Malignant Pancreatic Cystic Neoplasms Research Articles

Factors affecting the diagnostic value of liquid-based cytology by EUS-FNA in the diagnosis of pancreatic cystic neoplasms.

This study retrospectively evaluated the value of liquid-based cytology (LBC) alone for diagnosing pancreatic cystic neoplasms (PCNs) in a large sample and initially estimated factors that might affect LBC diagnostic ability. From April 2015 to October 2022, we prospectively enrolled 331 patients with suspected PCNs in our prospective database. Among them, 112 patients chosen to receive surgical resection were included. Only 96 patients who underwent EUS-guided cystic fluid LBC were finally studied. The diagnostic values of LBC for differentiating benign and malignant PCNs and subtypes of PCNs were evaluated. There were 71 female and 25 male patients with a mean age of 47.6 ± 14.4 years. The median cyst size was 43.4 mm. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of LBC for the differentiation of benign and malignant PCNs were 96.9%, 57.1%, 100%, 100%, and 96.7%, respectively. The overall diagnostic accuracy of LBC for specific cyst types was 33.3% (32/96). Cysts located in the pancreatic body/tail or with irregular shapes were more likely to obtain a definite LBC diagnosis. At the same time, age, sex, tumor size, cystic fluid viscosity, operation time, needle type, and presence of septation were not significantly different. Liquid-based cytology alone is useful for differentiating benign PCNs from malignant PCNs and can successfully characterize the PCN subtypes in one-third of patients. Pancreatic cystic neoplasms located in the body/tail or exhibiting irregular shapes are more likely to obtain a definite LBC diagnosis.

Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm

Pancreatic cystic neoplasms (PCNs) are recognized as precursor lesions of pancreatic cancer, with a marked increase in prevalence. Early detection of malignant PCNs is crucial for improving prognosis; however, current diagnostic methods are insufficient for accurately identifying malignant PCNs. Here, we utilized mass spectrometry (MS)-based glycosite- and glycoform-specific glycoproteomics, combined with proteomics, to explore potential cyst fluid diagnostic biomarkers for PCN. The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated, and its characteristics during the malignant transformation of PCN were analyzed. Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN, a group of cyst fluid glycoprotein biomarkers was identified. Through parallel reaction monitoring (PRM)-based targeted glycoproteomic analysis, we validated these chosen glycoprotein biomarkers in a second cohort, ultimately confirming N-glycosylated PHKB (Asn-935, H5N2F0S0; Asn-935, H4N4F0S0; Asn-935, H5N4F0S0), CEACAM5 (Asn-197, H5N4F0S0) and ATP6V0A4 (Asn-367, H6N4F0S0) as promising diagnostic biomarkers for distinguishing malignant PCNs. These glycoprotein biomarkers exhibited robust performance, with an area under the curve ranging from 0.771 to 0.948. In conclusion, we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN. These findings hold significant clinical implications, providing valuable insights for PCN decision-making, and potentially offering therapeutic targets for PCN treatment.

Preoperative ultrasound combined with routine blood tests in predicting the malignant risk of pancreatic cystic neoplasms.

Accurate preoperative identification of benign or malignant pancreatic cystic neoplasms (PCN) may help clinicians make better intervention choices and will be essential for individualized treatment. Preoperative ultrasound and laboratory examination findings, and demographic characteristics were collected from patients. Multiple logistic regression was used to identify independent risk factors associated with malignant PCN, which were then included in the nomogram and validated with an external cohort. The Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI) were calculated to evaluate the improvement in the predictive power of the new model with respect to that of a combined imaging and tumor marker prediction model. Malignant PCN were found in 83 (40.7%) and 33 (38.7%) of the model and validation cohorts, respectively. Multivariate analysis identified age, tumor location, imaging of tumor boundary, blood type, mean hemoglobin concentration, neutrophil-to-lymphocyte ratio, carbohydrate antigen 19-9, and carcinoembryonic antigen as independent risk factors for malignant PCN. The calibration curve indicated that the predictions based on the nomogram were in excellent agreement with the actual observations. A nomogram score cutoff of 192.5 classified patients as having low vs. high risk of malignant PCN. The model achieved good C-statistics of 0.929 (95% CI 0.890-0.968, P < 0.05) and 0.951 (95% CI 0.903-0.998, P < 0.05) in predicting malignancy in the development and validation cohorts, respectively. NRI = 0.268; IDI = 0.271 (P < 0.001 for improvement). The DCA curve indicated that our model yielded greater clinical benefits than the comparator model. The nomogram showed excellent performance in predicting malignant PCN and may help surgeons select patients for detailed examination and surgery. The nomogram is freely available at https://wangjunjinnomogram.shinyapps.io/DynNomapp/.

The Value of Serum Tumor Markers and Blood Inflammation Markers in Differentiating Pancreatic Serous Cystic Neoplasms and Pancreatic Mucinous Cystic Neoplasms.

Although many studies have emphasized the prognostic and diagnostic value of tumor markers and various inflammation-related markers, their clinical significance in differentiating benign and malignant pancreatic cystic neoplasms (PCNs) remains to be clarified. The present study explored the value of serum tumor markers and inflammation-related biomarkers in the differentiation of pancreatic serous cystic neoplasms (SCNs) and pancreatic mucinous cystic neoplasms (MCNs). A total of 79 patients with PCNs were included in this study, including 35 patients with SCNs and 44 patients with MCNs. Comparison of baseline data with preoperative results of serum tumor markers and associated inflammatory markers revealed significant differences in carbohydrate antigen 199 (CA199) and “lymphocyte × ALB” (LA) between the two groups (p = 0.0023, p = 0.0149, respectively). Univariate and multivariate regression analyses showed that an increase in CA199 and a decrease in LA were relevant risk factors for MCNs. Finally, the receiver operating characteristic (ROC) curve was generated, and the area under the ROC curve (AUC) was calculated to evaluate the prediction efficiency of each indicator. The results showed that CA199 and LA had good differential diagnostic efficacy for SCNs and MCNs. This is the first to report to demonstrate that LA can be used for the differential diagnosis of SNCs and MCNs.

A new combined criterion to better predict malignant lesions in patients with pancreatic cystic neoplasms.

Objective:Cystic lesions of the pancreas have been increasingly recognized. Some lesions exhibit benign behavior, while others have unequivocal malignant potential. Thus, accurate identification of malignancy in patients diagnosed with pancreatic cystic neoplasms (PCNs) remains a major challenge. The aim of this study was to define a combined criterion to better predict malignant lesions in patients with PCNs.Methods:We retrospectively analyzed 165 patients who underwent resection of PCNs from October 2011 to May 2017. The relationship among malignancy and serum carbohydrate antigen 19-9 (CA19-9), preoperative neutrophil-to-lymphocyte ratio (NLR), and the presence of enhanced solid component on imaging was analyzed.Results:NLR before surgery in patients with malignant PCNs (2.81±2.14) was significantly higher than that in patients diagnosed with pancreatic neuroendocrine tumor (1.90±0.69, P=0.013) or healthy volunteers (1.40±0.48; P<0.001). Serum CA19-9 ≥39 U/mL, NLR >1.976 and presence of enhanced solid component were independent predictors of PCN malignancy. A combined criterion meeting any two or more of the three elements including CA19-9 ≥39 U/mL, NLR >1.976, and presence of enhanced solid component on computed tomography imaging is an indicator with a high positive predictive value of 80.5% and a high negative predictive value of 87.9%, and thus, represents a highly accurate test (86.1%). Conclusions:The new combined criterion is an effective predictor of tumor malignancy in patients with PCNs.

Evaluation of the 2015 AGA guidelines on pancreatic cystic neoplasms in a large surgically confirmed multicenter cohort.

Absract Background and study aims The American Gastroenterological Association (AGA) recently published guidelines for the management of asymptomatic pancreatic cystic neoplasms (PCNs). We aimed to evaluate the diagnostic characteristics of the AGA guidelines in appropriately recommending surgery for malignant PCNs. Patients and methods A retrospective multicenter study was performed of patients who underwent endoscopic ultrasound (EUS) for evaluation of PCNs who ultimately underwent surgical resection from 2004 – 2014. Demographics, EUS characteristics, fine-needle aspiration (FNA) results, type of resection, and final pathologic diagnosis were recorded. Patients were categorized into 2 groups (surgery or surveillance) based on what the AGA guidelines would have recommended. Performance characteristics for the diagnosis of cancer or high-grade dysplasia (HGD) on surgical pathology were calculated. Results Three hundred patients underwent surgical resection for PCNs, of whom the AGA guidelines would have recommended surgery in 121 (40.3 %) and surveillance in 179 (59.7 %) patients. Among patients recommended for surgery, 45 (37.2 %) had cancer, whereas 76 (62.8 %) had no cancer/HGD. Among patients recommended for surveillance, 170 (95.0 %) had no cancer/HGD; however, 9 (5.0 %) patients had cancer that would have been missed. For the finding of cancer/HGD on surgical pathology, the AGA guidelines had 83.3 % sensitivity (95 % CI 70.7 – 92.1), 69.1 % specificity (95 % CI 62.9 – 74.8), 37.2 % positive predictive value (95 % CI 28.6 – 46.4), 95.0 % negative predictive value (95 % CI 90.7 – 97.7), and 71.7 % accuracy (95 % CI 67.4 – 74.6). Conclusions The 2015 AGA guidelines would have resulted in 60 % fewer patients being referred for surgical resection, and accurately recommended surveillance in 95 % of patients with asymptomatic PCNs. Future prospective studies are required to validate these guidelines.Meeting presentations: Presented in part at Digestive Diseases Week 2016

Analysis of the influence of gender on the clinicopathological features and prognosis of pancreatic cystic neoplasms

Objective: To compare the clinicopathological features and prognosis of pancreatic cystic neoplasms (PCN) between male and female patients. Methods: A total of 325 patients with histological confirmed PCN from January 2010 to October 2015 were enrolled. The clinicopathological features, laboratory examination, imaging features, treatment and prognosis were analyzed. Results: Of the 325 patients diagnosed as PCN, 104 were male and 221 were female. The average age of male patients was significantly higher than that of female patients (55.0±12.7 vs 47.9±13.4 years, P<0.001), however, the average tumor size of male patients was smaller than that of female patients (3.9±2.7 vs 4.9±3.0 cm, P=0.004). The location of PCN in male patients was predominantly located at pancreatic head and neck, and majority of male patients were mucinous cystic neoplasms. 1-year, 3-year and 5-year survival rates of patients with PCN were 98.5%, 92.6%, and 87.5%, respectively. 1-year, 3-year and 5-year survival rates of male patients were 97.8%, 84.9%, and 77.8%, however, those of female patients were 98.8%, 96.5%, and 92.2%, respectively. Female patients had better prognosis than male patients (χ2=5.543, P=0.019). Elevated CA19-9 (χ2=3.843, P=0.050), perineuronal invasion (χ2=6.250, P=0.012) and lymph node metastasis (χ2=4.529, P=0.033) were important prognostic factors for malignant mucinous cystic neoplasm. Conclusions: Male patients had low incidence of PCN, and were more common for mucinous cystic neoplasm. The long-term outcome of malignant PCN was poor. Even with complete resection, male patients still had worse prognosis. Close follow-up is recommended especially for male patients.

Preoperative platelet-to-lymphocyte ratio improves the performance of the international consensus guidelines in predicting malignant pancreatic cystic neoplasms

IntroductionTo determine if neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were predictive of malignancy in pancreatic cystic neoplasms (PCN) and if these improved the performance of the international consensus guidelines (ICG) in the initial triage of these patients. Methods318 patients with surgically-treated suspected PCN were retrospectively reviewed. Malignant neoplasms were defined as neoplasms harbouring invasive carcinoma. The optimal cut-off for NLR and PLR were determined by plotting the receiver operating characteristics (ROC) curves of NLR/PLR in predicting malignant PCN and utilizing the Youden index. ResultsThe optimal NLR and PLR cut-offs were determined to be 3.33 and 205, respectively. Univariate analyses demonstrated that symptomatic PCNs, age, obstructive jaundice, presence of solid component, dilatation of main pancreatic duct ≥10 mm, high NLR and high PLR were predictive of a malignant PCN. Multivariate analyses demonstrated that obstructive jaundice, presence of solid component, MPD ≥10 mm and high PLR but not NLR were independent predictors of a malignant PCN. A high PLR significantly predicted invasive carcinoma in patients classified within the ICGHR group. Comparison between the ROC curves of the ICG versus ICG plus high PLR in predicting malignant PCN demonstrated a significant improvement in the accuracy of the ICG when PLR was included [AUC 0.784 (95% CI: 0.740–0.829) vs AUC 0.822 (95% CI: 0.772–0.872) (p = 0.0032)]. ConclusionsHigh PLR is an independent predictor of malignancy in PCN. The addition of PLR as a criterion to the ICG improved the accuracy of these guidelines in detecting invasive neoplasms.

Preoperative platelet-to-lymphocyte ratio improves the performance of the international consensus guidelines in predicting malignant pancreatic cystic neoplasms

Preoperative platelet-to-lymphocyte ratio improves the performance of the international consensus guidelines in predicting malignant pancreatic cystic neoplasms

Abstract 2506: Differentiating pancreatic cystic neoplasms by global protease specificity

Abstract Decision-making for patients with pancreatic cystic lesions represents the greatest area of clinical uncertainty in the management of pancreatic disease today. Short of pancreas removal, there is no definitive technology that differentiates benign, pre- malignant, and malignant pancreatic cystic neoplasms. As a result, some patients die from undiagnosed cancers, while others undergo unnecessary pancreatic resections with considerable morbidity. The cyst fluid from these neoplasms is a rich resource for the discovery of new biomarkers because it is in direct contact with the involved cells, and it is sampled routinely as a part of clinical care. Amylase activity and CEA concentration are typically measured, but they lack prognostic value. Protein levels of proteases and their inhibitors differ between benign and malignant cystic neoplasms, however, effects on enzymatic activity and specificity profiles are unknown. We sought to identify and characterize proteolytic signatures specific to different stages of pancreatic carcinogenesis. We used a new protease substrate profiling technology recently developed in our lab, Multiplex Substrate-Profiling by Mass Spectrometry (MSP-MS), that can detect and classify the specificity of endo- and exopeptidases in a complex sample. This assay consists of a physiochemically diverse library of 228 tetradecapeptides designed by incorporating all combinations of neighbor and near-neighbor amino acid pairs to provide maximum specificity information. We have previously used this technology to determine the “proteolytic signatures” of mouse pancreatic cancer cell secretions and human neutrophil extracellular traps. MSP-MS has the unique ability to monitor all peptide bonds cleaved from this library of peptides, thereby simultaneously detecting aminopeptidase, carboxypeptidase and endopeptidase activity. This assay was applied to pancreatic cyst fluid derived from 4 low risk and 4 high risk lesions as determined by current clinical guidelines. The cleavage data from the respective categories was combined and compared. The proteases in the samples generated 773 cleavage sites in the low risk category and only 285 in the high risk category. Interestingly, only 220 of the sites were shared between groups. The signature from the low risk group had a trypsin-like specificity with arginine and lysine preferred at the P1 position, whereas the high risk group had minimal trypsin-like specificity and predominantly showed amino- and carboxypeptidase activity. These data suggest that protease profiling of pancreatic cyst fluid may facilitate risk stratification among pancreatic cystic lesions and thereby guide clinical decision-making. MSP-MS offers a unique technology to both identify active proteases in clinical samples of interest and measure total and specific proteolytic activity despite the presence of endogenous inhibitors. Citation Format: Dana A. Dominguez, Anthony J. O'Donoghue, Kimberly S. Kirkwood, Charles S. Craik. Differentiating pancreatic cystic neoplasms by global protease specificity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2506. doi:10.1158/1538-7445.AM2014-2506

Clinicopathological and CT features of mucinous cystic neoplasms of the pancreas

To evaluate the clinicopathological and CT features of mucinous cystic neoplasms (MCNs) of the pancreas and analyze the correlative risk factors for malignant pancreatic mucinous cystic neoplasms. Ninety-eight patients who underwent curative resection for mucinous cystic neoplasms of the pancreas at PLA General Hospital from April 1994 to January 2013 were included in this study. All clinicopathological data available were retrospectively analyzed. All patients were divided into benign tumors + premalignant lesion group (70 patients) and malignant tumor group (28 patients). Clinicopathological and CT features of the mucinous cystic neoplasms of the pancreas and risk factors of malignant pancreatic mucinous cystic neoplasms were analyzed. Mucinous cystic neoplasms were seen mostly in perimenopausal women (71.4%, 70/98 cases,), and 51.0% (50/98 cases) of the patients had obvious clinical signs, mostly non-specific abdominal pain, but jaundice was present only in cases of malignant mucinous cystic neoplasms. Benign mucinous cystic neoplasms were mostly located in the distal pancreas (74.3%) and characterized with septa and thin cystic wall, while more malignant mucinous cystic neoplasms were located at the proximal pancreas (57.1%) and characterized with thick cystic wall and solid components. Univariate analysis showed that findings associated with malignancy gender, age ≥ 60, presence of symptoms, jaundice, weight loss, tumor location, margin, wall thickness, solid components and dilation of the main pancreatic duct were significantly correlated with malignant tumor development (P < 0.05 for all). The results of multiple logistic regression analysis showed that thick wall and solid components were independent prognostic factors for malignancy (OR = 31.417 and 34.976, P < 0.05 for both). Gender, age ≥ 60, presence of symptoms, jaundice, weight loss, tumor location, margin, wall thickness, solid components and dilation of the main pancreatic duct are important diagnostic indices of malignant mucinous cystic tumors of the pancreas, while thick wall and solid components are independent risk factors of malignant pancreatic mucinous cystic neoplasms.

Pancreatic cystic neoplasms: a report of 139 cases

To review our experience in the diagnosis and treatment of pancreatic cystic neoplasms (PCN). The clinicopathological data of PCN were retrospectively analyzed and the relevant medical literatures reviewed. A total of 139 cases were treated at our hospital. There were serous cystic neoplasm (n = 38, SCN), mucinous cystic neoplasm (n = 32, MCN), intraductal papillary mucinous neoplasm (n = 9, IPMN) and solid pseudopapillary neoplasms (n = 60, SPN). The male-to-female ratio was 1: 3.63. The average age of disease onset was 46.1 years old. And 46.3% of them had no symptom at diagnosis. Among symptomatic ones, there were stomach ache (43.4%), location in body and tail of pancreas (58.2%) and solitary (99.5%). The accuracy of ultrasound type B, computed tomography (CT) and magnetic resonance imaging (MRI) were above 80%. The 5-year survival rate of benign PCNs was 100%. The 1, 3, 5-year survival rates of resected malignant PCNs were 70.2%, 47.9% and 39.5% respectively. However, the 5-year survival rate of those undergoing palliative surgery was only 16.7%. PCNs are more common in females. And the most common clinical presentation is stomach ache. Most PCNs are solitary tumors located in body and tail of pancreas and may be detected by imaging examinations. The prognosis is excellent for benign PCNs and malignant ones undergoing radical resection. However, the prognosis of those undergoing palliative surgery remains poor.

Prediction of Malignancy in Cystic Neoplasms of the Pancreas: A Population-Based Cohort Study

Pancreatic cystic neoplasms (PCNs) are being detected with increased frequency. The aims of this study were to determine the incidence of malignancy and develop an imaging-based system for prediction of malignancy in PCN. We conducted a retrospective cohort study of patients ≥18 years of age with confirmed PCN from January 2005 to December 2010 in a community-based integrated care setting in Southern California. Patients with history of acute or chronic pancreatitis were excluded. Malignancy diagnosed within 3 months of cyst diagnosis was considered as pre-existing. Subsequent incidence of malignancy during surveillance was calculated based on person-time at risk. Age- and gender-adjusted standardized incidence ratio (SIR) was calculated with the non-cyst reference population. Recursive partitioning was used to develop a risk prediction model based on cyst imaging features. We identified 1,815 patients with confirmed PCN. A total of 53 (2.9%) of patients were diagnosed with cyst-related malignancy during the study period. The surveillance cohort consisted of 1,735 patients with median follow-up of 23.4 months. Incidence of malignancy was 0.4% per year during surveillance. The overall age- and gender-adjusted SIR for pancreatic malignancy was 35.0 (95% confidence level 26.6, 46.0). Using recursive partitioning, we stratified patients into low (<1%), intermediate (1-5%), and high (9-14%) risk of harboring malignant PCN based on four cross-sectional imaging features: size, pancreatic duct dilatation, septations with calcification as well as growth. Area under the receiver operator characteristic curve for the prediction model was 0.822 (training) and 0.808 (testing). Risk of pancreatic malignancy was lower than previous reports from surgical series but was still significantly higher than the reference population. A risk stratification system based on established imaging criteria may help guide future management decisions for patients with PCN.

Mo1513 A Retrospective Analysis of Serial Fluid Analysis of Pancreatic Cystic Neoplasms Under EUS Surveillance: Is There Any Role in Repeat Cyst Fluid CEA Measurement?

Fluid analysis of pancreatic cystic neoplasms (PCNs) using EUS-fine needle aspiration (EUS-FNA) are routinely performed to differentiate mucinous vs. non-mucinous cysts. Specificity of cytology in the diagnosis of malignant PCNs is high but its sensitivity is low. In cyst fluid analysis, a CEA of >192 ng/mL is one of the standard criteria for diagnosing mucinous cysts, but it is not useful for differentiating malignant lesions. Most PCNs including mucinous cysts undergo interval surveillance, including repeat EUS, but the role and significance of repeat fluid analysis is poorly defined in patients with PCNs under serial EUS.

Pancreatic tuberculosis masquerading as pancreatic serous cystadenoma

Solitary pancreatic involvement of tuberculosis is rare, especially in an immunocompetent individual, and it may be misdiagnosed as pancreatic cystic neoplasms. Pancreatic cystic neoplasms are being identified in increasing numbers, probably because of the frequent use of radiology and advances in endoscopic techniques. However, they are composed of a variety of neoplasms with a wide range of malignant potential, and it is often difficult to differentiate pancreatic tuberculosis mimicking cystic neoplasms from benign or malignant pancreatic cystic neoplasms. Non-surgical diagnosis of pancreatic tuberculosis is inconclusive and continues to be a challenge in many cases. If so, then laparotomy should be employed to establish the diagnosis. Therefore, pancreatic tuberculosis should be kept in mind during the differential diagnosis of solitary cystic masses in the pancreas. We report a patient who had solitary pancreatic tuberculosis masquerading as pancreatic serous cystadenoma.