Cyst Fluid Analysis Research Articles

Management Guidelines for Pancreatic Cystic Lesions: Should we Adopt or Adapt the Current Roadmaps?

Pancreatic cystic lesions are very prevalent, especially in elderly patients and are increasingly being diagnosed because of the massive use of cross sectional imaging. Our knowledge about the natural history of these lesions is limited, especially in the case of intraductal papillary mucinous neoplasms. This fact explains why scientific societies guidelines statements are based on evidence graded as very low quality and helps the understanding of some of the different guidelines recommendations. Several guidelines have been recently revised to incorporate the new evidence published in the literature with the aim to help clinicians make the best decisions. American Gastroenterological Association guidelines, a revision of the International Consensus Guidelines, the American College of Gastroenterology and the European Study Group guidelines are the most recent. Herein we review the current guidelines on pancreatic cysts and focus our discussion on controversies and updates about the best imaging modalities, the indications for endoscopic ultrasound guided fine needle aspiration, cyst fluid analysis, indications for resection and surveillance strategies.

Pancreatic Cysts in the Elderly.

Incidental pancreatic cysts are common, and management strategies continue to evolve. This review summarizes diagnostic and management recommendations in older patients with these lesions based on guidelines and best clinical evidence. Diagnosis of cyst type has been enhanced with improved imaging and cyst fluid analysis and visualization. Recent outcome studies indicate that certain cyst types should be followed independent of patient age as long as certain criteria which are reviewed are met. Differentiation of pancreatic cyst type is important as this dictates the need for long-term follow-up. Because most cyst-related neoplasia occurs in older patients, surveillance should continue within certain guidelines.

Sequential molecular and cytologic analyses provides a complementary approach to the diagnosis of pancreatic cystic lesions: a decade of clinical practice

Many pancreatic cystic lesions (PCL) are of neoplastic nature with potential to progress to pancreatic adenocarcinoma. Early stratification of patients to either clinical observation or surgical intervention can considerably increase the survival rate. Recent studies have shown the value of molecular analysis to current diagnostic modalities.The aim of this study is to evaluate the diagnostic improvement by utilizing multiple sequential cytologic and molecular cyst fluid analyses. We prospectively evaluated 58 patients for whom multiple endoscopic ultrasound-guided fine-needle aspiration of cyst fluid specimens were available. Specimens were subjected to next generation sequencing to identify any recurrent gene mutations commonly found in PCL. The molecular findings were compared with cytologic and final diagnoses. Cytologic diagnoses were classified into 3 groups: non-diagnostic (first visit: 33.9%, cumulative: 15.8%, P = 0.03), negative (1st visit: 53.6%, cumulative: 56.1%, P = 0.85) and atypical/suspicious/positive (first visit: 12.5%, cumulative: 28.1%, P = 0.06). The mutational analyses were clustered into indeterminate/failure (first visit: 1.7%, cumulative: 0%), KRAS/GNAS/VHL group (first visit: 50.0%, cumulative: 53.4%) and any mutation (first visit: 50.0%, cumulative: 53.4%). Mutational analysis identifies up to 72% and 71% whereas cytologic analysis classified up to 46% and 63% of lesions correctly in first and multiple visits, respectively. The cytology and molecular analyses provide a complementary approach to patients with PCL. Power of molecular analysis in detection of a neoplastic lesion is significantly higher in one visit (P = 0.01) with comparable detection rates (P = 0.43) for both cytologic and molecular analyses after multiple visits.

The prospect of artificial intelligence in the differential diagnosis of pancreatic cysts

The title of the work we are here presenting “ Diagnostic ability of artificial intelligence using deep learning analysis of cyst fluid in differentiating malignant from benign pancreatic cystic lesions ” immediately strikes the interest of readers, especially of the ones performing pancreatic surgery (1). This article debates a theme of major concern for surgeons, the correct identification of a pancreatic cystic lesion, and a theme of major concern for the medical society and the society in general, the application of artificial intelligence (AI).

Cystic Lesions of the Pancreas: Differential Diagnosis and Cytologic-Histologic Correlation.

Pancreatic cystic lesions (PCLs) are very common, and their detection is increasing with the advances in imaging techniques. Because of the major implications for management, distinguishing between neoplastic and nonneoplastic PCLs is critical. Neoplastic cysts with potential to progress into cancer include mucinous PCLs (intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) and nonmucinous cysts (solid pseudopapillary tumors, serous cystic neoplasms, and neuroendocrine tumors with cystic degeneration). Nonneoplastic cysts with no risk of malignant transformation include pseudocysts, retention cysts, lymphoepithelial cysts, cystic pancreatic lymphangioma, and duplication cyst/ciliated foregut cysts. The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology with cyst fluid analysis in the diagnosis of PCLs has evolved during the last decade; however, a definitive diagnosis on cytologic specimens is hampered by the sparse cellularity and can be challenging. EUS-FNA can play an important role to differentiate low-risk from high-risk pancreatic cysts and to distinguish between patients with cysts who need clinical follow-up versus those who require surgery. To provide an integrative approach to diagnose pancreatic cystic lesions using EUS-FNA cytology and cyst fluid analysis, along with clinical, radiologic, histologic, genetic, and molecular characteristics. The review and analysis of the latest literature describing pancreatic cystic lesions. Accurate diagnosis of PCLs requires a multidisciplinary and multimodal team approach, including the integration of clinical findings, imaging, cytology, cyst fluid analysis, and molecular testing.

Safety of endoscopic ultrasound-guided ethanol ablation for pancreatic cystic lesions: A single-center experience of 214 patients

Endoscopic ultrasound-guided ethanol ablation (EUS-EA) for pancreatic cystic lesions (PCLs) has been used in recent years as a feasible treatment modality for low malignant probability PCLs or patients considered high-risk for surgery. The present study aimed to confirm the safety of EUS-EA and to find predictive factors for adverse event (AE). A retrospective review was performed from the prospectively maintained database of patients who underwent EUS-EA for PCLs from June 2006 to April 2018 at Seoul National University Hospital. The primary outcomes of the study were the rates of AEs and severe AEs by EUS-EA. The secondary outcome was the predictive factors of AEs including acute pancreatitis and abdominal pain. A total of 214 patients were evaluated and the diagnoses of PCLs according to cystic fluid analysis and clinical features were as follows: serous cystic neoplasm (32.2%), mucinous cystic neoplasm (26.6%), branch duct type intraductal papillary mucinous neoplasm (BD-IPMN) (29.4%), and pseudocyst (11.7%). Three patients (1.4%) experienced severe AEs. Overall, AEs occurred in 71 (33.2%) patients. BD-IPMN (OR: 2.87; 95% CI: 1.05-7.84; P = 0.040), multilocular cysts (OR: 3.59; 95% CI: 1.09-11.85; P = 0.036), suspected ethanol leakage during procedure (OR: 10.68; 95% CI: 1.98-57.53; P = 0.006), and sticky cystic fluid (OR: 3.83; 95% CI: 1.20-12.24; P = 0.024) were predictive factors for post-procedural acute pancreatitis. PCLs of uncinate process (OR: 2.99; 95% CI: 1.22-7.35; P = 0.017) and PCLs with exophytic portion (OR: 3.70; 95% CI: 1.96-7.01; P<0.001) were predictive factors for post-procedural abdominal pain. EUS-EA is a safe procedure with a very low rate of severe AEs. It seems possible to predict the AEs according to the features of the procedure and PCLs.

Etiologic Distribution of Pancreatic Cystic Lesions Identified on Computed Tomography/Magnetic Resonance Imaging.

This study aimed to determine the distribution of etiology of pancreatic cysts using established criteria/markers from cyst fluid analysis and cytology that have been reported to have high specificity in published literature. A retrospective study of pancreatic cysts using an endoscopic database from March 2002 and May 2013 was conducted. Pancreatic cysts <10 mm and cysts with a history of pancreatic cancer were excluded. In our cohort of 758 patients with pancreatic cyst(s), the cyst etiology was as follows: mucinous cyst/side-branch intraductal papillary mucinous neoplasms (SB-IPMNs)/mucinous cystic neoplasms (MCN; 48.2%), pseudocyst (27.6%), serous cystadenoma (11%), simple cysts (6.4%), mucinous cystadenocarcinoma (5.1%), and other (1%). Approximately 41% (n = 310) of the cysts were ≥3 cm in size and included the following: pseudocyst (39.7%), mucinous cysts/SB-IPMN/MCN (28.1%), serous cystadenoma (16.7%), mucinous cyst adenocarcinoma (9.7%), and simple cyst (4.8%). In 118 patients with a known history of acute pancreatitis, the cyst diagnoses included pseudocyst (68.7%), mucinous cyst/SB-IPMN/MCN (18.6%), benign/simple cyst (7.6%), and mucinous cystadenocarcinoma (2.5%). In patients with cystic pancreatic lesion noted on cross-sectional imaging, approximately half of the patients have lesions without malignancy or malignant potential and therefore not requiring surveillance. Endoscopic ultrasound/endoscopic ultrasound-guided fine-needle aspiration evaluation of the pancreatic cysts can help optimize their further management.

Integrated targeted metabolomic and lipidomic analysis: A novel approach to classifying early cystic precursors to invasive pancreatic cancer

Pancreatic cystic neoplasms (PCNs) are a highly prevalent disease of the pancreas. Among PCNs, Intraductal Papillary Mucinous Neoplasms (IPMNs) are common lesions that may progress from low-grade dysplasia (LGD) through high-grade dysplasia (HGD) to invasive cancer. Accurate discrimination of IPMN-associated neoplastic grade is an unmet clinical need. Targeted (semi)quantitative analysis of 100 metabolites and >1000 lipid species were performed on peri-operative pancreatic cyst fluid and pre-operative plasma from IPMN and serous cystic neoplasm (SCN) patients in a pancreas resection cohort (n = 35). Profiles were correlated against histological diagnosis and clinical parameters after correction for confounding factors. Integrated data modeling was used for group classification and selection of the best explanatory molecules. Over 1000 different compounds were identified in plasma and cyst fluid. IPMN profiles showed significant lipid pathway alterations compared to SCN. Integrated data modeling discriminated between IPMN and SCN with 100% accuracy and distinguished IPMN LGD or IPMN HGD and invasive cancer with up to 90.06% accuracy. Free fatty acids, ceramides, and triacylglycerol classes in plasma correlated with circulating levels of CA19-9, albumin and bilirubin. Integrated metabolomic and lipidomic analysis of plasma or cyst fluid can improve discrimination of IPMN from SCN and within PMNs predict the grade of dysplasia.

Tu1411 EXCELLENT ACCURACY OF GLUCOSE LEVEL IN CYSTIC FLUID FOR DIAGNOSIS OF PANCREATIC MUCINOUS CYSTS

Pancreatic cystic neoplasms (PCNs) are common incidental findings in clinical practice. EUS-FNA for cystic fluid (CF) analysis (cytology and CEA) is crucial in suspicious cysts. Glucose evaluation in PCF, using an “on-site glucometer”, is promising for PCF analysis.

Inmediate on-site diagnosis of mucinous pancreatic lesions by glucometric analysis of cystic fluid obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA)

Inmediate on-site diagnosis of mucinous pancreatic lesions by glucometric analysis of cystic fluid obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA)

Diagnostic ability of artificial intelligence using deep learning analysis of cyst fluid in differentiating malignant from benign pancreatic cystic lesions

The diagnosis of pancreatic cystic lesions remains challenging. This study aimed to investigate the diagnostic ability of carcinoembryonic antigen (CEA), cytology, and artificial intelligence (AI) by deep learning using cyst fluid in differentiating malignant from benign cystic lesions. We retrospectively reviewed 85 patients who underwent pancreatic cyst fluid analysis of surgical specimens or endoscopic ultrasound-guided fine-needle aspiration specimens. AI using deep learning was used to construct a diagnostic algorithm. CEA, carbohydrate antigen 19-9, carbohydrate antigen 125, amylase in the cyst fluid, sex, cyst location, connection of the pancreatic duct and cyst, type of cyst, and cytology were keyed into the AI algorithm, and the malignant predictive value of the output was calculated. Area under receiver-operating characteristics curves for the diagnostic ability of malignant cystic lesions were 0.719 (CEA), 0.739 (cytology), and 0.966 (AI). In the diagnostic ability of malignant cystic lesions, sensitivity, specificity, and accuracy of AI were 95.7%, 91.9%, and 92.9%, respectively. AI sensitivity was higher than that of CEA (60.9%, p = 0.021) and cytology (47.8%, p = 0.001). AI accuracy was also higher than CEA (71.8%, p < 0.001) and cytology (85.9%, p = 0.210). AI may improve the diagnostic ability in differentiating malignant from benign pancreatic cystic lesions.

Assessment of ApoC1, LuzP6, C12orf75 and OCC-1 in cystic glioblastoma using MALDI\u2013TOF mass spectrometry, immunohistochemistry and qRT-PCR

Mass spectrometric analysis of glioblastoma cyst fluids has disclosed a protein peak with m/z 6424–6433. Among the proteins, potentially generating this peak are ApoC1 and LuzP6. To further elucidate protein expression of glioblastoma cells, we analyzed MALDI–TOF results of cyst fluid, performed immunohistochemistry and mRNA analysis. MALDI–TOF protein extraction from 24 glioblastoma cyst fluids was performed with a weak cation exchange. 50 glioblastoma samples were stained with two custom-made antibodies against LuzP6 and commercial antibodies against ApoC1, C12orf75 and OCC-1 and analyzed. For mRNA detection, 16 tissue samples were stored in RNAlater, extracted using the miRNeasy kit and reversely transcribed. For 12 patients, synopsis of results from all three examinations was possible. MALDI–TOF confirmed the peak at 6433 Da in 75% of samples. Immunohistochemically, LuzP6 was detected in 92% (LuzP61–29) and 96% (LuzP630–58) of samples and ApoC1 in 66%. Mean mRNA levels were highest for ApoC1, followed by LuzP6. No correlation between mRNA expression, immunohistochemical staining and intensity of the MALDI–TOF peaks was found. An unequivocal identification of one protein as the source for the 6433 peak is not possible, but our results point to ApoC1 and LuzP6 as the underlying proteins.

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

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

The value of cytology in the management of patients with pancreatic cysts.

The value of cytology in the management of patients with pancreatic cysts.

Factors Influencing Cyst Infection in Autosomal Dominant Polycystic Kidney Disease

Background: Cyst infection is a frequent and serious complication of autosomal dominant polycystic kidney disease (ADPKD) that is often difficult to treat. However, the factors influencing cyst infection are still unknown. Therefore, we investigated clinical factors related to the duration of hospitalization and death due to cyst infection. Methods: All ADPKD patients undergoing cyst drainage or nephrectomy or partial hepatectomy at Toranomon Hospital from January 2004 to March 2016, in whom cyst fluid analysis showed bacteria or neutrophils indicating definite cyst infection, were reviewed retrospectively. Factors influencing the duration of hospitalization and death due to cyst infection were analyzed. Results: A total of 243 patients with cyst infection were enrolled, including 104 men and 139 women (mean age: 62.6 ± 10.0 years). Seventeen patients died of cyst infection. Multivariate logistic regression analysis revealed that hepatomegaly, positive cyst contents culture, and the maximum white blood cell (WBC) count were significantly associated with death from cyst infection. Death was significantly more likely if patients had massive hepatomegaly (≥5,113.2 mL) compared with mild hepatomegaly (< 1,898.7 mL; odds ratio 38.1; 95% CI 2.9–492.6, p = 0.0004). Multivariate Cox proportional hazards analysis revealed that older age, dialysis duration, hepatic transcatheter arterial embolization, maximum WBC count, and hepatomegaly were significantly associated with longer hospital stay for cyst infection, while female sex, nephrectomy, serum albumin, and serum cholinesterase were significantly associated with shorter hospital stay. Discharge alive from hospital was significantly associated with massive hepatomegaly versus mild hepatomegaly (hazard ratio 0.0072; 95% CI 0.0008–0.0659, p < 0.0001). Conclusions: Hepatomegaly was strongly associated with both death and longer hospital stay due to cyst infection.

Endoscopic ultrasound-guided through-the-needle microforceps biopsy in the evaluation of pancreatic cystic lesions: a multicenter study.

Background and study aims Accurate diagnosis and classification of pancreatic cysts (PCs) remains a challenge. The aims of this study were to: (1) evaluate the safety and technical success of a novel microforceps for EUS-guided through-the-needle biopsy (TTNB) of PCs; and (2) assess its diagnostic yield for mucinous PCs when compared to FNA cyst fluid analysis and cytology. Patients and methods This was a multicenter retrospective analysis of 47 patients who underwent EUS-FNA and TTNB for PCs between January 2014 and June 2017. Technical success was defined as acquisition of a specimen adequate for cytologic or histological evaluation. Cyst fluid carcinoembryonic antigen (CEA) was used to initially categorize cysts as non-mucinous (CEA < 192 ng/mL) or mucinous (CEA ≥ 192 ng/mL). Final diagnosis was based on identifiable mucinous pancreatic cystic epithelium on cytology, microforceps histology and/or surgical histology when available. Results Forty-seven patients with PCs (mean size 30.7 mm) were included. TTNB was successfully performed in 46 of 47 (97.9 %). Technical success was significantly lower with FNA (48.9 %) compared to TTNB (85.1 %) ( P < .001). For cysts with insufficient amount of fluid for CEA (n = 19) or CEA < 192 ng/mL, the cumulative incremental diagnostic yield of a mucinous PC was significantly higher with TTNB vs. FNA (52.6 % vs 18.4 %; P = .004). TTNB alone (34.4 %) diagnosed more mucinous PCs than either CEA ≥ 192 ng/mL alone (6.3 %) or when combined with FNA cytology (9.4 %). One episode of self-limited bleeding (2.1 %) and one of pancreatitis (2.1 %) occurred. Conclusions EUS-TTNB is safe and effective for evaluating PCs. TTNB may help increase the diagnostic yield of mucinous PCs.

Application of endoscopic ultrasound-guided-fine needle aspiration combined with cyst fluid analysis for the diagnosis of mediastinal cystic lesions.

BackgroundMediastinal 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.MethodsOver 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.ResultsBased 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.ConclusionEUS‐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.

Metabolomic and Lipidomic Profiling of Plasma and Cyst Fluid Allows the Detection and Characterization of Pancreatic Intraductal Papillary Mucinous Neoplasms

Background: Intraductal papillary mucinous neoplasm (IPMNs) of the pancreas may evolve from low- to high-grade dysplasia to invasive cancer. Accurate discrimination of IPMN-associated grade of dysplasia is an unmet clinical need for appropriate patient management and treatment. This study used an integrated metabolomics and lipidomics approach, aiming to define the metabolic profiles of IPMNs. Methods: Metabolomic and lipidomic profiles of peri-operative pancreatic cyst fluid and pre-operative fasted plasma from IPMN and serous cystic neoplasm (SCN) patients were determined single-blinded in this pancreas resection cohort (n=31). Targeted (semi)quantitative analysis of 100 metabolites from 24 classes and >1000 lipid species spanning 13 classes were performed. The datasets were correlated against histological diagnosis and clinical parameters after correction for confounding factors. Group classification and model performance was done with Partial Least Squares Discriminant Analysis (PLS- DA) and a Leave-One-Out cross validation (LOO-CV) strategy, respectively. Variable Importance in Projection (VIP) ranking scores were used to select the best explanatory molecules. Findings: Over 1000 different compounds were identified in plasma and cyst fluid. The IPMN biofluid profiles showed significant lipid pathway alterations compared to SCN controls. Integrated metabolomics and lipidomics data modeling allowed accurate discrimination between IPMN and SCN and could determine the IPMN-associated grade of dysplasia. Correlations were found between plasma lipid compounds of free fatty acids, ceramides, and triacylglycerol classes and the circulating levels of CA19-9, albumin and bilirubin (r>0·6, p<0·05). Interpretation: An integrated metabolomic and lipidomic analysis of plasma or cyst fluid can improve discrimination of IPMN from SCN and within PMNs predict the grade of dysplasia, which is highly relevant for pancreatic surgery management. Funding Statement: This work was supported by the Swedish Cancer Society (CAN2016/731 to MSC), (CAN 2014/634, CAN 2015/621, CAN 2017/409, CAN 2017/419 to MDC). Ruth och Richard Julins funds and Karolinska Institutet funds, SOF Strategic Odontological Research (to MSC). ALF SLL20150113 (to MDC), Biocenter Finland and HiLIFE, University of Helsinki (to AP and VV). Declaration of Interests: None. Ethics Approval Statement: This study follows the Helsinki convention and good clinical practice with permission of the Ethical Review Board Stockholm and the Karolinska Biobank Board (Dnr 2015/1580- 31/1).

Cyst infection in autosomal dominant polycystic kidney disease: penetration of meropenem into infected cysts

BackgroundCyst infection is a common and serious complication of autosomal dominant polycystic kidney disease (ADPKD) that is often refractory. Carbapenems are frequently needed to treat to patients with refractory cyst infection, but little is known about the penetration of newer water-soluble carbapenems into cysts. This study investigated the penetration of meropenem (MEPM) into infected cysts in patients with ADPKD.MethodsBetween August 2013 and January 2014, 10 ADPKD patients (14 infected cysts) receiving MEPM at Toranomon Hospital underwent drainage of infected cysts and definite cyst infection was confirmed through detection of neutrophils by cyst fluid analysis. The serum concentration of MEPM was measured just after intravenous administration and was compared with that in fluid aspirated from infected cysts.ResultsIn the patients undergoing cyst drainage, the mean serum MEPM concentration was 35.2 ± 12.2 μg/mL (range: 19.7 to 59.2 μg/mL, while the mean cyst fluid concentration of MEPM in the drained liver cysts (n = 12) or kidney cysts (n = 2) was 3.03 ± 2.6 μg/mL (range: 0 to 7.3 μg/mL). In addition, the mean cyst fluid/serum MEPM concentration ratio was 9.46 ± 7.19% (range: 0 to 18.8%). There was no relationship between the cyst fluid concentration of MEPM and the time until drainage after MEPM administration or between the cyst fluid/serum MEPM concentration ratio and the time until drainage.ConclusionThese findings suggest that MEPM shows poor penetration into infected cysts in ADPKD patients.Trial registrationThis study was registered with the University Hospital Medical Information Network (UMIN) as “Penetration of meropenem into cysts in patients with autosomal dominant polycystic kidney disease (ADPKD)”, UMIN ID 000011292 on July 26th, 2013.

Use of EUS-Guided Needle-Based Confocal Laser Endomicroscopy and Microforceps Biopsy to Prevent an Unnecessary Cyst-Gastrostomy

Introduction: Current radiologic and endoscopic studies for pancreatic cystic lesions have known poor sensitivity and accuracy for distinguishing any particular cystic lesion. The current case describes the use of two novel EUS-guided tools for the diagnosis and management of a large, symptomatic pancreatic cyst. Case Description: 30 year old female with prior history of pancreatitis presented with left upper quadrant abdominal pain. MRCP revealed a large 28 mm x 39 mm unilocular cyst in the tail of the pancreas. Based on the history, the possibility of a pancreatic pseudocyst was raised. However, given the patient's young age and female gender, as well as the cyst morphology and location, a clinical suspicion was raised for a possible mucinous cystic neoplasm (MCN). Given the diagnostic uncertainty, and the vast differences in management of these lesions, the decision was made to perform further diagnostic testing to help guide management. EUS evaluation with multimodality sampling was performed. nCLE imaging revealed multiple thickened epithelial bands lining the cyst wall. Four biopsies were then obtained using the MFB. Following this, FNA was performed. Seventeen ml of dark brown watery fluid was obtained. Cyst fluid analysis demonstrated glucose 1,500 ng/ml, amylase 11,859 u/L. Cytology revealed foamy macrophages and a few clusters of bland glandular cells. MFB pathology yielded tissue with ovarian-like stroma with mucinproducing epithelial lining consistent with an MCN. The patient was referred for a distal pancreatectomy. Final surgical pathology revealed the cyst wall to be lined by flat cuboidal epithelium and ovarian-type stroma without cytologic atypia, papillary architecture or epithelial proliferation. Final diagnosis favored an endometrial cyst of the pancreas over an atypical MCN. The patient had resolution of her symptoms following surgery. Discussion: Standard EUS-FNA and cyst fluid analysis are suboptimal in their ability to make a cytopathologic diagnosis of a pancreatic cyst. In the current case, standard biochemical fluid analysis produced conflicting results showing both an elevated cyst fluid CEA and amylase, and thus unable to distinguish an inflammatory pseudocyst from a neoplastic or non-inflammatory cystic lesion. Cyst fluid cytology was similarly non-diagnostic. However, the combined use of EUS-guided nCLE and MFB produced highly detailed diagnostic information allowing for appropriate management. Watch the video: https://goo.gl/XkPkfy