Intraductal Papillary Mucinous Neoplasm Of The Pancreas Research Articles

Su1231 The Clinicopathological Features of Intraductal Papillary Mucinous Neoplasm of the Bile Duct: Compared With Intraductal Papillary Mucinous Neoplasm of the Pancreas

[Background/Aim] In spite of intraductal papillary mucinous neoplasm of the bile duct (IPMNB) has been recently recognized, the clinicopathological features of IPMNB still remains unclear. The aim of this study is to resolve this problem by comparing IPMNB and intraductal papillary mucinous neoplasm of the pancreas (IPMNP). [Patients]Medical records of 7 patients with IPMNB, 12 patients with intraductal papillary non-mucinous neoplasm of the bile duct (IPNB) and 51 patients with IPMNP operated on between 2000 and 2010 at our department were reviewed retrospectively. [Results] As for the difference with IPMNB and IPNB, IPMNB had more immunohistochemical staining positive cases of MUC2 and longer for the illness than IPNB. There were no differences between IPMNB and IPNB about Age, gender and tumormarkers. As for the comparison between IPMNB and IPMNP, the malignant frequency, tumor-cell type and immunohistochemical positive staining of MUC2 of IPMNB was equal with main-duct type of IPMNP. [Conclusion]Our data suggested that IPMNB had similar clinicopathological characteristics compared with main-duct type of IPMNP, not branch-type of IPMNP. IPMNB have been proposed as the biliary counterpart of main-duct type of IPMNP. There are similarities and differences between IPMNB and IPNB.

Su1232 The Serum Level of B-FGF and Scf in Hepatitis C Patients and Its Prognosis With Hepatocelluler Carcinoma

[Background/Aim] In spite of intraductal papillary mucinous neoplasm of the bile duct (IPMNB) has been recently recognized, the clinicopathological features of IPMNB still remains unclear. The aim of this study is to resolve this problem by comparing IPMNB and intraductal papillary mucinous neoplasm of the pancreas (IPMNP). [Patients]Medical records of 7 patients with IPMNB, 12 patients with intraductal papillary non-mucinous neoplasm of the bile duct (IPNB) and 51 patients with IPMNP operated on between 2000 and 2010 at our department were reviewed retrospectively. [Results] As for the difference with IPMNB and IPNB, IPMNB had more immunohistochemical staining positive cases of MUC2 and longer for the illness than IPNB. There were no differences between IPMNB and IPNB about Age, gender and tumormarkers. As for the comparison between IPMNB and IPMNP, the malignant frequency, tumor-cell type and immunohistochemical positive staining of MUC2 of IPMNB was equal with main-duct type of IPMNP. [Conclusion]Our data suggested that IPMNB had similar clinicopathological characteristics compared with main-duct type of IPMNP, not branch-type of IPMNP. IPMNB have been proposed as the biliary counterpart of main-duct type of IPMNP. There are similarities and differences between IPMNB and IPNB.

MRCP Imaging of Intraductal Papillary-Mucinous Neoplasm of the Pancreas.

A 79-year-old man was admitted to the hospital with complaints of abdominal discomfort, jaundice and weight loss. His physical examination was unremarkable, but laboratory examinations revealed significant findings indicating steatorrhea and cholestasis. An ultrasound (US) study revealed marked dilatation of the main bile duct and bile duct as well as the associated branches, with no mass in the pancreatic head. A distended gallbladder was also observed on US. A magnetic resonance cholangiopancreatography (MRCP) revealed dilatation of the main pancreatic duct and side branches with irregular mural thickening and several filling defects (Figure A). These trends were also observed in 3-D volume rendering images (Figure B). Secondary to these findings, the gallbladder was distended, and the bile ducts were dilated. No mass was identified in the pancreas. The patient underwent endoscopic retrograde cholangiopancreatography (ERCP), and histopathological examination of the biopsy revealed intraductal papillary-mucinous neoplasm (IPMN). Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is characterized by the presence of a mucin-producing tumor and cystic dilatation of the branches of the pancreatic duct in the uncinate process (branch duct type), diffuse or segmental dilatation of the main pancreatic duct (main duct type) or dilatation of the main ducts and branch ducts (combined type). The dilated ducts often contain profuse mucin. This tumor is also known as a mucin-producing pancreatic tumor, mucinous ductal ectasia, intraductal mucin-hypersecreting tumor or ductectatic mucinous cystic tumor [1–2]. Dilatation of the main pancreatic duct and side branches led to diagnosis of combined-type IPMN. MRCP is especially helpful for staging and as a road map to surgical and percutaneous intervention. Because the increased spatial and contrast resolution increase the sensitivity to fluid and mucin on MRCP, the internal architecture of IPMNs and wall thickening of the main pancreatic duct and branches are better defined through the use of MRCP. The clinical and radiological presentation of IPMN and chronic pancreatitis are often indistinguishable. Talamini et al. [3–5] prospectively followed 473 patients with chronic pancreatitis, including 45 cases of IPMN, and found that approximately 12% of patients with IPMN have a history leading to a diagnosis of chronic pancreatitis, and roughly 2% of all chronic pancreatitis diagnoses are associated with IPMN. The misdiagnosis of IPMN as chronic pancreatitis can lead to serious delays in appropriate management. Curative surgery is only possible if the condition is detected early. Distinguishing a diagnosis of IPMN from chronic pancreatitis can only be achieved through histopathology [6]. Consequently, we considered chronic pancreatitis in the differential diagnosis of IPMN. The diagnosis is made through imaging studies that demonstrate characteristic dilatation of the branches or main duct of the pancreas and endoscopic studies that reveal thick mucin protruding through the bulging patulous duodenal papilla. The treatment decision with regard to IPMN is often based on the patient’s age at presentation, the presence or absence of symptoms, the location of the lesion in the pancreas, the extent of ductal involvement, and the presence or absence of malignant features [7, 8].

Intraductal papillary mucinous neoplasms of the pancreas—a surgical disease

Cystic pancreatic neoplasms are increasingly recognized, with intraductal papillary mucinous neoplasms of the pancreas (IPMNs) being the most frequently observed type. IPMNs are characterized by mucin production and epithelial growth within the pancreatic ducts, and are generally differentiated according to location: main pancreatic duct, its major side branches, or both (mixed type). IPMNs vary from benign to malignant and are considered precursor lesions of pancreatic adenocarcinoma. However, the exact time to neoplastic transformation and whether all IPMNs progress to malignant tumors is unclear. Surgical resection is warranted for all main-duct and mixed-type IPMNs (they harbor a high risk of malignancy of ~70%). By contrast, branch-duct IPMNs progress to cancer in only ~30% of cases. Thus, according to current guidelines (Sendai criteria), asymptomatic side-branch IPMNs <3 cm in size without suspicious radiological features (such as size progression) can be treated conservatively. Lately, even this approach has become controversial, owing to a number of Sendai-negative IPMNs showing malignant transformation. Although most IPMNs should be resected by standard oncological procedures (including lymphadenectomy), small Sendai-negative IPMNs can be treated with limited resections. This Review summarizes current knowledge of the treatment of IPMNs, with a particular focus on surgical approaches to this disease.

Comparison of International Consensus Guidelines Versus 18-FDG PET in Detecting Malignancy of Intraductal Papillary Mucinous Neoplasms of the Pancreas

To assess the reliability of the International Consensus Guidelines (ICG) and 18-fluorodeoxyglucose positron emission tomography (PET) in distinguishing benign from malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Since 2006 the ICG have been used to choose immediate surgery or surveillance for IPMN patients, but their low specificity increases the number of benign IPMNs that undergo resective surgery. PET has proved highly sensitive and specific in detecting malignancy in cystic neoplasms of the pancreas, including IPMNs. Patients suspected with IPMNs of the pancreas seen at our Department from January 1989 to July 2010 were identified and classified as cases of main duct, mixed type and branch type IPMN. The indication for resection or surveillance was verified a posteriori for all patients according to the ICG. PET was considered positive for a Standardized Uptake Value ≥2.5. Surveillance included clinical examination, laboratory tests, CA 19-9 serum levels, and computed tomography and/or magnetic resonance and magnetic resonance cholangiopancreatography every 6 months for 2 years and yearly thereafter. Endoscopic ultrasound was rarely performed. PET was repeated in clinically or radiologically suspect cases, or if tumor markers increased. Sixty-one main duct or mixed type and 101-branch type IPMNs were included in the study. A histological diagnosis was available for 81 of 162 patients, missing for 1 locally advanced IPMN, whereas 62 patients are under surveillance and it proved impossible to contact 18. Conservative surgery was performed in 16 of 68 patients with benign IPMNs. The sensitivity, specificity, positive and negative predictive value, and accuracy of the ICG in detecting malignancy were 93.2, 22.2, 59.4, 72.7, and 61.2, whereas for PET they were 83.3, 100, 100, 84.6, and 91.3. PET is more accurate than the ICG in distinguishing benign from malignant (invasive and noninvasive) IPMNs. Prophylactic IPMN resection in young patients fit for surgery should be guided by the ICG, whereas PET should be performed in older patients, cases at increased surgical risk, or when the feasibility of parenchyma-sparing surgery demands a reliable preoperative exclusion of malignancy.

A case of intraductal papillary mucinous neoplasms after recurrent acute pancreatitis.

We report a case of main pancreatic duct (MPD)-type intraductal papillary mucinous neoplasms of the pancreas (IPMNs), in whom diagnostic imaging modalities showed abnormal findings after 4 episodes of acute pancreatitis. The patient was 51years old at his first admission for acute pancreatitis. He experienced two more episodes of acute pancreatitis, though repeated computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) showed no abnormality to explain the cause of the pancreatitis. After 3½ years from his first episode of pancreatitis, CT and endoscopic ultrasonography revealed pancreatic duct dilation of the pancreas head. Seven years after the first admission, a second ERCP and intraductal ultrasonography revealed a partially dilated MPD with papillary tumors. He underwent pancreaticoduodenectomy, and the pathological diagnosis was intraductal papillary mucinous adenoma with moderate atypia. This case suggests that acute pancreatitis can precede visualized IPMNs. Therefore, acute recurrent pancreatitis with unknown etiology should be followed up for the possibility of IPMNs, in order to detect neoplastic changes in the early stage to provide a better prognosis for the patient.

Usefulness of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance cholangiography for detecting mucin retention in bile ducts: a rare intraductal papillary mucinous neoplasm of the bile duct

We report a 75-year-old man with radiological evidence of a 4.5 × 3.0 cm cystic mass and polypoid masses in the left hepatic lobe. Study of surgical specimens returned a definitive diagnosis of intraductal papillary mucinous neoplasm of the bile duct (IPMN-B). IPMN-B, thought to be the counterpart of intraductal papillary mucinous neoplasm of the pancreas (IPMN), is frequently associated with marked mucin production. We describe a rare case of IPMN-B in which gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance cholangiography was useful for detecting mucin retention in the bile ducts.

Cystic tumors of the liver: On the problems of diagnostic criteria

We report on three cases of cystic neoplasms of the liver with mucinous epithelium. Case 1 showed a low-grade cystic neoplasm with ovarian-like stroma (OS). Case 2 showed a low-grade cystic neoplasm without OS, and case 3 showed a high-grade cystic neoplasm without OS. In all three cases, bile duct communication (BDC) was absent. Currently, pancreatic mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm of the pancreas (IPMN) are clearly distinguishable. However, MCN of the liver and intraductal papillary neoplasm of the bile duct (IPN-B) are not as easily distinguished. According to the latest WHO classification (2010), these conditions are classed as typical MCN of the liver, MCNs of the liver without OS, or IPN-Bs without BDC. The clinicopathological differences between MCN without OS and IPN-B without BDC are controversial. We present three cases describing these presentations and discuss the difficulties related to the diagnostic criteria used to distinguish between MCN of the liver and IPN-B.

Intraductal papillary mucinous neoplasm

A 75-year-old male with a history of dyslipidemia, no alcohol abuse, acute pericarditis and two pancreatitis episodes 16 and 3 years ago, consulted due to a new pancreatitis episode (amylase 536 IU/l). Abdominal CT and MRI showed irregular, rosary-like dilatation of the duct of Wirsung in the body and tail (Fig. 1). In the pancreatic body-tail, echoendoscopy revealed a 15-mm duct of Wirsung with dilatation of the secondary branches and intramural ductal projections. The duct of Wirsung was punctured, yielding mucin material and ductal-type cells without atypias; amylase 38,858 IU/l, CEA 1,604 IU/l and CA19.9 46,000 IU/l. The colonoscopy findings proved normal. Serum CA19.9 was 43 IU/l. With the diagnosis of intraductal papillary mucinous neoplasm of the pancreas (IPMN), a laparoscopic distal pancreatectomy was performed with preservation of the splenic vessels (Fig. 2). The histological study showed an intraductal proliferation affecting the principal duct and secondary branches, with a cylindrical epithelium of intestinal appearance and abundant mucous secretion (Fig. 3). Lacunar mucus accumulations were observed in the pancreatic stroma, without tumour cells. The observed dysplasia proved intense, though without invasive carcinoma (Fig. 3). The surgical margins were free of disease. There has been no evidence of relapse after 18 months of follow-up.

DIRECT PERORAL CHOLANGIOSCOPY AND PANCREATOSCOPY FOR DIAGNOSIS OF A PANCREATOBILIARY FISTULA CAUSED BY AN INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF THE PANCREAS: A CASE REPORT

Here, we report a case of a pancreatobiliary (PB) fistula caused by an intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The PB fistula was suspected after endoscopic retrograde cholangiopancreatography (ERCP) and diagnosed after direct visualization with a direct peroral cholangioscopy and pancreatoscopy by using an ultra-slim endoscope. No previous reports exist on the precise diagnosis of a PB fistula with direct peroral cholangioscopy and pancreatoscopy. In our case report, a 69-year-old man underwent an ERCP because of a pancreatic head mass and biliary tract obstruction. During ERCP, a fistula between the common bile duct (CBD) and main pancreatic duct (MPD) was suspected. After endoscopic sphincterotomy, we examined both the CBD and MPD with an ultra-slim videoendoscope (GIF-N260; Olympus Optical Co, Tokyo, Japan) under direct visualization and biopsy of the mass. The analysis of the biopsy specimen confirmed this mass to be an IPMN of the pancreas. When we examined the CBD, one fistula with copious mucin secretion was identified at the distal CBD. In conclusion, direct peroral cholangioscopy and pancreatoscopy using the ultra-slim endoscope is an efficient tool for diagnosis of PB fistula and pancreatic IPMN.

Invasive Carcinoma Arising in Intraductal Papillary Mucinous Neoplasms of the Pancreas

The purpose of this study was to characterize the clinicopathological features of invasive carcinomas arising in intraductal papillary mucinous neoplasms of the pancreas (IPMN) by histological subtype of the invasive component and to compare the outcomes of these patients to a cohort of matched patients with conventional ductal pancreatic adenocarcinoma. Two distinct histological subtypes of invasive carcinomas arising in IPMNs have been described, colloid carcinoma and tubular carcinoma. Previous reports have suggested prognostic differences between these 2 subtypes but a matched comparison of colloid carcinoma, tubular carcinoma, and conventional pancreatic adenocarcinoma has not been reported. The clinicopathological variables of 59 patients resected for an invasive component of IPMN were analyzed with detailed pathologic review of histopathologic subtype (colloid carcinoma and tubular carcinoma). Using a postresection pancreatic adenocarcinoma nomogram, patients with either tubular or colloid carcinoma were matched on a 1:1 basis with patients resected for conventional ductal pancreatic adenocarcinoma. Clinicopathological factors and overall outcome was analyzed between the matched groups. Fifty-nine patients underwent resection for IPMN with an associated invasive carcinoma (IPMN-INV). The estimated 3- and 5-year survival rates were 76% and 68%, respectively. Tubular carcinoma was present in 35 patients (59%) and 24 patients (41%) had colloid carcinoma. Tubular carcinoma subtype [hazard ratio (HR) 3.7, 95% confidence interval (CI) 1.2-11.6] and the presence of positive regional lymph nodes (HR 3.2 95% CI 1.2-8.2) were clinicopathological factors predictive of decreased survival by multivariate analysis. The 5-year estimated survival rates for tubular carcinoma and colloid carcinoma were 55% and 87%, respectively (P = 0.01). When compared with patients with conventional ductal pancreatic ductal adenocarcinoma resected during the same time period matched by a prognostic nomogram, patients with colloid carcinoma had a significantly longer survival outcome compared with patients with conventional adenocarcinoma (P = 0.0001). By contrast, survival after resection between patients with the tubular subtype (3-year estimated survival, 61%) and the matched group with conventional adenocarcinoma (3-year estimated survival, 21%) (P = 0.87) was not statistically different. In this study, the colloid carcinoma histological subtype of invasive IPMN had a more statistically favorable survival outcome than the tubular subtype. Patients with invasive tubular IPMN had no statistically significant difference in survival as matched patients with conventional ductal pancreatic carcinoma.

Intracystic CEA and Long-Term Follow-up of Intraductal Papillary Mucinous Neoplasm of the Pancreas (IPMN)

Intracystic CEA and Long-Term Follow-up of Intraductal Papillary Mucinous Neoplasm of the Pancreas (IPMN)

Genetic Markers of Malignant Transformation in IPMN of the Pancreas: A Meta-Analysis

Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has been recognized as an important precursor to pancreatic cancer. Since the WHO established a consensus in 1996 for grading IPMNs, numerous studies have characterized genetic mutations associated with these various histologic grades. However, the molecular basis for progression into cancer remains poorly understood. We hypothesize that malignant transformation of IPMN reflects a progression in molecular changes. To determine the risk of malignant transformation associated with specific genetic abnormalities, we performed themost comprehensive meta-analysis to date of genetic associations with IPMN grade. Methods: We conducted a meta-analysis reviewing Pubmed, Cochrane Library, and Embase databases from January 1996 thru October 2010. We included only studies that adhered to 1996 WHO guidelines for distinguishing adenoma and borderline IPMNs (IPM-A, IPM-B) vs. carcinoma in situ and invasive carcinoma (IPM-C) based on surgically resected specimens. Quantitative meta-analysis was performed of gene candidates using both fixedand random-effects models. The I2 test was used to evaluate study heterogeneity. Results: We identified 178 studies that satisfied the inclusion criteria (1,343 IPMN samples). In pooled analysis there was an overall positive association for IPM-C with MUC-1 expression (OR 5.90; 95% C.I. 2.5413.70), k-Ras mutations (OR 1.90; 95% C.I. 1.04-3.47), and p53 mutations (OR 2.00; 95% C.I. 0.80-4.98). The strongest positive association for IPM-C vs. IPM-A/B was with telomerase mutations (OR 15.95; 95% C.I. 6.32-40.25), consistent with this genetic abnormality occurring relatively later in the histologic progression of IPMN into cancer. Expression of MUC5AC was not associated with IPM-C vs. IPM-A/B (OR 0.71; 95% C.I. 0.23-2.23). We further summarize associations with 91 additional genes including Shh, Cox2, Smad4, APC, and S100A4 as well as findings from cyst and pancreatic fluid assays. Conclusion: This metaanalysis identifies MUC-1 expression and mutations in telomerase, p53 and k-Ras genes as molecular changes associated with IPMN progression to cancer. These associations provide a basis for the use of molecular markers in diagnostic grading of IPMNs as well as a basis for therapeutic targets.

Similarities and Differences Between Intraductal Papillary Tumors of the Bile Duct With and Without Macroscopically Visible Mucin Secretion

Intraductal papillary neoplasms of the bile duct (IPNB) have been recently proposed as the biliary counterpart of intraductal papillary mucinous neoplasms of the pancreas (IPMN-P). However, in contrast to IPMN-P, IPNB include a considerable number of the tumors without macroscopically visible mucin secretion. Here we report the similarities and differences between IPNB with and without macroscopically visible mucin secretion (IPNB-M and IPNB-NM). Surgically resected 27 consecutive cases with IPNB were divided into IPNB-M (n=10) and IPNB-NM (n=17), and their clinicopathologic features were examined. Clinically, both tumors were similar. Pathologically, the most frequent histopathologic types were pancreatobiliary in IPNB-NM and intestinal in IPNB-M. Various degrees of cytoarchitectural atypia within the same tumor were exhibited in 8 IPNB-M, but only 3 in IPNB-NM. Although the tumor size was similar, 9 IPNB-NM were invasive carcinoma, whereas all but 1 IPNB-M with carcinoma were in situ or minimally invasive. Immunohistochemically, positive MUC2 expression was significantly more frequent in IPNB-M than in IPNB-NM, whereas MUC1 tended to be more frequently expressed in IPNB-NM compared with IPNB-M. Among IPNB-NM with positive MUC1 expression, 3 had negative MUC2 and MUC5AC expressions. These tumors showed a tubulopapillary growth with uniform degree of cytoarchitectural atypia. All IPNB-M were negative for p53, and the frequency of positive p53 protein in IPNB-NM was at the middle level of that in IPNB-M and nonpapillary cholangiocarcinoma. In conclusion, IPNB-M showed striking similarities to IPMN-P, but IPNB-NM contained heterogeneous disease groups.

Use of endoscopic ultrasound scoring to estimate the malignant potential of branch duct type intraductal papillary-mucinous neoplasms of the pancreas.

182 Background: Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are characterized by intraductal papillary epithelial growth, mucin hypersecretion, and cystic dilation of main or branch pancreatic ducts. However, it is still difficult to differentiate between benign and malignant, when it only involves the branch duct. The purpose of this study was to evaluate the role of endoscopic ultrasound (EUS) scoring in predicting malignancy in branch-duct type IPMNs, thus providing a convenient guideline to a clinician before considering surgical resection. Methods: We retrospectively reviewed all patients between Dec 1997 and April 2010 who underwent diagnostic and/or preoperative EUS for IPMNs. Borderline malignancy and invasive carcinoma were defined as a malignancy. Results: Of the 32 patients (mean age, 62 years), 13 male and 19 female were identified. Twelve people underwent operation, and there were 23 benign cases, and 9 malignant cases (borderline, n=6; invasive carcinoma, n=3). Among the six parameters (age, cyst size, mural nodule, associated main pancreatic duct dilation, patulous opening, thick septum) that have been known as important parameters for predicting malignancy in main duct type IPMNs, four were significant by Fisher's exact tests—namely, cyst size (p=.002), mural nodule (p =.003), associated main pancreatic duct dilation (p =.001), patulous opening (p =.05). In sizing the cysts, we scored 0 (cyst size ≤10 mm), 1 (11-20 mm), 2 (21-30 mm), 3 (&gt;30 mm). In sizing the mural nodules, we scored 0 (no mural nodule), 1 (&lt;5 mm), 2 (5-&lt;10 mm), 3 (≥10 mm). For main pancreatic duct dilation, we scored 2, if there presented any associated main pancreatic duct dilation, and 0 if not. For the patulous opening, we scored 1 for present, 0 for not. Patients were dispersed from the highest score nine, to the lowest score zero. Mean score for benign cases was 2.47 (±1.59 SD), and 6.33 (±1.87 SD) for malignant cases (p =.001). Conclusions: We strongly recommend a radical surgery for patients scoring above 7(score 7, 8, 9), and a consideration of operation for scoring between 4 and 6, and careful follow up for scoring below 3. No significant financial relationships to disclose.

Extrapancreatic tumors in intraductal papillary mucinous neoplasm of the pancreas.

189 Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has a favorable prognosis, but seems to be associated with a high incidence of extrapancreatic tumors. The purpose of this study was to evaluate the incidence and clinicopathologic features of extrapancreatic tumors associated with IPMN compared with pancreas cancer. Methods: Thirty-seven patients with IPMN of the pancreas and eighty-four patients with pancreas cancer, confirmed by surgical resection and typical findings of endoscopic ultrasonography and CT imaging between October 1, 1998, and August 31, 2009, were included. All pancreas cancers were diagnosed with surgical resection and biopsy. These patients were examined for the development of extrapancreatic tumors. Results: Of 37 patients with IPMN, 14 (38%) had 18 extrapancreatic tumors, and 10 (27%) had 13 extrapancreatic malignancies. Five, six, and two extrapancreatic malignancies had been diagnosed before, during, and after the diagnosis of IPMN. Gastric adenocarcinoma (3 patients, 23%) and colorectal carcinoma (3 patients, 23%) were the most common neoplasms. Other extrapancreatic tumors included lung cancer (n=2), prostatic cancer (n=1), renal cell carcinoma (n=1), cholangiocellular carcinoma (n=1), urinary bladder cancer (n=1), and gallbladder cancer (n=1), respectively. As benign tumor, there were two gallbladder adenoma, one gastric adenoma, one colonic adenoma and one benign ovarian cystic neoplasm, respectively. On the other side, of 84 patients with pancreas cancer, 9 (10%) had 9 extrapancreatic tumors and 2 (2%) had extrapancreatic malignancies which were stomach cancer (n=1, 1%) and breast cancer (n=1, 1%) respectively. As benign tumor, there were colon adenoma (n=3), hepatic hemangioma (n=2), gastric adenoma (n=1), and uterine myoma (n=1). Conclusions: IPMN is associated with high incidence of extrapancreatic tumors, particularly gastric and colorectal neoplasm but pancreas cancer did not show associations with extrapancreatic tumor. Upper gastrointestinal endoscopy and colonoscopy should be done, and systemic surveillance for the possible occurrence of other tumors may allow early detection of extrapancreatic tumor in patients with IPMN. No significant financial relationships to disclose.

Immunohistochemical analysis of claudin expression in pancreatic cystic tumors

Aberrant expression of the claudin family of proteins has been reported in many human cancers, including pancreatic ductal carcinoma. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) and mucinous cystic neoplasms (MCN) are considered precancerous lesions that are able to progress towards pancreatic ductal adenocarcinoma. We analyzed the expression of several claudin family members using surgical IPMN and MCN specimens to clarify the relationships between claudin expression and clinicopathological features. Twenty-nine and 25 consecutive cases of IPMN and MCN were selected and the expression of claudin-2, -4 and -18 was analyzed by immunohistochemistry. In addition, IPMN and MCN histological grade as well as IPMN subtypes were analyzed in relation to claudin expression. The 29 cases of IPMN comprised of 3 (10.3%) adenomas, 18 (62.1%) borderline malignancies and 8 (27.6%) carcinomas. The 25 cases of MCN comprised of 13 (52%) adenomas, 5 (20%) borderline malignancies and 7 (28%) carcinomas. Claudin-2, -4 and -18 showed strong expression both in IPMN and MCN, with the exception of claudin-4 in MCN. The expression grades of claudin-2 in both IPMN and MCN became weaker with increased histological grade. On the other hand, the expression grades of claudin-4 and -18 became stronger with increased histological grade in both IPMN and MCN. With regard to histological subtype, claudin-4 expression was the strongest in pancreatobiliary type IPMN, and claudin-18 expression was the strongest in gastric type IPMN. The distinct expression patterns of claudin-2, -4 and -18 suggest that claudins may serve as useful molecular markers for tumor differentiation and progression in IPMN and MCN.

Molecular Pathogenesis of Intraductal Papillary Mucinous Neoplasms of the Pancreas

Over the last 3 decades, there have been substantial improvements in diagnostic imaging and sampling techniques to evaluate pancreatic diseases. The modern technology has helped us to recognize premalignant conditions of pancreas including mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMNs). Differentiation between benign and malignant lesions and early detection of any malignant transformation in premalignant lesion are extremely important for further management decisions. Diagnostic cytology has limited sensitivity to further differentiate between benign, premalignant, and malignant lesions of the pancreas. There is limited information about the epidemiological risk factors and molecular mechanisms leading to development and further progression to malignancy of IPMNs. Several studies have shown that pancreatic juice and pancreatic tissue from the lesion can be tested for molecular markers including K-ras, p53, and p16 to differentiate between cancer and chronic inflammatory process. We review cellular signaling pathways that contribute to pathogenesis of IPMNs of the pancreas to further identify potential biomarkers and molecular targets.

Pancreatic cyst fluid and serum mucin levels predict dysplasia in intraductal papillary mucinous neoplasms of the pancreas.

There are no reliable markers of dysplasia in patients with incidentally discovered intraductal papillary mucinous neoplasms of the pancreas (IPMN). IPMN dysplasia may be associated with mucin protein (MUC) expression and histopathologic subtype. We hypothesize that MUC expression in cyst fluid and serum can identify lesions with high risk of malignancy. Cyst fluid and serum were collected from 40 patients during pancreatectomy for IPMN between 2005 and 2009. Samples were grouped into low-risk (low-grade or moderate dysplasia, n = 21) and high-risk groups (high-grade dysplasia or carcinoma, n = 19). Mucin expression (MUC1, MUC2, MUC4, and MUC5AC) was assessed utilizing enzyme-linked immunosorbent assays. MUC2 and MUC4 cyst fluid concentrations were elevated in high-risk versus low-risk groups (10 ± 3.0 ng/ml vs. 4.4 ± 1.2 ng/ml, p = 0.03; 20.6 ± 10.6 ng/ml vs. 4.5 ± 1.4 ng/ml, p = 0.03, respectively). Corresponding serum samples revealed higher levels of MUC5AC in high-risk compared with low-risk patients (19.9 ± 9.3 ng/ml vs. 2.2 ± 1.1 ng/ml, p = 0.04). Histopathologic subtype was significantly associated with grade of dysplasia, and the intestinal subtype displayed increased MUC2 cyst fluid concentrations (13.8 ± 6.5 ng/ml vs. 4.1 ± 0.9 ng/ml, p = 0.02). In this study, high-risk IPMN showed elevated cyst fluid concentrations of MUC2 and MUC4, and increased serum levels of MUC5AC. High-risk IPMN also displayed a distinct mucin expression profile in specific histologic subtypes. These data, if validated, may allow surgeons to more appropriately select patients for operative resection.

P.3.e.005 Total blood cholesterol levels and serum creatine kinase activity in violent psychiatric inpatients

To evaluate the CT features of intraductal papillary mucinous neoplasms of the pancreas (IPMNs), and to compare with pathological findings in order to identify CT features that can be helpful in differentiating benign IPMNs from malignant IPMNs.The CT findings in 25 patients were reviewed for tumor location, tumor type, dilatation of the main pancreatic duct (MPD), MPD involvement, mural node or solid attenuating component, tumor size in branch duct or mixed duct type, dilatation of common bile duct (CBD) and invasion of surrounding structures. The data was subjected to Chi-Square Tests or Fisher's Exact Test using SPSS13.0 software with p value < 0.05 indicating significant statistical difference.Presence of mural node or solid enhancing component, size of mural node or solid enhancing component ≥7 mm, dilatation of CBD was more common in malignant IPMNs (p < 0.05). None of tumor location, tumor type, dilatation of MPD, MPD involvement, tumor size, and invasion of surrounding structures was statistically significant in differentiating benign from malignant IPMNs.CT features suggestive of malignant or invasive IPMNs include presence of mural node or solid enhancing component, size of mural node or solid enhancing component ≥7 mm, and dilatation of CBD.