Pancreatic cystic neoplasms:a comprehensive approach to diagnosis and management

Pancreatic cystic neoplasms present a complex diagnostic scenario encompassing low-and high-grade malignancies.Their prevalence varies widely,notably increasing with age,reaching 75%in individuals older than 80 years.Accurate diagnosis is crucial,as errors occur in approximately one-third of resected cysts discovered incidentally.Various imaging modalities such as computed tomography,magnetic resonance imaging,and endoscopic techniques are available to address this challenge.However,risk stratification remains problematic,with guideline inconsistencies and diagnostic accuracy varying according to cyst type.This review proposed a stepwisemanagement approach,considering patient factors,imaging results,and specific features.This patient-centered model offers a structured framework for optimizing the care of individuals with pancreatic cystic neoplasms.

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

Objective: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.Methods: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.Results: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-tolymphocyte 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.Conclusions: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/.

EUS for pancreatic cystic neoplasms: The roadmap to the future is much more than just a few shades of gray

Pancreatic cystic and neoplasms are being diagnosed with increasing frequency. Accurate diagnosis and determination of benign versus malignant lesions is crucial for determining need for surveillance versus surgery or endoscopic therapy as well as avoiding unnecessary surgery in cysts with no malignant potential. Tumor markers such as KRAS and GNAS hold promise, but which molecular marker or a combination of markers is most useful and cost effective remains to be seen. Advanced imaging with confocal laser endomicroscopy can serve as an optical biopsy and play a part in the diagnostic algorithm. Microforceps aided biopsy of pancreatic cyst wall and tumor contents hold great promise as they allow direct tissue acquisition. Much progress has been made in the role of EUS guided evaluation of pancreatic cystic neoplasms over the last several years, and with the advances enumerated above, the future is more than just a few shades of grey. Future studies should include prospective multiarm trials of microforceps biopsy versus conventional EUS-FNA and use of biochemical and molecular markers, confocal laser endomicroscopy or a combination thereof to determine best approach to pancreatic cystic neoplasms. In Osler's words, ‘Medicine is a science of uncertainty and an art of probability'. Incorporation of advanced imaging and molecular markers into a new diagnostic algorithm with subsequent validation through retrospective and prospective studies has the potential to increase diagnostic accuracy and guide optimal management of patients and improve outcomes.

Online calculator for predicting the risk of malignancy in patients with pancreatic cystic neoplasms: A multicenter, retrospective study

BACKGROUND Efficient and practical methods for predicting the risk of malignancy in patients with pancreatic cystic neoplasms(PCNs)are lacking.AIM To establish a nomogram-based online calculator for predicting the risk of malignancy in patients with PCNs.METHODS In this study,the clinicopathological data of target patients in three medical centers were analyzed.The independent sample t-test,Mann–Whitney U test or chi-squared test were used as appropriate for statistical analysis.After univariable and multivariable logistic regression analysis,five independent factors were screened and incorporated to develop a calculator for predicting the risk of malignancy.Finally,the concordance index(C-index),calibration,area under the curve,decision curve analysis and clinical impact curves were used to evaluate the performance of the calculator.RESULTS Enhanced mural nodules[odds ratio(OR):4.314;95%confidence interval(CI):1.618–11.503,P=0.003],tumor diameter≥40 mm(OR:3.514;95%CI:1.138–10.849,P=0.029),main pancreatic duct dilatation(OR:3.267;95%CI:1.230–8.678,P=0.018),preoperative neutrophil-to-lymphocyte ratio≥2.288(OR:2.702;95%CI:1.008–7.244,P=0.048],and preoperative serum CA19-9 concentration≥34 U/mL(OR:3.267;95%CI:1.274–13.007,P=0.018)were independent risk factors for a high risk of malignancy in patients with PCNs.In the training cohort,the nomogram achieved a C-index of 0.824 for predicting the risk of malignancy.The predictive ability of the model was then validated in an external cohort(C-index:0.893).Compared with the risk factors identified in the relevant guidelines,the current model showed better predictive performance and clinical utility.CONCLUSION The calculator demonstrates optimal predictive performance for identifying the risk of malignancy,potentially yielding a personalized method for patient selection and decision-making in clinical practice.

Endoscopic ultrasound-guided injective ablative treatment of pancreatic cystic neoplasms

With the development of cross-sectional imaging modalities and the increasing attention being paid to physical examinations, the prevalence of pancreatic cystic neoplasms(PCNs) has increased. PCNs comprise a broad differential spectrum with some PCNs having low or no malignant potential and others having high malignant potential. The morbidity and mortality rates related to major pancreatic surgical resection are high. Long-term surveillance may not only increase the financial burden and psychological stress for patients but also result in a missed malignancy. Minimally invasive endoscopic ultrasound(EUS)-guided ethanol ablation was first reported in 2005. Several other agents, such as paclitaxel, lauromacrogol, and gemcitabine, were reported to be effective and safe for the treatment of PCNs. These ablative agents are injected through a needle inserted into the cyst via transgastric or transduodenal puncture. This treatment method has been substantially developed in the last 15 years and is regarded as a promising treatment to replace surgical resection for PCNs. While several reviews of EUS-guided ablation have been published, no systematic review has evaluated this method from patient preparation to follow-up in detail. In the present review, we systematically describe EUS-guided injective ablation with regard to the indications, contraindications, preoperative treatment, endoscopic procedure, postoperative care and follow-up, evaluation method, treatment efficiency, safety profile, tips and tricks, and current controversies and perspectives.

Current considerations on intraductal papillary neoplasms of the bile duct and pancreatic duct

Pancreatobiliary intraductal papillary neoplasms(IPNs)represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated.Despite advances in diagnostic methods,identifying these premalignant lesions is still challenging for treatment providers.Modern imaging,biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up.Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases.The balance between the risk of malignancy and any risk of resection guides management policy;therefore,treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata.IPN of the bile duct is more aggressive;thus,early diagnosis and surgery are crucial.The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.

Pancreatic cystic neoplasms:current and future approaches to identify patients at risk

Pancreatic cystic neoplasms(PCNs)are a group of entities with distinct risks and various treatments.Identification of the PCN patients at risk is thus critical.A correct diagnosis is the key to select high-risk patients.However,the misdiagnosis rate is extremely high even computer tomography,magnetic resonance imaging,and endoscopic ultrasonography were applied.Current approaches for differential diagnosis and identifying high-risk patients in certain types of PCNs are not powerful enough to make a clinical acceptable accuracy of diagnosis.The approaches mainly rely on imaging and tumor marker test.We here summarized the current approaches,and reviewed novel approaches under development.For instance,cyst fluid test of glucose or vascular endothelial growth factor A shows the best performance in identifying mucinous cystic neoplasms or serous cystic neoplasms.Multidisciplinary team(MDT)discussion is another way to improve the accuracy of diagnosis.Combination of MDT with validated novel approaches with high sensitivity and specificity is the best way to select truly high-risk patients with PCNs.

Pancreatic intraductal papillary mucinous neoplasms:Current diagnosis and management

Intraductal papillary mucinous neoplasms(IPMNs)represent approximately 1%of all pancreatic neoplasms and 25%of cystic neoplasms.They are divided into three types:main duct-IPMN(MD-IPPMN),branch duct-IPMN(BD-IPMN),and mixed type-IPMN.In this review,diagnostics,including clinical presentation and radiological investigations,were described.Magnetic resonance imaging is the most useful for most IPMNs.Management depends on the type and radiological features of IPMNs.Surgery is recommended for MD-IPMN.For BD-IPMN,management involves surgery or surveillance depending on the tumor size,cyst growth rate,solid components,main duct dilatation,high-grade dysplasia in cytology,the presence of symptoms(jaundice,new-onset diabetes,pancreatitis),and CA 19.9 serum level.The patient’s age and comorbidities should also be taken into consideration.Currently,there are different guidelines regarding the diagnosis and management of IPMNs.In this review,the following guidelines were presented:Sendai International Association of Pancreatology guidelines(2006),American Gastroenterological Association guidelines,revised international consensus Fukuoka guidelines(2012),revised international consensus Fukuoka guidelines(2017),and European evidence-based guidelines according to the European Study Group on Cystic Tumours of the Pancreas(2018).The Verona Evidence-Based Meeting 2020 was also presented and discussed.

Serum tumor markers not useful in screening patients with pancreatic mucinous cystic lesions associated with malignant changes

BACKGROUND: Serum cancer antigen 19-9(CA19-9) provides additional information about mucinous cystic pancreatic neoplasm(MPN). This study was undertaken to assess both CA19-9 and carcinoembryonic antigen(CEA) serum concentrations in consecutive patients affected by MPNs and other chronic benign and malignant pancreatic diseases. We also evaluated whether serum CA19-9 and CEA determinations provide additional information such as the presence of invasive carcinoma in MPN patients.METHODS: Serum CA19-9 and CEA from 91 patients with pancreatic diseases were tested by commercially available kits at the time of diagnosis. The upper reference limit of serum CA19-9 was 37 U/m L and that of serum CEA was 3 ng/m L.RESULTS: Thirty-five patients was diagnosed with chronic pancreatitis(CP), 32 with MPN, and 24 with pancreatic ductal adenocarcinoma(PDAC) confirmed histologically. Surgery was carried out in 5 CP patients, in 10 MPN patients(7 of them had severe dysplasia), and 9 PDAC patients. Serum CA19-9 activity was high in 12(34.3%) CP patients, in 7(21.9%) MPN patients, and in 12(50.0%) PDAC patients(P=0.089). High serum CEA concentrations were noted in 6(17.1%) CP patients, in 6(18.8%) MPN patients, and in 12(50.0%) PDAC patients(P=0.010). In the 7 MPN patients associated with histologically confirmed severe dysplasia, 3(42.9%) patients had elevated serum activity of serum CA19-9, and 2(28.6%) patients had high levels of CEA.CONCLUSION: Serum determination of oncological markers is not useful in selecting MPN patients with malignant changes.

Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions

BACKGROUND Pancreatic cystic lesions(PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant lesions.AIM To evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen(CA)19-9, CA72-4], carcinoembryonic antigen(CEA), serine protease inhibitor Kazal-type 1(SPINK1), interleukin 1 beta(IL1-β), vascular endothelial growth factor A(VEGF-A), and prostaglandin E2(PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions.METHODS This study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound(EUS) and EUS-fine needle aspiration(EUS-FNA) for characterization and sampling of different PCLs.RESULTS The mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance(59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively(P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance(P < 0.0001). In contrast, IL-1β, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic lesions.CONCLUSION EUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.