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Introduction: The aim of this study was to determine if neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were predictive of malignancy in mucin-producing pancreatic cystic neoplasms (MpPCN)., Methods: One hundred and twenty patients with MpPCN were retrospectively reviewed. Malignant neoplasms were defined as neoplasms harbouring invasive carcinoma or high grade dysplasia. A high NLR and PLR were defined as ≥2.551 and ≥208.1, respectively., Results: High NLR was significantly associated with symptomatic tumors, larger tumors, solid component, main-duct IPMN, and Sendai high risk category. High PLR was significantly associated with jaundice and Sendai high risk category. On univariate analyses, symptomatic tumors, jaundice, solid component, dilated pancreatic duct, and both a high NLR and PLR were significant predictors of malignant and invasive MpPCN. On multivariate analyses, solid component and dilated pancreatic duct were independent predictors of malignant and invasive MpPCN. PLR was an independent predictor for invasive MpPCN. When MpPCN were stratified by the Fukuoka and Sendai Guidelines, both a high NLR and PLR were significantly associated with malignant neoplasms within the high risk categories., Conclusions: PLR is an independent predictor of invasive carcinoma. The addition of PLR as a criterion to the FCG and SCG significantly improved the predictive value of these guidelines in detecting invasive neoplasms., (© 2015 Wiley Periodicals, Inc.)

The present study demonstrated that luminal membrane mesothelin expression is a reliable prognostic factor in gastric cancer. Intraductal papillary mucinous neoplasms (IPMNs) often exhibit a spectrum of dysplasia, ranging between adenoma and carcinoma. Therefore, an immunohistochemical analysis of mesothelin expression in IPMN was performed in the present study, focusing on the localization of mesothelin. IPMNs were classified into two groups, IPMNs associated with invasive carcinoma and low-high (L-H) grade dysplasias. The tumors were classified as mesothelin-positive or -negative and in the mesothelin-positive cases, the localization of mesothelin was evaluated as luminal membrane- or cytoplasmic-positive. Among the 37 IPMNs, mesothelin expression was observed in 21 samples (56.8%), including 46.2% (12 out of 26) of the L-H dysplasia and 81.8% (9 out of 11) of the invasive carcinoma samples (P=0.071). Luminal membrane localization was observed in 10 samples (27%), including 15.4% (4/26) of the L-H dysplasia samples and 54.5% (6 out of 11) of the invasive carcinoma samples (P=0.022). Six patients experienced post-operative recurrence, with five of the recurrent tumors exhibiting mesothelin expression and all six exhibiting luminal membrane localization. It was concluded that immunohistochemical examinations for mesothelin expression and localization are clinically useful for prognostic assessments and decision making regarding further treatment subsequent to surgical procedures in patients with IPMN.

Background: It has been reported that many branch duct intraductal papillary mucinous neoplasms (BD-IPMN) with a mural nodule (MN) reveal adenocarcinomas. On the other hand, invasive cancer derived from BD-IPMN without MN on endoscopic ultrasound (EUS) also exists. The aim of this study was to elucidate the clinicopathological features of invasive cancer derived from BD-IPMN without MN on EUS., Methods: Twenty-one patients pathologically diagnosed with invasive cancer derived from BD-IPMN were included in this study., Results: Based on the height of MNs on EUS, the subjects could be clearly classified as 12 patients whose background BD-IPMNs had high MNs (nodule-forming type IPMN) and nine whose background BD-IPMNs showed no MNs (flat type IPMN). The background BD-IPMN of the 12 patients with nodule-forming type IPMN were non-gastric type. On the other hand, the background BD-IPMN of the nine patients with flat type IPMN was gastric type. The recurrence rate was higher (33% vs. 67%) and the 5-year survival was worse (76% vs. 33%) in flat type IPMN., Conclusions: There may be a pathway for the development of invasive cancer without the formation of an MN in BD-IPMN, and attention should be paid even to the patients with BD-IPMN which does not present an MN., (© 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

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

The clinical importance of intraductal papillary mucinous neoplasms (IPMN) of the pancreas has been increasing due to the large number of newly diagnosed cases. A meta-analysis was used to assess the accuracy of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) for the identification of malignant and invasive IPMN. A literature search of PubMed and Web of Knowledge was conducted. Studies included in the analysis addressed the diagnostic accuracy of serum CEA and CA19-9 and pooled estimates of sensitivity, specificity, positive- and negative-likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and receiver operating characteristic curves were calculated using random-effects models. Predefined subgroup analysis was performed. Fifteen studies (published between 2001 and 2013) were analyzed, including a total of 1,629 patients. Pooled estimates of CEA in malignant and invasive IPNM prediction were: Pooled sensitivity, 18 and 18%; pooled specificity, 93 and 95%; PLR, 2.83 and 3.54; NLR, 0.89 and 0.89; and DOR, 3.35 and 3.6, respectively. Pooled estimates of CA19-9 in malignant and invasive IPMN prediction were: Pooled sensitivity, 40 and 52%; pooled specificity, 89 and 88%; PLR, 2.93 and 3.78; NLR, 0.74 and 0.6; and DOR, 4.34 and 6.33, respectively. In conclusion, serum CEA has low sensitivity and high specificity for malignant and invasive IPMN. Serum CA19-9 is a useful non-invasive preoperative tool for differentiating between invasive and benign IPMN and should be taken into account in the decision to perform surgery.

Abstract: The appropriate management for patients with multifocal branch-duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas involving the entire pancreatic gland remains unclear. We present a 66-year-old woman who underwent pylorus-preserving pancreaticoduodenectomy for a branch-duct intraductal papillary mucinous carcinoma demonstrating a grape-like multilocular cyst, 35 mm in diameter, in the head of the pancreas along with numerous number of small branch-duct IPMNs in the whole pancreas. Histologically, the multifocal cystic lesions were lined by a single row of columnar mucin-containing epithelial cells without atypia. The patient has been doing well without any recurrence during 9-year follow-up after surgery. Surgical removal of the prominent lesions suspicious of malignancy and a close observation of the remaining lesions in the remnant pancreas may be a reasonable treatment plan for patients with multifocal branch-duct IPMNs involving the entire pancreatic gland. [Copyright &y& Elsevier]

Peroral pancreatoscopy (POPS) under duodenoscopic assistance provide direct visual assessment of the pancreatic duct, tissue sampling, and therapeutic interventions. Sometimes, pancreatoscopy can confirm accurate diagnosis, such as differential diagnosis of filling defects between intraductal tumors and stones. However, it is often difficult to differentiate malignant from benign strictures solely on pancreatoscopy. It is currently considered that intraductal papillary mucinous neoplasm (IPMN) is the most suitable indication of POPS. POPS has several problems: image resolution, fragility and maneuverability. Concerning image resolution, the quality has been improved with the development of a video pancreatoscope. Moreover, the recently developed endoscopic optical technology of narrow band imaging (NBI) is now available to video pancreatoscopy. This will allow direct visual assessment. Although currently POPS has several problems, further improvement will assist POPS to become a useful modality in combination with NBI. [ABSTRACT FROM AUTHOR]

Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) consist of main duct (MD) type and branch duct (BD) type. The authors describe their way of thinking regarding diagnostic modalities and management for BD type IPMNs. Endoscopic ultrasonography (EUS) and intraductal ultrasonography (IDUS) provide high resolution images of main and branch pancreatic ducts. The cases with nodules demonstrated by EUS and/or IDUS regardless of the size are the indication of operation. There were 235 cases with BD type IPMN who underwent EUS and IDUS between April 1991 and June 2005. A total of 94 patients underwent surgical resection and were histopathologically diagnosed (carcinoma, 10 cases; adenoma, 64 cases; hyperplasia, 20 cases). Diagnoses of 79 cases with nodules detected by EUS or IDUS preoperatively were 10 carcinomas, 61 adenomas and eight hyperplasias. Diagnoses of 15 cases without nodules but with symptoms were three adenomas, 12 hyperplasias and no carcinoma. The authors think that the combination of EUS and IDUS is the best way for diagnosing BD type IPMNs in the present state. [ABSTRACT FROM AUTHOR]

Although it is not always easy to distinguish benign from malignant intraductal papillary mucinous neoplasms of the pancreas by the imaging techniques, the cytological examination of pancreatic juice is a useful method to differentiate them. Therefore, the present paper describes the authors’ cytological criteria of pancreatic juice in intraductal papillary mucinous neoplasms. [ABSTRACT FROM AUTHOR]

Backgrounds/aims: Appropriate management for multifocal branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas is still controversial. This study was intended to reveal surgical outcomes of surgical resection for multifocal BD-IPMNs, with BD-IPMNs in the remnant pancreas., Methods: Between January 1995 and December 2013, 699 patients underwent the pancreatic resection due to IPMN of pancreas in our institution. Among them, 37 patients showed multifocal BD-IPMNs. After excluding patients who had BD-IPMNs completely resected, medical records of 22 patients with remained BD-IPMNs in the remnant pancreas were retrospectively reviewed., Results: Mean patient age was 65±6.4 years. Types of surgery included central pancreatectomy (n=1), distal pancreatectomy (n=14), and standard pylorus-preserving pancreaticoduodenectomy (n=7). Specimen pathology showed that IPMN was either at low/intermediate-grade dysplasia (n=17) or at high-grade dysplasia (n=2). Three patients had IPMN associated with invasive carcinoma. Their mean follow-up period was 40.4 months. During follow-up, one mortality occurred 35.2 months after the operation which was not associated with IPMN. There was no clinically significant disease progression or recurrence of IPMN in the remnant pancreas during the follow-up period., Conclusions: Our results support that we can safely preserve the pancreas parenchyma with multifocal BD-IPMNs. Benign-looking multifocal BD-IPMNs in the remnant pancreas do not affect the survival of patients.

Background & Aims: International guidelines for the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas recommend surgical resection of those with specific characteristics. We performed a meta-analysis to evaluate the risk of malignancy associated with each of these features of IPMNs., Methods: We performed a comprehensive search of MEDLINE from January 1, 1996, to November 11, 2011, for studies that included any of the features mentioned in the consensus guidelines for surgical resection of main duct and branch duct IPMNs. Data were analyzed from 41 studies for the following features: cyst size greater than 3 cm, the presence of mural nodules, dilated main pancreatic duct, symptoms, and main duct vs branch duct IPMNs. Malignant IPMNs were defined as those with carcinoma in situ or more advanced histology. A separate meta-analysis was performed for each risk factor to calculate pooled odds ratios (ORs). A random-effects model was used, based on the assumption of variation among study populations., Results: The risks of malignancy associated with individual cyst features were as follows: cyst size greater than 3 cm (OR, 62.4; 95% confidence interval [CI], 30.8-126.3), presence of a mural nodule (OR, 9.3; 95% CI, 5.3-16.1), dilatation of the main pancreatic duct (OR, 7.27; 95% CI, 3.0-17.4), and main vs branch duct IPMN (OR, 4.7; 95% CI, 3.3-6.9). There was a moderate level of heterogeneity among studies (I(2) range, 34-67)., Conclusions: Based on a meta-analysis, cyst features proposed by the international guidelines for resection of IPMN were highly associated with malignancy. However, based on our findings, not all cyst features should be weighted equally when considering risk of malignancy; cyst size greater than 3 cm was associated most strongly with malignant IPMN., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Pancreatic cancer is a lethal disease. Overall survival is typically 6 months from diagnosis. Determination of prognostic factors in pancreatic cancer that would allow identification of patients who could potentially benefit from aggressive treatment is important. However, until date, there are no established reliable prognostic factors for pancreatic cancer patients. Herein, we propose a beneficial biomarker which is significantly correlated with the prognosis in pancreatic cancer patients. Atypical protein kinase C λ/ι (aPKCλ/ι) is overexpressed and has been implicated in the progression of several cancers. We tested the expression levels of aPKCλ/ι in two types of pancreatic neoplasm, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs), by immunohistochemistry. Examination of the aPKCλ/ι expression levels in surgically resected specimens of PDCA (n = 115) demonstrated that the expression levels of aPKCλ/ιin PDAC had prognostic implications, independent of the Tumor-Node-Metastasis classification and World Health Organization tumor grade. In the case of IPMNs (n = 46) also, the expression levels of aPKCλ/ιin IPMN were found to be of prognostic importance, independent of the World Health Organization histological grade or morphological type. Interestingly, high expression levels of aPKCλ/ι were significantly correlated with a worse histological grade (p = 0.010) and advanced stage of the tumor (p = 0.0050) in IPMN patients. These findings suggest that high expression levels of aPKCλ/ι could be involved in the malignant transformation of IPMNs. Based on these observations, we propose the expression level of aPKCλ/ι as a prognostic marker common to different types of pancreatic neoplasms., (Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Solid pseudopapillary neoplasm (SPN) is a rare and low-grade malignant pancreatic neoplasm composed of poorly cohesive monomorphic neoplastic cells forming solid and pseudopapillary structures with frequent hemorrhagic-cystic degeneration. Intraductal papillary mucinous neoplasm (IPMN) is a pancreatic exocrine tumor composed of intraductal papillary growth of mucin containing neoplastic cells in the main pancreatic duct or its major branches. In the case presented here, a 53-year-old, Japanese man was found to have multiple cystic lesions and dilatation of the main pancreatic duct in the neck of the pancreas. Histological examination revealed a main-duct and branch-duct type IPMN, of the gastric-type, involving the neck of the pancreas, associated with a 0.5 cm SPN in the caudal side of the IPMN. We diagnosed this case as synchronous SPN and IPMN. As far as we know, only one other case of synchronous SPN and IPMN has been reported. Both the present case and the previously reported case showed abnormal nuclear expression of β-catenin in SPN, whereas IPMN showed no abnormal nuclear expression. These results suggest that β-catenin abnormality is not a common pathogenetic factor of synchronous SPN and IPMN.

Aim: To identify a practical approach for preoperative decision-making in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas., Methods: 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., Results: 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., Conclusion: Combining preoperative CT/MRI images and CA19-9 level may provide useful information for surgical decision-making in IPMNs.

Intraductal papillary mucinous neoplasms (IPMN) are mucin producing cystic neoplasms of the pancreas histologically classified as having non-invasive and invasive components. The five-year survival rates for non-invasive and associated invasive carcinoma are 90% and 40%, respectively in resected IPMN lesions. Invasive carcinoma within IPMN lesions can be further classified by histological subtype into colloid carcinoma and tubular carcinoma. Estimated five-year survival rates following resection of colloid carcinoma range from 57%-83% and estimated five-year survival following resection of tubular carcinoma range from 24%-55%. The difference in survival outcome between invasive colloid and tubular IPMN appears to be a function of disease biology, as patients with the tubular subtype tend to have larger tumors with a propensity for metastasis to regional lymph nodes. When matched to resected conventional pancreatic adenocarcinoma lesions by the Memorial Sloan Kettering Cancer Center pancreatic adenocarcinoma nomogram, the colloid carcinoma histological subtype has an improved estimated five-year survival outcome compared to conventional pancreatic adenocarcinoma, 87% and 23% (P = 0.0001), respectively. Resected lesions with the tubular carcinoma subtype overall have a similar five-year survival outcome compared to conventional pancreatic adenocarcinoma. However, when these groups were stratified by regional lymph node status patients with negative regional lymph nodes and the tubular subtype experienced significantly better survival than patients with a similar nodal status and ductal adenocarcinoma with estimated five-year survival rates of 73% and 27% (P = 0.01), respectively.

With the widespread use of cross-sectional imaging, particularly computed tomography (CT) and magnetic resonance imaging (MRI), and the continuous improvement in the image quality of these techniques, the diagnosis of incidental pancreatic cysts has increased dramatically in the last decades. While the vast majority of these cysts are not clinically relevant, a small percentage of them will evolve into an invasive malignant tumor making their management challenging. Mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMN) are the most common pancreatic cystic lesions with malignant potential. Imaging findings on CT and MRI correlate tightly with the presence of malignant degeneration in these neoplasms. IPMN can be classified based on their distribution as main duct, branch duct or mixed type lesions. MRI is superior to CT in demonstrating the communication of a branch duct IPMN with the main pancreatic duct (MPD). Most branch duct lesions are benign whereas tumors involving the MPD are frequently associated with malignancy. The presence of solid nodules, thick enhancing walls and/or septae, a wide (> 1 cm) connection of a side-branch lesion with the MPD and the size of the tumor > 3 cm are indicative of malignancy in a branch and mixed type IPMN. A main pancreatic duct > 6 mm, a mural nodule > 3 mm and an abnormal attenuating area in the adjacent pancreatic parenchyma on CT correlates with malignant disease in main duct and mixed type IPMN. An accurate characterization of these neoplasms by imaging is thus crucial for selecting the best management options. In this article, we review the imaging findings of IPMN including imaging predictors of malignancy and surgical resectability. We also discuss follow-up strategies for patients with surgically resected IPMN and patients with incidental pancreatic cysts.

Intraductal papillary mucinous neoplasms (IPMN) can be difficult to distinguish from other cystic lesions of the pancreas. To understand better and discuss the current knowledge on this topic, the literature and the institutional experience at a large pancreatic disease center have been reviewed. A combination of preoperative demographic, historical, radiographic, laboratory data, as well as postoperative pathologic analyses can often distinguish IPMN from other lesions in the differential diagnosis.

In the last decade, intraductal papillary mucinous neoplasms (IPMNs) have become commonly diagnosed. From a morphological standpoint, they are classified in main-duct IPMNs (MD-IPMNs) and branch-duct IPMNs (BD-IPMNs), depending on the type of involvement of the pancreatic ductal system by the neoplasm. Despite the fact that our understanding of their natural history is still incomplete, recent data indicate that MD-IPMNs and BD-IPMNs show significant differences in terms of biological behaviour with MD-IPMNs at higher risk of malignant degeneration. In the present paper, clinical and epidemiological characteristics, rates of malignancy and the natural history of MD-IPMNs and BD-IPMNs are analyzed. The profile of IPMNs involving both the main pancreatic duct and its side branches (combined-IPMNs) are also discussed. Finally, general recommendations for management based on these differences are given.

Intraductal papillary mucinous neoplasms (IPMNs) can involve the main pancreatic duct (MD-IPMNs) or its secondary branches (BD-IPMNs) in a segmental of multifocal/diffuse fashion. Growing evidence indicates that BD-IPMNs are less likely to harbour cancer and in selected cases these lesions can be managed non operatively. For surgery, clarification is required on: (1) when to resect an IPMN; (2) which type of resection should be performed; and (3) how much pancreas should be resected. In recent years parenchyma-sparing resections as well as laparoscopic procedures have being performed more frequently by pancreatic surgeons in order to decrease the rate of postoperative pancreatic insufficiency and to minimize the surgical impact of these operations. However, oncological radicality is of paramount importance, and extended resections up to total pancreatectomy may be necessary in the setting of IPMNs. In this article the type and extension of surgical resections in patients with MD-IPMNs and BD-IPMNs are analyzed, evaluating perioperative and long-term outcomes. The role of standard and parenchyma-sparing resections is discussed as well as different strategies in the case of multifocal neoplasms.

Objective: To determine whether intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a different genetic background compared with ductal adenocarcinoma (PDAC). Summary Background Data: The biologic and clinical behavior of IPMNs and IPMN-associated adenocarcinomas is different from PDAC in having a less aggressive tumor growth and significantly improved survival. Up to date, the molecular mechanisms underlying the clinical behavior of IPMNs are incompletely understood. Methods: 128 cystic pancreatic lesions were prospectively identified during the course of 2 years. From the corresponding surgical specimens, 57 IPMNs were separated and subdivided by histologic criteria into those with low-grade dysplasia, moderate dysplasia, high-grade dysplasia, and invasive cancer. Twenty specimens were suitable for DNA isolation and subsequent performance of array CGH. Results: While none of the IPMNs with low-grade dysplasia displayed detectable chromosomal aberrations, IPMNs with moderate and high-grade dysplasia showed frequent copy number alterations. Commonly lost regions were located on chromosome 5q, 6q, 10q, 11q, 13q, 18q, and 22q. The incidence of loss of chromosome 5q, 6q, and 11q was significantly higher in IPMNs with high-grade dysplasia or invasion compared with PDAC. Ten of 13 IPMNs with moderate dysplasia or malignancy had loss of part or all of chromosome 6q, with a minimal deleted region between linear positions 78.0 and 130.0. Conclusions: This study is the first to use array CGH to characterize IPMNs. Recurrent cytogenetic alterations were identified and were different than those described in PDAC. Array CGH may help distinguish between these 2 entities and give insight into the differences in their biology and prognosis.