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Due to the poor prognosis of pancreatic cancer, novel diagnostic modalities for early diagnosis and new therapeutic strategy are urgently needed. Recently, microRNA-21 (miR-21) was reported to be strongly overexpressed in pancreatic cancer as well as in other solid cancers. We investigated the functional roles of miR-21, which have not been fully elucidated in pancreatic cancer. miR-21 expression was assessed in pancreatic cancer cell lines (14 cancer cell lines, primary cultures of normal pancreatic epithelial cells and fibroblasts, and a human normal pancreatic ductal epithelial cell line) and pancreatic tissue samples (25 cancer tissues and 25 normal tissues) by quantitative real-time reverse transcription-PCR amplification. Moreover, we investigated the proliferation, invasion, and chemoresistance of pancreatic cancer cells transfected with miR-21 precursor or inhibitor. miR-21 was markedly overexpressed in pancreatic cancer cells compared with nonmalignant cells, and miR-21 in cancer tissues was much higher than in nonmalignant tissues. The cancer cells transfected with the miR-21 precursor showed significantly increased proliferation, Matrigel invasion, and chemoresistance for gemcitabine compared with the control cells. In contrast, inhibition of miR-21 decreased proliferation, Matrigel invasion, and chemoresistance for gemcitabine. Moreover, miR-21 positively correlated with the mRNA expression of invasion-related genes, matrix metalloproteinase-2 and -9, and vascular endothelial growth factor. These data suggest that miR-21 expression is increased in pancreatic cancer cells and that miR-21 contributes to the cell proliferation, invasion, and chemoresistance of pancreatic cancer.[Mol Cancer Ther 2009;8(5):1067–74]

Supplementary Table from MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance

Supplementary Figure Legends from MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance

Supplementary Fig. from MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance

Background Elevated bile amylase level in patients with pancreaticobiliary maljunction (PBM) or high confluence of pancreaticobiliary ducts (HCPBD) is well known as a risk factor for gallbladder carcinoma (GBC) development. However, the effects of occult pancreaticobiliary reflux (OPR), a condition characterized by high bile amylase level in the presence of an anatomically normal pancreaticobiliary junction, on GBC development remain unclear. The aim of this study was to assess the relationship between OPR and GBC. Methods Clinicopathological data of 52 patients who were preoperatively diagnosed with gallbladder (GB) tumor (22 malignant, 30 benign) were retrospectively reviewed. All of the patients underwent preoperative endoscopic retrograde cholangiopancreatography to evaluate pancreaticobiliary junction morphology and bile amylase level. The relationship between the histological diagnosis of GB lesions, and pancreaticobiliary junction morphology and bile amylase level were investigated. Results PBM, HCPBD, and normal pancreaticobiliary junction (NPJ) were identified in 12, 9, and 31 patients, respectively. The rates of GBC in patients with PBM, HCPBD, and NPJ were 58% (7/12), 67% (6/9), and 29% (9/31), respectively. Of the 31 patients with NPJ, 22 had OPR and 9 of these had GBC. None of the patients with NPJ and normal bile amylase level had GBC. Additionally, among patients with NPJ, bile amylase level was significantly higher in patients with GBC than in patients with benign tumors. Conclusions OPR, like PBM and HCPBD, is a risk factor for GBC development. This article is protected by copyright. All rights reserved.

A woman in her 70s developed deep vein thromboembolism(DVT)and pulmonary embolism(PE)during chemotherapy for advanced transverse colon cancer. After the first treatment with heparin and warfarin, the anticoagulant was changed to edoxaban to reduce the risk of bleeding. She continued receiving chemotherapy for 4 years. We recommend edoxaban as the first choice of anticoagulant for patients with DVT and PE requiring chemotherapy with fluoropyrimidine-based antineoplastic agents.

As a strategy to diagnose early-stage pancreatic ductal adenocarcinoma (PDAC) is urgently needed, we aimed to clarify characteristics of early-stage PDAC.We retrospectively reviewed medical records of 299 consecutive patients who underwent R0 or R1 surgical resection for PDAC between 1994 and 2013 and compared clinical characteristics between patients with early-stage (stages 0-I by Japanese General Rules for Pancreatic Cancer) and advanced-stage (stages II-IV) disease. Diagnostic processes were also analyzed.Twenty-four patients (8%) had early-stage PDAC (stage 0: 11; stage I: 13). Univariate and multivariate analyses showed that presence or history of intraductal papillary mucinous neoplasm (P0.01), history of pancreatitis (P0.01), and presence or history of extrapancreatic malignancies (P = 0.01) independently predicted detection of early-stage PDAC. Cytological examination during endoscopic retrograde pancreatography cytology was ∼65% sensitive in preoperative diagnosis of early-stage PDAC, whereas other imaging modalities were only 29% to 38% sensitive; 9 of 24 early-stage PDACs were diagnosed by endoscopic retrograde pancreatography cytology alone.Endoscopic retrograde pancreatography cytology for patients with intraductal papillary mucinous neoplasm or pancreatitis may help diagnose early-stage PDAC. Surveillance of extrapancreatic malignancies might also provide opportunities to detect early-stage PDAC as a second malignancy.

Live demonstration of endoscopy is one of the most attractive and useful methods for education and is often organized locally in hospitals. However, problems have been apparent in terms of cost, preparation, and potential risks to patients. Our aim was to evaluate a new approach to live endoscopy whereby remote hospitals are connected by the Internet for live endoscopic demonstrations. Live endoscopy was transmitted to the Congress of the Japan Gastroenterological Endoscopic Society by 13 domestic and international hospitals. Patients with upper and lower gastrointestinal diseases and with pancreatobiliary disorders were the subjects of a live demonstration. Questionnaires were distributed to the audience and were sent to the demonstrators. Questions concerned the quality of transmitted images and sound, cost, preparations, programs, preference of style, and adverse events. Of the audience, 91.2% (249/273) answered favorably regarding the transmitted image quality and 93.8% (259/276) regarding the sound quality. All demonstrators answered favorably regarding image quality and 93% (13/14) regarding sound quality. Preparations were completed without any outsourcing at 11 sites (79%) and were evaluated as 'very easy' or 'easy' at all but one site (92.3%). Preparation cost was judged as 'very cheap' or 'cheap' at 12 sites (86%). Live endoscopy connecting multiple international centers was satisfactory in image and sound quality for both audience and demonstrators, with easy and inexpensive preparation. The remote transmission of live endoscopy from demonstrators' own hospitals was preferred to the conventional style of locally organized live endoscopy.

The cell surface protein Transmembrane 4 L6 family member 1 (TM4SF1) has been detected in various tumors, and its expression on tumor cells is implicated in cancer cell metastasis and patient prognosis. The role of TM4SF1 in malignant tumors remains poorly understood, particularly in pancreatic cancer. We performed immunohistochemical staining to analyze the expression of TM4SF1 in resected pancreatic tissues and investigated the correlation between TM4SF1 expression and prognosis. The function of TM4SF1 in the invasion and migration of pancreatic cancer cells was analyzed in vitro using an RNA interference technique. In pancreatic cancer tissues, TM4SF1 expression was detected in cancer cells, and patients with high tumor levels of TM4SF1 showed longer survival times than those with low TM4SF1 levels (P=0.0332). In vitro, reduced TM4SF1 expression enhanced the migration (P

The aims of this study were to investigate the GNAS mutational status in pancreatic intraductal papillary mucinous neoplasm (IPMN) with and without distinct pancreatic ductal adenocarcinoma (PDAC) and to evaluate the significance of GNAS analysis using duodenal fluid (DF) in patients with IPMN.The clinicopathologic features of 110 patients with IPMN including 16 with distinct PDAC were reviewed. The GNAS status in the IPMN tissue and 23 DF specimens was assessed by sensitive mutation scanning methods.The GNAS mutation rate in IPMN with distinct PDAC was significantly lower than that in IPMN without PDAC (4/16, 25%, vs 61/94, 65%; P = 0.0047). By multivariate analysis, GNAS wild-type and gastric type IPMNs were significantly associated with distinct PDAC. Of 45 GNAS wild-type IPMNs, 10 (43%) of 23 gastric type IPMNs had distinct PDAC, whereas only 2 (9%) of 22 non-gastric type IPMNs had distinct PDAC (P = 0.017). The GNAS status in DF was consistent with that in tissue in 21 (91%) of 23 patients.Distinct PDACs frequently develop in the pancreas with gastric type IPMN without GNAS mutations. Duodenal fluid DNA test would predict the GNAS status of IPMN, whereas the detection of the gastric subtype using noninvasive test remains to be determined.

Although autoantibodies to cancer antigens are candidates for biomarkers, no comprehensive studies to detect cancer-specific antibodies have been performed. This study identified autoantibodies in the sera of pancreatic cancer (PC) patients using proteomics based on a wheat germ cell-free protein production system. We constructed a biotinylated protein library of 2,183 genes. Interactions between biotinylated proteins and serum antibodies were detected by AlphaScreen® assay. Relative luminescence signals of each protein in 37 PC patients and 20 healthy controls were measured, and their sensitivity and specificity for PC were calculated. Luminescence signals of nine proteins were significantly higher than those of healthy controls, with calcium and integrin binding 1 (CIB1) protein showing the greatest significance (p = 0.002). Sensitivity, specificity, positive predictive value and negative predictive value of CIB1 autoantibody alone for PC were 76, 70, 82, and 61 %, respectively, and 97, 35, 74, and 88 %, respectively, when the four most significant proteins were combined. Presence of these autoantibodies did not vary significantly with other clinicopathological characteristics. Several autoantibodies, including CIB1, are potential biomarkers for PC.

We herein present a 71-year-old man who underwent pancreatoduodenectomy with the diagnosis of follicular pancreatitis. We could not completely deny malignancy by a preoperative imaging study. Endoscopic ultrasonography-guided fine needle aspiration biopsy demonstrated clusters of benign acinar cells and no proliferation of atypical lymphoid cells or rich plasma cells. Histologically, the prominent lymphoid follicle formation was seen in an ill-defined mass, 15 mm in size, in the pancreatic parenchyma. Duct-centered fibrotic rims were seen in the pancreatic ducts accompanied by mild fibrotic change between the follicles and obliterative phlebitis. No neoplastic epithelial cells were observed in the resected specimen, and infiltrating lymphocytes did not show any morphological atypia and monoclonal proliferation by immunohistochemical staining with B and T cell markers. In addition, we could exclude IgG4-related disease, because plasmacytic cells were rarely positive for IgG4. Although follicular pancreatitis is rare, this mass-forming inflammatory disease (pancreatitis) should be included in the preoperative differential diagnosis of pancreatic cancer.

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.

OBJECTIVES CD105 expression correlates with prognosis for several cancers. However, its significance in pancreatic cancer is unclear. METHODS We analyzed CD105 expression in resected pancreatic cancer tissue and pancreatic cancer cell lines, compared the properties of CD105(+) and CD105(-) cells using quantitative RT-PCR and migration assays, and evaluated the relationship between CD105(+) cells and pancreatic stellate cells (PSCs). RESULTS Immunohistochemistry showed that the frequency of CD105 expression was higher in pancreatic cancer than that in normal tissue(8% vs 0%, respectively). In flow cytometry, CD105 was expressed in pancreatic cancer cells, whereas weak CD105 expression was detected in normal pancreatic ductal epithelial cells. Quantitative RT-PCR showed that E-cadherin mRNA expression was suppressed and vimentin mRNA was overexpressed in CD105(+) cells (P < 0.05). Migration of CD105(+) cancer cells was strongly enhanced (more than that of CD105(+) cells) in coculture with PSCs (P < 0.05). CD105 expression did not correlate to clinicopathologic characteristics or the Kaplan-Meier survival analysis. CONCLUSIONS Suppression of an epithelial marker and over expression of a mesenchymal marker suggest that epithelial-mesenchymal transition is induced in CD105(+) pancreatic cancer cells. CD105(+) pancreatic cancer cell migration is strongly enhanced by PSCs, suggesting that these cells play a role in the pancreatic cancer microenvironment.

Background It is difficult to predict the malignant potential of pancreatic neuroendocrine tumors (PNETs) precisely. This study investigated the validity of a new grading system adopted by the World Health Organization 2010 classification to determine risk factors for recurrence of PNETs. Methods Data of 70 patients with PNETs who underwent curative resection were retrospectively examined by uni- and multivariate analyses. Histopathological findings were re-reviewed by experienced pathologists. NET G1 was defined as mitotic count

Recent improvements in diagnostic modalities are increasing the frequency of detection of small-sized branch duct intraductal papillary mucinous neoplasms (BD-IPMNs). International consensus guidelines for IPMN recommend surveillance without immediate resection for small-sized (

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.

Intraductal papillary mucinous neoplasms (IPMN) are drawing more attention and being detected more frequently. This review focuses on current understanding of the management of IPMN, regarding morphological classification, subclassification by cell lineage features, molecular abnormalities, radiological and imaging evaluation, progression to cancer, incidence and risk factors for malignancy, risk of distinct pancreatic adenocarcinoma and extrapancreatic malignancies, treatment strategy, and types of surgical resection. In particular, missing links in solving the IPMN puzzles are described with regard to differential diagnosis, role of cyst fluid analysis, multifocal IPMN, histological evaluation of the surgical specimen, observation without resection, follow up of patients after resection, role of adjuvant therapy for invasive carcinoma, screening for other neoplasms in patients with IPMN on follow up, prognostic factors influencing long-term outcomes, and role of endoscopic therapy.

OBJECTIVES: Branch duct intraductal papillary mucinous neoplasms of the pancreas (BD-IPMNs) often are composed of multifocal lesions. We aimed to clarify the clinicopathologic features of multifocal BD-IPMNs. METHODS: Medical records of 211 patients with BD-IPMNs (169 solitary and 42 multifocal) were retrospectively analyzed. We compared the pathological grade of resected IPMNs and the resulting clinical course between solitary and multifocal BD-IPMNs. RESULTS: Sixty-nine patients (54 with solitary and 15 with multifocal BD-IPMNs) underwent pancreatectomy, and of these patients, 62 exhibited at least 1 malignant predictor. There was no significant difference in the prevalence of malignancy in the resected BD-IPMNs between the 2 groups. In the remaining 142 patients who exhibited no malignant predictors, both groups demonstrated no differences in morphologic changes of BD-IPMNs. Seventeen distinct ductal carcinomas were identified in both groups, and there was no difference in the prevalence of ductal carcinoma between the 2 groups. Moreover, there was no significant difference in the disease-specific survival rate between the 2 groups. CONCLUSIONS: In patients with multifocal BD-IPMNs, resection is only warranted for lesions that exhibit malignancy predictors; moreover, closer attention to the potential presence or development of distinct ductal carcinoma in patients with multifocal and solitary BD-IPMNs is warranted.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is often found with distinct pancreatic ductal adenocarcinoma (PDAC) in the same pancreas. The aim of this study was to clarify whether endoscopic retrograde pancreatography (ERP) would be useful for the early detection of concomitant PDACs in patients with IPMNs.Medical records of 179 patients who were histologically confirmed to have IPMNs after resection between 1987 and 2011 were reviewed. The patients having concomitant PDACs were selected, and the diagnostic abilities to detect concomitant PDACs of computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS), and ERP were compared between early (stages 0-I according to Japanese General Rules for Pancreatic Cancer) and advanced (stages II-IV) PDACs.A total of 23 PDACs developed synchronously or metachronously in 20 patients, and the prevalence of PDACs concomitant with IPMNs was 11.2 % (20/179). Sensitivities of CT (16 vs. 87 %), MRI (29 vs. 93 %), and EUS (29 vs. 92 %) in the early group were significantly lower than those in the advanced group (p0.01). On the other hand, the sensitivity of ERP in the early group was as high as that in the advanced group (86 vs. 82 %, respectively, p0.99). Among 7 early PDACs, 3 were diagnosed only by ERP.ERP has an important role in the early diagnosis of distinct PDACs in patients with IPMNs. Further investigation is necessary to clarify the indication and the timing of ERP during management of IPMNs in term of early detection of concomitant PDACs.

Background Frequency and characteristics of metachronous occurrence of multifocal intraductal papillary mucinous neoplasms (IPMNs) or distinct pancreatic ductal adenocarcinomas (PDACs) in the remnant pancreas during follow-up evaluation after pancreatectomy for IPMNs have not been well known. The aim of this study was to investigate the outcomes after resection of IPMNs, especially focusing on the metachronous occurrence of multifocal IPMNs and distinct PDACs. Methods Medical records of 172 patients who underwent resection of IPMNs were reviewed retrospectively, and the data regarding the occurrence of metachronous IPMNs or PDACs in the remnant pancreas during a mean postoperative follow-up period of 64 months were collected. Results The incidence including synchronous and metachronous multifocal occurrence of IPMNs was 20% (34 of 172), and that of distinct PDACs was 9.9% (17 of 172). Ten metachronous IPMNs developed in the remnant pancreas after a mean time of 23 postoperative months (range, 12–84 mo), and 2 with main duct IPMNs (both were carcinoma in situ) required remnant pancreatectomy. Six distinct PDACs developed in the remnant pancreas after a mean time of 84 postoperative months (range, 12–150 mo). Four of them were found to have a tumor with a size of less than 2 cm, whereas the remaining 2 PDACs were found to be unresectable more than 10 years after resection of IPMNs. Conclusions Intense long-term follow-up evaluation is necessary for the early detection of metachronous occurrence of distinct PDACs as well as malignant IPMNs after resection of IPMNs.

Because of the rarity and variety of pancreatic neuroendocrine tumors (PNETs), there have been few reports regarding the indication for lymph node dissection in patients with these tumors. This study aimed to evaluate the risk of lymph node metastasis of PNETs based on the tumor size and hormonal production.Data for a total of 66 patients who had PNETs resected at our department between 1987 and 2010 were retrospectively studied. The clinicopathological features, including the disease-specific survival rate, were assessed based on the status of lymph node metastasis at the time of initial surgical resection. Then the cut-off point of tumor size to predict lymph node metastasis was estimated.There were 12 patients (18%) with lymph node metastasis. The frequency of lymph node metastasis tended to be higher in gastrinomas than that in other tumors (43 vs. 15%; P = 0.08). The size of PNETs with lymph node metastasis was significantly larger than that of the PNETs without metastasis (P = 0.04). The postoperative survival rate in the PNET patients with lymph node metastasis was significantly lower than that in the patients without metastasis (P0.0001). Only 2 (8%) of 26 PNETs with a tumor size of15 mm had lymph node metastasis, and both of these were gastrinomas. On the other hand, 10 (25%) of the remaining 40 PNETs with a tumor size of ≥15 mm had lymph node metastasis. Notably, there were no PNETs with lymph node metastasis in 22 non-gastrinomas with a tumor size of15 mm.Non-gastrinomas with a tumor size of ≥15 mm and all gastrinomas would be an indication for pancreatectomy with lymph node dissection.

Although patients with cholecystocholedocholithiasis are generally referred to cholecystectomy after endoscopic sphincterotomy (ES) and common bile duct clearance, we often have a conflict whether cholecystectomy is necessary in very elderly patients with comorbid diseases. The aim of this study is to assess whether cholecystectomy in very elderly patients is justified after ES.Patients with cholecystocholedocholithiasis who underwent ES and stone extraction and were followed-up for more than 10 years were retrospectively reviewed. We divided these patients into two groups: the elderly group (equal to or more than 80 years old) and young group (less than 80 years old) and compared late biliary complications and mortality.The 10-year cumulative incidence of overall biliary complications was significantly lower in cholecystectomized patients than in patients with gallbladder in situ in the young group (7.5 vs. 21.7%, p = 0.0037), but not different in the elderly group (8.3 vs. 7.4%, p = 0.92). When each complication was evaluated separately, the rate of recurrent common bile duct stones (CBDS) was not different, but that of acute cholecystitis was significantly lower in the elderly group than in the young group (4.1 vs. 22.6%, p = 0.011).In very elderly patients the incidence of acute cholecystitis is low even when the gallbladder is preserved after endoscopic treatment of CBDS, with a similar risk of CBDS recurrence. Thus, it may not be necessary to recommend cholecystectomy after ES for CBDS in very elderly patients.

本例は56歳女性，誘因なく突然の左上腹部痛を自覚し近医で白血球数とCRPの上昇を指摘された．CTで膵周辺に2つの嚢胞（膵尾部；13cm単房性，噴門部左後方；7cm多房性）と左側に胸水を認めた．2ヶ月後のCTで膵尾部嚢胞は変化なかったが，後腹膜多房性嚢胞は縮小し炎症反応も軽減した．また，腫瘍マーカーはCA19-9が200867U/ml と569.7U/ml の間を1ヶ月毎に大きく増減した．膵炎の可能性もあったが，CA19-9と共に一時的にCEAも240.6ng/ml と上昇し，膵尾部の大きな嚢胞には変化がないことから，膵炎を伴う膵粘液性嚢胞腺癌の可能性も考え，膵体尾部切除術を行った．病理診断では異型を示す粘液産生性の腫瘍細胞が間質浸潤をきたし，嚢胞周囲に卵巣様間質を認めることから浸潤性粘液性嚢胞腺癌であった．粘液性嚢胞腺癌でも膵管への浸潤により膵炎で発症することがあり注意が必要である．

Biliary diverticulum or type II congenital biliary dilation accounts for only 1-2% of all patients with congenital biliary dilation. The association between pancreaticobiliary maljunction (PBM) and this type of anomaly remains unclear. A 40-year-old Japanese woman presented with a history of repeated upper abdominal pain for more than 30 years. Computed tomography showed a cystic lesion (diameter 30 mm) arising from the common bile duct. Magnetic resonance cholangiopancreatography revealed a biliary diverticulum (diameter 33 mm) and the cystic duct entering the diverticulum. There was no dilation of the intrahepatic or extrahepatic ducts. Endoscopic retrograde cholangiopancreatography demonstrated PBM. A diagnosis of type II biliary diverticulum with PBM was made, and the patient underwent laparoscopic resection of the diverticulum combined with cholecystectomy. Pathological examination of the resected specimen showed slight inflammation, but no malignancy in the diverticulum or gallbladder. The patient's postoperative course was uneventful. To our knowledge, this is the first report of successful laparoscopic resection of biliary diverticulum associated with pancreaticobiliary maljunction.

Identification of prognostic markers would be useful in the clinical management of patients with pancreatic ductal adenocarcinoma (PDAC). The clinical relevance of claudin-4 (CLDN4), recently identified as overexpressed in PDAC, is unknown. Using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), we analyzed CLDN4 mRNA expression in a panel of 9 pancreatic cancer cell lines and formalin-fixed paraffin-embedded (FFPE) tissues from 100 patients with PDAC. The CLDN4 expression levels were then correlated with clinicopathological variables and patient outcome. We also performed immunohistochemical analysis in 20 FFPE samples of PDAC to investigate the expression of CLDN4 protein. Increased expression of CLDN4 was confirmed in all the pancreatic cancer cell lines tested compared with normal ductal epithelial cells and fibroblasts. We found that low expression of CLDN4 was significantly associated with shorter survival in patients with PDAC (hazard ratio; 1.362, 95% confidence interval; 1.011–1.873, P = 0.0419). Patients with high CLDN4 expression survived longer for a median of 63.0 months, compared with 14.7 months in patients with low CLDN4 expression (P = 0.0067). In immunohistochemical analysis, the level of CLDN4 mRNA expression was significantly correlated with the expression of CLDN4 protein (P = 0.0168). Increased expression of CLDN4 mRNA predicts better prognosis in PDAC.

Objective To evaluate the prevalence of circumportal pancreas (CP) and any coexisting anomaly. In addition, three cases of surgically confirmed CP are presented. Methods The study group consisted of 317 consecutive potential liver transplant donor candidates who had undergone thin-section MDCT studies for the evaluation of vascular anatomy. MDCT images were retrospectively reviewed to assess the presence or absence of CP. If CP was present, the transverse diameter of the aberrant pancreatic tissue was measured on axial images, and the course of the main pancreatic duct (MPD) was classified into ante-portal (normal) or retro-portal. In addition, the prevalence of variant hepatic arterial anatomy was compared between cases with and without CP. Results Eight of 317 liver transplant donor candidates (2.5%) were found to have CP at CT. The transverse diameter of the aberrant pancreatic tissue ranged from 5 to 18 mm (mean ± SD: 10 ± 4 mm). One of eight (12.5%) showed the MPD to be retro-portal. A variant hepatic artery was noted in two of the of eight (25%) patients, which was similar to the finding for those without CP [72 out of 309 (23%)]. Conclusion The prevalence of circumportal pancreas was 2.5%.

Background/Aims: There are several reports regarding intraductal papillary mucinous neoplasms (IPMNs) detected after the occurrence of acute pancreatitis. Although the presence of symptoms is regarded as a factor for predicting malignant IPMNs, there have been few reports demonstrating whether a history of acute pancreatitis is a predictor of malignancy. The aim of this study was to evaluate the relationship between a history of acute pancreatitis and clinicopathological features of IPMNs including the papillary subtype. Methods: The data of 150 IPMNs resected between 1990 and 2009 were retrospectively reviewed. They were classified into IPMNs with or without history of acute pancreatitis, and then the clinicopathological features were compared between the 2 groups. Results: Nineteen (13%) of the 150 patients had a history of acute pancreatitis. Nine of them had repeated episodes of pancreatitis; however, severe pancreatitis was uncommon. The diameter of the main pancreatic duct of the pancreatitis group was significantly larger than that of the nonpancreatitis group (p = 0.04). The pancreatitis group had a significantly higher frequency of carcinoma derived from IPMNs than the nonpancreatitis group (p = 0.03). The incidence of intestinal-type IPMNs in the pancreatitis group was significantly higher than that in the nonpancreatitis group (p Conclusion: Acute pancreatitis associated with IPMNs could predict malignant intestinal-type tumor.

With the rapid and marked progress in gastrointestinal endoscopy, the education of doctors in many new diagnostic and therapeutic procedures is of increasing importance. Telecommunications (telemedicine) is very useful and cost-effective for doctors’ continuing exposure to advanced skills, including those needed for hepato-pancreato-biliary diseases. Nevertheless, telemedicine in endoscopy has not yet gained much popularity. We have successfully established a new system which solves the problems of conventional ones, namely poor streaming images and the need for special expensive teleconferencing equipment. The digital video transport system, free software that transforms digital video signals directly into Internet Protocol without any analog conversion, was installed on a personal computer using a network with as much as 30 Mbps per channel, thereby providing more than 200 times greater information volume than the conventional system. Kyushu University Hospital in Japan was linked internationally to worldwide academic networks, using security software to protect patients’ privacy. Of the 188 telecommunications link-ups involving 108 institutions in 23 countries performed between February 2003 and August 2009, 55 events were endoscopy-related, 19 were live demonstrations, and 36 were gastrointestinal teleconferences with interactive discussions. The frame rate of the transmitted pictures was 30/s, thus preserving smooth high-quality streaming. This paper documents the first time that an advanced tele-endoscopy system has been established over such a wide area using academic high-volume networks, funded by the various governments, and which is now available all over the world. The benefits of a network dedicated to research and education have barely been recognized in the medical community. We believe our cutting-edge system will be a milestone in endoscopy and will improve the quality of gastrointestinal education, especially with respect to endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography (EUS) procedures.

Repeated pancreatectomy for pancreatic carcinoma is extremely rare. We report two such patients who underwent pancreatectomy for carcinoma developing in the pancreatic remnant after pylorus-preserving pancreatoduodenectomy (PpPD) for invasive pancreatic ductal carcinoma. One patient underwent PpPD for invasive pancreatic ductal carcinoma and received adjuvant chemotherapy. Follow-up computed tomography (CT) demonstrated a low-density mass in the remnant pancreas, which was diagnosed as a carcinoma by endoscopic ultrasound-guided fine-needle aspiration cytology 5 years 10 months after PpPD. She underwent curative resection of the remnant pancreas and is alive and well 13 months after the second operation. The other patient underwent PpPD for invasive pancreatic ductal carcinoma. Follow-up CT showed a low-density mass in the remnant pancreas after 2 years 11 months. He received systemic chemotherapy with S-1 for 3 months. The tumor shrank, and the patient underwent curative resection of the remnant pancreas 3 years 1 month after the initial operation. Repeated pancreatectomy may provide a chance of long survival for patients with carcinoma developing in the remnant pancreas after pancreatectomy if the recurrence occurring at long term is limited to the remnant pancreas.

Laparoscopic distal pancreatectomy (LDP) has been shown to be an effective surgical option for benign lesions in the body and tail of the pancreas. However, its advantages and disadvantages have not been well characterized. In this study, we compared the outcomes of LDP and open pancreatectomy performed in our clinic.Peri- and postoperative outcomes were retrospectively compared between patients with benign pancreatic disorders who underwent open distal pancreatectomy (ODP) (n = 35) and those who underwent LDP (n = 40). The peri- and postoperative factors analyzed included operative time, blood loss, hospital stay, postoperative recovery, biochemical findings, and complications.LDP was associated with significantly less operative blood loss (363 versus 606 mL; P = 0.001) and shorter hospital stay (22 versus 27 day; P = 0.009), but longer operative time (342 versus 250 min; P = 0.000), compared with ODP. There were no significant differences between the two groups in complication rates or postoperative recovery, except for the significantly shorter duration of postoperative pain-killer intake and earlier improvement of the biochemical analysis in LDP than in ODP.LDP appears to be a safe, desirable procedure for the management of benign pancreatic diseases, with outcomes similar to ODP.

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.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.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.Invasive carcinoma derived from the nonintestinal type IPMN characterized by lymphatic invasion and tubular invasive pattern is associated with a poor prognosis.

Prevention of iatrogenic injuries is of paramount importance in difficult laparoscopic cholecystectomies (LC). The objective of this study was to analyze the effectiveness of cholangiography using a pre-inserted endoscopic naso-biliary drain (ENBD) for navigation during difficult cholecystectomies. The study design was a retrospective case analysis. In 508 patients who underwent LC in a tertiary referral university hospital from 1996 through 2007, difficult cholecystectomy was anticipated in 26 patients due to possibly aberrant biliary anatomy (four patients), unclear cystic duct anatomy during magnetic resonance cholangiopancreatography (MRCP) and/or endoscopic retrograde cholangiopancreatography (ERCP) (three patients), and acute cholecystitis (19 patients). An ENBD was inserted during ERCP prior to LC for cholangiography (ENBDC) to facilitate safe dissection during LC. Prevalence of biliary complications was assessed as the main outcome measurement. The majority (68%) of the patients who underwent ENBDC had complicated cholecystitis. Advanced technical expertise was not required for insertion of an ENBD. In retrospect, ENBDC was useful in prevention of a possible catastrophe in 69% of cases. Open conversion was necessary in five patients and biliary complications occurred in five patients only in the non-ENBD group. There were no procedure-related complications. One limitation of the study was that it was not randomized and there was no comparison with patients without ENBDC. ENBDC is a useful and safe tool in the prevention of iatrogenic bile duct injuries in LC.

症例は50歳，男性．以前より慢性石灰化膵炎を指摘されていた．腹痛のため近医受診したところ，膵仮性嚢胞の増大を認め，当院内科入院となった．胃後壁膵仮性嚢胞に対して超音波内視鏡下嚢胞ドレナージが施行されたが，十分に奏効しなかった．右上腹部痛，高アミラーゼ血症が持続するため，手術目的に当科転科となった．CT, MRIで，膵頭部および膵尾部に仮性嚢胞を認めた．また，主膵管内に多数の結石とその上流の主膵管拡張を認めた．膵頭部の仮性嚢胞に対しては嚢胞空腸吻合術を，膵尾部の仮性嚢胞に対しては，経胃的嚢胞胃吻合術を施行した．さらに，膵管ドレナージは膵臓と胃が強固に癒着していたため，経胃的アプローチにて，術中エコー下に拡張した主膵管を同定し，膵管胃吻合術を行った．術後経過は良好であった．経胃的膵管胃吻合術の報告例はなく，膵前面に到達できない癒着のある症例では膵管ドレナージの1つの有用な術式である．

PurposeMidkine (MK) has been reported to be a possible molecular marker for the diagnosis of pancreatic cancer. We investigated the feasibility of quantitative analysis of MK mRNA by quantitative real-time RT-PCR (qRT-PCR) as a promising tool for the diagnosis of pancreatic cancer. Results We found that pancreatic cancer tissues expressed significantly higher levels of MK mRNA than intraductal pancreatic mucinous neoplasm (IPMN) and non-neoplastic pancreatic tissues (P < 0.05); in contrast, we did not find any differences in MK mRNA expression between IPMN and non-neoplastic pancreatic tissues. Additionally, we observed that poorly differentiated carcinoma samples expressed higher levels of MK mRNA than well-differentiated carcinoma samples, although a significant difference was not observed. Conclusions The present data suggests that quantitative analysis of MK mRNA provides an objective and sensitive evaluation and may be a promising modality for the diagnosis of pancreatic cancer and the prediction of its prognosis.

To clarify the usefulness of molecular biomarkers for distinguishing invasive carcinoma derived from intraductal papillary mucinous neoplasms (IPMNs [Inv-IPMN]) from concomitant pancreatic ductal adenocarcinoma (PDAC).Data from 19 patients with resected concomitant PDAC were retrospectively reviewed. KRAS/GNAS mutations and immunohistochemical (IHC) expression of p53 and p16/CDKN2A were assessed in both IPMN and distinct PDAC. As controls, KRAS/GNAS mutations and IHC labeling were assessed between invasive and noninvasive components in 1 lesion of 22 independent patients.KRAS/GNAS mutation status of invasive and noninvasive components in Inv-IPMN was consistent in 18 (86%) of 21 patients. Conversely, mutational patterns in IPMN and distinct PDAC in the same pancreas differed from each other in 17 (89%) of 19. There were 10 (53%) and 8 (42%) of 19 patients who showed the same p53 and p16/CDKN2A staining between concomitant PDAC and distinct IPMN. In the Inv-IPMN cohort, 19 (86%) of 22 patients showed the same IHC expression pattern between the noninvasive and invasive components.It may be possible to distinguish Inv-IPMN from concomitant PDAC by assessing these molecular biomarkers. More precise distinction of Inv-IPMN and concomitant PDAC will lead to adequate recognition of the natural history of IPMNs and hence optimal management.

To identify factors predicting the development of high-risk lesions in the remnant pancreas after surgery for intraductal papillary mucinous neoplasm (IPMN).IPMN has unique features, including multifocality, adenoma-carcinoma sequence, and the development of distinct pancreatic ductal adenocarcinoma (PDAC) in the same pancreas. Careful attention should, therefore, be paid to the metachronous occurrence of high-risk lesions, including high-grade dysplasia or invasive carcinoma (HGD/INV) of IPMN and concomitant PDAC in the remnant pancreas after partial pancreatectomy for IPMN.Clinicopathologic and surveillance data for 195 patients who underwent partial pancreatectomy for IPMN were reviewed retrospectively.Thirteen patients exhibited metachronous development of high-risk lesions including 6 HGD/INV and 7 concomitant PDACs in the remnant pancreas. The 5- and 10-year cumulative incidences of metachronous high-risk lesions in the remnant pancreas were 7.8% and 11.8%, respectively. Twelve of 13 patients had high-risk lesions at the time of initial surgery, and 10 of the 13 IPMNs were located in the distal pancreas. The IPMN subtypes initially resected were gastric in 6 patients, intestinal in 5, and pancreatobililary in the remaining 2. Univariate and multiple regression analyses identified pathologic results of HGD/INV and IPMN located in the distal pancreas as independent predictive factors for metachronous HGD/INV of IPMN, and the pancreatobiliary subtype of IPMN and presence of concomitant PDAC for metachronous PDAC.Patients undergoing partial pancreatectomy for IPMN are at high risk of developing lesions requiring surgery in the remnant pancreas, and close, long-term surveillance should be considered in these patients.

This retrospective study was conducted to find preoperatively assessable risk factors for postoperative pancreatic fistula (POPF) in patients undergoing laparoscopic distal pancreatectomy (LDP) using a slow compression method with a stapler, which we call pen-firing compression (PFC).Fifty-two patients underwent LDP, of whom 42 underwent PFC for pancreatic division using a stapler. The relationship between preoperatively assessable factors and the incidence of clinical POPF was statistically analyzed.Overall rate of POPF was 7.1% in 42 patients. Univariate analysis showed that greater BMI (p = 0.004) and thicker pancreatic stump (0.0022) were significant risk factors for POPF. BMI and stump thickness remained significant (P0.0001, P0.0001) by multivariate analysis. Cutoff points estimated by ROC curve were 27 kg/m2 for BMI and 27 mm for stump thickness.High BMI value and thick pancreatic stump are significant risk factors for POPF after LDP. Alternative treatment of the pancreatic stump may prevent POPF in high-risk patients.