consensus was approved by the Board of Directors of the Chilean Pancreas Club for publication.

Determining when endoscopic ultrasound changes management for patients with pancreatic cystic neoplasms.

INTRODUCTION: Pancreatic cystic neoplasms (PCNs) are being incidentally detected at an increased rate due to increased CT and MRI usage. EUS is an emerging tool that can differentiate between benign and malignant features of pancreatic cysts. We hoped to identify the specific cross-sectional imaging findings and patient characteristics that warrant EUS referral. METHODS: We conducted a retrospective case-control chart review, evaluating patients, who were diagnosed with pancreatic cysts and underwent EUS between January 1, 2010 and December 31, 2017. RESULTS: EUS was found to change management when CT imaging found cyst size > 4 cm (OR = 4.07, p < 0.01), cyst size > 3 cm (OR = 3.79, p < 0.001) and associated solid component to the cyst (OR = 5.95, p < 0.01). Additionally, patient characteristics, including age less than 50 years, male sex and 10-pack year smoking history were significantly associated with EUS change in management. DISCUSSION: Our findings suggest that EUS referral should be coordinated based on the findings of specific HRFs, with support from high risk patient characteristics, rather than the accumulation of multiple HRFs, as suggested by existing guidelines.