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Background: Main duct intraductal papillary mucinous neoplasms (MD-IPMNs) may occur in 1 or multiple segments of the pancreatic duct. Unlike multifocal branch duct (BD)-IPMNs, the clonality of multisegmental MD-IPMNs remains unclear. GNAS mutations are common and specific for IPMNs, and mutational assessment might be useful to determine the clonality of IPMNs as well as to detect high-risk IPMN with distinct ductal adenocarcinoma (pancreatic ductal adenocarcinoma [PDAC]). Our aim was to clarify clonality using GNAS status in multisegmental MD-IPMNs., Methods: We retrospectively reviewed the medical records of 70 patients with MD-IPMN. Histologic subtypes and KRAS/GNAS mutations were investigated, and the clonal relationships among multisegmental MD-IPMNs were assessed. Mutational analysis was performed using high-resolution melting analysis and subsequent Sanger/pyrosequencing., Results: Thirteen patients had multiple synchronous and/or metachronous lesions. Seven of these 13 patients had multiple MD-IPMNs; 3 had multiple MD-IPMNs and distinct BD-IPMNs; 1 had multiple MD-IPMNs and a distinct PDAC; 1 had a solitary MD-IPMN, BD-IPMN, and PDAC; and 1 had a solitary MD-IPMN and PDAC. KRAS/GNAS mutations were consistent in 10 of 11 multisegmental MD-IPMNs, whereas MD-IPMNs, BD-IPMNs, and PDACs tended to show different mutational patterns. The frequency of malignant IPMNs was significantly higher in the multisegment cohort; malignant IPMNs constituted 90% (9/10) of the multiple cohort and 56% (32/57) of the solitary cohort (P = .04). Mutant GNAS was more frequently observed in the intestinal subtype (94%) than the others., Conclusion: MD-IPMNs can be characterized by monoclonal skip progression. Close attention should be paid to the possible presence of skip areas during or after partial pancreatectomy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas may have concomitant distinct pancreatic ductal adenocarcinoma (PDAC). We evaluated the safety and usefulness of intraoperative irrigation cytology of the remnant pancreas (IICP) during pancreatectomy to detect remnant distinct PDAC in patients with IPMN., Methods: The records of all 48 patients with IPMN who underwent IICP during partial pancreatectomy at our institution from April 2007 to March 2012 were reviewed retrospectively. After division of the pancreas, a 4-French tube was inserted into the main pancreatic duct of the remnant pancreas from the cut edge, and fluid for cytologic examination was obtained by saline irrigation through the tube. If the third IICP was positive, patients underwent additional pancreatic resection. Clinical and pathologic outcomes were evaluated., Results: The third IICP was positive in 5 patients. Postoperative pathologic examination showed that these patients all had remnant distinct PDAC in the additionally resected specimen, which was not detectable on preoperative imaging examination or on intraoperative macroscopic examination, ultrasonography, or palpation. This PDAC was stage 0 in 4 patients and stage III in 1 patient. No procedure-related complications were observed. One patient developed peritoneal metastasis after 10 months, 1 developed liver metastasis after 20 months, and 1 developed PDAC in the remnant pancreas after 24 months., Conclusion: IICP seems to be a safe and useful method for detection of early stage PDAC concomitant with IPMN that cannot be detected by preoperative imaging or intraoperative examination., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Pancreatic cancer is associated with a devastating prognosis, partially because of its aggressive metastatic ability. Identification of prognostic markers of metastasis would be useful in the clinical management of postoperative patients with pancreatic cancer. Mal, T-cell differentiation protein 2 (MAL2) has been identified as a molecule predictive of metastases; the clinical relevance of MAL2 in pancreatic cancer is unknown., Methods: Orthotopic human pancreatic cancer xenografts from the pancreatic cancer cell line SUIT-2 were established in nude mice. Only liver metastasis was harvested and cultured. These metastatic cycles were repeated 5 times to establish a highly metastatic cell line, termed metastatic SUIT-2 (MS). We investigated proliferation and motility of MS cells compared with those of the parent SUIT-2. Microarray analysis was performed to investigate differences in gene expression. We also performed immunohistochemical analysis of 89 formalin-fixed, paraffin-embedded human pancreatic cancer tissue samples to investigate the clinical significance of MAL2 expression., Results: MS cells showed a greater metastatic rate after orthotopic implantation than parental SUIT-2. MS cells had increased motility but decreased proliferation compared with parental SUIT-2. Microarray analyses showed that 26 genes were significantly upregulated (>10-fold) in MS cells compared with parental SUIT-2, particularly MAL2 expression. Immunohistochemical analysis showed that high expression of MAL2 was associated with a lesser survival of postoperative patients (P = .03) and a high rate of distant metastasis (P = .008)., Conclusion: We characterized a newly established pancreatic cancer cell line with highly metastatic potential. MAL2 is a promising predictive marker for distant metastasis and short survival in patients with resected pancreatic cancer., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: International consensus guidelines for the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas provide several factors that can be used to predict which IPMNs will become malignant.The sensitivity of each factor's predictive accuracy, however, is relatively low, making it difficult to determine the appropriate treatment in individual cases. The aim of this study was to investigate whether increasing the number of predictive factors might augment the sensitivity of the established guidelines to detect malignant IPMNs., Methods: The medical records of 138 patients with IPMNs resected at our institution were reviewed. Possible malignant predictors were analyzed by univariate and multivariate analysis, and the effects of the number of factors and the predictive score of the pathologic results were examined. The cutoff points for the number of predictors to discriminate between malignant and nonmalignant IPMNs were established by constructing receiver operating characteristic curves., Results: A predictive analysis could not be carried out for the main duct IPMNs because of the high prevalence of malignancy and the small number of significant predictors associated with them. For malignant branch duct IPMNs, however, we identified 4 predictive factors that helped determine the correct diagnosis as follows: (1) the presence of a cyst ≥30 mm in diameter; (2) the presence of mural nodules; (3) a history of acute pancreatitis; and (4) atypical results of pancreatic juice cytology. An increase in the number of these factors significantly affected the sensitivity to predict malignancy. The area under the curve for the number of predictors for malignant branch duct IPMNs was 0.856, and the sensitivity and specificity were 96% and 71%, respectively, when the cutoff point was set at 2. The predictive scoring system also showed the same values of sensitivity and specificity for the number of factors., Conclusion: Patients with branch duct IPMNs who have 2 or more of the 4 predictive factors described above should undergo standard pancreatectomy with lymph node dissection, whereas patients who present with 0 or 1 predictive factor can be treated by minimal pancreatectomy without nodal dissection or by careful observation without resection. All patients with main duct IPMNs, therefore, should be treated with resection as suspected malignancies., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Aim: We sought to evaluate the feasibility of the lateral approach for laparoscopic splenic vessel-preserving distal pancreatectomy (LA-SVPDP)., Background: Complete preservation of the splenic vessels is an ideal outcome in spleen-preserving distal pancreatectomy (SPDP). However, the preservation of the vessels is challenging in laparoscopic surgery because the splenic vein is often embedded in the pancreatic parenchyma. Herein we have described LA-SVPDP, the most feasible method for laparoscopic SPDP, and the outcome of our initial experience., Patients: Twenty-three patients underwent laparoscopic SPDP. Before we adopted LA-SVPDP, 8 patients underwent the Warshaw method and 6 underwent SVPDP. After the adoption of LA-SVPDP, 8 patients underwent LA-SVPDP and 1 donor underwent the Warshaw method., Results: None of patients undergoing LA-SVPDP required conversion to an open operation, whereas 2 patients undergoing the other procedures were converted to open operations. Five out of 8 patients who underwent the Warshaw method showed engorgement of the gastric veins, revealed by computed tomography. However, only 1 of the 5 patients showed mild gastric varices on endoscopy., Conclusion: Although the Warshaw method is acceptable with a low incidence of gastric varices in our analysis, SVPDP is a feasible approach for SPDP. Our LA-SVPDP technique may contribute to safer and easier SVPDP in laparoscopic surgery., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is divided into 4 subtypes: an intestinal type, a gastric type, a pancreatobiliary type, and an oncocytic type. The purposes of this study were to clarify the outcomes and the characteristics of invasive carcinoma derived from IPMN (invasive IPMC) by focusing on these subtypes with a comparison to conventional invasive ductal carcinoma (IDC) of the pancreas., Methods: A total of 30 patients with invasive IPMC were reviewed, and the tumors were divided into 2 pathologic subtypes, intestinal and nonintestinal type. The prognosis and characteristics of the 2 subtypes were evaluated. Furthermore, the prognosis of 119 patients with conventional IDC was compared with that of patients with invasive carcinoma derived from the intestinal or nonintestinal type IPMN., Results: The 5-year survival rate of patients with the nonintestinal type (0.0%) was as poor as that of patients with conventional IDC (19.9%; P = .67). The patients with the intestinal type (66.7%) had a more favorable prognosis than patients with conventional IDC (P < .001). The nonintestinal type was characterized by positive lymphatic invasion and tubular invasive pattern., Conclusion: Invasive carcinoma derived from the nonintestinal type IPMN characterized by lymphatic invasion and tubular invasive pattern is associated with a poor prognosis., (Copyright 2010 Mosby, Inc. All rights reserved.)

Background: Several neural and hormonal factors are known to affect the motility of the sphincter of Oddi. However, the precise mechanisms of the control of sphincter motility have not been completely explored. We investigated the relationship of canine biliary sphincter motility when it is extrinsically denervated by neural isolation of the pancreatoduodenal region., Methods: Interdigestive and postprandial sphincter motility in a denervated pancreatoduodenal segment and effects of cholecystokinin-octapeptide were studied in 7 conscious dogs. Data were compared with those of 7 neurally intact control dogs., Results: After extrinsic denervation of the pancreatoduodenal region, sphincter motility exerted a cyclic change in concert with the duodenal myoelectric cycles; this change involved short cyclic bursts of motor activity, which gradually increased in intensity. The increase in the cyclic bursts of motor activity was also cyclic and associated with an increase in the plasma motilin concentration. Neural isolation of the pancreatoduodenal region increased sphincter basal pressure and motility index (integral per minute). In the denervated biliary sphincter, the feeding pattern and temporary inhibitory effect of feeding, as seen in controls, were absent, which suggests the role of extrinsic nerves in delivering bile into the duodenum after feeding. In the denervated dogs, cholecystokinin-octapeptide caused excitation of the sphincter activity, instead of relaxation observed in controls., Conclusions: Extrinsic innervation to the pancreatoduodenal region has an inhibitory effect on biliary sphincter motility. Abnormalities in extrinsic innervation to the biliary sphincter might increase the resistance of the sphincter to the bile flow and induce bile stagnation.