Combination of cyst fluid CEA and CA 125 is an accurate diagnostic tool for differentiating mucinous cystic neoplasms from intraductal papillary mucinous neoplasms

Background/objectivesDespite 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.MethodsA 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.ResultsReceiver 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%).ConclusionsOur 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.     

Utility of endoscopic ultrasound, cytology and fluid carcinoembryonic antigen and CA 19-9 levels in pancreatic cystic lesions

AIM： To assess the diagnostic accuracy of endoscopic ultrasound （EUS）, fluid tumor markers and cytology in distinguishing benign from （pre）malignant pancreatic cystic lesions.
METHODS： 46 consecutive patients, referred to a gastroenterologist and surgeon for a symptomatic or incidental pancreatic cyst, were reviewed. EUS, cytology, and carcinoembryonic antigen （CEA） and carbohydrate antigen （CA 19-9） levels were compared with the final diagnosis, based on surgical pathology and/or imaging follow-up of at least 12 mo. Cysts were classified as benign （pseudocyst, serous cystadenoma） or malignant/ pre-malignant （mucinous cystic neoplasm）. Receiver- operator characteristics （ROC） curve analysis was performed. RESULTS： The mean age was 56 years; 29% were male and median cyst diameter was 3 cm. Final outcome was obtained in 41 （89%） patients. Twenty-three （56%） of these 41 had surgical pathology. Twenty-three （56%） had benign lesions and 18 （44%） had malignant/premalignant lesions. Sensitivity, specificity and positive and negative predictive value of EUS alone to distinguish benign from malignant/premalignant pancreatic cystic lesions were 50%, 56%, 36% and 54% and for cytology were 71%, 96%, 92% and 85%, respectively. The corresponding values for the ROC-derived ideal cutoffs were 75%, 90%, 75%, 90% for CA 19-9 （〉 37 U/mL） and 70%, 85%, 79% and 78% for CEA （〉 3.1 ng/mL）. Subgroup analysis of those with surgical pathology yielded almost identical performance and cutoffs.
CONCLUSION： Cytology and cyst fluid tumor marker analysis is a very useful tool in distinguishing benign from （pre）malignant pancreatic cystic lesions.     

Cyst fluid glucose: An alternative to carcinoembryonic antigen for pancreatic mucinous cysts

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.     

Role of endoscopic ultrasonography in the diagnosis and treatment of cystic tumors of the pancreas

Endoscopic ultrasound (EUS) allows high resolution imaging of the pancreas. EUS is a very useful technique for evaluating morphological features of a cystic tumors of the pancreas. These features include thick wall type, tumor protruding type, thick septal type, microcystic type, thin septal type and simple type. Malignant cystic lesions may present as a hypoechoic cystic/solid mass or as a complex cyst and are frequently associated with a dilated main pancreatic duct. There is some overlap between EUS appearances of non-neoplastic and neoplastic cystic pancreatic lesions. EUS guided FNA of cystic pancreatic lesions can play an important role in the differential diagnosis of these lesions and deciding about the need for surgery by evaluating cytology and tumor markers such as CEA in cyst fluid. There is some emerging data on EUS guided treatment of cystic pancreatic tumors by injection of alcohol.     

Updates in diagnosis and management of pancreatic cysts

Incidental pancreatic cysts are commonly encountered with some cysts having malignant potential. The most common pancreatic cystic neoplasms include serous cystadenoma, mucinous cystic neoplasm and intraductal papillary mucinous neoplasm. Risk stratifying pancreatic cysts is important in deciding whether patients may benefit from endoscopic ultrasound (EUS) or surgical resection. Surgery should be reserved for patients with malignant cysts or cysts at high risk for developing malignancy as suggested by various risk features including solid mass, nodule and dilated main pancreatic duct. EUS may supplement magnetic resonance imaging findings for cysts that remain indeterminate or have concerning features on imaging. Various cyst fluid markers including carcinoembryonic antigen, glucose, amylase, cytology, and DNA markers help distinguish mucinous from nonmucinous cysts. This review will guide the practicing gastroenterologist in how to evaluate incidental pancreatic cysts and when to consider referral for EUS or surgery. For presumed low risk cysts, surveillance strategies will be discussed. Managing pancreatic cysts requires an individualized approach that is directed by the various guidelines.     

Endosonography in the diagnosis and management of pancreatic cysts

Rapid advances in radiologic technology and increased cross-sectional imaging have led to a sharp rise in incidental discoveries of pancreatic cystic lesions. These cystic lesions include non-neoplastic cysts with no risk of malignancy, neoplastic non-mucinous serous cystadenomas with little or no risk of malignancy, as well as neoplastic mucinous cysts and solid pseudopapillary neoplasms both with varying riskof malignancy. Accurate diagnosis is imperative as management is guided by symptoms and risk of malignancy. Endoscopic ultrasound(EUS) allows high resolution evaluation of cyst morphology and precise guidance for fine needle aspiration(FNA) of cyst fluid for cytological, chemical and molecular analysis. Initially, clinical evaluation and radiologic imaging, preferably with magnetic resonance imaging of the pancreas and magnetic resonance cholangiopancreatography, are performed. In asymptomatic patients where diagnosis is unclear and malignant risk is indeterminate, EUSFNA should be used to confirm the presence or absence of high-risk features, differentiate mucinous from non-mucinous lesions, and diagnose malignancy. After analyzing the cyst fluid for viscosity, cyst fluid carcinoembryonic antigen, amylase, and cyst wall cytology should be obtained. DNA analysis may add useful information in diagnosing mucinous cysts when the previous studies are indeterminate. New molecular biomarkers are being investigated to improve diagnostic capabilities and management decisions in these challenging cystic lesions. Current guidelines recommend surgical pancreatic resection as the standard of care for symptomatic cysts and those with high-risk features associated with malignancy. EUSguided cyst ablation is a promising minimally invasive, relatively low-risk alternative to both surgery and surveillance.     

Pancreatic cystic neoplasms: diagnosis and management

PCNs are composed of a wide range of lesions from benign cysts to malignancies . Although a cross-sectional imaging provides a sensitive screening test, EUS with FNA and cyst fluid analysis greatly increase the diagnostic certainty. Cyst fluid CEA offers the greatest accuracy in the differentiation between mucinous and nonmucinous PCNs. In the future, endoscopic ablation therapy might offer an alternative to the traditional surgical approach.     

Endoscopic ultrasound-guided fine needle aspiration in diagnosis of cystic pancreatic lesions

Background and study aimspancreatic cysts are commonly found lesions and proper diagnosis is very important for planning further management. The study aims to evaluate the role of cyst fluid amylase and tumour markers as cancer antigen (CA 19-9) and carcinoembryonic antigen (CEA) in addition to mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions.Patients and methodsThis prospective study was conducted on 184 patients diagnosed to have pancreatic cystic lesions from January 2013 to January 2018. Fluid analysis for CA 19-9, CEA, amylase, mucin stain and cytopathology were done. We compared these data with the final diagnosis based on histopathology after surgical resection, positive cytopathology and long period of follow up of the patients for at least 18 months.ResultsThe highest AUC was that of cystic CEA with cut-off value of 160 ng/ml; it had a sensitivity of 60.4% and a specificity of 85%. The best cut-off value for cystic CA 19-9 was 1318 U/ml with a sensitivity of 64.1% and a specificity of 68.1%. The cut-off value of cyst amylase level was 5500 U/L, with 84.2% sensitivity and 37.1% specificity. The sensitivity of mucin stain in detecting mucinous cystic neoplasm was 85.45%, specificity was 86.05% with accuracy 85.87%.ConclusionCyst fluid analysis by investigating amylase, mucin, CA 19-9, CEA and EUS examination improves the diagnosis of different pancreatic cysts.     

Endoscopic ultrasound guided fine needle aspiration for the diagnosis of pancreatic cystic neoplasms: A meta-analysis

Background and objectivesMucinous cystic neoplasms and intraductal papillary mucinous tumours have greater malignant potential than serous cystic neoplasms. EUS alone is inadequate for characterising these lesions but the addition of FNA may significantly improve diagnostic accuracy. The performance of EUS-FNA is highly variable in published studies.AimTo determine the diagnostic accuracy of EUS-FNA to differentiate mucinous versus non-mucinous cystic lesions with cyst fluid analysis for cytology and carcinoembryonic antigen (CEA) by performing a meta-analysis of published studies.MethodsRelevant studies were identified via structured database search and included if they used a reference standard of definitive surgical histology or clinical follow-up of at least 6 months. Data from selected studies were pooled to give summary sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio and Receiver Operating Characteristic (ROC) curve. Pre-defined subgroup analysis was performed.ResultsEighteen studies (published 2002–2011) were included, with a total of 1438 patients. For cytology, pooled sensitivity was 54(95%CI 49–59)% and specificity 93(90–95)%. The diagnostic odds ratio (DOR) was 13.3 (4.37–49.43), with I² of 77.1%. For CEA sensitivity was 63(59–67)% and specificity 88(83–91)%. The DOR was 10.76(6.29–18.41) with an I² of 25.4%. The diagnostic accuracy of EUS-FNA was enhanced in prospective studies and studies of <36 months duration. No impact of publication bias on our results was demonstrated.ConclusionsFine-needle aspiration has moderate sensitivity but high specificity for mucinous lesions. EUS-FNA, when used in conjunction with cross sectional imaging, is a useful diagnostic tool for the correct identification of mucinous cysts.     

Cyst fluid analysis obtained by EUS-guided FNA in the evaluation of discrete cystic neoplasms of the pancreas: a prospective single-center experience

BACKGROUND: Accurate assessment of pancreatic cystic neoplasms is imperative before selecting available treatment options, such as surgical resection, drainage, or conservative therapy. Available modalities, CT and magnetic resonance imaging, have been inconsistent in diagnosis. Reports involving EUS and cyst fluid analysis have been encouraging, including studies of EUS features and/or cyst fluid analysis, which may differentiate pancreatic cystic neoplasms. OBJECTIVE: To retrospectively determine cyst fluid characteristics that differentiate cystic neoplasms. DESIGN: Patient evaluation included (1) EUS features (reported elsewhere) and (2) cyst fluid analysis (carcinoembryonic antigen [CEA], carbohydrate antigen 19-9 [CA 19-9], amylase and lipase, viscosity [VIS], mucin stain, and cytology). Exclusion criteria included the following: intraductal papillary mucinous tumor lesions, bloody cyst aspirate, neuroendocrine tumors, and patients without surgical histopathology. SETTING: Pancreatic Biliary Center, St Luke's Medical Center, Milwaukee, Wisconsin. PATIENTS: A total of 102 patients (60 women, 42 men; age, 23-76 years) presented for evaluation of pancreatic cystic neoplasm; 71 underwent surgical resection. RESULTS: Seventy-one of 102 patients who underwent surgery presented the following histopathologic correlates: 23 pseudocysts (PC), 13 serous cystadenoma (SCyA), 21 mucinous cystadenoma (MCyA), and 14 mucinous cystadenocarcinoma (MCyA-CA). Cyst fluid analysis of these patients showed the following: VIS was lower in PC (mean, 1.3) and SCyA (1.27) when compared with MCyA (1.84) and MCyA-CA (1.9). All mucinous neoplasms had VIS >1.6, whereas only 2 mucinous cystic neoplasms (MCN) had VIS = 1.6 (both PC). The CEA level was significantly higher in MCyA (adenoma [878 ng/mL], carcinoma [27,581 ng/mL]) vs PC (189 ng/mL), and SCyA (121 ng/mL). Amylase levels were higher in PC (7210 U/L) compared with cystic neoplasm (SCyA, 679 U/L; MCyA, 1605 U/L; MCyA-CA, 569 U/L). CONCLUSIONS: Differential diagnosis of pancreatic cystic neoplasm is significantly enhanced by cyst fluid analysis. Elevated CEA (> or =480 ng/mL) and VIS (>1.6) accurately predict MCN from SCyA and PC. Malignant from benign MCN can be differentiated by CEA levels > or =6000 ng/mL.     

Macrocystic serous cystadenoma of the pancreas: clinicopathologic features in seven cases.

BACKGROUND: Serous cystic neoplasms of the pancreas are uncommon tumors classified as microcystic adenomas. In this article, the authors report clinico-pathologic features of seven cases of macrocystic variant of the serous cystadenoma. METHODS: Seven patients (5 females and 2 males) with a diagnosis of cystic lesion of the pancreas were observed after 1995. Clinical, radiological, and pathologic features, including immunohistochemistry, were reported. Enzymes and tumor markers CEA, CA 19-9, CA 125, CA 15-3, CA 72-4, and mucin-like carcinoma-associated antigen (MCA) were investigated in the serum and cyst fluid of the patients. Cytology was also performed. RESULTS: Six patients were symptomatic complaining abdominal pain. All cases had radiologic evidence of unilocular cyst of the pancreas. The suspected diagnosis was consistent with mucinous cystic neoplasm. Serum tumor markers were all in the normal range. After surgery, pathology showed in all cases a cyst lined with cuboidal, periodic acid-Schiff (PAS)-positive epithelium, without mucin content or atypia. Minute microcysts were found surrounding the main cavity. Immunohistochemical stains were positive for cytokeratin, CA19-9, CA15-3, CA 72-4, and MCA. CEA was unexpressed. CA 125 in the cyst fluid were found elevated in three cases and CA 19-9 in three cases. Cytology was negative in all cases. CONCLUSION: When a unilocular pancreatic cyst is found, without history of pancreatitis and gallstones, having low serum tumor markers levels and negativity of CA 72-4 and MCA in the cyst fluid, the diagnosis of the macrocystic variant of the serous cystadenoma may be suggested. At present, the diagnosis is still based on pathological examination after cyst removal.     

Performance of endosonography-guided fine needle aspiration and biopsy in the diagnosis of pancreatic cystic lesions

OBJECTIVE: Preoperative diagnosis of cystic lesions of the pancreas remains difficult despite improvement in imaging modalities and cystic fluid analysis. The aim of our study was to assess the performance of endoscopic ultrasonography (EUS) and EUS-guided fine needle aspiration (FNA) in the diagnosis of pancreatic cystic lesions. METHODS: Data from a series of 127 consecutive patients with pancreatic cystic lesions were prospectively studied. EUS and EUS-guided FNA were performed in all patients, and cystic material was used for cytological and histological analysis as well as for biochemical and tumor markers analysis. Performance of EUS diagnosis, biochemical and tumor markers, and FNA diagnosis were compared with the final histological diagnosis obtained at surgery or postmortem examination. Sixty-seven patients underwent surgery and therefore constituted our study group. RESULTS: EUS provided a tentative diagnosis in 113 cases (89%). Cytohistological FNA provided a diagnosis in 98 cases (77%). When the results of EUS and EUS-guided FNA were compared with the final diagnosis (67 cases), EUS correctly identified 49 cases (73%), whereas FNA correctly identified 65 cases (97%). Sensitivity, specificity, positive predictive value, and negative predictive value of EUS and EUS-guided FNA to indicate whether a lesion needed further surgery were 71% and 97%, 30% and 100%, 49% and 100%, and 40% and 95%, respectively. Carbohydrate antigen 19-9 > 50,000 U/ml had a 15% sensitivity and a 81% specificity to distinguish mucinous cysts from other cystic lesions, whereas it had a 86% sensitivity and a 85% specificity to distinguish cystadenocarcinoma from other cystic lesions. CONCLUSIONS: EUS-guided FNA is a valuable tool in the preoperative diagnostic assessment of pancreatic cystic lesions.     

内镜超声引导下细针穿刺细胞学及囊液癌胚抗原分析诊断胰腺囊性病变的价值

目的探讨内镜超声引导下细针穿刺（EUS-FNA）细胞学检查、囊液癌胚抗原（cEA）分析对区分胰腺囊性病变良恶性的诊断价值。方法对27例胰腺囊性病变患者行EUS-FNA细胞学检查和囊液CEA分析,绘制囊液CEA受试者工作特征曲线并通过Youden指数确定诊断临界值,以手术病理诊断为金标准,统计分析EUS、EUS-FNA细胞学及囊液CEA分析鉴别诊断胰腺囊性病变良恶性的敏感度、特异度、阳性预测值、阴性预测值和准确率。结果手术病理确诊良性病变14例、潜在恶性／恶性病变13例。EUS鉴别诊断胰腺囊性病变良恶性的准确率、敏感度、特异度、阳性预测值、阴性预测值分别为77．8％（21／27）、69．2％（9／13）、85．7％（12／14）、81．8％（9／11）、75．0％（12／16）;EUS-FNA细胞学上述指标分别为85．2％（23／27）、76．9％（10／13）、92．9％（13／14）、90．9％（10／11）、81．3％（13／16）;以囊液CEA值22．24ng／ml为诊断临界值,上述指标分别为74．1％（20／27）、84．6％（11／13）、64．3％（9／14）、68．8％（11／16）、81．8％（9／11）。结论EUS-FNA细胞学鉴别诊断胰腺囊性病变良恶性具有较高的准确率和特异度,而囊液CEA分析（诊断临界值22．24ng／m1）鉴别诊断胰腺囊性病变良恶性的敏感度较高,选择合适的胰腺囊液CEA分析诊断临界值结合EUS-FNA细胞学检查可以基本满足临床鉴别胰腺囊性病变良恶性的需要。     

Macrocystic form of serous pancreatic cystadenoma

OBJECTIVES: Macrocystic serous cystadenoma of the pancreas are benign lesions with sometimes difficult diagnostic issues. We aimed to describe clinicopathological and imaging features with cyst fluid analysis in a series of patients undergoing surgery for macrocystic serous cystadenoma. METHODS: Eight patients underwent pancreatic resection for a macrocystic lesion of the pancreas diagnosed on ultrasonography or CT. Endoscopic ultrasonography and preoperative fine-needle aspiration were performed in seven patients. Immunohistochemical analysis of the surgical specimen with antibodies to carcinoembryonic-antigen (CEA), carbohydrate antigen (CA) 19-9, estrogen receptor, and progesterone receptor antibodies was performed in all cases. RESULTS: Patients included seven women and one man, with a mean age of 48 yr. Lesions were incidentally discovered on ultrasonography in six patients and had a mean size of 3 cm (range, 1.5-5 cm). Endoscopic ultrasonography revealed millimetric cysts in three cases. In the seven aspirated cysts, cytological analysis was non-contributive, but biochemical analysis showed low content of CEA (< 5 ng/ml) and CA72.4 (< 40U/ml) in all but two. At histology, cysts were lined by clear cuboidal cells. They focally expressed CA19-9 but were negative for anti-CEA, antiestrogen receptor, and antiprogesterone receptor antibodies. Microscopic cysts in the wall of the lesions were demonstrated in five cases. CONCLUSIONS: Macrocystic serous cystadenoma is a particular variant of pancreatic serous cystadenoma. Endoscopic ultrasonography may be useful in detecting peripherally located millimetric cysts in unilocular lesions, and measurement of enzymes and tumor markers in cyst fluid may also contribute to the diagnosis showing low concentrations.     

Macrocystic pancreatic cystadenoma: The role of EUS and cyst fluid analysis in distinguishing mucinous and serous lesions

BACKGROUND: Benign pancreatic serous cystadenoma usually is morphologically distinguishable from mucinous cystadenomas, which require resection because of their malignant potential. A macrocystic variant of serous cystadenoma recently has been described, rendering this important distinction more difficult. The aim of this study was to determine the EUS and tumor marker characteristics of mucinous cystadenoma compared with macrocystic serous cystadenomas. METHODS: Medical records for consecutive patients seen between 1995 and 2002, with a histopathologic diagnosis of mucinous cystadenoma or macrocystic serous cystadenoma after surgery, who had undergone a detailed EUS examination, including EUS-guided FNA, were retrospectively reviewed. RESULTS: A resection specimen was available for 32 mucinous cystadenomas and 9 macrocystic serous cystadenomas. No significant differences were observed with regard to clinical data (age, gender, presence of symptoms), lesion size, and location within the pancreas. All mucinous cystadenomas had a discernible cyst wall (thickened, 66%; focal parietal nodules, 25%) compared with 56% of macrocystic serous cystadenomas (p<0.0001). A thick echo content also was more frequent in mucinous cystadenoma (56% vs. 11%; p=0.04; statistical significance removed by the Bonferroni correction). Microcysts were only observed in macrocystic serous cystadenomas (44%; p=0.0008). The combination of a cyst wall that is thickened and the absence of microcysts had a sensitivity of 100% and specificity of 78% for the diagnosis of mucinous cystadenoma compared with macrocystic serous cystadenoma. Although intracystic carbohydrate-associated antigen 72-4 and mucins M1 were non-discriminatory, low carcinoembryonic antigen (<5 ng/mL) and carbohydrate-associated antigen 19-9 (<50,000 U/mL) values were found in macrocystic serous lesions (respectively, 100% and 100%; p=0.0002 and p=0.0002). CONCLUSIONS: Although there is considerable overlap, helpful EUS characteristics that differentiate mucinous cystadenoma from macrocystic serous cystadenoma include a thick cyst wall and microcysts. These features, coupled with analysis of aspirated fluid for tumor markers (especially carcinoembryonic antigen), should help to confirm the diagnosis.     

Molecular assessment of endoscopically collected pancreatic juice and duodenal fluid from patients with pancreatic diseases

One concern associated with pancreatic diseases is the poor prognosis of pancreatic cancer. Even with advances in diagnostic modalities, risk stratification of premalignant lesions and differentiation of pancreatic cysts are challenging. Pancreatic lesions of concern include intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, serous cystadenomas, pseudocysts, and retention cysts, as well as cystic degeneration of solid tumors such as solid pseudopapillary neoplasms and pancreatic neuroendocrine neoplasms. Pancreatic juice obtained during endoscopic retrograde cholangiopancreatography has previously been used for the detection of KRAS mutation. Recently, duodenal fluid, which can be obtained during the relatively minimally invasive procedures of endoscopic ultrasound (EUS) and esophagogastroduodenoscopy, and cyst fluid collected by EUS-guided fine-needle aspiration (FNA) were used for molecular biological analysis. Furthermore, advanced analytic methods with high sensitivity were used for the detection of single and multiple markers. Early detection of malignant pancreatic tumors and risk stratification of premalignant tumors can be performed using duodenal fluid samples with a single marker with high sensitivity. Technological advances in simultaneous detection of multiple markers allow for the differentiation of cystic pancreatic tumors. One thing to note is that the clinical guidelines do not recommend pancreatic cyst fluid and pancreatic juice (PJ) sampling by EUS-FNA and endoscopic retrograde cholangiopancreatography, respectively, in actual clinical practice, but state that they be performed at experienced facilities, and duodenal fluid sampling is not mentioned in the guidelines. With improved specimen handling and the combination of markers, molecular markers in PJ samples may be used in clinical practice in the near future.     

Comparison of endoscopic ultrasound and computed tomography in the assessment of pancreatic cyst size using pathology as the gold standard

Background/objectivesAccurate assessment of whether a cyst is greater than 3 cm is an essential component when considering resection especially for mucinous lesions. The most accurate method of assessing cyst size is uncertain with many patients undergoing several complimentary imaging modalities. This study aimed to compare the accuracy of endoscopic ultrasound (EUS) with CT scanning in assessing pancreatic cyst size compared to histology.MethodsPatients referred for EUS of a pancreatic cystic lesion from April 2003 to August 2011. Patient age and gender, lesion size and site were recorded and compared using cyst size at histology compared to EUS and CT recorded within 3 months of surgery. Subgroup analysis was performed with respect to cyst site and proven mucinous lesions.Results357 patients were included of which 70 (mean age 60.6 years, 24 males) had undergone surgical resection. The resected cysts were located 30/17/23 in the head/body/tail of the pancreas. Median size at histology was 32 mm compared to 35 mm at EUS (p = 0.47) and 35 mm at CT (p = 0.52). For mucinous lesions alone, median size at histology was 32 mm compared to 33 mm at EUS (p = 0.46) and 35 mm at CT (p = 0.39). EUS and CT had comparable sensitivity, specificity, negative predictive value, positive predictive value and accuracy for all cyst types and locations.ConclusionsCT and EUS measurements are not significantly different to pathological size following resection of pancreatic cystic lesions. CT and EUS are interchangeable investigations for determining cyst size pre-operatively although EUS has the additional advantage of fluid sampling.     

Cytopathological Analysis of Cyst Fluid Enhances Diagnostic Accuracy of Mucinous Pancreatic Cystic Neoplasms

Widespread use of cross-sectional imaging and increasing age of the general population has increased the number of detected pancreatic cystic lesions. However, several pathological entities with a variety in malignant potential have to be discriminated to allow clinical decision making. Discrimination between mucinous pancreatic cystic neoplasms (PCNs) and nonmucinous pancreatic lesions is the primary step in the clinical work-up, as malignant transformation is mostly associated with mucinous PCN. We performed a retrospective analysis of all resected PCN in our tertiary center from 2000 to 2014, to evaluate preoperative diagnostic performance and the results of implementation of the consensus guidelines over time. This was followed by a prospective cohort study of patients with an undefined pancreatic cyst, where the added value of cytopathological mucin evaluation to carcinoembryonic antigen (CEA) in cyst fluid for the discrimination of mucinous PCN and nonmucinous cysts was investigated. Retrospective analysis showed 115 patients operated for a PCN, with a correct preoperative classification in 96.2% of the patients. High-grade dysplasia or invasive carcinoma was observed in only 32.3% of mucinous PCN. In our prospective cohort (n = 71), 57.7% of patients were classified as having a mucinous PCN. CEA ≥192 ng/mL had an accuracy of 63.4%, and cytopathological mucin evaluation an accuracy of 73.0%. Combining these 2 tests further improved diagnostic accuracy of a mucinous PCN to 76.8%. CEA level and mucin evaluation were not predictive of the degree of dysplasia. These findings show that adding cytopathology to cyst fluid biochemistry improves discrimination between mucinous PCN and nonmucinous cysts.     

Macrocystic serous cystadenoma of the pancreas

Summary Background. Serous cystic neoplasms of the pancreas are uncommon tumors classified as microcystic adenomas. In this article, the authors report clinico-pathologic features of seven cases of macrocystic variant of the serous cystadenoma. Methods. Seven patients (5 females and 2 males) with a diagnosis of cystic lesion of the pancreas were observed after 1995. Clinical, radiological, and pathologic features, including immunohistochemistry, were reported. Enzymes and tumor markers CEA, CA 19-9, CA 125, CA 15-3, CA 72-4, and mucin-like carcinoma-associated antigen (MCA) were investigated in the serum and cyst fluid of the patients. Cytology was also performed. Results. Six patients were symptomatic complaining abdominal pain. All cases had radiologic evidence of unilocular cyst of the pancreas. The suspected diagnosis was consistent with mucinous cystic neoplasm. Serum tumor markers were all in the normal range. After surgery, pathology showed in all cases a cyst lined with cuboidal, periodic acid-Schiff (PAS)-positive epithelium, without mucin content or atypia. Minute microcysts were found surrounding the main cavity. Immunohistochemical stains were positive for cytokeratin, CA19-9, CA15-3, CA 72-4, and MCA. CEA was unexpressed. CA 125 in the cyst fluid were found elevated in three cases and CA 19-9 in three cases. Cytology was negative in all cases. Conclusion. When a unilocular pancreatic cyst is found, without history of pancreatitis and gallstones, having low serum tumor markers levels and negativity of CA 72-4 and MCA in the cyst fluid, the diagnosis of the macrocystic variant of the serous cystadenoma may be suggested. At present, the diagnosis is still based on pathological examination after cyst removal.     

EUS diagnosis of cystic lesions of the pancreas

Summary Background. Cystic tumors of the pancreas are composed of benign, premalignant, malignant, and inflammatory lesions that are traditionally difficult to diagnose. Most of the tumors are initially detected on CT/US scanning, but often the morphological characteristics are insufficient for making a definitive diagnosis. Endoscopic ultrasound (EUS) may be an ideal tool for imaging of these lesions because it can provide highly detailed imaging without interference by bowel or air. Furthermore, EUS can direct fine needle aspiration of the lesions, providing cyst fluid for cytologic examination. The findings of cyst fluid cytology can be complemented by the use of cyst fluid tumor makers such as CEA. Using the morphologic appearance by endosonography, the results of cytology, and tumor marker analysis, EUS can often differentiate between benign, malignant, and inflammatory cystic lesions of the pancreas.