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Pancreatic Cystic Neoplasms (PCN) represent a diverse group of tumors, some of which may progress to pancreatic cancer. Considering their high prevalence in the general population, the development of reliable biomarkers is crucial. The ideal biomarker will accurately diagnose the subtype of PCN and assess the risk of high-grade dysplasia or invasive cancer. Cyst fluid analysis has emerged as a promising approach to accomplish this goal, yet no single marker has yet gained unanimous support for routine inclusion in PCN evaluation., Competing Interests: Disclosure A.V. Maker is an inventor of record on the following pending or issued patent: WO2018183603A1 (PCT/US2018/025,027). T. Pollini and L. Todeschini have no conflict of interest. Funding Authors acknowledge the support of the Inner Child Foundation and the Shorenstein Foundation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Distinguishing mucinous (M) pancreatic cystic neoplasms (PCNs) from non-mucinous (NM) is challenging but crucial. Low intracystic glucose level has shown diagnostic tool promise, however further investigation is needed to understand metabolic processes., Aims: To compare the diagnostic accuracy of intracystic glucose and CEA levels in a large cohort and explore lactate levels as potential marker., Methods: PCNs≥15 mm which underwent EUS-fine needle aspiration were prospectively enrolled. Glucose, CEA and lactate levels were measured. Diagnostic accuracy for M-PCN diagnosis was evaluated using surgical/cytology reports or multidisciplinary evaluations., Results: 169 PCNs were included (64 % M-PCNs). Median intracystic glucose was significantly lower in M-PCNs (1 mg/dL) compared to NM-PCNs (101 mg/dL); mean intracystic CEA was significantly higher in M-PCNs (152.5 ng/mL) compared to NM-PCNs (0.3 ng/mL). ROC curve analysis revealed best glucose cut-off ≤58 mg/dL (accuracy 93.5 %) and CEA cut-off >2.5 ng/mL (accuracy 90.5 %) for M-PCNs. Intracystic lactates were significantly lower in M-PCNs correlating directly with glucose. Single glucose dosage evidenced best diagnostic accuracy respect markers combination., Conclusion: Intracystic glucose demonstrated high diagnostic utility for M-PCNs differentiation, surpassing CEA. Lactate levels correlated with glucose, suggesting their uptake by M-PCNs cells. These findings contribute to a better metabolic landscape understanding glucose use as diagnostic marker., Competing Interests: Conflict of interest None., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Pancreatic cyst fluid analysis plays an important role in distinguishing between mucinous and non-mucinous cyst lesions. We aimed to compare the diagnostic performances of cyst fluid carcinoembryonic antigen (CEA), CA 19-9, and glucose in differentiating mucinous from non-mucinous neoplastic pancreatic cystic lesions (PCLs) and determine the best cut-off levels., Methods: Patients' data were evaluated retrospectively. 102 patients' PCLs were grouped as non-neoplastic ( n = 25), non-mucinous neoplastic ( n = 20), mucinous neoplastic ( n = 47) and pancreatic adenocarcinomas with cystic degeneration ( n = 10); and CEA, CA 19-9, and glucose levels were compared. Receiver-operating characteristic analysis was performed, and the ideal cut-off values were determined., Results: Cyst fluid CEA and CA 19-9, levels were significantly higher ( P < 0.001, P < 0.001, respectively) and glucose levels were significantly lower ( P = 0.001) in mucinous than in non-mucinous neoplastic PCLs. Area under curve with 95% confidence interval of CEA, glucose and CEA and glucose test combination was 0.939 (95% CI = 0.885-0.993, P = 0.001), 0.809 (95% CI = 0.695-0.924, P < 0.001) and 0.937 (95% CI = 0.879-0.995), respectively. CEA cut-offs to rule-in and rule-out mucinous neoplastic were 135.1 ng/mL (sensitivity = 62%, specificity = 94.7%) and 6.12 ng/mL (sensitivity = 94.1%, specificity = 80.4%), respectively. Glucose cut-off of 2.8 mmol/L was chosen both to rule-in and rule-out mucinous neoplastic PCLs (sensitivity = 78%, specificity = 80%). Co-analysis of CEA and glucose to distinguish mucinous from non-mucinous neoplastic PCLs had sensitivity = 87.8%, specificity = 93.3%, and diagnostic accuracy = 89.3%., Conclusions: We concluded that co-analysis of cyst fluid CEA (cut-off = 135.1 ng/mL) and glucose (cut-off = 2.8 mmol/L) at novel cut-offs had the best testing performance to rule-in mucinous neoplastic PCLs. To rule-out mucinous PCLs co-analysis of CEA (cut-off = 6.12 ng/mL) and glucose (cut-off = 2.8 mmol/L) added value to prediction.

Pancreatic cystic lesions (PCL) are increasingly diagnosed. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) cytology is often used for diagnostic confirmation but can be inconclusive. In this study, the role of molecular analyses in the pre-operative diagnostics of PCL is evaluated. Targeted Next Generation Sequencing (NGS) applied on cytology smears was retrospectively evaluated in a cohort of 37 resected PCL. Usefulness of NGS on fresh cyst fluids was tested in a prospective cohort of patients with newly diagnosed PCL (n = 71). In the retrospective cohort, cytology plus NGS displayed higher sensitivity (94.1% vs. 87.1%) and specificity (100% vs. 50%) than cytology alone for the detection of mucinous neoplasms. In the prospective cohort, sensitivity and specificity of conventional cytology alone were 54.2% and 100% for the detection of mucinous neoplasia and 50.0% and 100% for the detection of high-grade dysplasia, respectively. Adding NGS, all lesions which underwent histopathologic verification (12/71, 17%) could be classified without false positive or false negative results regarding the detection of mucinous neoplasm so far. NGS analysis of cfDNA in PCL fluids is feasible and can increase diagnostic accuracy in the detection of mucinous neoplasms compared to cytology alone. However, algorithms for the detection of high-risk lesions need further improvement.

Objectives and Design: Endometriosis-related pain can be caused by anatomical distortions as well as environmental factors such as inflammation and oxidative stress. The aim of this study is to investigate the relationship between the severity of dysmenorrhea in patients with ovarian endometrioma (OMA) and cyst fluid (CF) concentrations of irons, including total iron, heme iron, and free iron., Method: Eighty-three patients who were histologically diagnosed with OMA were enrolled in the Department of Gynecology, Nara Medical University Hospital, between 2013 and 2019. The patients were divided into 4 groups according to the severity of dysmenorrhea: no pain, mild, moderate, and severe. Iron concentration was measured by the inductively coupled plasma optical emission spectrometry method., Results: There were no significant differences among the 4 groups in variables such as age at diagnosis, preoperative CA125, preoperative CA19-9, cyst size, and tumor laterality (unilateral or bilateral). There was a positive correlation between the severity of dysmenorrhea and total iron (p < 0.001) and heme iron (p = 0.016) concentrations. Multiple regression analyses revealed that the CF concentration of total iron (hazard ratio 18.75, 95% confidence interval: 2.26-155.35, p = 0.007) was a significant independent variable associated with the severity of dysmenorrhea. A receiver operating characteristic curve analysis showed that a total iron exceeding 290.8 mg/L was associated with severe dysmenorrhea with a sensitivity of 90.9% and a specificity of 65.7%., Limitations: This study excluded patients with adenomyosis, superficial endometriosis, or deep endometriosis, resulting in a smaller number of cases. Iron levels could not be compared to the endometriosis stage using the r-ASRM score., Conclusions: There is no clear evidence that iron predicts the severity of endometriosis-related pain. However, iron may be closely associated with dysmenorrhea., (© 2021 S. Karger AG, Basel.)

Background: MicroRNA-371a-3p (miR-371), the novel serum biomarker of testicular germ cell tumours (GCTs), is produced by undifferentiated subtypes of GCTs but not by teratoma. Cystic teratoma developing from retroperitoneal metastases of GCT subsequent to chemotherapy had been shown to contain high levels of classical serum tumour markers of GCT in the presence of normal marker levels in serum. To date, no information is available regarding the presence of miR-371 in the cystic fluid of residual teratoma after chemotherapy., Methods: Four patients (age 18-26 years) undergoing retroperitoneal lymph node dissection (RPLND) for cystic residual masses resulting from chemotherapy of bulky retroperitoneal GCT had measurements of miR-371 in both serum and cystic fluid aspirated from surgical specimens. Measurement of the miR was performed with quantitative real-time PCR using miR-30b-5p as reference. Results were tabulated and analysed in a descriptive manner., Results: Histologically, all of the surgical specimens involved teratoma only with no evidence of vital undifferentiated GCT tissue. All patients were cured. Prior to RPLND, miR-371 serum levels were not measurable or close to zero in all of the patients. Cystic fluid revealed elevated levels of miR-371 in 3 patients and traces of miR in one., Conclusions: The detection of miR-371 in the cystic fluid of teratoma is somewhat enigmatic since this GCT subtype usually does not express the miR. Two hypotheses may explain the finding: First, miR-371 molecules were released into the cystic fluid by active GCT tissue prior to chemotherapy. High levels were kept after regression of vital GCT tissue because the cystic lumen is without a specific drainage system. Second, teratoma cells lining the interior cyst wall may shed small amounts of miR-371 into the lumen. Because of the lacking drainage system, even small levels may accumulate. The present finding adds to the understanding of the biology of the novel biomarker of GCT., (© 2020 S. Karger AG, Basel.)

A significant proportion of patients with intraductal papillary mucinous neoplasms (IPMNs) undergo surgical resection in order to prevent or treat pancreatic cancer at the risk of significant perioperative morbidity. Efforts have been made to stratify the potential risk of malignancy based on the clinical and radiographic features of IPMN to delineate which cysts warrant resection versus observation. An analysis of the cyst fluid obtained by preoperative endoscopic examination appears to be correlative of cyst type and risk, whereas serum markers and radiographic findings have not yet reached a level of sensitivity or specificity that proves they are clinically meaningful. In this review, we investigate the current cyst fluid analysis studies and present those that have shown promise in effectively stratifying high-risk versus low-risk lesions. While new cyst fluid markers continue to be identified, additional efforts in testing panels and marker composites in conjunction with clinical algorithms have also shown promise in distinguishing dysplasia and the risk of malignancy. These should be tested prospectively in order to determine their role in guiding the surveillance of low-risk lesions and to evaluate the new markers detected by proteomics and genetic sequencing.

Cystic echinococcosis is a chronic and complex zoonotic disease. The mechanisms underlying the parasite's establishment, growth and persistence are not completely understood, and are thought be modulated by a crosstalk through extracellular vesicles. Here, EVs were isolated from the hydatid cyst fluid of patients with cystic echinococcosis and protoscolex culture supernatant. Proteomic analysis of these EVs revealed several parasite- and human-derived proteins. Very few studies have performed proteomic analysis of EVs isolated from HCF and PCS. Our proteomic analysis of the EVs derived from HCF and PCS facilitated identification of 1175 proteins, wherein 1026 and 38 proteins were exclusively identified in the EVs derived from HCF (HCF-EVs) and PCS (PCS-EVs), respectively, and 111 proteins were shared in both. The results of co-culture of PCS-EVs with murine peripheral blood mononuclear cells showed that PCS-EVs significantly regulated T lymphocyte functions in a dose-dependent manner. Collectively, our results provide valuable information on parasite survival strategies and new insights into the role of these EVs in the establishment and persistence of hydatid cysts., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background/aims: The aim of the present study was to investigate whether pancreas cyst fluids should be divided into two for cytological diagnosis and biochemical tests., Materials and Methods: The present study was conducted with fluids aspirated from 12 pancreas cysts. The fluids were divided into two and sent to the cytopathology (fluid 1) and biochemistry (fluid 2) laboratories. Fluid 1 was centrifuged at the cytopathology laboratory. Cytology slides were prepared from the deposit, and the supernatant was sent to the biochemistry laboratory. Fluid 2 was centrifuged at the biochemistry laboratory, and amylase, carcinoembryonic antigen, and cancer antigen 19.9 levels were determined in the supernatant. These procedures were repeated for fluid 1 from the cytopathology laboratory. The remaining fluid 2 was sent to the cytopathology laboratory. Fluid 1-like slides were prepared from fluid 2 in the cytopathology laboratory. Cytological diagnoses of fluid 1 and fluid 2 were compared, and the Pearson correlation coefficient for biochemical test results was identified., Results: 92% of fluid 1 and 50% of fluid 2 were diagnostic. Biochemical test results of fluid 1 and fluid 2 were similar, and the Pearson correlation coefficient was high., Conclusion: Our results showed that pancreatic cyst fluids did not need to be divided into two for cytological diagnosis and biochemical tests. Following centrifugation of the whole fluid at the cytopathology laboratory, the deposit and the supernatant can be used for cytological diagnosis and for biochemical tests, respectively. With this protocol, the sensitivity of cytological diagnoses and biochemical tests of pancreatic cyst fluids may increase.

Odontogenic keratocysts (OKCs) are jaw cystic lesions which are characterized by local invasion and high recurrence rate. The majority of OKCs are exposed to microorganisms and occur along with focal inflammatory infiltrates. Cyst fluids are biological fluids that contain a large content of cytokines and immune globulins. Inhibitory receptor such as programmed death receptor 1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1), which can induce a coinhibitory signal in activated T cells, plays a vital role in the differentiation, exhaustion and apoptosis of T cells. Cell derived microvesicles, carrying a cargo of functional proteins, nucleic acids and lipids, are important communication tools in the development of diseases. However, the expression of PD-L1 in OKCs tissues and whether PD-L1 could be carried by microvesicles are unexplored. Presently, we have isolated cyst fluid microvesicles and identified cell derived PD-L1 + cyst fluid microvesicles. PD-L1 was located in the membrane of the cyst fluid microvesicles. The main cellular origins of PD-L1 + cyst fluid microvesicles were dendritic cells followed by lymphocytes. Elevated PD-L1 + cyst fluid microvesicles were detected in the OKCs compared with dentigerous cysts. Isolated cyst fluid microvesicles could bind to the membrane of activated CD8 T cells and inhibit proliferation of stimulated peripheral blood CD8 T cells. In conclusion, the present study suggests that elevated PD-L1 + cyst fluid microvesicles might be related with the cyst development of OKCs.

Technological advances and the widespread use of medical imaging have led to an increase in the identification of pancreatic cysts in patients who undergo cross-sectional imaging. Current methods for the diagnosis and risk-stratification of pancreatic cysts are suboptimal, resulting in both unnecessary surgical resection and overlooked cases of neoplasia. Accurate diagnosis is crucial for guiding how a pancreatic cyst is managed, whether with surveillance for low-risk lesions or surgical resection for high-risk lesions. This review aims to summarize the current literature on confocal endomicroscopy and cyst fluid molecular analysis for the evaluation of pancreatic cysts. These recent technologies are promising adjuncts to existing approaches with the potential to improve diagnostic accuracy and ultimately patient outcomes., Competing Interests: Conflict-of-interest statement: The authors disclose no conflicts of interest.

Pancreatic cystic lesions (PCLs) have been increasingly recognized in clinical practice. Although inflammatory cysts (pseudocysts) are the most common PCLs detected by cross-sectional imaging modalities in symptomatic patients in a setting of acute or chronic pancreatitis, incidental pancreatic cysts with no symptoms or history of pancreatitis are usually neoplastic cysts. For these lesions, it is imperative to identify mucinous cysts (intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) due to the risk of their progression to malignancy. However, no single imaging modality alone is sufficient for a definitive diagnosis of all PCLs. The cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration provides additional information for the differential diagnosis of PCLs. Current recommendations suggest sending cyst fluid for cytology evaluation and measurement of carcinoembryonic antigen (CEA) levels. Unfortunately, the sensitivity of cytology is greatly limited, and cyst fluid CEA has demonstrated insufficient accuracy as a predictor of mucinous cysts. More recently, cyst fluid glucose has emerged as an alternative to CEA for distinguishing between mucinous and nonmucinous lesions. Herein, the clinical utility of cyst fluid glucose and CEA for the differential diagnosis of PCLs was evaluated., Competing Interests: Conflict-of-interest statement: Author does not have any conflicts of interest.

Background: Current standard-of-care technologies, such as imaging and cyst fluid analysis, are unable to consistently distinguish intraductal papillary mucinous neoplasms (IPMNs) of the pancreas at high risk of pancreatic cancer from low-risk IPMNs. The objective was to create a single-platform assay to identify IPMNs that are at high risk for malignant progression., Study Design: Building on the Verona International Consensus Conference branch duct IPMN biomarker review, additional protein, cytokine, mucin, DNA, and microRNA cyst fluid targets were identified for creation of a quantitative polymerase chain reaction-based assay. This included messenger RNA markers: ERBB2, GNAS, interleukin 1β, KRAS, MUCs1, 2, 4, 5AC, 7, prostaglandin E2R, PTGER2, prostaglandin E synthase 2, prostaglandin E synthase 1, TP63; microRNA targets: miRs 101, 106b, 10a, 142, 155, 17, 18a, 21, 217, 24, 30a, 342, 532, 92a, and 99b; and GNAS and KRAS mutational analysis. A multi-institutional international collaborative contributed IPMN cyst fluid samples to validate this platform. Cyst fluid gene expression levels were normalized, z-transformed, and used in classification and regression analysis by a support vector machine training algorithm., Results: From cyst fluids of 59 IPMN patients, principal component analysis confirmed no institutional bias/clustering. Lasso (least absolute shrinkage and selection operator)-penalized logistic regression with binary classification and 5-fold cross-validation used area under the curve as the evaluation criterion to create the optimal signature to discriminate IPMNs as low risk (low/moderate dysplasia) or high risk (high-grade dysplasia/invasive cancer). The most predictive signature was achieved with interleukin 1β, MUC4, and prostaglandin E synthase 2 to accurately discriminate high-risk cysts from low-risk cysts with an area under the curve of up to 0.86 (p = 0.002)., Conclusions: We have identified a single-platform polymerase chain reaction-based assay of cyst fluid to accurately predict IPMNs with high malignant potential for additional studies., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

A 55-yr-old woman presented with abdominal bloating for approximately 1 year. Imaging studies showed a cyst in the body of the pancreas with proximal pancreatic ductal dilation. An endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed. Cytologic findings from the cyst fluid were consistent with a mucinous neoplastic cyst, and the possibility of malignancy could not be entirely excluded. A KRAS mutation analysis was performed on the cyst fluid using the Idylla system and circulating tumor KRAS (ctKRAS) cartridge (Biocartis, Mechelen, Belgium), which tests for actionable mutations in exons 2, 3, and 4 of the KRAS gene. Idylla testing detected a KRAS G12D mutation in the cyst fluid. The patient subsequently underwent a distal subtotal pancreatectomy with splenectomy. Microscopic examination of the resected tissue revealed an intraductal papillary mucinous neoplasm (IPMN) with an associated invasive carcinoma. KRAS testing on the resected tumor tissue confirmed the G12D mutation detected in the cyst fluid earlier. The described rapid testing of KRAS directly from the pancreatic cyst fluid can complement cytology assessment to classify pancreatic cysts more reliably and can potentially be of significant help when other cyst findings are nondiagnostic., (© 2019 Al-Turkmani et al.; Published by Cold Spring Harbor Laboratory Press.)

Previous studies showed that Echinococcus granulosus infection reduces allergic airway inflammation in experimentally infected hosts and the cystic fluid of E. granulosus is known to activate regulatory T (CD4 + CD25 + Foxp3 + T, Treg) cells. To evaluate the effects of cystic fluid of E. granulosus on allergic airway inflammation, we investigated the regulation of the inflammatory reaction by cystic fluid using an allergic airway inflammation animal model. Cystic fluid was administered to C57BL/6 mice seven times every other day, after which allergic airway inflammation was induced using ovalbumin and aluminum. The airway resistance, number of eosinophils and other immune cells in the bronchoalveolar lavage fluid, and levels of Th2 and Th17-related cytokines were significantly reduced by cystic fluid pre-treatment in allergic airway inflammation-induced mice. The number IL-4 + CD4 + T cells decreased, the number of Treg cells increased in the lung-draining lymph nodes and spleen of cystic fluid pre-treated mice. In conclusion, E. granulosus-derived cystic fluid may alleviate the Th2 allergic airway inflammatory response via Treg cells. Further studies of the immune regulation of cystic fluid may lead to the development of therapeutic agents for immune disorders., (Copyright © 2019. Published by Elsevier Inc.)

Background: Mediastinal cystic lesions account for approximately 15-20% of all mediastinal masses and are difficult to differentiate because of similar imaging manifestation. The aim of this study was to differentiate mediastinum cystic lesions through endoscopic ultrasound-guided-fine needle aspiration (EUS-FNA) and parameters from cyst-fluid analysis., Methods: Over a period of eight years, 37 patients suspected with mediastinal cystic lesions were assessed. Cyst fluid was collected via EUS-FNA and further examined using cytological and biochemical techniques. Definitive diagnosis was established based on cytology, surgical pathology, and/or clinical follow-up., Results: Based on the final pathological reports or long-term follow-up, 19 patients were diagnosed with benign cysts, 14 with benign or malignant tumors, 2 with tuberculosis, 1 with an abscess, and 1 with a pancreatic pseudocyst. Computed tomography or magnetic resonance imaging mistakenly distinguished eight cases as solid masses (27.03%), but EUS revealed cystic characteristics. Carcinoembryonic antigen and lactate dehydrogenase (LDH) were evaluated from the cyst fluid obtained by EUS-FNA. There was no statistically significant difference in carcinoembryonic antigen values between benign and malignant cysts; however the average LDH value in the malignancy group was significantly higher than in the benign group., Conclusion: EUS-FNA showed great potential for differentiating mediastinal lesions by combining imaging manifestation and cytological examination. The elevated LDH value from cyst fluid chemical analysis could be used as an auxiliary indicator for diagnosing malignancy., (© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Rationale and Objectives: The purpose of this work is to determine if the speed of sound value of a breast cyst can aid in the clinical management of breast masses. Breast macrocysts are defined as fluid-filled tissue masses >1 cm in diameter and are thought to be aberrations of normal development and involution, often associated with apocrine metaplasia. The benign natural history of breast cysts is well known, and it is important to obtain high specificity in breast imaging to avoid unnecessary biopsies in women who have benign diseases, particularly those with dense breast tissue. Transmission ultrasound is a tomographic imaging modality that generates high-resolution, 3D speed of sound maps that could be used to identify breast tissue types and act as a biomarker to differentiate lesions. We performed this study to investigate the microanatomy of macrocysts observed using transmission ultrasound, as well as assess the relationship of speed of sound to the physical and biochemical parameters of cyst fluids., Materials and Methods: Cyst fluid samples were obtained from 37 patients as part of a case-collection study for ultrasound imaging of the breast. The speed of sound of each sample was measured using a quantitative transmission ultrasound scanner in vivo. Electrolytes, protein, cholesterol, viscosity, and specific gravity were also measured (in the aspirated cyst fluid) to assess their relationship to the speed of sound values obtained during breast imaging., Results: We found positive correlations between viscosity and cholesterol (r = 0.71) and viscosity and total protein × cholesterol (r = 0.78). Additionally, we performed direct cell counts on cyst fluids and confirmed a positive correlation of number of cells with speed of sound (r = 0.74). The speed of sound of breast macrocysts, as observed using transmission ultrasound, correlated with the cytological features of intracystic cell clumps., Conclusion: On the basis of our work with speed as a classifier, we propose a spectrum of breast macrocysts from fluid-filled to highly cellular. Our results suggest high-speed cysts are mature macrocysts with high cell counts and many cellular clumps that correlate with cyst microanatomy as seen by transmission ultrasound. Further studies are needed to confirm our findings and to assess the clinical value of speed of sound measurements in breast imaging using transmission ultrasound., (Copyright © 2018 Academic Radiology. Published by Elsevier Inc. All rights reserved.)

Objective: 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., Design: 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., Results: 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)., Conclusions: 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., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

A 1 yr old intact male miniature dachshund presented for posturing to urinate without voiding and nocturia. Physical examination revealed congenital reproductive abnormalities and a fluid-filled structure caudal to the urinary bladder. The dog was diagnosed with a prostatic cyst and underwent an exploratory laparotomy with an attempt to remove the cyst. Twelve weeks later, the dog returned with recurring clinical signs, and the cyst was found to have returned back to its original size. A second intact male miniature dachshund presented at 7 mo of age for stranguria. Physical examination revealed congenital reproductive abnormalities and a fluid-filled structure on rectal palpation, much like the first dog. The dog was diagnosed with a prostatic cyst and underwent an exploratory laparotomy. An attempt was made to close communication between the prostate and cyst. The dog re-presented 3 wk later for recurrence of clinical signs, and the prostatic cyst was found to have increased in size. Both dogs were euthanized because of recurrence of clinical signs. This report describes the presence of prostatic cysts in two young dogs with congenital abnormalities of the genital and reproductive tracts and the similarities seen in human boys diagnosed with prostatic utricles.

Background: Inspissated cyst fluid may be identified on pancreatic cyst aspiration cytology. We report on the cytomorphologic characteristics of inspissated cyst fluid on EUS-FNA of pancreatic cysts and correlate this finding with histopathology or multimodal (cytology, cyst fluid analysis, molecular pathology, imaging) classification of cyst type., Methods: The department archives were searched for pancreatic cyst fine-needle aspiration biopsies that contained dessicated, crystalline or inspissated material on cytologic preparations., Results: Twenty-eight cases of pancreatic cysts containing inspissated material were identified. The cytomorphology of the inspissated material ranged from fibrillary fan-like structure (54%), ball-like structures (57%), and granular material (43%). When present, the fibrillary inspissated material was associated with neoplastic mucinous cysts in 11/15 (73%) cases, but was also seen in 2 pseudocysts, 1 serous cystadenoma, and 1 cyst of uncertain type (suggestive of mucinous cyst on EUS). The presence of fibrillary inspissated cyst material on cytology had a positive predictive value of 79% and a specificity of 63% for a neoplastic mucinous cyst., Conclusion: Although not highly specific, the presence of inspissated cyst fluid with fibrillary architecture should be recognized by cytopathologists and interpreted as at least "atypical" given the potential association with neoplastic mucinous cysts of the pancreas., (© 2018 Wiley Periodicals, Inc.)

Purpose: The aim of this study was to investigate the value of biochemical profile of cyst fluid and diffusion-weighted imaging (DWI) in differentiating hepatic hydatid cysts (HCs) from liver simple cysts., Materials and Methods: Forty-six patients underwent MR imaging. Twenty-nine patients had 29 hydatid cysts and 17 patients had liver simple cysts. Thirteen patients with hydatid cysts and seven patients with liver simple cysts were evaluated with cyst fluid biochemical analysis. The concentration of glucose, protein, calcium ion (Ca 2+ ) electrolyte, macroscopic appearance, and parasitological sediment were evaluated in this study., Results: In the respect of biochemical analysis cyst fluid, the concentration of glucose and calcium ion of HCs was significantly higher than that of the liver simple cysts. In the respect of DWI, in the b 1000 s/mm 2 value in respect of mean application data center (ADC) values, there was a statistically significant difference between HCs group (the mean value was (2.50±0.79)×10 -3  mm/s 2 ) and liver simple cysts group (the mean value was (2.92±0.66)×10 -3  mm/s 2 ). However, no statistically significant results were obtained in the ADC measurements of b 500 s/mm 2 between two groups., Conclusion: The analysis of cyst fluid combined with the measurement of ADC values in the b 1000 s/mm 2 value could be considered a promising parameter as an alternative to the differential diagnosis of hepatic hydatid cysts from liver simple cysts., (© 2017 Wiley Periodicals, Inc.)

Rationale: In recent years, the molecular components of pancreatic cyst fluid have been used for diagnosis and prognosis. Because the protein markers that are currently used in clinical tests are unreliable, proteomic studies to find new protein markers are being conducted. However, such researches have been limited due to the complexity of pancreatic cyst fluid and the immaturity of proteomic techniques., Methods: To overcome these limitations and provide a pancreatic cyst proteome dataset, we examined cyst fluid proteome with tandem mass spectrometry. The proteomic analysis was performed using a Orbitrap-based mass spectrometer (Q-Exactive) coupled with a 50-cm-long nano-liquid chromatography column. Protein mutations were identified using mutation sequence database search., Results: A total of 5850 protein groups were identified from microliters of cyst fluid. Among those, 3934 protein groups were reported for the first time in pancreatic cyst fluid. Although high-abundance proteins were not depleted in the experiment, our dataset detected almost all pancreatic tumor markers such as mucin family members, S100 proteins, and CEA-related proteins. In addition, 590 protein mutation marker candidates were discovered., Conclusions: We provide a comprehensive cyst proteome dataset that includes cystic cellular proteins and mutated proteins. Our findings would serve as a rich resource for further IPMN studies and clinical applications. The MS data have been deposited in the ProteomeXchange with identifier PXD005671 (http://proteomecentral.proteomexchange.org/dataset/PXD005671)., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Brain tumors may have cysts, whose content of nutrients could influence tumor cell microenvironment and growth., Objective: To measure nutrients in cyst fluid from glioblastoma multiforme (GBM) and metastatic brain tumors., Methods: Quantification of nutrients in cyst fluid from 12 to 18 GBMs and 4 to 10 metastatic brain tumors., Results: GBM cysts contained glucose at 2.2 mmol/L (median value; range <0.8-3.5) and glutamine at 1.04 mmol/L (0.17-4.2). Lactate was 7.1 mmol/L (2.4-12.5) and correlated inversely with glucose level (r = -0.77; P < .001). Amino acids, including glutamate, varied greatly, but median values were similar to previously published serum values. Ammonia was 75 μmol/L (11-241). B vitamins were present at previously published serum values, and riboflavin, nicotinamide, pyridoxal 5΄-phosphate, and cobalamin were higher in cyst fluid than in cerebrospinal fluid. Inorganic phosphate was 1.25 mmol/L (0.34-3.44), which was >3 times higher than in ventricular cerebrospinal fluid: 0.35 mmol/L (0.22-0.66; P < .001). Tricarboxylic acid cycle intermediates were in the low micromolar range, except for citrate, which was 240 μmol/L (140-590). In cystic metastatic malignant melanomas and lung tumors values were similar to those in GBMs., Conclusion: Tumor cysts may be a nutrient reservoir for brain tumors, securing tumor energy metabolism and synthesis of cell constituents. Serum is one likely source of cyst fluid nutrients. Nutrient levels in tumor cyst fluid are highly variable, which could differentially stimulate tumor growth. Cyst fluid glutamate, lactate, and phosphate may act as tumor growth factors; these compounds have previously been shown to stimulate tumor growth at concentrations found in tumor cyst fluid., (Copyright © 2016 by the Congress of Neurological Surgeons)

Background and Aims: The effect of EUS-guided pancreatic cyst ablation (PCA) on sonographic morphology and cyst fluid cytology is unknown. The aim of this study was to evaluate morphologic, cytologic, and change in cyst fluid DNA after PCA., Methods: In a prospective single-center study, consecutive patients with suspected benign 10- to 50-mm pancreatic cysts underwent baseline EUS-FNA and EUS-PCA followed 2 to 3 months later by repeat EUS, cyst fluid analysis, and possible repeat PCA. Surveillance imaging after ablation was performed at least annually and classified as complete response (CR), partial response, or persistent, with <5%, 5% to 25%, and 25% of the original cyst volume, respectively., Results: Thirty-six patients underwent EUS-PCA with ethanol alone (n = 8) or ethanol and paclitaxel (n = 28), and CR occurred in 19 patients (56%). After EUS-PCA, EUS showed an increase in wall diameter in 68%, decreased number of septations in 24%, increased debris in 24%, loss of mural nodule or novel calcification in 21%, and alteration of fluid viscosity in 48%. Follow-up cytology showed increased epithelial cellularity in 27%, loss or decreased cellular atypia in 15%, increased or appearance of macrophages in 24%, and inflammatory cells in 15%. Postablation DNA amount increased and quality decreased in 71% each. Between the CR and non-CR patients, there was no significant difference in frequency of sonographic or cytologic features. In the CR group, mean DNA quantity was significantly increased after ablation (P = .023) without a change in quality (P = .136)., Conclusions: EUS-PCA induces morphologic and cytologic changes of pancreatic cysts, none of which appears to predict overall imaging-defined response to ablation. (Clinical trial registration numbers: NCT00233038 and NCT01643460.)., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Management of pancreatic cysts is based on neoplastic-nonneoplastic discrimination. Endoscopic ultrasound (EUS) enables to differentiate neoplastic-nonneoplastic lesions and also allows fine-needle aspiration (FNA). In this study, we aim to assess feasibility and clinical relevance of cytological and biochemical analysis in differential diagnosis of cystic pancreatic lesions in patients who had undergone endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) due to pancreatic cysts., Methods: Participants were 96 patients who had undergone EUS-FNA for differential diagnosis of pancreatic cysts. Pancreatic cysts were classified as benign-mucinous, nonmucinous, and malignant according to patient history, physical examination, EUS appearance, and cystic fluid assessment. Tumor markers (CEA, CA(cancer antigens) 72.4, CA 19-9) , amylase, lipase and cytological assesment were compared between 3 different groups. Receiver-operating characteristics (ROC) curves were constructed to identify appropriate cut-off values., Results: Fluid CEA and CA 72.4 levels for benign-mucinous and malignant cysts were significantly higher than for nonmucinous cysts (P ≤ 0.04). A cut-off CEA level of 207 ng/mL differentiated mucinous etiology with a sensitivity of 72.7%, specificity of 97.7%, and accuracy of 89.5%. The sensitivity, specificity, and accuracy of the CA 72.4 cut-off level of 3.32 ng/mL were 80%, 69.5%, and 73.6%, respectively., Conclusion: Cyst fluid CEA and CA 72.4 levels have a high accuracy in discriminating mucinous from nonmucinous cysts. When combined with cytology their accuracy rate increases., Competing Interests: The authors have no funding and conflicts of interests to disclose.

Background and Aims: Pancreatic cystic neoplasms (PCNs) often need interval surveillance, including repeat EUS, but the role of repeat FNA with fluid analysis is poorly defined. The aim of this analysis is to evaluate the potential clinical significance of serial carcinoembryonic antigen (CEA) measurements by EUS-guided FNA (EUS-FNA) in the surveillance for PCNs., Patients: Patients who underwent EUS-FNA for PCNs were studied retrospectively. EUS-FNA findings were compared between index and prior procedures among patients who underwent repeat EUS-FNA., Results: A total of 400 patients with PCNs underwent EUS-FNA. Eighty-seven of those patients had prior EUS-FNA with cyst fluid analysis. Patients with repeat FNA were significantly more likely to have multiple cysts (57% vs 41%; P = .008), multilocular cysts (75% vs 62%; P = .042), connection to pancreatic duct (33% vs 18%; P = .005), and higher initial CEA levels (94.8 vs 25.6 ng/mL; P = .003) compared with patients who had only a single FNA. A comparison of prior and index FNAs did not show significant differences in EUS or cyst fluid analysis findings. After log transformation, the association between CEA level at prior and index FNA was moderate (R 2  = 0.626; P < .001), but cystic fluid CEA classification with a cutoff value of 192 ng/mL changed in 17 patients (20%), without significant changes in EUS findings., Conclusions: Repeat surveillance EUS-FNA resulted in stable CEA levels in the majority of patients, with spurious fluctuations of CEA in approximately 20% of patients. These data call into question any clinical significance attributed to an isolated interval rise in CEA level, especially in light of a stable EUS examination., (Copyright © 2016. Published by Elsevier Inc.)

We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids. Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers. In contrast, no mutations were found in the cyst fluids of 18 patients with benign tumors or non-neoplastic cysts. Though large, prospective studies are needed to demonstrate the safety and clinical utility of this approach, our results suggest that the genetic evaluation of cyst fluids might be able to inform the management of the large number of women with these lesions.

Background/aims: Pancreatic cystic lesions have a broad spectrum of differential diagnosis. There is an ongoing demand to identify specific and sensitive cystic fluid markers for the differential diagnosis of pancreatic cysts. We aimed to evaluate the diagnostic value of cystic fluid chromogranin A (CgA) in the differential diagnosis of pancreatic cysts., Materials and Methods: Patients who underwent endoscopic ultrasound (EUS)-guided aspiration for pancreatic cysts were included in the study. Cytopathological analysis and biochemical analysis, including cystic fluid carcinoembryonic antigen (CEA), amylase, Ca 19-9, and CgA, were performed., Results: Fifty-three patients were included in the study. The final diagnosis of patients was 14 pancreatic pseudocysts, 10 intraductal papillary mucinous neoplasms (IPMNs), 8 mucinous cystic neoplasms (MCN), 8 serous cystadenomas (SCAs), 2 cystic pancreatic neuroendocrine tumors (PNETs), and 11 others. The mean CgA levels were 50.51±130.04 ng/mL in pseudocysts, 12.38±8.59 in MCN, and 13.76±10.90 in cystic PNET. There was only one patient with a very high cystic fluid CgA (515.49 ng/mL) and was diagnosed as pseudocyst developed in chronic pancreatitis patient. Two patients with cystic PNET had normal levels of cystic fluid CgA., Conclusion: Cystic fluid CgA is not a useful marker for the differential diagnosis of cystic PNETs. It also has no value in the differential diagnosis of other pancreatic cysts.

Background: Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer., Methods: In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant) and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC) coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn). The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes., Results: The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline) and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC)., Conclusion: Mucinous benign and LMPs along with mucinous low-grade carcinomas appear to be different from serous and high-grade mucinous carcinomas based on their O-glycan profiles.

Objectives: Better diagnostic tools are needed to differentiate pancreatic cyst subtypes. A previous metabolomic study showed cyst fluid glucose as a potential marker to differentiate mucinous from non-mucinous pancreatic cysts. This study seeks to validate these earlier findings using a standard laboratory glucose assay, a glucometer, and a glucose reagent strip., Methods: Using an IRB-approved prospectively collected bio-repository, 65 pancreatic cyst fluid samples (42 mucinous and 23 non-mucinous) with histological correlation were analyzed., Results: Median laboratory glucose, glucometer glucose, and percent reagent strip positive were lower in mucinous vs. non-mucinous cysts (P<0.0001 for all comparisons). Laboratory glucose<50 mg/dl had a sensitivity of 95% and a specificity of 57% (LR+ 2.19, LR- 0.08). Glucometer glucose<50 mg/dl had a sensitivity of 88% and a specificity of 78% (LR+ 4.05, LR- 0.15). Reagent strip glucose had a sensitivity of 81% and a specificity of 74% (LR+ 3.10, LR- 0.26). CEA had a sensitivity of 77% and a specificity of 83% (LR+ 4.67, LR- 0.27). The combination of having either a glucometer glucose<50 mg/dl or a CEA level>192 had a sensitivity of 100% but a low specificity of 33% (LR+ 1.50, LR- 0.00)., Conclusions: Glucose, whether measured by a laboratory assay, a glucometer, or a reagent strip, is significantly lower in mucinous cysts compared with non-mucinous pancreatic cysts.

Background and Study Aims: Current diagnostic testing is inadequate to determine the malignant potential of pancreatic cysts, resulting in overcautious patient management. Integrated molecular pathology (IMP) testing combines molecular analysis with first-line test results (cytology, imaging, and fluid chemistry) to assess the malignant potential of pancreatic cysts. This multicenter study aimed to determine the diagnostic accuracy of IMP for pancreatic adenocarcinoma, and the utility of IMP testing under current guideline recommendations for managing pancreatic cysts., Patients and Methods: Patients who had undergone previous IMP testing as prescribed by their physician and for whom clinical outcomes were available from retrospective record review were included (n = 492). Performance was determined by correlation between clinical outcome and previous IMP diagnosis ("benign"/"statistically indolent" vs. "statistically higher risk [SHR]"/ "aggressive") or an International Consensus Guideline (Sendai 2012) criteria model for "surveillance" vs. "surgery." The Cox proportional hazards model determined hazard ratios for malignancy., Results: Benign and statistically indolent IMP diagnoses had a 97 % probability of benign follow-up for up to 7 years and 8 months from initial IMP testing. SHR and aggressive diagnoses had relative hazard ratios for malignancy of 30.8 and 76.3, respectively (both P < 0.0001). Sendai surveillance criteria had a 97 % probability of benign follow-up for up to 7 years and 8 months, but for surgical criteria the hazard ratio was only 9.0 (P < 0.0001). In patients who met Sendai surgical criteria, benign and statistically indolent IMP diagnoses had a > 93 % probability of benign follow-up, with relative hazard ratios for SHR and aggressive IMP diagnoses of 16.1 and 50.2, respectively (both P < 0.0001)., Conclusion: IMP more accurately determined the malignant potential of pancreatic cysts than a Sendai 2012 guideline management criteria model. IMP may improve patient management by justifying more relaxed observation in patients meeting Sendai surveillance criteria. IMP can more accurately differentiate between the need for surveillance or surgery in patients meeting Sendai surgical criteria., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Cystic echinococcosis (CE), caused by Echinococcus granulosus metacestode, invokes a serious public health concern. Early diagnosis has great impacts on reduction of disability-adjusted life years. Several antigen B-related molecules (EgAgB; EgAgB1-5) are known to be immunopotent, but detection of EgAgB is variable in many patients and may not allow reliable interpretation of its immunological relevance. More importantly, the immunoproteome profile of hydatid fluid (HF) has not been addressed., Methods: We conducted a proteome analysis of the HF of a single fertile cyst of CE1 and CE2 stages through two-dimensional electrophoresis (2-DE). Each protein spot was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). We subsequently determined the immunoproteome profile employing patient sera of entire disease spectrum from CE1 to CE5 stages., Results: We identified 40 parasite proteins, of which EgAgB (28 spots) and antigen 5 (EgAg5; 5 molecules) were abundant. EgAgB proteoforms constituted the majority, mostly EgAgB1 (24 spots), followed by EgAgB2 and EgAgB4 (2 spots each). EgAgB3 was detected only by liquid chromatography-MS/MS. EgAgB5 was not recognized. We also detected 38 host proteins, which were largely composed of serum components, antioxidant/xenobiotic enzymes, and enzymes involved in carbohydrate metabolism. CE1 and CE2 HF exhibited comparable spotting patterns, but CE2 HF harbored greater amounts of EgAgB and EgAg5 complexes. CE sera demonstrated complicated immune recognition patterns according to the disease progression; CE2 and CE3 stages exhibited strong antibody responses against diverse EgAgB and EgAg5 proteoforms, while CE1, CE4, and CE5 stages mainly reacted to EgAg5 and cathepsin B. Patient sera of alveolar echinococcosis (AE) cross-reacted with diverse EgAgB isoforms (36%). EgAg5 and cathepsin B also demonstrated cross-reactions with sera from neurocysticercosis and sparganosis., Conclusions: Our results demonstrated that detection of a single defined molecule may not properly diagnose CE, since specific immunodominant epitopes changed as the disease progresses. Immunoproteome analysis combined with imaging studies may be practical in the differential diagnosis of CE from AE and other cystic lesions, as well as for staging CE, which are pertinent to establish appropriate patient management.

Objective: The purpose of this study was to investigate cyst fluid levels of total iron, heme iron and free iron in benign endometriotic cysts and endometriosis-associated ovarian cancer (EAOC) and to demonstrate the significance of these biomarkers in differential diagnosis between EAOC and endometriotic cysts., Methods: Cyst fluid samples were obtained from eleven patients with EAOC and thirty-six women with benign endometriotic cysts at the time of surgery., Results: The median (± SD) total iron levels for endometriotic cysts and EAOC cysts were 244.4 ± 204.9 mg/L and 14.2 ± 36.6 mg/L, respectively. EAOC patients had much lower levels of iron-related compounds compared with endometriotic cyst samples (p< 0.001). When the total iron results were analyzed using the receiver operating characteristics (ROC) curve method, the optimum diagnostic cut-off point was 64.8 mg/L, sensitivity was 90.9%, specificity was 100%, positive predictive value (PPV) was 100%, and negative predictive value (NPV) was 97.3%. Patient demographic characteristics such as tumor size, age at operation, parity and menopause were not correlated with cyst fluid iron levels., Conclusions: We conclude for the first time that iron-related compounds are important biomarkers that can predict malignant transformation with high sensitivity and specificity for women with endometriosis.

Background: Pancreatic cyst size >3 cm is a worrisome rather than high-risk feature for malignancy based on the 2012 International Guidelines for the management of mucinous cysts. The value of cytology in preoperative evaluation and surgical triage is unclear., Methods: All pancreatic cysts >3 cm resected over a 7-year period were evaluated for clinical, radiologic, and pathologic information. Performance of cytology for the detection of malignancy and surgical triage compared with imaging was assessed., Results: There were 93 histologically confirmed cysts, 52 of which were mucinous and 41 of which were nonmucinous. Of these, 37% were malignant, including 16 nonmucinous malignancies and 18 mucinous cysts (12 with invasive carcinoma, 6 with high-grade dysplasia). Thirty-nine cysts (41% malignant, 59% benign) were not subject to endoscopic ultrasound-fine needle aspiration (EUS-FNA) prior to resection (average size, 6.0 cm). Fifty-four were evaluated by EUS-FNA, with 35 available for review (average size, 5.4 cm). Cytology/cyst fluid analysis had the highest specificity (88.9%) compared with imaging, whereas magnetic resonance imaging (MRI) showed the highest sensitivity (100%). MRI had the highest predictive value for mucinous (100%) versus nonmucinous cysts (100%). MRI and EUS were able to predict malignancy from the presence of high-risk imaging features in all cases. Some benign cases also showed high-risk imaging features on MRI (28.6%), computed tomography (32.3%), and EUS (45.8%). Cytology correctly classified 5 of 6 benign cysts with high-risk imaging as benign., Conclusions: Preoperative evaluation of pancreatic cysts >3 cm is warranted, as many are nonmucinous cysts and not high-grade. Cytology is more specific than imaging for the detection of malignancy in cysts >3 cm., (© 2014 American Cancer Society.)

Background/objectives: Despite advances in imaging techniques, diagnosis and management of pancreatic cystic lesions still remains challenging. The objective of this study was to determine the utility of cyst fluid analysis (CEA, CA 19-9, CA 125, amylase, and cytology) in categorizing pancreatic cystic lesions, and in differentiating malignant from benign cystic lesions., Methods: A retrospective analysis of 68 patients with histologically and clinically confirmed cystic lesions was performed. Cyst fluid was obtained by surgical resection (n = 45) or endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) (n = 23). Cyst fluid tumor markers and amylase were measured and compared between the cyst types., Results: Receiver operating characteristic (ROC) curve analysis of the tumor markers demonstrated that cyst fluid CEA provided the greatest area under ROC curve (AUC) (0.884) for differentiating mucinous versus non-mucinous cystic lesions. When a CEA cutoff value was set at 67.3 ng/ml, the sensitivity, specificity and accuracy for diagnosing mucinous cysts were 89.2%, 77.8%, and 84.4%, respectively. The combination of cyst fluid CEA content >67.3 ng/ml and cyst fluid CA 125 content >10.0 U/ml segregated 77.8% (14/18) of mucinous cystic neoplasms (MCNs) from other cyst subtypes. On the other hand, no fluid marker was useful for differentiating malignant versus benign cystic lesions. Although cytology (accuracy 83.3%) more accurately diagnosed malignant cysts than CEA (accuracy 65.6%), it lacked sensitivity (35.3%)., Conclusions: Our results demonstrate that cyst fluid CEA can be a helpful marker in differentiating mucinous from non-mucinous, but not malignant from benign cystic lesions. A combined CEA and CA 125 approach may help segregate MCNs from IPMNs., (Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

The combination of top-down and bottom-up platforms was utilized for the LC-MS proteomic characterization of the intracystic fluid of adamantinomatous craniopharyngioma pediatric brain tumor disease. Proteins and peptides characterization was achieved by high-resolution LC-ESI-LTQ-Orbitrap-MS analysis while low-resolution LC-ESI-IT-MS was applied for the complete screening of the samples and the evaluation of the protein distribution within patients. Top-down analyses were applied to liquid/liquid extracted samples while bottom-up analyses were performed after trypsin digestion of both untreated and pretreated samples. The two proteomic approaches were complementary for the characterization of the proteome of craniopharyngioma intracystic fluid. Proteins and peptides involved in inflammation, mineralization processes and lipid transport were identified, in agreement with the calcium flecks, cholesterol granules and bone residues characteristic of this fluid. Apolipoprotein A-I, A-II, C-I and J, hemoglobin fragments, ubiquitin, α-2-HS-glycoprotein or fetuin A, α-1-antichymotrypsin, vitamin D binding protein, and α-1-acid glycoprotein were characterized. These data could be relevant for the comprehension of the processes involved in the pathogenesis of the disease and the development of the cyst and could contribute to the individuation of therapeutic targets for the reduction of the cyst volume delaying and/or avoiding invasive surgical treatments., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background and Study Aims: Endoscopic ultrasound (EUS)-guided ethanol lavage with paclitaxel injection has been shown to be effective for the treatment of pancreatic cystic neoplasms; however, the evidence for effectiveness is based primarily on cyst resolution on imaging. The aim of this study was to evaluate changes in pancreatic cyst fluid DNA following EUS-guided pancreatic cyst ablation (PCA) with ethanol and paclitaxel., Patients and Methods: In a single-center, prospective study, patients with suspected benign pancreatic cysts (15 - 50 mm in diameter; ≤ 5 compartments) underwent EUS-PCA with ethanol and paclitaxel followed 3 months later by repeat EUS-FNA, cyst aspiration for repeat DNA analysis, and possible repeat EUS-PCA. Abdominal imaging was repeated 3 - 4 months and 12 months after the second EUS. Changes in baseline pancreatic cyst fluid DNA, procedural complications, and radiographic changes in cyst volume were evaluated., Results: A total of 22 patients (median age 67 years; 15 women) with cysts in the head or uncinate (n = 10), body or neck (n = 8), and tail (n = 4), measuring a median diameter of 25 mm (range 15 - 43 mm), underwent one (n = 22) or two (n = 9) EUS-PCA procedures. Baseline cyst DNA included mutations in 11 patients (50 %). Postablation cyst fluid (n = 19) showed elimination of all baseline mutations in eight patients, new mutations in three, and no changes in eight without a baseline mutation. The largest per-protocol postablation image-defined volume change (n = 20) from either of the follow-up abdominal imaging studies (n = 20) demonstrated complete response ( < 5 % original volume) in 10 patients (50 %), partial response (5 % - 25 % original volume) in 5 (25 %), and a persistent cyst (> 25 % original volume) in 5 (25 %). During a median follow-up of 27 months (range 17 - 42 months), adverse events from all EUS-PCAs (n = 31) included abdominal pain alone in four patients (13 %), pancreatitis in three (10 %), peritonitis in one (3 %), and gastric wall cyst in one (3 %). The adverse events were classified as moderately severe in four patients (three with pancreatitis, one with peritonitis)., Conclusion: EUS-PCA with ethanol and paclitaxel may possibly eliminate mutant DNA in neoplastic pancreatic cysts. This technique leads to complete or partial image-defined resolution in 75 % of cysts but may lead to rare adverse events., Clinical Trial Registration: ClinicalTrials.gov (NCT01643460)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic cysts obtains cyst fluid for cytologic and biochemical analysis, which may determine whether the cyst is mucinous and malignant, contributing to patient management. Despite this added value, EUS-FNA remains controversial in the preoperative assessment of pancreatic cysts. The objective of this study was to assess the utility of EUS-FNA in a cohort of small pancreatic cysts that were benign on imaging studies., Methods: All pancreatic cysts that underwent initial EUS-FNA in 2006 and 2007 were retrospectively analyzed. Ninety-two patients with pancreatic cysts met the inclusion criteria. Patients who had high-risk or worrisome features on imaging studies were excluded. Cytology, histology, and cyst fluid analysis data were collected. The main outcome measurements were radiologic and clinical follow-up as well as cytopathologic and histologic results., Results: EUS-FNA supported a diagnosis of a mucinous cyst in 38 of 92 patients (41%) by carcinoembryonic antigen (CEA) measurement and/or cytology. Cytology demonstrated an absence of high-grade atypia (HGA) in 89 of 92 patients (97%). The mean follow-up was 4.4 years (range, 0-7.7 years), during which 6 cysts were surgically resected and 16 cysts were resampled by at least 1 subsequent EUS-FNA. The overall negative predictive value of cytologic examination for HGA was 99%., Conclusions: EUS-FNA is a screening test that contributes to a triple-negative test for pancreatic cysts--no high-risk stigmata, no worrisome features, and no HGA on cytology--providing a negative predictive value of 99% for conservative management., (© 2013 American Cancer Society.)