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 Preoperative Imaging Modalities for the Assessment of Malignant Potential of Pancreatic Cystic Lesions: A Network Meta-analysis.

PURPOSE: The aims of this study are to compare the performance of various preoperative imaging modalities for assessing the malignant potential of pancreatic cystic lesions (PCLs) through a network meta-analysis (NMA) and to clarify the role of 18 F-FDG PET in the management of patients with PCL. METHODS: PubMed, EMBASE, and Cochrane Library were searched for the studies evaluating the performance of preoperative imaging modalities for identifying malignant PCLs. The NMA was performed for 4 representative categories of various imaging modalities in terms of diagnostic performance for differentiating malignant from benign PCL and intraductal papillary mucinous neoplasms only as a subgroup analysis. To calculate the probability of each imaging modality being the most effective diagnostic method, the surface under the cumulative ranking curve values were obtained. RESULTS: A total of 1018 patients from 17 direct comparison studies using 2 or more preoperative imaging modalities were included for differentiating malignant from benign PCL. The positive predictive value (PPV) and accuracy of 18 F-FDG PET were significantly higher than that of CT (PPV: odds ratio [OR], 2.66; 95% credible interval [CrI], 1.21-6.17; accuracy: OR, 2.63; 95% CrI, 1.41-5.38) or MRI (PPV: OR, 2.50; 95% CrI, 1.09-6.26; accuracy: OR, 2.50; 95% CrI, 1.28-5.47) in all PCLs, as well as in the subgroup analysis for intraductal papillary mucinous neoplasm only. 18 F-FDG PET showed the highest surface under the cumulative ranking curve values in all diagnostic performance areas of sensitivity, specificity, PPV, negative predictive value, and accuracy, followed by MRI or CT. CONCLUSIONS: The results from this NMA suggest that 18 F-FDG PET is the best preoperative imaging modality for differentiating malignant from benign PCLs and that it can be used for the preoperative evaluation of PCLs.

Cytologic Assessment of Cystic/Intraductal Lesions of the Pancreatobiliary Tract.

CONTEXT.­: Because of new and improved imaging techniques, cystic/intraductal pancreatobiliary tract lesions are increasingly being discovered, and brushings or endoscopic ultrasound/computed tomography/magnetic resonance imaging-guided fine-needle aspiration biopsies from these lesions have become an integral part of pathologists' daily practice. Because patient management has become increasingly conservative, accurate preoperative diagnosis is critical. Cytologic distinction of low-risk (pseudocysts, serous cystadenoma, lymphoepithelial cysts, and squamoid cysts of the pancreatic duct) from high-risk pancreatic cysts (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) requires incorporation of clinical, radiologic, and cytologic findings, in conjunction with chemical and molecular analysis of cyst fluid. Cytopathologists must ensure appropriate specimen triage, along with cytologic interpretation, cyst classification, and even grading of some (mucinous) cysts. Epithelial atypia in mucinous cysts (intraductal papillary mucinous neoplasm and mucinous cystic neoplasm) has transitioned from a 3-tiered to a 2-tiered classification system, and intraductal oncocytic papillary neoplasms and intraductal tubulopapillary neoplasms have been separately reclassified because of their distinctive clinicopathologic characteristics. Because these lesions may be sampled on brushing or fine-needle aspiration biopsy, knowledge of their cytomorphology is critical. OBJECTIVE.­: To use an integrated, multidisciplinary approach for the evaluation of cystic/intraductal pancreatobiliary tract lesions (incorporating clinical, radiologic, and cytologic findings with [chemical/molecular] cyst fluid analysis and ancillary stains) for definitive diagnosis and classification. DATA SOURCES.­: Review of current literature on the cytopathology of cystic/intraductal pancreatobiliary tract lesions. CONCLUSIONS.­: Our knowledge/understanding of recent updates in cystic/intraductal pancreatobiliary lesions can ensure that cytopathologists appropriately triage specimens, judiciously use and interpret ancillary studies, and incorporate the studies into reporting.

Pancreatic Cystic Lesions and Malignancy: Assessment, Guidelines, and the Field Defect.

The widespread use of high-spatial-resolution cross-sectional imaging has led to an increase in detection of incidental pancreatic cystic lesions. These lesions are a diverse group, ranging from indolent and premalignant lesions to invasive cancers. The diagnosis of several of these lesions can be suggested on the basis of their imaging appearance, while many other lesions require follow-up imaging and/or aspiration. The smaller cystic lesions, often branch-duct intraductal papillary mucinous neoplasms, have overlapping imaging characteristics that make diagnostic assessment of the natural history and malignancy risk confusing. Expert panels have developed societal guidelines, based on a consensus, for surveillance of these lesions. However, these guidelines are often inconsistent and are constantly evolving as additional scientific data are accumulated. Identification of features associated with increased risk of malignancy is important for proper management. The concept of field defect, whereby pancreatic adenocarcinoma develops at a site different from the site of the pancreatic cyst, adds to the complexity of screening guidelines. As a result of the differences in guidelines, key stakeholders (eg, radiologists, gastroenterologists, and surgeons) must review and come to a consensus regarding which guideline, or combination of guidelines, to follow at their individual institutions. Standardized reporting and macros are helpful for ensuring the uniformity of interpretations. Radiologists play a critical role in the detection and characterization of pancreatic cystic lesions, in the follow-up recommendations for these lesions, and in the detection of associated cancer. An invited commentary by Zaheer is available online. Online supplemental material is available for this article. ©RSNA, 2021.

Comparison of endoscopic ultrasound, computed tomography and magnetic resonance imaging in assessment of detailed structures of pancreatic cystic neoplasms.

AIM: To evaluate the advantages of endoscopic ultrasound (EUS) in the assessment of detailed structures of pancreatic cystic neoplasms (PCNs) compared to computed tomography (CT) and magnetic resonance imaging (MRI). METHODS: All patients with indeterminate PCNs underwent CT, MRI, and EUS. The detailed information, including size, number, the presence of a papilla/nodule, the presence of a septum, and the morphology of the pancreatic duct of PCNs were compared among the three imaging modalities. The size of each PCN was determined using the largest diameter measured. A cyst consisting of several small cysts was referred to as a mother-daughter cyst. Disagreement among the three imaging modalities regarding the total number of mother cysts resulted in the assumption that the correct number was the one in which the majority of imaging modalities indicated. RESULTS: A total of 52 females and 16 males were evaluated. The median size of the cysts was 42.5 mm by EUS, 42.0 mm by CT and 38.0 mm by MRI; there was no significant difference in size as assessed among the three imaging techniques. The diagnostic sensitivity and ability of EUS to classify PCNs were 98.5% (67/68) and 92.6% (63/68), respectively. These percentages were higher than those of CT (73.1%, P < 0.001; 17.1%, P < 0.001) and MRI (81.3%, P = 0.001; 20.3%, P < 0.001). EUS was also able to better assess the number of daughter cysts in mother cysts than CT (P = 0.003); however, there was no significant difference between EUS and MRI in assessing mother-daughter cysts (P = 0.254). The papilla/nodule detection rate by EUS was 35.3% (24/68), much higher than those by CT (5.8%, 3/52) and MRI (6.3%, 4/64). The detection rate of the septum by EUS was 60.3% (41/68), which was higher than those by CT (34.6%, 18/52) and by MRI (46.9%, 30/64); the difference between EUS and CT was significant (P = 0.02). The rate of visualizing the pancreatic duct using EUS was 100%, whereas using CT and MRI it was less than 10%. CONCLUSION: EUS helps visualize the detailed structures of PCNs and has many advantages over CT and MRI. EUS is valuable in the diagnosis and assessment of PCNs.

Impact of EUS-guided fine-needle biopsy sampling with a new core needle on the need for onsite cytopathologic assessment: a preliminary study.

BACKGROUND AND AIMS: FNA is the primary method of EUS tissue acquisition. In an attempt to improve our yield of EUS-guided tissue acquisition, we compared fine-needle biopsy (FNB) sampling without rapid onsite evaluation (ROSE) with FNA with ROSE and assessed the concordance of FNA and FNB sampling. METHODS: This was a retrospective review of prospectively collected data from consecutive patients. Patients underwent FNB sampling and FNA of the same single lesion, with the same needle gauge and number of passes. FNA with ROSE was performed with a standard FNA needle. FNB sampling was performed with a new dedicated core needle. FNA samples were assessed with ROSE, and a final interpretation was provided by cytopathology staff; FNB samples were analyzed by surgical pathologists, each not made aware of the other's opinion. RESULTS: Thirty-three patients underwent 312 passes in 42 different lesions. A diagnosis of malignancy was more likely with FNB sampling than with FNA (72.7% vs 66.7%, P = .727), although statistical significance was not reached. FNA and FNB sampling had similar sensitivities, specificities, and accuracies for cancer (81.5% vs 88.9%, 100% vs 100%, and 84.8% vs 90.9%, respectively). FNB sampling provided qualitative information not reported on FNA, such as degree of differentiation in malignancy, metastatic origin, and rate of proliferation in neuroendocrine tumors. CONCLUSIONS: FNB sampling without ROSE using a dedicated core needle performed as well as FNA with ROSE in this small cohort, suggesting that FNB sampling with this new core needle may eliminate the need for an onsite cytopathologic assessment, without loss of diagnostic accuracy.

Cytologic categorization of pancreatic neoplastic mucinous cysts with an assessment of the risk of malignancy: A retrospective study based on the Papanicolaou Society of Cytopathology guidelines.

BACKGROUND: Cytology plays a pivotal role in the preoperative diagnosis of pancreatic cysts. Here the Papanicolaou Society of Cytopathology (Pap Society) guidelines were used to reclassify and assess the malignancy risk of cytology diagnoses of histologically proven pancreatic neoplastic mucinous cysts. METHODS: A database search (January 2000 to June 2014) was performed for pancreatic neoplastic mucinous cyst resections with endoscopic ultrasound-guided fine-needle aspiration within the preceding year. Histologic diagnoses were reclassified according to the 2010 Word Health Organization criteria. For atypical/suspicious/positive cytology diagnoses, the cytology slides were reviewed, blinded to the histologic diagnoses. The cysts were reclassified according to the Pap Society guidelines, and the findings were correlated with the histology. RESULTS: One hundred thirty-eight cases of pancreatic neoplastic mucinous cysts were retrieved. Eleven cases with atypical/suspicious cytology diagnoses with unavailable slides were excluded. The remaining 127 cases included 81 intraductal papillary mucinous neoplasms and 46 mucinous cystic neoplasms. The sensitivity of cytology for the diagnosis of neoplastic mucinous cysts was 76.4%. The sensitivity, specificity, and accuracy of cytology for the diagnosis of malignancy (high-grade dysplasia or worse) were 48.3%, 94.9%, and 84.3%, respectively. The risk of malignancy was 17.4% for the nondiagnostic category, 0% for the negative category, 13% for the neoplastic category, 63.6% for the atypical category, 80% for the suspicious category, and 100% for a positive diagnosis. CONCLUSIONS: This study reveals that the Pap Society guidelines allow the accurate categorization of pancreatic neoplastic mucinous cysts with cytology. The diagnostic categories (from negative to positive) are associated with an increasing risk of malignancy, and this can further aid in patient management and risk stratification.

Prevalence, Diagnosis and Management of Pancreatic Cystic Neoplasms: Current Status and Future Directions.

Cystic neoplasms of the pancreas are found with increasing prevalence, especially in elderly asymptomatic individuals. Although the overall risk of malignancy is very low, the presence of these pancreatic cysts is associated with a large degree of anxiety and further medical investigation due to concerns about malignancy. This review discusses the different cystic neoplasms of the pancreas and reports diagnostic strategies based on clinical features and imaging data. Surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines, is also discussed, with special reference to intraductal papillary mucinous neoplasm (IPMN; particularly the branch duct variant), which is the lesion most frequently identified incidentally. IPMN pathology, its risk for development into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk are discussed. Finally, surgical treatment, strategies for surveillance of pancreatic cysts, and possible future directions are discussed.

Needle-based confocal laser endomicroscopy in pancreatic cystic tumors assessment.

Pancreatic cystic tumors (PCT) are relatively common findings in general population due to the widespread use of cross-sectional imaging. PCT can be benign, with premalignant potential or malignant, a different management being applied for each type: benign cysts are usually referred for follow-up (based on imaging), while premalignant or malignant lesions should be surgically resected. The aim of this review is to describe the latest imaging technique that could be used for PCT diagnosis and to establish its clinical impact. Endoscopic ultrasound (EUS) is generally used to evaluate a pancreatic mass and to identify its characteristics. It offers a good visualization of the lesion. When combined with fine needle aspiration and cystic fluid analysis, the diagnosis potential is increased, although its accuracy for differentiating benign and malign tumors remains modest. EUS-guided needle-based confocal laser endomicroscopy (nCLE) is a new imaging technique that uses a miniprobe thin enough to be passed through a 19G needle. It provides in vivo images of the pancreas at a cellular level, offering the possibility to assess any changes that might have occurred. Several studies have shown that nCLE is feasible to use for PCT evaluation, imaging criteria being established with 100% specificity for intraductal papillary mucinous neoplasms (IPMN) and serous cystadenoma (SCA). Regarding the safety, more studies are needed. EUS-guided nCLE appears to be a new imaging technique that provides encouraging results for differential diagnosis between mucinous/non-mucinous cysts.

Does a family history of pancreatic ductal adenocarcinoma and cyst size influence the follow-up strategy for intraductal papillary mucinous neoplasms of the pancreas?

OBJECTIVE: This study aimed to evaluate the relationship between pancreatic ductal adenocarcinoma (PDAC) family history and PDAC development in patients followed up for intraductal papillary mucinous neoplasms (IPMNs) and to assess the cyst size relevance in determining follow-up strategies. METHODS: We analyzed 300 patients with branch duct and mixed-type IPMN who were followed up at our facility. RESULTS: Among the patients aged 70 years or older, the frequency of PDAC did not differ significantly between those with 1 first-degree relative with PDAC and those without a family history. Although patients with IPMNs of greater than or equal to 30 mm were followed up for a significantly shorter duration than those patients with IPMNs of less than 30 mm, the frequency of IPMN progression and malignant IPMN was significantly greater in the former. The frequency of IPMN progression and pancreatic cancer did not differ significantly according to IPMN size (<10, 10-20, and 20-30 mm) in cases without mural nodules. CONCLUSIONS: Patients with 1 first-degree relative with PDAC can be followed up using the same criteria for patients without a family history. Special attention should be paid to IPMN progression and malignant transformation in patients with IPMNs of greater than or equal to 30 mm, but cyst size need not be considered when determining follow-up strategies for patients with IPMNs of less than 30 mm without mural nodules.

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

BACKGROUND/OBJECTIVES: Accurate 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. METHODS: Patients 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. RESULTS: 357 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. CONCLUSIONS: CT 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.

The role of cytology in the preoperative assessment and management of patients with pancreaticobiliary tract neoplasms.

OBJECTIVE: Endoscopic ultrasound-guided fine-needle aspiration and bile duct brushings are utilized in the cytologic evaluation of solid and cystic pancreaticobiliary tract lesions. We sought to determine the diagnostic accuracy of cytology. METHODS: Five hundred seventy-nine pancreatic resections with 727 corresponding cytology specimens were identified from 1997 to 2012. Histologic diagnoses included benign, carcinoma, pancreatic endocrine neoplasm (PEN), nonepithelial neoplasms, cystic neoplasms, and ampullary adenomas. Standard interpretative categories-nondiagnostic, negative, atypical, suspicious, and positive--were utilized for preoperative cytology specimens. RESULTS: For solid masses, the sensitivity and specificity of positive fine-needle aspiration (FNA) cytology for detecting carcinoma were 74 and 100 %, respectively. FNAs performed better than brushings (sensitivity, 40 %; specificity, 98 %) in detecting carcinomas. Similar findings were seen for PENs and nonepithelial neoplasms. For cystic lesions, the sensitivity of FNA for predicting malignancy was lower (24 %) with a specificity of 97 %. Sequentially combining suspicious and atypical categories with the positive category resulted in increases in sensitivity and decreases in specificity for all cases except for cystic lesions. CONCLUSIONS: Cytology adds to the assessment of solid masses, but its utility in cystic lesions is less clear. Consideration of a suspicious cytologic interpretation as a positive diagnosis for triaging patients to surgery is supported by our study.

Cytology adds value to imaging studies for risk assessment of malignancy in pancreatic mucinous cysts.

OBJECTIVE: Evaluate the value of cytology relative to imaging features in risk assessment for malignancy as defined in the Sendai Guidelines. BACKGROUND: The Sendai Guidelines list symptoms, cyst size >30 mm, dilated main pancreatic duct (MPD) >6 mm, mural nodule (MN) and "positive" cytology as high risk stigmata for malignancy warranting surgical triage. METHODS: We reviewed clinical, radiological and cytological data of 112 patients with histologically confirmed mucinous cysts of the pancreas evaluated in a single tertiary medical center. Cytology slides were blindly re-reviewed and epithelial cells grouped as either benign or high-grade atypia (HGA) [≥high-grade dysplasia]. Histologically, neoplasms were grouped as benign (low-grade and moderate dysplasia) and malignant (in situ and invasive carcinoma). Performance characteristics of cytology relative to other risk factors were evaluated. RESULTS: Dilated MPD, MN, and HGA were independent predictors of malignancy (p < 0.0001), but not symptoms (p = 0.29) or cyst size >30 mm (p = 0.51). HGA was the most sensitive predictor of malignancy in all cysts (72%) and in small (≤30 mm) branch-duct intraductal papillary mucinous neoplasm (BD IPMN; 67%), whereas also being specific (85 and 88%, respectively). MN and dilated MPD were highly specific (>90%), but insensitive (39%-44%). Cytology detected 30% more cancers in small cysts than dilated MPD or MN and half of the cancers without either of these high-risk imaging features. CONCLUSIONS: Cytology adds value to the radiological assessment of predicting malignancy in mucinous cysts, particularly in small BD IPMN.

First assessment of needle-based confocal laser endomicroscopy during EUS-FNA procedures of the pancreas (with videos).

BACKGROUND: Challenges in EUS-guided FNA (EUS-FNA) include sampling error, nondiagnostic cytology, and limited on-site cytological evaluation. A prototype needle-based confocal laser endomicroscopy (nCLE) probe is a submillimeter probe that provides real-time imaging at the microscopic level through the FNA needle. OBJECTIVE: To evaluate the feasibility of nCLE during EUS-FNA of pancreatic lesions. DESIGN: Feasibility study. SETTING: Multicenter, tertiary care. PATIENTS: Eighteen patients presenting for EUS-FNA. INTERVENTIONS: Patients were injected with 2.5 mL of 10% fluorescein. The lesion was interrogated with the nCLE probe positioned at the tip of a 19-gauge FNA needle. MAIN OUTCOME MEASUREMENTS: Device integrity, technical ease, safety, and image acquisition. RESULTS: Cases included 16 cysts and 2 masses. There were no device malfunctions. Technical challenges were encountered in 6 of 18 attempts to image and reflected challenges with a postloading technique, the longer ferule tip, and a transduodenal approach. Technical feasibility to perform imaging with nCLE during a pancreatic EUS-FNA procedure was achieved in 17 of 18 cases. Ten cases had good to very good image quality. Two serious adverse events occurred; both were pancreatitis requiring hospitalization. LIMITATIONS: Limited sample size, small number of patients with confirmed pathological diagnosis, lack of coregistered pathology and images. CONCLUSIONS: nCLE in the pancreas is technically feasible via a 19-gauge needle under endosonographic guidance. Future studies will address identification of structures, diagnostic accuracy, and complication profiles. The rate of pancreatitis needs to be further clarified and mitigated.

Optimizing management of pancreatic cysts--prospective re-assessment for 157 cases.

BACKGROUND/AIMS: Ongoing debate continues regarding the appropriate management of pancreatic cysts (PCs). Disagreement prevails regarding frequency of needed follow-up, if and when to perform any PC needle biopsy and indications for surgical resection. EUS is increasingly used to help determine management of PCs. METHODOLOGY: One hundred and fifty seven consecutive patients with PCs were identified out of 5000 patients who underwent EUS between 1995-2007. In 2008, these patients were then prospectively provided clinical follow-up, and CEA, CA19-9 and CRP. RESULTS: No symptoms could be definitively related to the PCs. Twenty four of 157 patients with suspected malignant cysts, mucinous cysts or IPMN had undergone surgical treatment. Whipple's operation was performed in 14 patients and distal pancreatectomy in 10 patients. Fifty PCs were located in the head of pancreas. In 89 patients prospective blood tests were performed; in 6 of them elevated levels of CA-19-9 were detected, 3 of these also had elevated serum CEA. Twelve patients had increased CRP values. No complication (requiring hospitalization) and no mortality related to EUS had occurred. CONCLUSIONS: Elements identified as important for assessment of PCs included: size, serum and fluid markers, imaging characteristics and clinical follow-up. These factors should be included in the recommended guidelines.

Asymptomatic pancreatic cysts: a decision analysis approach to observation versus resection.

OBJECTIVES: Pancreatic cysts are being found with increasing frequency. Although symptomatic cysts should be resected, what to do about asymptomatic cysts is less clear. The purpose of this study was to determine threshold values to choose resection over observation for a patient with an asymptomatic pancreatic cyst. METHODS: Decision analysis assesses the consequences of a decision based on occurrence probabilities. This decision analysis assessed 1 decision, to resect or observe a patient with an asymptomatic pancreatic cyst. The consequences for resection are operative mortality/no operative mortality, short-term morbidity of patients surviving the operation, benign/malignant cyst, and life expectancy after resection of malignant lesions. The probabilities are based on the extant literature. The age-specific life expectancy for benign cysts was considered the same as for the general age-specific population from the 2002 United States Life Table. Because the operative mortality, distribution of benign versus malignant cysts, and life expectancy after resection or observation for malignant cysts vary, sensitivity analysis was done to assess the threshold values of these factors when resection becomes favored over observation. RESULTS: The baseline decision analysis is based on the following assumptions: 30% of lesions are malignant, operative mortality rate is 3%, and the 5-year survival rate of resected malignant cysts is 50%. Varying on age, the risk of the cystic lesion being malignant to favor resection is greater than 11.6% to 15.5%, the operative mortality rate has to be less than 7.4% to 13.8%, and the life expectancy gain by resecting, rather than observing a malignant lesion, has to be greater than 3.49 to 5.38 years. CONCLUSIONS: The decision to resect must be based on the surgeon's operative mortality rate, the predicted operative mortality for the individual patient, the probability that the lesion is malignant, and the survival difference between resecting and observing malignant cystic lesions. Overall, for resection to be recommended, the physician must believe that the risk that the lesion is malignant is approximately 15% or greater, that the life expectancy gained from resection be approximately 5 years or greater, and that the surgeons' operative mortality rate be approximately 8% or less.

Papillary cystic tumors of the pancreas: assessment of malignant potential by analysis of progesterone receptor, flow cytometry, and ras oncogene mutation.

BACKGROUND: Although the biologic behavior of papillary cystic tumor (PCT) of the pancreas is more favorable than the adenocarcinoma, a malignant form has been reported. There has been much controversy as to the histologic evidence for malignancy. The purpose of this study is to evaluate whether the ras oncogene mutation is present in the PCT, together with hormone receptor status and DNA flow cytometry that can be used to predict tumor aggressiveness. MATERIALS AND METHODS: In 6 collected cases of PCT, estrogen receptors (ER) and progesterone receptors (PR) were detected by immunohistochemical techniques, DNA ploidy and S-phase fraction (SPF) were studied by flow cytometry, and H, K, and N-ras oncogene mutation were analyzed by polymerase chain reaction (PCR). RESULTS: General strong positive immunostaining of PR and negative staining of ER are found in all 6 cases of PCT, including 5 adolescent girls and one 55-year-old women with areas of anaplastic transformation. Flow cytometry analysis revealed diploid DNA in all 6 cases but higher SPF in the anaplastic portion of the old one. None of the 6 cases showed H-, K-, or N-ras oncogene mutation. CONCLUSIONS: These results suggest PR status and ras oncogene mutation appear to be not useful in predicting aggressive behavior. DNA ploidy and S-phase fraction may provide useful information for prognosis, but their more precise prognostic value of PCT needs a larger number of cases to clarify.

Clinical assessment compared with cyst fluid analysis in the differential diagnosis of cystic lesions in the pancreas.

BACKGROUND: In adults 80% to 90% of cystic lesions in the pancreas are pseudocysts and the remainder are mostly neoplastic cysts. To choose optimal treatment for an individual patient, exact nonoperative diagnosis would be preferable. This study was done to assess the value of cyst fluid analysis, compared with clinical and radiologic findings, in the differential diagnosis of pancreatic cystic lesions. METHODS: Twenty-two patients with a cystic lesion in the pancreas underwent operation, cyst wall biopsy, and aspiration of cyst fluid. Carcinoembryonic antigen (CEA), CA 19-9, pancreatitis-associated protein (PAP), and total protein concentration, amylase activity, and cytologic findings were studied. Final diagnosis was pseudocyst in 14 patients, serous cystadenoma in two, mucinous cystadenoma in two, and mucinous cystadenocarcinoma in four patients. RESULTS: Clinical and radiologic judgment correctly differentiated pseudocysts and neoplastic cysts. Cyst fluid aspiration did not succeed in two patients with mucinous cystadenocarcinomas because of the high fluid viscosity. Cyst fluid amylase activity was high (greater than 16,000 IU/ml) in all but one pseudocyst and low (less than 83 IU/ml) in all but one neoplastic cyst. CEA level was lower in pseudocysts than in neoplastic cysts, but with an overlapping value between the groups. Mean CA 19-9 concentration was higher in pseudocysts than in neoplastic cysts, but with wide overlap between the groups. Pancreatitis-associated protein and total protein concentration and cystic fluid cytologic findings did not differ between various types of cysts. CONCLUSIONS: Clinical judgment including careful history and radiologic studies seems to be the most reliable method of differentiating neoplastic pancreatic cysts from pseudocysts. Amylase and CEA levels give suggestive information, but cyst fluid analysis may be misleading in an individual patient.