Mixed Intraductal Papillary Mucinous Neoplasms Research Articles

A comparative study between computed tomography and endoscopic ultrasound in the detection of a mural nodule in intraductal papillary mucinous neoplasm –Multicenter observational study in Japan

Background/objectivesThe detection of malignancy is a major concern in the management of intraductal papillary mucinous neoplasm (IPMN). The height of the mural nodule (MN), estimated using endoscopic ultrasound (EUS) and computed tomography (CT), has been considered crucial for predicting malignant IPMN. Currently, whether surveillance using CT or EUS alone is sufficient for detecting MNs remains unclear. This study aimed to compare the ability of CT and EUS to detect MNs in IPMN. MethodsThis multicenter, retrospective observational study was conducted in 11 Japanese tertiary institutions. Patients who underwent surgical resection of IPMN with MN after CT and EUS examinations were eligible to participate. The MN detection rates between CT and EUS were examined. ResultsTwo-hundred-and-forty patients who underwent preoperative EUS and CT had pathologically confirmed MNs. The MN detection rates of EUS and CT were 83% and 53%, respectively (p < 0.001). Additionally, the MN detection rate of EUS was significantly higher than that of CT regardless of morphological type (76% vs. 47% in branch-duct-type IPMN; 90% vs. 54% in mixed IPMN; 98% vs. 56% in main-duct-type IPMN; p < 0.001). Further, pathologically confirmed MNs ≥5 mm were more frequently observed on EUS than on CT (95% vs. 76%, p < 0.001). ConclusionsEUS was superior to CT for the detection of MN in IPMN. EUS surveillance is essential for the detection of MNs.

Pancreatic medullary carcinoma developed on a pancreatic intraductal papillary mucinous neoplasm with loss of MSH2 and MSH6 expression: a case report

BackgroundPancreatic medullary carcinoma (PMC) is a rare pancreatic tumor, usually showing the presence of microsatellite instability, mostly MLH1 silencing, and a wild-type KRAS mutation status. We report here a PMC arising from a Pancreatic Intraductal Papillary Mucinous Neoplasm (IPMN), both having KRAS and TP53 mutations.Case presentationWe report the case of a 73-year-old woman presenting with right iliac fossa pain. MRI revealed a 16 mm diameter mass in the pancreas, leading to a pancreatic duct stricture and upstream a dilatation of the distal pancreatic duct of Wirsung. A fine needle aspiration was performed, and pathology analysis revealed malignant glandular cells. The patient underwent distal pancreatectomy.Gross examination revealed an12 mm indurated white lesion, adjacent to a cystic lesion extending into the rest of the pancreatic body.Microscopically, the cystic area represented a mixed (gastric-type and pancreatobiliary-type) IPMN, involving the main and secondary pancreatic ducts with low-grade and high-grade dysplasia. In the periphery of this IPMN, a 14mm associated invasive carcinoma was observed, characterized by focal gland formation and by poorly differentiated cells with a syncytial appearance, associated with a dense lymphoplasmocytic and neutrophilic infiltrate.Immunohistochemical analyses showed loss of MSH2 and MSH6 expression. Microsatellite instability was confirmed by molecular test.Molecular analysis was performed both on the invasive carcinoma and on the high-grade dysplasia IPMN, revealing the same mutation profile with KRAS and TP53 mutations.The proposed diagnosis was mixed IPMN with associated invasive medullary carcinoma that presented loss of MSH2 and MSH6 expression.ConclusionsThe present case reports for the first time, at the best of our knowledge, the coexistence of IPMN lesions and PMC, both having the same molecular alterations. It also describes the second case of PMC with microsatellite instability, MSH2 and MSH6 silenced.

Case study: low grade dysplasia of intraductal papillary mucinous neoplasm progression to metastatic pancreatic adenocarcinoma despite complete pathologic resection

Presenter: Dena Steiner MD | Saint Elizabeth's Medical Center Background: Intraductal Papillary Mucinous Neoplasm (IPMN) management has been closely monitored due to the potentially high morbidity of unnecessary resection and the high mortality of delayed diagnosis of pancreatic cancer. Methods: This case study demonstrates a newly developed pancreatic cancer from the bed of a minimally symptomatic 4x3 cm low grade IPMN found on imaging with pancreatic dilation, mucin, a 15 x 10 mm mural nodule and multiple septations. Endoscopic ultrasound cytology was inconclusive for malignant cells, and a subsequent whipple procedure was revealing for mixed duct IPMN with low grade dysplasia, negative margins and 14 negative nodes. Results: One year later, he presented with bloating and subsequent imaging revealed metastatic cancer at the pancreatic bed and liver. He underwent chemotherapy and received palliative care following this diagnosis. Conclusion: Typically, low grade dysplasia in IPMNs subjugates them to a benign categorization, however this case challenges that determination. Malignant potential remains in these lesions with low grade dysplasia; and the mere presence of an IPMN may be a marker that all the patient’s pancreatic cells are at risk for malignant degeneration. Additionally, subcategorization into gastric, intestinal, pancreaticobiliary and oncocytic subtypes and determination of MUC13 expression may provide improved risk stratification.

Natural history and optimal treatment strategy of intraductal papillary mucinous neoplasm of the pancreas: Analysis using a nomogram and Markov decision model.

With the increase in detection of intraductal papillary mucinous neoplasms (IPMN), a tailored approach is needed. This study was aimed at exploring the natural history of IPMN and suggest optimal treatment based on malignancy risk using a nomogram and Markov decision model. Patients with IPMN who underwent surveillance or surgery were included. Changes in worrisome features/high-risk stigmata and malignancy conversion rate were assessed. Life expectancy and quality-adjusted life year (QALY) were compared using a nomogram predicting malignancy. Overall, 2006 patients with histologically confirmed or radiologically typical IPMN were enrolled. Of these, 1773 (88.4%), 81 (4.0%), and 152 (7.6%), respectively, had branch duct (BD)-, main duct-, and mixed-type IPMN at initial diagnosis. The cumulative risk of developing worrisome feature or high-risk stigmata was 19.0% and 35.0% at 5- and 10-year follow-up, respectively. The progression of malignancy rate at 10-year follow-up was 79.9% for main and mixed IPMNs and 5.9% for BD-IPMN. Nomogram-based malignancy risk prediction is well correlated with natural history based on pathologic biopsy and shows good stratification of survival. The decision model recommends surgery to maximize survival and QALY especially in those with >35% malignancy risk. Compared with main duct- and mixed-type IPMN, which have a high risk of malignancy (79.9%), BD-IPMN is very indolent (5.9%). The nomogram-based decision model suggests surgery rather than surveillance for patients with a high malignancy risk. The optimal treatment strategy between surgery and surveillance should consider patients' health status, malignancy risk, and centers' experience.

Main duct and mixed type intraductal papillary mucinous neoplasms without enhancing mural nodules: Duct diameter of less than 10 mm and segmental dilatation of main pancreatic duct are findings support surveillance rather than immediate surgery

ObjectiveThe guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMNs) recommend surgical resection of all main-duct (MD) and mixed-type IPMNs in surgically fit patients. We conducted this study to identify the rates of high-grade dysplasia (HGD) and invasive carcinoma according to the morphological features of the main pancreatic duct (MPD) in patients with MD and mixed IPMN. MethodsWe performed a retrospective study of 259 patients with histologically proven MD and mixed-type IPMNs who underwent surgery at six academic institutions. ResultsThe rate of HGD and invasive carcinoma was 11.1% (24/216) in patients without enhancing mural nodules (MNs) and 69.8% (30/43) in patients with MNs. Multivariate analysis showed that MPD diameter of ≥10 mm [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.155–5.505; P = 0.02], diffuse MPD dilatation (OR, 3.2; 95% CI, 1.152–8.998; P = 0.02), and presence of enhancing MNs in MPD (OR, 9.6; 95% CI, 3.928–23.833, P < 0.0001) were significant predictors of HGD and invasive carcinoma. Of the 216 patients without enhancing MNs, 79 patients (36.6%) having both segmental MPD dilatation and MPD diameter of <10 mm showed significantly lower rates of HGD and invasive carcinoma (3/79, 3.8%) than patients having both diffuse MPD dilatation and MPD diameter ≥10 mm (9/36, 25%, P = 0.001). ConclusionsMD and mixed-type IPMNs having segmental MPD dilatation with MPD dilation <10 mm and no enhancing MNs on imaging showed a significantly lower rate of HGD and invasive carcinoma, and watchful follow-up instead of immediate surgical resection might be possible in these patients.

The CT fish mouth ampulla sign: a highly specific finding in main duct and mixed intraductal papillary mucinous neoplasms.

Main duct and mixed intraductal papillary mucinous neoplasms (IPMN) are pre-malignant cystic pancreatic neoplasms associated with pancreatic duct dilatation. Distinguishing these from benign causes of pancreatic duct dilatation is important in order to allow appropriate surveillance or surgery. A patulous duodenal papilla with extrusion of mucus at endoscopic evaluation, the endoscopic fish mouth ampulla (E-FMA) sign, is reported in main duct and mixed IPMN. We aimed to establish whether a CT correlate (CT-FMA) of this sign exists and whether this was associated with the presence of invasion or high-grade dysplasia. We defined the CT-FMA sign as an uninterrupted column of water attenuation material running from the pancreatic duct to the duodenal lumen. A retrospective, blinded review of 44 patients with histologically confirmed IPMN and 87 age-matched controls with pancreatic duct dilatation on CT was undertaken. A case-control series matched for the degree of pancreatic duct dilatation was used to compare the rates of invasion or high-grade dysplasia between main duct and mixed IPMN patients, with and without a CT-FMA sign. The CT-FMA sign could be identified in 18.5% patients with main duct/mixed IPMN with specificity 100%, positive predictive value 100% and negative predictive value 79.8%. A significant association was found between CT-FMA in main duct/mixed IPMN compared to controls, but not with the presence of high-grade dysplasia or invasion. The CT-FMA sign is a newly reported, highly specific sign of MD and mixed IPMN. If a fish mouth ampulla is identified at CT, a diagnosis of main duct or mixed IPMN is highly likely.

The validity of the surgical indication for intraductal papillary mucinous neoplasm of the pancreas advocated by the 2017 revised International Association of Pancreatology consensus guidelines.

This study was performed to evaluate the surgical indication for intraductal papillary mucinous neoplasm (IPMN) advocated by the 2017 revised International Association of Pancreatology consensus guidelines (IAPCG2017). The medical records of 63 patients who underwent pancreatectomy for IPMN were retrospectively reviewed. Thirteen patients had main-duct IPMN, 25 had mixed IPMN, and 25 had branch-duct IPMN with frequencies of high-grade dysplasia or invasive carcinoma of 62, 24, and 28%, respectively. The sensitivity and specificity of high-risk stigmata for high-grade dysplasia or invasive carcinoma advocated by the IAPCG2017 were 90 and 67%, respectively. Of 17 patients with invasive carcinoma, all patients had high-risk stigmata, and 16 had an enhanced mural nodule (MN) of ≥ 5mm. The sensitivity and specificity of a ≥ 5-mm enhanced MN for predicting invasive carcinoma were 94% and 87%, respectively. Introducing a size threshold for enhanced MNs into the assessment of high-risk stigmata increases the specificity without jeopardizing the sensitivity. The surgical indication for any type of IPMN may be determined using only a ≥ 5-mm enhanced MN. When the type of IPMN is classified strictly, about half of IPMNs are mixed type, and most are benign. The surgical indication for mixed IPMN should be reconsidered.

Diagnostic Accuracy of Preoperative Imaging for Differentiation of Branch Duct Versus Mixed Duct Intraductal Papillary Mucinous Neoplasms.

The aim of this study is to determine the diagnostic accuracy of preoperative evaluation to detect main pancreatic duct involvement in pancreatic cystic lesions thus differentiating mixed intraductal papillary mucinous neoplasm (IPMN) from branch duct (BD)-IPMN. The pathology database of pancreatic resections from 2000 to 2014 was reviewed. Main pancreatic duct-IPMNs and IPMNs with intracystic mass/nodules were excluded. The preoperative test characteristics were analyzed using surgical histopathology as the "gold standard." Sixty BD-IPMNs and 23 mixed-IPMNs were identified. Mixed-IPMNs were larger (mean [standard deviation], 4.14 [2.9] vs 2.74 [1.9] mm; P = 0.03) and demonstrated frequent high-grade dysplasia/adenocarcinoma (43% vs 12%, P = 0.004) than BD-IPMNs. Endoscopic ultrasound (EUS) (sensitivity, 80%; specificity, 78%; accuracy, 79%) had the best diagnostic accuracy, whereas magnetic resonance imaging (MRI) (sensitivity, 83%; specificity, 63%; accuracy, 68%) had the highest sensitivity for the diagnosis of mixed-IPMN. A combination of EUS and MRI reached maximum sensitivity but with decreased accuracy (sensitivity, 100%; specificity, 64%; accuracy, 67%). The area under the curve for receiver operation curve was 0.71 whereas the optimal cyst size to detect main duct involvement was 3 cm. For preoperative evaluation of pancreatic cystic lesions without evidence of intracystic nodules, a combination of MRI and EUS should be considered for improved detection of main duct involvement.

AB096. P070. Feasibility and efficacy of an analysis using FFPE blocks of resected pancreas with micro CT

: Recently, the importance of 3D imaging constructed by computed tomography (CT) data is increasing in clinical practice especially for preoperative usage. On the other hand, Micro-CT (inspeXio SMX-90CT, Kyoto, Shimadzu Corporation) can provide exceptionally high-resolution imaging with pixels in the dozens of micrometers range. When we use micro-CT for imaging of formalin fixed paraffin embedded pancreatic specimens, it gives us a chance to resolve clinical questions and discrepancy which may emerge perioperatively, particularly between preoperative diagnosis and pathological results. Pancreatic ductal adenocarcinoma is one of the lethal diseases, so it is important to detect and resect in the earlier stage. Intraductal papillary mucinous neoplasm (IPMN) is known as one of the precursor lesions of the pancreas, developing from low grade to high grade dysplasia that may further progress to invasive cancer. International Consensus Guideline for management of IPMN has been published in 2012. According to this guideline, indications of pancreatectomy are the presence of main and mixed duct IPMN, or branch duct IPMN with “high-risk stigmata of malignancy present”. On the other hand, branch duct IPMN with “worrisome features” requires more thorough examination before deciding to do a surgical resection. Sometimes, it is not easy to identify such small features like mural nodules, or critical site of caliber change of pancreatic duct in resected specimen pathologically. Herein, we show the feasibility and efficacy of the usage of micro-CT in evaluating IPMN lesions to reveal the answer for these uncertainties.

Assessment of a Revised Management Strategy for Patients With Intraductal Papillary Mucinous Neoplasms Involving the Main Pancreatic Duct

According to the 2012 International Consensus Guidelines, the diagnostic criterion of intraductal papillary mucinous neoplasms (IPMNs) involving the main duct (MD IPMNs) or the main and branch ducts (mixed IPMNs) of the pancreatic system is a main pancreatic duct (MPD) diameter of 5.0 mm or greater on computed tomography (CT) or magnetic resonance imaging (MRI). However, surgical resection is recommended for patients with an MPD diameter of 10.0 mm or greater, which is characterized as a high-risk stigma. An MPD diameter of 5.0 to 9.0 mm is not an indication for immediate resection. To determine an appropriate cutoff (ie, one with high sensitivity and negative predictive value) of the MPD diameter on CT or MRI as a prognostic factor for malignant disease and to propose a new management algorithm for patients with MD or mixed IPMNs. This retrospective cohort study included 103 patients who underwent surgical resection for a preoperative diagnosis of MD or mixed IPMN and in whom IPMN was confirmed by surgical pathologic findings at a single institution from July 1, 1996, to December 31, 2015. Malignant disease was defined as high-grade dysplasia or invasive adenocarcinoma on results of surgical pathologic evaluation. An appropriate MPD diameter on preoperative CT or MRI to predict malignant disease was determined using a receiver operating characteristic curve analysis. The prognostic value of the new management algorithm that incorporated the new MPD diameter cutoff was evaluated. Among the 103 patients undergoing resection for an MD or mixed IPMN (59 men [57.3%]; 44 women [42.7%]; median [range] age, 71 [48-86] years), 64 (62.1%) had malignant disease. Diagnostic accuracy for malignant neoplasms was highest at an MPD diameter cutoff of 7.2 mm (area under the receiver operating characteristic curve, 0.70; 95% CI, 0.59-0.81). An MPD diameter of 7.2 mm or greater was also an independent prognostic factor for malignant neoplasms (odds ratio, 12.76; 95% CI, 2.43-66.88; P = .003) on logistic regression analysis after controlling for preoperative variables. The new management algorithm, which included an MPD diameter of 7.2 mm or greater as one of the high-risk stigmata, had a higher sensitivity (100%), negative predictive value (100%), and accuracy (66%) for malignant disease than the 2012 version of the International Consensus Guidelines (95%, 57%, and 63%, respectively). In this single-center, retrospective analysis, an MPD diameter of 7.2 mm was identified as an optimal cutoff for a prognostic factor for malignant disease in MD or mixed IPMN. These data support lowering the accepted criteria for MPD diameter when selecting patients for resection vs surveillance so as not to overlook cancer in IPMN.

Risk Factors for Progression or Malignancy in Main-Duct and Mixed-Type Intraductal Papillary Mucinous Neoplasm of the Pancreas.

The 2012 international guidelines state that surgery should be considered for all surgically fit patients with pancreatic main-duct (MD)/mixed intraductal papillary mucinous neoplasms (IPMNs). This study evaluated the follow-up results of MD/mixed IPMNs and risk factors for progression or malignancy. Patients with MD/mixed IPMNs were retrospectively enrolled and divided into surgical and nonsurgical groups. These 2 groups were compared and further categorized as progression/malignancy or not. In the nonsurgical group, disease progression was defined as radiologic tumor growth or adjacent organ invasion. Data from 101 patients (73 males; mean [SD] age, 66.3 [9.1] years), including 27 and 74 in the nonsurgical and surgical groups, respectively, were analyzed. Mural nodules were more frequently detected in the surgical group (7.4% vs 31.1%, P = 0.018), whereas more multifocal cysts were observed in the nonsurgical group (40.7% vs 20.3%, P = 0.037). Forty-one patients (40.6%) showed progression or malignancy. Multivariate analysis showed that main pancreatic duct of 10 mm or greater (odds ratio, 4.368; P = 0.024) and pre-existing diabetes (odds ratio, 3.077; P = 0.046) were independent risk factors for progression or malignancy. A watchful waiting strategy could be feasible for some patients with MD/mixed IPMNs, particularly those with a main pancreatic duct of less than 10 mm and without diabetes.

Low progression of intraductal papillary mucinous neoplasms with worrisome features and high-risk stigmata undergoing non-operative management: a mid-term follow-up analysis

ObjectiveTo evaluate mid-term outcomes and predictors of survival in non-operated patients with pancreatic intraductal papillary mucinous neoplasms (IPMNs) with worrisome features or high-risk stigmata as defined by International Consensus Guidelines...

Validity of the management strategy for intraductal papillary mucinous neoplasm advocated by the international consensus guidelines 2012: a retrospective review.

The aim of this study was to investigate the validity of the management strategy for intraductal papillary mucinous neoplasms (IPMNs) advocated by the international consensus guidelines 2012 (ICG2012). The medical records of 49 patients who underwent pancreatectomy for IPMN were retrospectively reviewed. According to preoperative imaging, 10 patients (20%) had main-duct IPMNs, 20 (41%) had mixed IPMNs, and 19 (39%) had branch-duct IPMNs, with malignancy frequencies of 80, 15, and 37%, respectively. Twenty-seven patients had high-risk stigmata and 21 had worrisome features, with malignancy frequencies of 59 and 10%, respectively. The sensitivity, specificity, and positive and negative predictive values of high-risk stigmata for malignancy were 88, 65, 59, and 91%, respectively. Lesions were malignant in 88% of patients with an enhanced solid component, which was significantly correlated with the prevalence of malignancy (P<0.01). However, of the 10 patients who underwent pancreatectomy solely due to a main pancreatic dilation of ≥10mm, 9 (90%) had benign IPMNs. Many mixed IPMNs defined according to ICG2012 are benign. Although the management strategy advocated by ICG2012 has been improved relative to the Sendai criteria, the different high-risk stigmata carry unequal weights. Consequently, ICG2012 remains suboptimal for predicting malignant IPMN.

Risk for Colorectal Adenomas Among Patients with Pancreatic Intraductal Papillary Mucinous Neoplasms: a Prospective Case-Control Study.

It has been reported that patients with intraductal papillary mucinous neoplasms of the pancreas are at an increased risk of colorectal cancer. The aim of our study was to investigate whether patients with intraductal papillary mucinous neoplasms are at a higher risk of colorectal adenomas with respect to the general population, as this condition represents the precursor of sporadic colorectal cancer. A case-control study was conducted at the Catholic University and University Sapienza, Rome, Italy. The cases were patients with intraductal papillary mucinous neoplasms without history of colorectal cancer, who had underwent screening colonoscopy for the first time. The controls were individuals who had underwent first time colonoscopy for screening or evaluation of non-specific abdominal symptoms. Chi-square and Fisher tests were used to compare the distributions of categorical variables. We enrolled 122 cases and 246 controls. Colorectal polyps were found in 52 cases (42.6%) and 79 controls (32.1%) (p<0.05). In 29 cases (23.8%) and 57 controls (23.2%) histological examination disclosed adenomatous polyps (p=0.90). There was no difference between the groups in relation to the presence of polyps with low-grade (19.7% vs. 19.8%, p=0.98) and high-grade dysplasia (4.9% vs. 4.5%, p=0.85). Patients with intraductal papillary mucinous neoplasms of the pancreas are not at an increased risk for the development of adenomatous colorectal polyps.

Acute Pancreatitis is a Predictive Factor for Malignancy in Mixed or Main Duct Intraductal Papillary Mucinous Neoplasms

Objectives: It is still unclear whether acute pancreatitis (AP) is a predictor of malignancy. Using patients enrolled from a single institution, the objective of this study was to determine whether AP as a complication of intraductal papillary mucinous neoplasm (IPMN) predicts malignancy, and to clarify the clinicopathological characteristics of IPMN with AP. Methods: The clinicopathological features of 87 patients who underwent surgical resection for IPMN between October 1998 and May 2010 were investigated. In this study, malignancy was defined as high-grade dysplasia (noninvasive carcinoma) and invasive carcinoma. Macroscopic classification was based on the 2012 international consensus guidelines and IPMN with a main pancreatic duct size of >5 mm was classified as either mixed or main duct IPMN. Results: Among the patients, who underwent surgical resection for IPMN, AP was present in 18% (16/87) and malignancy was present in 43% (37/87). The median period from the first AP episode until surgery was 5.5 months (range: 1.0-116.3 months). There was no significant difference in the frequency of malignancy between IPMN patients with and without AP [63% (10/16) vs. 38% (27/71); p=0.096]. In mixed or main duct IPMN, malignancy was more frequent in patients with AP than in those without AP [91% (10/11) vs. 48% (22/46); P=0.016]. Comparison of the clinicopathological features between malignant IPMN with and without AP showed that the frequency of highgrade dysplasia (non-invasive carcinoma) was significantly higher in the former [80% (8/10) vs. 37% (10/27); P=0.029]. Conclusions: AP itself may not be a predictive factor for malignancy in IPMN, but may be such a predictor in mixed or main duct IPMN. AP is also an important clinical sign that must not be overlooked, as it may indicate the presence of malignant lesions at an earlier stage.

Interobserver agreement for detection of malignant features of intraductal papillary mucinous neoplasms of the pancreas on MDCT.

The purpose of this retrospective study was to measure interobserver agreement in the assessment of malignant imaging features of intraductal papillary mucinous neoplasms (IPMNs) on MDCT. Pancreatic protocol CT studies were reviewed for 84 patients with resected IPMNs. Maximal diameter of the dominant cyst, presence of a mural nodule, presence of a solid component, and diameters of the main pancreatic duct (MPD) and common bile duct (CBD) were measured by four radiologists independently. In each patient, the IPMN was classified into one of three types: main duct, branch duct, or mixed IPMN. Interobserver agreement of lesion features was examined using the intraclass correlation coefficient (ICC) for continuous features and Fleiss kappa for categorical features. The final dataset included 55 branch duct IPMNs, nine main duct IPMNs, and 20 mixed IPMNs. Moderate agreement (ĸ = 0.458; 95% CI, 0.345-0.564) was observed in assigning branch duct, main duct, or mixed IPMN subtypes. Measurement agreement was substantial to excellent for dominant cyst (ICC = 0.852; 95% CI, 0.777-0.907), MPD (0.753, 0.655-0.837), and CBD (0.608, 0.463-0.724) but only fair to moderate for the detection of the presence of mural nodule (ĸ = 0.284, 0.125-0.432) or solid component (ĸ = 0.405, 0211-0.577). Substantial to excellent interobserver agreement in the measurement of cyst diameter, MPD, and CBD support their use for characterizing malignant features of IPMN on MDCT. However, the subjective interpretation of the presence of solid components and mural nodules by individual radiologists was more variable.

MUC2 expression and prevalence of high-grade dysplasia and invasive carcinoma in mixed-type intraductal papillary mucinous neoplasm of the pancreas

Background/objectivesMorphological types and mucin protein expressions classify intraductal papillary mucinous neoplasms (IPMNs). Main duct (MD)-IPMN mostly consists of intestinal type (I-type), which expresses MUC2. Branch duct (BD)-IPMN mostly consists of gastric type (G-type), which does not express MUC2. However, the definition of mixed-type IPMN has yet to be clarified and it contains various histological types. The aim of this study was to investigate the relationship between MUC2 expression and the presence of high-grade dysplasia (HGD) and invasive carcinoma, especially in mixed-type IPMN. MethodsThis retrospective study included 101 consecutive patients with surgically resected IPMNs between April 2001 and October 2012. All patients were morphologically classified into four distinct types (I-type, G-type, PB-type: pancreatobilliary, O-type: oncocytic) and immunohistochemical reactivity of various anti-mucin antibodies were investigated. ResultsAccording to the classification of the 2012 international guidelines, the numbers (and histomorphological types: I/G/PB/O) of MD, mixed-type, and BD-IPMNs were 16 (12/4/0/0), 45 (16/28/1/0), and 40 (0/38/1/1). Prevalence of MUC2 expression in MD, mixed-type, and BD-IPMNs were 75% (12/16), 36% (16/45), and 0% (0/40). In mixed-type IPMN, the prevalence of HGD and/or invasive carcinoma in MUC2-positive IPMN was significantly higher than that of MUC2-negative IPMN (HGD + invasive carcinoma: 88% vs. 38%, p = 0.0017; invasive carcinoma: 50% vs. 21%, p = 0.042). Multivariate analysis showed that MUC2 expression is an independent predictive factor of HGD and invasive carcinoma in mixed IPMN (odds ratio 14.6, 95% CI 2.5–87.4, p = 0.003). ConclusionsIn mixed-type IPMN, MUC2 expression clearly identified HGD and invasive carcinoma and may provide most appropriate surgical indication.

Decision making for pancreatic resection in patients with intraductal papillary mucinous neoplasms

To identify a practical approach for preoperative decision-making in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Between March 1999 and November 2006, the clinical characteristics, pathological data and computed tomography/magnetic resonance imaging (CT/MRI) of 54 IPMNs cases were retrieved and analyzed. The relationships between the above data and decision-making for pancreatic resection were analyzed using SPSS 13.0 software. Univariate analysis of risk factors for malignant or invasive IPMNs was performed with regard to the following variables: carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and the characteristics from CT/MRI images. Receiver operating characteristic (ROC) curve analysis for pancreatic resection was performed using significant factors from the univariate analysis. CT/MRI images, including main and mixed duct IPMNs, tumor size > 30 mm or a solid component appearance in the lesion, and preoperative serum CA19-9 > 37 U/mL had good predictive value for determining pancreatic resection (P < 0.05), but with limitations. Combining the above factors (CT/MRI images and CA19-9) improved the accuracy and sensitivity for determining pancreatic resection in IPMNs. Using ROC analysis, the area under the curve reached 0.893 (P < 0.01, 95%CI: 0.763-1.023), with a sensitivity, specificity, positive predictive value and negative predictive value of 95.2%, 83.3%, 95.2% and 83.3%, respectively. Combining preoperative CT/MRI images and CA19-9 level may provide useful information for surgical decision-making in IPMNs.

The role of GNAS mutation in diagnosis of mucinous pancreatic cysts.

e21048 Background: Pancreatic cysts pose a challenge in patient management primarily due to difficulties distinguishing non-mucinous cysts from potentially pre-malignant mucinous ones, and in determining the malignant potential of mucinous cysts. Mutations to the GNAS gene have been identified as a marker for intraductal papillary mucinous neoplasm (IPMN). [1,2] We evaluated the significance of GNAS mutation in diagnosis of pancreatic cysts. Methods: We retrieved archival DNA from 237 cyst fluids. 200 specimens were chosen with 100 KRAS mutant and 100 KRAS wild type in a range of CEA values. 37 specimens were chosen with a molecular diagnosis of aggressive biological behavior, to enrich for malignant IPMNs. We sequenced each fluid’s DNA from for codon 201 of GNAS. Molecular criteria for mucinous cysts included KRAS mutation, elevated DNA, or ≥2 high clonality LOH mutations. Results: Of the 237 specimens, 25 were not amplifiable due to degraded DNA, 52 (25%) had a GNAS mutation, and 160 had no GNAS mutation. Of the 52 GNAS mutated specimens, 5 were diagnosed as biologically aggressive based on significant associated mutations, 28 as statistically indolent based on associated molecular changes, and 19 as benign (no accompanying mutations). The proportion of GNAS mutations decreased with increasing molecular changes linked to malignancy. Data from [1] shows no statistical difference in frequency of GNAS mutation in side branch vs. main vs. mixed IPMNs (p= 0.46). Similarly, in our cohort, 6 cases had clear imaging features of a side branch IPMN, and of these 2 (33%) had a mutation in GNAS. Using molecular criteria for identification of mucinous cysts, 166 were mucinous and 71 non-mucinous. Incorporation of GNAS into the molecular determination of mucinous etiology identified 13 additional cases (7%). Conclusions: Use of GNAS increases sensitivity for detection of mucinous lesions. GNAS does not appear to correlate with molecular measures of biological aggressiveness. These findings confirm those in [1], that GNAS should be used in conjunction with a panel of molecular markers for evaluating the malignant potential of pancreatic cystic lesions.

Differentiating Branch Duct and Mixed IPMN in Endoscopically Collected Pancreatic Cyst Fluid via Cytokine Analysis

Background. Differentiating branch duct from mixed intraductal papillary mucinous neoplasm (BD-IPMN) is problematic, but clinically important as mixed IPMNs are managed surgically, while some BD-IPMN may be followed. Inflammatory mediator proteins (IMPs) have been implicated in acute and chronic inflammatory and malignant pancreatic diseases. Aim. To compare IMP profile of pancreatic cyst fluid collected endoscopically from BD-IPMN and mixed IPMN. Methods. Pancreatic cyst fluid from ten patients (5 BD-IPMN and 5 mixed IPMN) was collected by endoscopic ultrasound-guided fine needle aspiration or endoscopic retrograde cholangiopancreatography. Concentrations of 89 IMPs in these samples were determined using a multiplexed bead-based microarray protein assay and compared between BD-IPMN and mixed IPMN. Results. Eighty-six of 89 IMPs were detected in at least one of the 10 samples. Fourteen IMPs were detected only in mixed IPMN, while none were only in BD-IPMN. Of these, TGF-β1 was most prevalent, present in 3 of 5 mixed IPMNs. Seventy-two IMPs were detected in both BD-IPMN and mixed IPMNs. Of these, only G-CSF (P < 0.05) was present in higher concentrations in mixed IPMNs. Conclusion. TGF-β1 and G-CSF detected in endoscopically collected pancreatic cyst fluid are potential diagnostic biomarkers capable of distinguishing mixed IPMN from BD-IPMN.