Nonmucinous Cysts Research Articles

Intraductal Papillary Mucinous Neoplasms (IPMN): Diagnosis, Classification, and Risk Assessment - A Review of Current Medical Knowledge

Introduction In recent years, the widespread utilisation of advanced imaging modalities has led to a surge in the detection rate of pancreatic cystic lesions, particularly intraductal papillary mucinous neoplasms (IPMN). Consequently, this review aims to provide a comprehensive examination of IPMN, focusing on elucidating its intricate facets including definition, epidemiology, pathogenesis, classification, imaging modalities for diagnosis, analysis of pancreatic cyst fluid, evaluation of malignant potential, and identification of pertinent features. Brief Overview of Current Knowledge: IPMN represents a diagnostic conundrum owing to its variable biological behaviour encompassing both benign and malignant spectra, necessitating meticulous evaluation and risk stratification. Various imaging techniques such as MRI, CT, EUS and abdominal ultrasonography serve pivotal roles in the diagnostic algorithm and risk assessment of IPMN. Additionally, the analysis of pancreatic cyst fluid, incorporating biomarkers and the string sign test, assumes a critical role in discerning mucinous from non-mucinous cysts and gauging malignant potential. Discriminating high-risk stigmata and worrisome features serve as a compass for clinical decision-making regarding the imperative of surgical intervention versus vigilant surveillance. Summary Despite persistent challenges, the ongoing evolution of diagnostic modalities and risk assessment methodologies augur well for refining therapeutic strategies and enhancing clinical outcomes in managing IPMN. This review underscores the imperative of sustained research endeavours in the realm of pancreatic oncology to enrich our comprehension of IPMN pathophysiology and to optimise clinical care paradigms.

Revisiting the performance of cyst fluid carcinoembryonic antigen as a diagnostic marker for pancreatic mucinous cysts: a comprehensive 20-year institutional review

ObjectiveElevated pancreatic cyst fluid carcinoembryonic antigen (CEA) has been routinely used to classify mucinous cysts. This study incorporates original data that established the CEA ≥192 ng/mL threshold with over 20...

Improving diagnostic yield of pancreatic serous cystadenoma with cyst fluid ancillary testing, adjunct immunohistochemistry, and additional fine-needle biopsy sampling.

Fine-needle aspiration (FNA) diagnosis of pancreatic serous cystadenoma (SCA) remains challenging. This retrospective study aimed to evaluate the roles of cyst fluid ancillary testing and combined fine-needle biopsy (FNB) in improving the diagnostic yield. The authors retrospectively reviewed cytology cases that were histologically confirmed SCAs. Clinical features and FNA cyst fluid biochemical and molecular analysis results along FNB findings were reviewed. The study cohort included 31 cases from 13 male and 18 female patients with a mean age of 65. The original cytologic diagnoses were nondiagnostic (n=6, 19%), negative for malignant cells/cyst contents (n=7, 23%), atypical cells (n=3, 10%), nonmucinous cyst (n=11, 35%), and serous cystadenoma (n=4, 13%). Cyst fluid carcinoembryonic antigen (CEA) analysis was performed in 17 cases, all of which showed a low CEA level (<192 ng/mL). All 14 cases with molecular testing showed a wild-type KRAS. Inhibin immunohistochemistry was retrospectively performed on the FNA cell blocks, inhibin was positive in six of seven cases tested. In 15 cases with concurrent FNA and FNB biopsies, the diagnosis of SCA was seen in only one FNA case (7%) but 13 FNB cases (87%). This study suggests that FNA diagnosis of SCA remains challenging even with ancillary testing including cyst fluid CEA level and KRAS mutation analysis. Adjunct inhibin immunostaining may help improve the cytologic diagnosis of selective SCA cases. FNB appears superior to FNA for a definite diagnosis of SCA.

Amplified Sciences PanCyst Pro Panel to accurately identify non-mucinous pancreatic cyst fluid.

617 Background: Pancreatic cysts are rarely symptomatic, and, consequently, are detected incidentally during routine imaging analyses for unrelated disorders. Guidelines for diagnosis of pancreatic cysts rely on imaging and supportive analyses of fluid extracted during endoscopic ultrasound with fine-needle aspiration (EUS-FNA). Unfortunately, currently available protein markers and assays are not sufficiently accurate to rule-out patients in whom a non-mucinous pancreatic cyst has formed. Since non-mucinous pancreatic cysts seldom progress to cancer, this patient population is at risk of being subjected to the severe physical, emotional, and financial burdens associated with unwarranted surveillance, testing, and possible surgical intervention. Furthermore, identification of mucinous pancreatic cysts does not establish the risk of progression to cancer (rule-in) or the need for surgical intervention. Methods: To address the unmet needs in pancreatic cyst diagnosis, Amplified Sciences has combined a panel of markers with a clinically translated surface enhanced Raman spectroscopy (SERS)-based protease activity assay as a rule-out diagnostic tool. The tri-analyte panel was tested on a cohort of 185 retrospective samples gathered from three separate institutions (UPMC, IU Health, and UCSF) and consumed only 12 µL of cyst fluid per sample. The goals of this study were to establish the negative predictive value (NPV) of this panel prior to translation to a CLIA-regulated laboratory and create a preliminary algorithm for analysis. Results: The results of this statistically powered study show that protease activity outperforms carcinoembryonic antigen (CEA), a current standard diagnostic marker for pancreatic cyst fluid, in sensitivity, specificity, and NPV. Furthermore, in combination, the tri-analyte panel identifies non-mucinous pancreatic cysts with 99% sensitivity and a negative predictive value &gt;95%. Conclusions: These results support the use of this panel in clinical settings as a diagnostic tool to rule-out patients from surgical intervention, as well as the use of SERS as an optical detection mode for clinical diagnostics. Future work will continue to address the unmet need for improved diagnostic information through multiplexed analyses of markers that consume comparatively minimal volume of pancreatic cyst fluid samples. Studies will also seek to build on the SERS platform by introducing more dyes, substrates, assays, and analytical methods. Amplified Sciences would like to acknowledge significant efforts to build the clinical samples cohort from Gina Zhu, Kelli Ifuku, and Dr. Kimberly Kirkwood from USCF, Christine Decapite and Dr. Randall Brand from UPMC, and Michele Yip-Schneider and Dr. C. Max Schmidt from IU Health.

Analysis of Clinical Samples of Pancreatic Cyst's Lesions with A Multi-Analyte Bioelectronic Simot Array Benchmarked Against Ultrasensitive Chemiluminescent Immunoassay.

Pancreatic cancer, ranking as the third factor in cancer-related deaths, necessitates enhanced diagnostic measures through early detection. In response, SiMoT-Single-molecule with a large Transistor multiplexing array, achieving a Technology Readiness Level of 5, is proposed for a timely identification of pancreatic cancer precursor cysts and is benchmarked against the commercially available chemiluminescent immunoassay SIMOA (Single molecule array) SP-X System. A cohort of 39 samples, comprising 33 cyst fluids and 6 blood plasma specimens, undergoes detailed examination with both technologies. The SiMoT array targets oncoproteins MUC1 and CD55, and oncogene KRAS, while the SIMOA SP-X planar technology exclusively focuses on MUC1 and CD55. Employing Principal Component Analysis (PCA) for multivariate data processing, the SiMoT array demonstrates effective discrimination of malignant/pre-invasive high-grade or potentially malignant low-grade pancreatic cysts from benign non-mucinous cysts. Conversely, PCA analysis applied to SIMOA assay reveals less effective differentiation ability among the three cyst classes. Notably, SiMoT unique capability of concurrently analyzing protein and genetic markers with the threshold of one single molecule in 0.1mL positions it as a comprehensive and reliable diagnostic tool. The electronic response generated by the SiMoT array facilitates direct digital data communication, suggesting potential applications in the development of field-deployable liquid biopsy.

Diagnostic performance of intracystic carcinoembryonic antigen (CEA) versus glucose in differentiation of mucinous and non-mucinous pancreatic cysts.

Pancreatic cysts have various potential for malignant transformation. Differentiating mucinous from non-mucinous cysts is crucial to make the right decision about further management, since mucinous cysts carry the risk of malignancy. Using endoscopic ultrasound (EUS) guided fine needle aspiration to determine intracystic carcinoembryonic antigen (CEA) levels is the recommended method for identifying mucinous cysts, although intracystic glucose assessment has also proved to be an effective tool. This study aims to compare the diagnostic performance of intracystic glucose and CEA in distinguishing between mucinous and non-mucinous pancreatic cystic lesions. In this single center study, we prospectively collected and analyzed the data of 91 consecutive patients who underwent endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) with cytological analysis and measurement of intracystic CEA and glucose levels. The cyst type was classified based on radiological and EUS morphology, string sign, CEA, cytological and histological findings in resected cases. The diagnosis was established retrospectively by three experienced gastroenterologists blinded for glucose level in cases without definitive cytology or histology. We calculated the sensitivity, specificity, the positive- and negative predictive value of glucose and CEA respectively, and compared the two methods. The sensitivity of intracystic glucose versus CEA proved to be 96.2% vs. 69.2% in identifying mucinous cysts, while the specificity of glucose was shown to be 79.5%, compared to 100% for CEA. Intracystic glucose is a sensitive, easily accessible biomarker in identifying mucinous pancreatic cysts, however, the specificity is lower compared to CEA. The measurement of intracystic glucose level could help in decision-making in daily clinical practice, however the diagnostic performance of the method remains inferior to "through-the-needle" techniques, such as confocal laser endomicroscopy and Moray forceps biopsy.

Challenges of cytopathological pancreas diagnostics

The cytologic diagnostics of solid and cystic pancreatic lesions with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is an integral part of the clinical workup and the decision of asurgical versus aconservative approach. Cystic lesions are increasingly being diagnosed due to improved imaging and represent numerous neoplastic as well as non-neoplastic epithelial and non-epithelial entities, which differ in biological behavior and prognosis. In particular, the differentiation of mucinous and non-mucinous cysts is significant for further clinical management. Regressive cellular changes, gastrointestinal contaminants, and overlapping morphologic changes of reactively altered ductal epithelial cells and cells of well-differentiated neoplasms and preneoplasms are special challenges of cytological diagnostics. For auniform cytological classification of findings, an internationally developed seven-level classification system has been published and co-published by the World Health Organization (WHO). This classification system takes into account both morphological findings and further procedures on cytological material such as next-generation sequencing and immunocytochemistry and is based on the WHO classification for pancreatic tumors. Against this background, important cytologic diagnostic criteria of various solid and cystic lesions relevant in clinical practice are presented in this article, considering diagnostic possibilities and pitfalls as well as differential diagnoses.

S50 Utilization of Analytic Morphomics to Differentiate Mucinous From Nonmucinous Pancreatic Cysts

S50 Utilization of Analytic Morphomics to Differentiate Mucinous From Nonmucinous Pancreatic Cysts

B-343 Validation of Glucose Test in Pancreatic Cyst Fluid

Abstract Background Pancreatic cysts may be detected in 40 to 50 percent of patients who undergo abdominal magnetic resonance imaging for unrelated reasons. Mucinous cysts such as intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are known precursor lesions of pancreatic ductal adenocarcinoma. Therefore, it is imperative to identify mucinous cysts from nonmucinous cysts. In addition to cytology analysis, biomarker analysis in cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration can also provide information for the differential diagnosis of a mucinous cyst. Carcinoembryonic antigen (CEA) has been used as the biomarker to differentiate mucinous and nonmucinous pancreatic cysts with a sensitivity of around 63% and specificity of around 88%. Recently, glucose in pancreatic cyst fluid has been shown to have a better sensitivity (92%) and specificity (87%) in the differentiation of mucinous cysts using a threshold of &amp;lt;50 mg/dL. Therefore, it is consequential for clinical laboratories to validate glucose tests in pancreatic cyst fluid samples. In this study, we report the validation of the glucose test in pancreatic cyst fluid samples using the glucose assay on an automated chemistry analyzer. Methods The glucose assay, GLUC3, on Roche Cobas c702 analyzer was used to measure glucose in pancreatic cyst fluid samples. For linearity and recovery studies, cyst fluid samples were spiked with stock glucose solutions of known concentrations in a way that the spiked fluid samples always contained no less than 90% of the cyst fluid. Linearity was determined by assaying nine samples with glucose concentrations from 0–718 mg/dL. For the recovery study, various amounts of glucose were added to a cyst fluid sample containing undetectable glucose. The expected glucose concentrations in these samples are 23.2, 46.4, 92.7, and 159 mg/dL, respectively. Intra-run and inter-run precisions were determined by measuring glucose ten times in a run and in 10 separated runs, respectively, in 9 cyst fluid samples containing various amounts of glucose ranging from 0–718 mg/dL. The effect of hemoglobin was tested by spiking one cyst fluid sample with a hemolysate. Stability was determined by testing one sample at 0 and 24 h at room temperature, respectively. Results The assay was linear from 0–718 mg/dL of glucose with a slope of 1.05 and an intercept of 3.5. The recovery ranged from 103% to 111% in samples containing 23.2, 46.4, 92.7, and 159 mg/dL glucose, respectively. Both the intra-run and inter-run precisions for the nine samples with different glucose concentrations had a coefficient of variation of &amp;lt;5%. The samples were stable at room temperature for the study period of 24 h. No interference was observed at hemoglobin of 477 mg/dL. Conclusion Our study indicates that the glucose assay, GLUC3, on Roche Cobas c702 analyzer can be used to measure glucose in pancreatic cyst fluid samples. Our results show that glucose measurement in pancreatic cyst fluid had a good recovery and reproducible results with precision being &amp;lt;5%. This test may aid in the differential diagnosis of pancreatic mucinous cysts.

B-358 Application of Surface-Enhanced Raman Spectroscopy to Improve Sensitivity of Clinical Assays

Abstract Background Current efforts to expand the pool of available markers that can be analyzed in clinical settings is hampered by limited volumes of biomaterial-rich fluids and low concentrations of certain analytes, coupled with poor sensitivity of existing detection techniques. Although progress has been made using advanced sample preparation or assay techniques such as miRNeasy or ELISA for genomic and protein assays, respectively, little research has focused on adapting new optical methods as detection modes in the clinic. Amplified Sciences has developed an enzymatic activity assay platform using SERS detection to improve diagnostic sensitivities in multiple disease indications. Along with the experts at Wasatch Photonics, research focused on adaptation of this assay platform has enabled investigation of multiple markers of disease that had previously been undervalued or overlooked, as well as stacking of multiple markers in precious, low-volume samples. Methods Building upon previously published data using gastricsin as a marker to identify benign, non-mucinous pancreatic cysts, Amplified Sciences has added several SERS laser wavelengths, and different sample preparation methods to the existing platform. To examine the sensitivities of laser and dye combinations, solutions representative of assay samples containing rhodamine-dimer dye-labeled peptide were tested using Wasatch Photonics Raman spectrometers at 532, 638, 785, and 830 nm laser wavelengths. Samples at different pH were analyzed after addition of colloidal Au or Ag nanoparticles to determine the impacts of sample preparation on SERS spectral features. After drying in a desiccator overnight, the samples were reanalyzed to assess the stability of the SERS signals. As a pertinent application of this technology, an activity assay was developed for the known COVID protease 3ClPro. Release of rhodamine dimer dye as a result of 3ClPro cleavage of the substrate was quantified using SERS. The data were analyzed using Bruker OPUS Software package, and plotted using Graphpad Prism 9. Results Each laser, buffer, and metal used for SERS provided a unique spectral signature, suggesting that different transitions are available and potentially tunable depending on the application under investigation. Sensitivity was, as expected, best with the 532 nm SERS system purportedly due to enhancement factors, and the resonance impacts of rhodamine dyes at 532 nm. It was found that the Limit of Detection of Rhodamine-dimer dye was 100-fold lower with SERS compared to fluorescence, even after a 3-fold dilution with colloidal Ag. However, the remaining lasers could be more finely tuned, and, thus, provide alternate spectral properties, and different sensitivities which has implications when new dye classes are introduced into the platform. Furthermore, when SERS was applied to the 3ClPro assay, it was determined that activity could be detected below the dimerization concentration of 3ClPro, described in the literature as ∼25 nM. Also, a monomeric version of 3ClPro that is expected to have no reactivity with the substrate was found to display activity above background at concentrations as low as 1 µM. Conclusion SERS is an appropriate method for measuring activity in clinically relevant markers of disease, with tunable characteristics based upon the dye composition and the spectrometer in use.

Addressing the unmet clinical need for low-volume assays in early diagnosis of pancreatic cancer

The incidental detection of pancreatic cysts, an opportunity for the early detection of pancreatic cancer, is increasing, owing to an aging population and improvements in imaging technology. The classification of pancreatic cystic precursors currently relies on imaging and cyst fluid evaluations, including cytology and protein and genomic analyses. However, there are persistent limitations that obstruct the accuracy and quality of information for clinicians, including the limited volume of the complex, often acellular, and proteinaceous milieu that comprises pancreatic cyst fluid. The constraints of currently available clinical assays lead clinicians to the subjective and inconsistent application of diagnostic tools, which can contribute to unnecessary surgery and missed pancreatic cancers. Herein, we describe the pathway toward pancreatic cyst classification and diagnosis, the volume requirements for several clinically available diagnostic tools, and some analytical and diagnostic limitations for each assay. We then discuss current and future work on novel markers and methods, and how to expand the utility of clinical pancreatic cyst fluid samples. Results of ongoing studies applying SERS as a detection mode suggest that 50 µL of pancreatic cyst fluid is more than sufficient to accurately rule out non-mucinous pancreatic cysts with no malignant potential from further evaluation. This process is expected to leave sufficient fluid to analyze a follow-up, rule-in panel of markers currently in development that can stratify grades of dysplasia in mucinous pancreatic cysts and improve clinical decision-making.

The Milan System for Reporting Salivary Gland Cytopathology: the experience of a tertiary cancer center with emphasis on non-mucinous cysts and improving diagnostic results

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced in 2018 to standardize cytology reporting and guide patient treatment. We aimed to evaluate the utility of this system applied to patients at our cancer center. We retrospectively reviewed cases of salivary gland fine-needle aspirations (FNAs) performed in our institution (2019-2022). All were performed by radiologists and immediately assessed for specimen adequacy. The cytologic findings were classified into the MSRSGC except for non-mucinous cystic contents (NMCC) where the lesion was radiologically consistent with a cyst and totally collapsed after FNA. Such lesions were categorized as non-neoplastic (NN) instead of non-diagnostic (ND). The cytologic findings were compared to corresponding histologic findings (212 available cases), and the risk of malignancy was calculated. Five hundred five FNAs were categorized as: 25 (4.95%) ND; 86 (17.03%) NN, of which 39 were NMCC; 9 (1.78%) atypia of undetermined significance; 138 (27.33%) benign neoplasms; 57 (11.29%) salivary gland neoplasm of undetermined malignant potential; 16 (3.17%) suspicious for malignancy; and 174 (34.46%) malignant. The risk of malignancy rates for the following categories were: ND, 40%; NN, 25%; atypia of undetermined significance, 0%; benign neoplasms, 1%; salivary gland neoplasm of undetermined malignant potential, 54.54%; suspicious for malignancy, 90.9%; and malignant, 100%. Thirty-one NMCC with available follow-up resolved/remained stable. Our results validate the reproducibility of the MSRSGC applied in our cancer center. Based on the benign course of cysts with NMCC, we propose that such cases be categorized as NN, provided the cyst is totally resolved after FNA.

Exploring a novel composite method using non-contrast EUS enhanced microvascular imaging and cyst fluid analysis to differentiate pancreatic cystic lesions

Background and AimsDifferentiating pancreatic cystic lesions (PCLs) remains a diagnostic challenge. The use of high-definition imaging modalities which detect tumor microvasculature have been described in solid lesions. We aim to evaluate the usefulness of cystic microvasculature when used in combination with cyst fluid biochemistry to differentiate PCLs. MethodsWe retrospectively analyzed 110 consecutive patients with PCLs from 2 Italian Hospitals who underwent EUS with H-Flow and EUS fine needle aspiration to obtain cystic fluid. The accuracy of fluid biomarkers was evaluated against morphological features on radiology and EUS. Gold standard for diagnosis was surgical resection. A clinical and radiological follow up was applied in those patients who were not resected because not surgical indication and no signs of malignancy were shown. ResultsOf 110 patients, 65 were diagnosed with a mucinous cyst, 41 with a non-mucinous cyst, and 4 with an undetermined cyst. Fluid analysis alone yielded 76.7% sensitivity, 56.7% specificity, 77.8 positive predictive value (PPV), 55.3 negative predictive value (NPV) and 56% accuracy in diagnosing pancreatic cysts alone. Our composite method yielded 97.3% sensitivity, 77.1% specificity, 90.1% PPV, 93.1% NPV, 73.2% accuracy. ConclusionsThis new composite could be applied to the holistic approach of combining cyst morphology, vascularity, and fluid analysis alongside endoscopist expertise.

Diagnosis and Management of Pancreatic Cysts: A Comprehensive Review of the Literature.

The prevalence of pancreatic cysts has been rising due to the widespread use of cross-sectional imaging (CT scan and MRI) of the abdomen. While most pancreatic cysts are benign and do not require treatment or surveillance, a significant minority are premalignant and rarely malignant. The risk stratification of these lesions is not straightforward, and individual risk assessment, cyst size, distribution, and alarming morphologic features (when present) can guide the next steps in management. Neoplastic pancreatic cysts are mucinous or non-mucinous. Endoscopic ultrasound with fine-needle aspiration is often required to classify pancreatic cysts into mucinous and non-mucinous cysts and to assess the malignant potential. Advances in endoscopic techniques (confocal laser endomicroscopy, microforceps biopsy) can provide a definitive diagnosis of pancreatic cysts in some cases; however, the use of these techniques involves a higher risk of adverse events.

Validation of combined carcinoembryonic antigen and glucose testing in pancreatic cyst fluid to differentiate mucinous from non-mucinous cysts

BackgroundMore accurate diagnosis of mucinous cysts will reduce the risk of unnecessary pancreatic surgery. Carcinoembryonic antigen (CEA) and glucose in pancreatic cyst fluid (PCF) can differentiate mucinous from non-mucinous pancreatic cystic neoplasms (PCN). The current study assessed the value of combined CEA and glucose testing in PCF.MethodsCross-sectional validation study including prospectively collected PCF from patients undergoing endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) and pancreatic surgery. We performed laboratory measurements for CEA and glucose and measured glucose levels by a hand glucometer. Primary outcome was diagnostic accuracy evaluated by receiver operator curves (ROC), sensitivity, specificity, positive, and negative predictive value (PPV, NPV).ResultsOverall, PCF was collected from 63 patients, including 33 (52%) with mucinous and 30 (48%) with non-mucinous PCN. Histopathology (n = 36; 57%), cytopathology (n = 2; 3%), or clinical and/or radiological diagnosis (n = 25; 40%) was used as reference standard. Combined CEA (cut-off ≥ 192 ng/ml) and laboratory glucose testing (cut-off ≤ 50 mg/dL) reached 92% specificity and 48% sensitivity, whereas either positive CEA (cut-off ≥ 20 ng/ml) or glucose testing (cut-off ≤ 50 mg/dL) showed 97% sensitivity and 50% specificity. Sensitivity and specificity were 80% and 68% for CEA ≥ 20 ng/mL versus 50% and 93% for CEA ≥ 192 ng/mL (the conventional cut-off level). Laboratory and glucometer glucose both reached 100% sensitivity and 60% and 45% specificity, respectively. None of the biomarkers and cut-offs reached a PPV exceeding 90%, whereas both glucose measurements had a NPV of 100% (i.e., high glucose excludes a mucinous cyst).ConclusionCombined CEA and glucose testing in PCF reached high specificity and sensitivity for differentiating mucinous from non-mucinous PCN. Glucose testing, whether alone or combined with the new CEA cut-off (≥ 20 ng/mL), reached > 95% sensitivity for mucinous cysts, whereas only glucose reached a NPV > 95%.Graphical abstract

Recent advances in detecting premalignant pancreatic cysts

The incidental discovery of pancreatic cysts in asymptomatic patients is on the rise due to the widespread use of cross-sectional imaging. The challenge in the management of pancreatic cysts is in distinguishing those with malignant potentials, like mucinous pancreatic cysts, from non-mucinous cysts that have negligible malignant potentials. Similarly, it can be difficult to identify mucinous cysts that harbour high-grade dysplasia or early cancer. This review focuses on the recent advances in detecting pancreatic cancer and cysts with premalignant potential.

Endoscopic Ultrasound-Based Evaluation of Pancreatic Cysts: New Invasive Modalities

Pancreatic cysts are a heterogenous group of lesions that can be differentiated into mucinous and non-mucinous cysts based on their malignant potential. Crosssectional imaging alone is inadequate to reliably distinguish between the two groups. Endoscopic ultrasound (EUS) and fine needle aspiration has been used for analysis of the cyst morphology and cyst fluid. Traditional markers such as fluid carcinoembryonic antigen and cytology have been useful particularly for the assessment of indeterminate cysts or those with high-risk features, but the overall diagnostic accuracy is still sub-par. As a result, new techniques have been described to improve the ability of EUS to risk stratify a pancreatic cyst. In this review, we describe some of the novel EUS‑based techniques in the evaluation of pancreatic cysts, namely needle-based confocal laser endomicroscopy, through the needle cystoscopy, and through the needle biopsy techniques.

Pancreatic cyst fluid interleukin-1 beta (IL-1β) level in predicting the risk of malignancy in pancreatic cysts

Pancreatic cystic lesions (PCLs) may be accidentally discovered in up to 13.5% of cases. These PCLs are of multiple types, including mucinous cysts (intra-ductal papillary mucinous neoplasms [IPMN] and mucinous cystic neoplasms [MCN]) that have a risk of malignant transformation. The difficulty in differentiation between the various PCLs and their unpredictable risk of malignant transformation makes their management difficult. The new diagnostic tools of PCLs often include endoscopic ultrasound guided fine needle aspiration (EUS-FNA) for pancreatic cyst fluid analysis. This study aimed to determine if cystic fluid IL-1β can predict the risk of malignancy and the degrees of dysplasia of pancreatic cysts. The study included 50 PCL patients. They were subjected to radiological, biochemical, serological, and histopathological examinations. Pancreatic cyst fluid IL-1β was analyzed using an ELISA. Our data indicated that cyst fluid IL-1 β can differentiate between benign and malignant cysts at cut-off value >150 pg/ml; with sensitivity and specificity of 84.00% and 56.00% respectively. Also, cyst fluid IL-1 β can differentiate between mucinous and non- mucinous pancreatic cysts at cut-off value >150 pg/ml; with a sensitivity and specificity of 83.33% and 53.78%, respectively. However, cyst fluid IL-1 β cannot differentiate between degrees of dysplasia of IPMN. In conclusion, our study suggested that pancreatic cyst fluid IL-1β can differentiate between.

Accuracy and agreement of a large panel of endosonographers for endomicroscopy-guided virtual biopsy of pancreatic cystic lesions

BackgroundAlthough emerging data evidences that EUS-guided needle-based confocal laser endomicroscopy (nCLE) accurately diagnoses pancreatic cystic lesions (PCLs), there are a lack of interobserver agreement (IOA) studies utilizing reference histopathological diagnosis and for specific PCL subtypes. Hence, we sought to assess the IOA, intra-observer reliability (IOR), and diagnostic performance of EUS-nCLE using a large cohort of patients with histopathological diagnosis amongst a broad panel of international observers. MethodsEUS-nCLE videos (n = 76) of subjects with PCLs [intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystadenoma (SCA), pseudocyst, and cystic-neuroendocrine tumors/solid pseudopapillary neoplasm (cystic-NET/SPN)], simulating clinical prevalence rates were obtained from 3 prospective studies. An international panel of 13 endosonographers with nCLE experience, blinded to all PCL data, evaluated the video library twice with a two-week washout for PCL differentiation (mucinous vs. non-mucinous) and subtype diagnosis. ResultsThe IOA (κ = 0.82, 95% CI 0.77–0.87) and IOR (κ = 0.82, 95% CI 0.78–0.85) were “almost perfect” to differentiate mucinous vs. non-mucinous PCLs. For PCL subtype, IOA was highest for SCA (almost perfect; κ = 0.85), followed by IPMN (substantial, κ = 0.72), and cystic-NET/SPN (substantial, κ = 0.73). The IOA was moderate for MCN (κ = 0.47), and pseudocyst (κ = 0.57). Compared to histopathology, observers differentiated mucinous vs. non-mucinous PCLs with high accuracy (94.8%, 95% CI 93.3–96.1). For detecting specific PCLs subtypes, EUS-nCLE was highly accurate in diagnosing non-mucinous cysts (SCA: 98%; cystic-NET/SPN: 96%; pseudocyst: 96%) and slightly less accurate for mucinous lesions (IPMN: 86%; MCN: 84%). ConclusionDiagnosis of PCLs by EUS-nCLE guided virtual biopsy is very accurate and reliable for the most prevalent pancreatic cysts in clinical practice.

Deep Learning for Automatic Differentiation of Mucinous versus Non-Mucinous Pancreatic Cystic Lesions: A Pilot Study

Endoscopic ultrasound (EUS) morphology can aid in the discrimination between mucinous and non-mucinous pancreatic cystic lesions (PCLs) but has several limitations that can be overcome by artificial intelligence. We developed a convolutional neural network (CNN) algorithm for the automatic diagnosis of mucinous PCLs. Images retrieved from videos of EUS examinations for PCL characterization were used for the development, training, and validation of a CNN for mucinous cyst diagnosis. The performance of the CNN was measured calculating the area under the receiving operator characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values. A total of 5505 images from 28 pancreatic cysts were used (3725 from mucinous lesions and 1780 from non-mucinous cysts). The model had an overall accuracy of 98.5%, sensitivity of 98.3%, specificity of 98.9% and AUC of 1. The image processing speed of the CNN was 7.2 ms per frame. We developed a deep learning algorithm that differentiated mucinous and non-mucinous cysts with high accuracy. The present CNN may constitute an important tool to help risk stratify PCLs.