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In a 66-year-old patient morphologic features of a pulmonary veno-occlusive disease were found. Besides, a striking foreign body giant cell reaction with phagocytosis of altered elastic tissue in totally or partially occluded venous blood vessels resembled the so-called pulmonary sideroelastosis, an entity originally described by Ceelen. In this case report, a possible pathogenetic relation between sideroelastosis pulmonum and pulmonary veno-occlusive disease is discussed.

CONTEXT: Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas. OBJECTIVE: To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection. DESIGN, SETTING, AND PATIENTS: The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers. INTERVENTIONS: One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life. RESULTS: Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; χ2 = 1.33; P = .25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald χ2 = 4.53, P = .03). CONCLUSIONS: Among patients with resected periampullary adenocarcinoma, adjuvant chemotherapy, compared with observation, was not associated with a significant survival benefit in the primary analysis; however, multivariable analysis adjusting for prognostic variables demonstrated a statistically significant survival benefit associated with adjuvant chemotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00058201.

Background Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer related death. It is lethal in nearly all patients, due to an almost complete chemoresistance. Most if not all drugs that pass preclinical tests successfully, fail miserably in the patient. This raises the question whether traditional 2D cell culture is the correct tool for drug screening. The objective of this study is to develop a simple, high-throughput 3D model of human PDAC cell lines, and to explore mechanisms underlying the transition from 2D to 3D that might be responsible for chemoresistance. Methods Several established human PDAC and a KPC mouse cell lines were tested, whereby Panc-1 was studied in more detail. 3D spheroid formation was facilitated with methylcellulose. Spheroids were studied morphologically, electron microscopically and by qRT-PCR for selected matrix genes, related factors and miRNA. Metabolic studies were performed, and a panel of novel drugs was tested against gemcitabine. Results Comparing 3D to 2D cell culture, matrix proteins were significantly increased as were lumican, SNED1, DARP32, and miR-146a. Cell metabolism in 3D was shifted towards glycolysis. All drugs tested were less effective in 3D, except for allicin, MT100 and AX, which demonstrated effect. Conclusions We developed a high-throughput 3D cell culture drug screening system for pancreatic cancer, which displays a strongly increased chemoresistance. Features associated to the 3D cell model are increased expression of matrix proteins and miRNA as well as stromal markers such as PPP1R1B and SNED1. This is supporting the concept of cell adhesion mediated drug resistance.

The most significant change in the clinical course of acute pancreatitis over the past decades has undoubtedly been the decrease in mortality. Almost all deaths caused by acute pancreatitis are observed in patients with severe acute pancreatitis. Today, there is no doubt that pancreatic infection is the major risk factor in necrotizing pancreatitis with regard to morbidity and mortality in the later phase of the disease (Beger et al. 1986; Buchler et al. 2000; Werner et al. 2005). While pancreatic necrosis develops within the first week, superinfection of pancreatic and peripancreatic necrosis is usually observed 2-3 weeks after the onset of the disease (Beger et al. 1986; Werner et al. 2003). The frequency of infection correlates with the extent of necrosis. The profile of the organisms suggests an origin in the gastrointestinal tract. The ways in which microorganisms reach the pancreas include transperitoneal spread and the spread along the pancreatic duct ascending from the duodenum or descending from the bile duct, as well as via lymph or the bloodstream.

Pancreatic endocrine tumors are relatively uncommon, accounting for approximately five to ten cases per million persons per year (Heitz et al. 2004). They may be classified as functioning or nonfunctioning. Functioning tumors (those with secretory neuropeptide function) are usually associated with classical syndromes. These include VIPomas, gastrinomas, glucagonomas, and insulinomas (Ramage et al. 2005). At least one third of the tumors may be nonfunctioning, despite typical pathological appearances of well-differentiated endocrine tumors or carcinomas (Clarke et al. 1997). Circulating levels of gut hormones may be detected even in the absence of symptoms (Clarke et al. 1997; Rindi et al. 2006).

Aims: Local peritoneal involvement (LPI) and extramural venous invasion (EMVI) are of prognostic value in Dukes’ B colonic cancers and may be used to select patients for adjuvant chemotherapy. There is marked variation in the frequency with which they are reported however, ranging from 7% to 39% and 10% to 90%, respectively. A grading system for diagnosing LPI has been proposed by Shepherd et al. and partially incorporated into the Royal College of Pathologists guidelines for reporting colorectal cancer. This study aimed to determine the degree of interobserver variation in the reporting of LPI and EMVI amongst a group of experienced pathologists with a special interest in gastrointestinal pathology. Methods and results: Four pathologists specialising in gastrointestinal pathology independently assessed LPI according to the grading system described by Shepherd et al. and the presence or absence of EMVI on 138 and 131 slides of pT3 and pT4 colonic cancers, respectively. Kappa statistics were performed to assess interobserver agreement. Kappa values for LPI ranged from κ = 0.74 (substantial agreement) to κ = 0.89 (almost perfect agreement). Kappa values for EMVI ranged from κ = 0.29 (poor agreement) to κ = 0.59 (moderate agreement). Conclusions: Using Shepherd’s grading system there was good agreement between pathologists in reporting LPI in colonic carcinomas. The reporting of EMVI in colonic carcinomas on haematoxylin and eosin-stained slides had only poor to moderate agreement however, even amongst gastrointestinal pathologists working together in a single unit. Introduction of standardized criteria and/or the use of an elastin stain in the diagnosis of EMVI may assist in improving interobserver agreement.

Background In a previous study we reported an 85% R1 rate for pancreatic cancer following the use of the rigorous, fully standardized Leeds Pathology Protocol (LEEPP). As this significantly exceeded R1 rates observed by others, we investigated the reproducibility of margin assessment using the LEEPP in a larger, prospective, observational cohort study and correlated clinicopathological data with survival. Methods Clinicopathological features, including exact site and multifocality of margin involvement, and survival were collated from a prospective series of 83 pancreatoduodenectomies for pancreatic ( n = 27), ampullary ( n = 24) and bile duct cancer ( n = 32). Data were compared with those of the previous study in which the same pathology protocol, based on axial slicing and extensive tissue sampling from the circumferential margin, had been used. Results The R1 rate was high in pancreatic (82%) and bile duct (72%) cancer and significantly lower in ampullary cancer (25%). Margin positivity was often multifocal, the posterior margin being most frequently involved. Margin status correlated with survival in the entire cohort ( P = 0.006) and the pancreatic subgroup ( P = 0.046). These findings were consistent with observations in our previous study. Conclusions Margin involvement in pancreatic cancer is a frequent and prognostically significant finding when specimens are assessed using the LEEPP.

Benign tumours of the biliary tract are an extremely rare group of neoplasms. The diagnosis of these rare tumours is established on histopathological analysis following resection. Coincidence of a biliary adenoma of the distal common bile duct and a synchronous adenocarcinoma of the peri-ampullary duodenum has never been reported in the literature.We report a case of a papillary adenoma in the common bile duct in a 75-year-old female, who had synchronous invasive adenocarcinoma of the peri-ampullary duodenum.Isolated papillary adenoma of the bile duct is extremely rare, and in this unusual case it coincided with a peri-ampullary duodenal adenocarcinoma. However, this is a rare instance of an incidental finding within the distal bile duct following pancreaticoduodenectomy for curative treatment of a peri-ampullary adenocarcinoma.

The aim of the study was to present clinical outcomes of patients with malignant pancreatic neuroendocrine tumours (NET) following surgical resection with curative intent. Clinical and pathological factors that influenced the outcomes were also analysed.Retrospective case note study.All patients with pancreatic NET that underwent surgery over a 7-year period (1999-2006).Twelve patients were identified with a median age at diagnosis of 54 years (range: 24-79 years). Common presenting symptoms include abdominal pain (n=8) and weight loss (n=3). Overall morbidity was 25% with one post-operative death. The median follow-up period was 41 months (range: 9-156 months). The overall 2- and 5-year actuarial survival rates were 88% and 70%, respectively. The overall survival was better in patients treated with surgery compared to patients managed medically (P0.001). The disease-free survival rates were 62% at 2 and 5 years, respectively. Recurrent disease occurred in four patients and the median disease-free interval was 6 months (range: 3-14 months). On univariate analysis, angio-invasion (P=0.015) and degree of differentiation (P=0.024) were associated with developing recurrent disease.Surgical resection of malignant pancreatic NET results in good long-term survival in selected patients.

Human endogenous retroviruses (HERVs) account for up to 9% of the human genome and include more than 800 elements related to betaretroviruses. While mouse mammary tumor virus (MMTV) is the accepted etiological agent of mammary tumors in mice, the role of retroviral elements in human breast cancer remains elusive. Here, we performed a comprehensive microarray-based analysis of overall retroviral transcriptional activities in 46 mammary gland tissue specimens representing pairs of nonmalignant and tumor samples from 23 patients. An analysis of nonmalignant tissue samples revealed a distinct, mammary gland-specific HERV expression profile that consists of 18 constitutively active HERV taxa. For corresponding tumor samples, a general trend toward lower levels of HERV transcription was observed, suggesting common regulatory mechanisms. In various subsets of patients, however, increased transcript levels of single class I HERV families (HERV-T, HERV-E, and HERV-F) and several class II families, including HML-6, were detected. An analysis of transcribed HML-6 sequences revealed either the activation of some or the increased activity of several proviral loci. No evidence for MMTV or human MMTV-like virus transcripts was found, indicating that transcriptionally active, MMTV analogous, exogenous viruses were not present in the breast cancer samples analyzed.

There are a variety of differential diagnoses for an abnormal mass arising from the pancreas of which isolated pancreatic or peripancreatic tuberculosis is an extremely rare diagnosis with a variety of elusive presentations.We report such a case which masqueraded as malignancy in 43-year-old man presenting with jaundice, weight loss and new onset diabetes.Tuberculosis should be considered as a differential diagnosis to an obscure pancreatic mass which may result in local complications amenable to surgery.

Annular pancreas is an uncommon congenital abnormality. Co-existence of this condition with a pancreaticobiliary malignancy is an exceptionally rare occurrence.We present a case report of a 78-year-old woman with jaundice due to an ampullary carcinoma associated with an annular pancreas treated by pancreaticoduodenectomy.A collection of previously reported cases is reviewed together with the relevant literature. Obstructive jaundice is an uncommon feature of annular pancreas; hence the possibility of co-existent pancreaticobiliary malignancy should be excluded.

Meeting abstracts Expansion of antigen-specific T cells, from peripheral blood specific for tumor-associated antigens (TAAs) is a prerequisite for the advanced cellular therapy. Such antigen-specific T cells should express a Th1-functional phenotype and are able to enter tumor-tissue. We identified

Meeting abstracts The generation of T lymphocytes with specific reactivity against autologous tumor cells is a prerequisite for effective targeted cellular therapies. We established a protocol for tumor infiltrating lymphocytes (TILs) cultures from small biopsies or surgically resected material

Poster: "ECR 2016 / C-2276 / Multidetector CT of pancreatic ductal adenocarcinoma: effect of tube-voltage and iodine-load on tumour conspicuity, vessel involvement and image quality " by: "L. Loizou1, N. Albiin2, B. Leidner1, E. Axelsson1, M. Fischer1, R. Segersvard1, C. Verbeke1, A. Sundin3, N. Kartalis 1; 1Huddinge/SE, 2Stockholm/SE, 3Uppsala/SE"

Pancreatic cystic neoplasms (PCNs) are a high prevalence disease. It is estimated that about 20% of the general population is affected by PCNs. Some of those lesions can progress till cancer, while others behave in a benign fashion. In particular intraductal papillary mucinous neoplasms of the pancreas can be considered as the pancreatic analogon to colonic polyps. Treatment of these precursor lesions at an early stage can potentially reduce pancreas cancer mortality and introduce a new "era" of preemptive pancreatic surgery. However, only few of those lesions have an aggressive behavior. The accuracy of preoperative diagnosis, i.e., the distinction between the various PCNs is around 60%, and the ability to predict the future outcome is also less accurate. For this reason, a significant number of patients are currently over-treated with an unnecessary, high-risk surgery. Furthermore, the majority of patients with PCN are on life-long follow-up with imaging modality, which has huge cost implications for the Health Care System for limited benefits considering that a significant proportion of PCNs are or behave like benign lesions. The current guidelines for the diagnosis and management of PCNs are more based on expert opinion than on evidence. For all those reasons, the management of cystic tumors of the pancreas remains a controversial area of pancreatology. On one hand, the detection of PCNs and the surgical treatment of pre-cancerous neoplasms can be considered a big opportunity to reduce pancreatic cancer related mortality. On the other hand, PCNs are associated with a considerable risk of under- or over- treatment of patients and incur high costs for the Health Care System.

Solid pseudopapillary tumour of the pancreas is an uncommon tumour, which predominantly occurs in young females and is of unknown origin.We describe five cases with diverse clinical and/or histological features, including one unusually aggressive case resulting in early death.There is great variability in the presentation and clinical course of these tumours with further research needed to define their histogenesis and biological behaviour.

Cystic lesions of the pancreas in association with chronic pancreatitis are a diagnostic and therapeutic challenge.The aim of the study was to study clinical and radiological features that may differentiate between benign and malignant cystic lesions of the pancreas and examine the indications for surgery in these patients.Retrospective case note study.Patients with concomitant cystic lesions of the pancreas and chronic pancreatitis stated in radiology reports between 1995 and 2005.Thirty-one patients were identified with alcohol-related chronic pancreatitis with a median age of 53 years (range: 27-82 years). Eight patients (26%) had deranged liver function tests and four (13%) presented a raised CA 19.9. Radiological features of cystic lesions of the pancreas included median cyst size of 3 cm (range: 0.8-10 cm), solitary cyst in 28 patients (90%) and multi-loculated in 3 patients (10%). Dilatation of the main pancreatic duct was seen in seven cases (23%). Overall, 12 patients (39%) underwent surgery, 13 patients (42%) were managed with radiological follow-up, five patients (16%) were managed conservatively and one patient (3%) was treated with chemotherapy for advanced malignancy. Overall, three cases (10%) of this series had malignant cystic lesions of the pancreas. Malignant cystic lesions of the pancreas are associated with deranged liver function tests, elevated CA 19.9, and are larger solitary cysts on imaging.The differentiation between benign and malignant cystic lesions of the pancreas remains a diagnostic challenge, although malignant cysts tend to be solitary and larger. The high prevalence of malignancy merits an aggressive approach to follow-up and early surgical intervention.

Retroperitoneal enteric duplication cysts (EDC) are rare lesions and its presentation during adulthood is a diagnostic challenge for clinicians. The diagnosis of this condition is established following histopathological analysis, which often requires surgical intervention.We report a case of a retroperitoneal enteric duplication cysts, presenting as a cystic lesion of the pancreas in a 19-year-old woman.We recommend surgical intervention for retroperitoneal EDCs due to its potential local complications including pressure effects on surrounding structures and neoplastic change.

Hypothesis High-grade dysplasia (HGD) of the gastric epithelium is associated with high prevalence of invasive carcinoma, and distinction by endoscopic biopsy is difficult. Design Cohort study, 1996 to 2003. Setting Tertiary care center. Patients Consecutive sample of 22 patients with initial diagnosis of gastric HGD by endoscopic biopsy. Biopsy specimens were separately reviewed by 3 experienced pathologists. Clinical management was individually decided. Main Outcome Measures Strength of interpathologist agreement (κ) and final pathological diagnosis. Results The diagnosis was revised to intramucosal carcinoma in 14% to 32% of patients or suspicious for invasive carcinoma in 23% to 41%. The strength of agreement between any 2 pathologists for distinguishing between dysplasia and invasive carcinoma was fair (κ = 0.35-0.36). A diagnosis of intramucosal carcinoma or suspicious for invasive carcinoma by 2 pathologists correlated strongly with subsequent detection of invasive carcinoma. Three patients underwent gastrectomy for HGD, and invasive carcinoma was detected in all (2 patients, T1 N0; 1 patient, T2 N0). Six patients had invasive carcinoma on endoscopic surveillance at a median of 15 months (range, 3-34 months) after diagnosis of HGD and underwent endoscopic mucosal resection (2 patients, T1 NX), gastrectomy (2 patients, T1 N0), or no resection (2 patients). Another patient had metastatic gastric adenocarcinoma despite having a diagnosis of only HGD by endoscopy. Seven patients (32%) died of unrelated causes, without invasive carcinoma, at a median of 19 months (range, 1-38 months). Three patients were alive with persistent HGD at 26 to 61 months. Two patients had no dysplasia on follow-up. Conclusions Experienced pathologists often disagreed in distinguishing invasive carcinoma from HGD in gastric biopsy specimens. One third of patients with gastric HGD died of causes unrelated to cancer. Invasive carcinoma was detected in 67% of the remainder.

The capacity of the colon for potassium (K+) secretion increases in end-stage renal disease (ESRD), to the extent that it makes a substantial contribution to K+ homeostasis. This colonic K+ adaptive response may reflect enhanced active K+ secretion, and be associated with an increase in apical membrane K+ permeability. In this study, this hypothesis was tested in patients with normal renal function or ESRD, by evaluating the effect of barium ions (a K+ channel inhibitor) on rectal K+ secretion using a rectal dialysis technique, and the expression of high conductance (BK) K+ channel protein in colonic mucosa by immunohistochemistry. Under basal conditions, rectal K+ secretion was almost threefold greater (p < 0.02) in ESRD patients (n = 8) than in patients with normal renal function (n = 10). Intraluminal barium (5 mmol/l) decreased K+ secretion in the ESRD patients by 45% (p < 0.05), but had no effect on K+ transport in patients with normal renal function. Immunostaining using a specific antibody to the BK channel alpha-subunit revealed greater (p < 0.001) levels of BK channel protein expression in surface colonocytes and crypt cells in ESRD patients (n = 9) than in patients with normal renal function (n = 9), in whom low levels of expression were mainly restricted to surface colonocytes. In conclusion, these results suggest that enhanced colonic K+ secretion in ESRD involves an increase in the apical K+ permeability of the large intestinal epithelium, which most likely reflects increased expression of apical BK channels.

Cyclooxygenase-2 (COX-2) is a key modulatory molecule in inflammation and neoplasia. Increasing evidence suggests a role for COX-2 in pancreatic cancer (PAC). However, expression of COX-2 in pancreatic intraepithelial neoplasia (PanIN), the precursor lesion of PAC which is often present in chronic pancreatitis (CP), has received little attention.COX-2 immunostaining was performed on sections of PAC (n = 26), CP (n = 34), PanIN (n = 68) and normal pancreas (n = 11). Sections were also stained for macrophages (CD68), activated pancreatic stellate cells (alphaSMA), and collagen (Sirius Red) as markers of fibrosis. Semiquantitative scoring was based on the extent and intensity of immunostaining.COX-2 expression was increased in PAC compared to normal (p = 0.02) with 89% of cases exceeding COX-2 immunostaining in normal ducts. In PanIN lesions, COX-2 expression increased with escalating severity of the PanIN change (por = 0.01). COX-2 expression was increased in PanIN-2/3 compared to normal pancreas and CP (por = 0.001). In ducts of CP, COX-2 expression did not differ from that in normal tissue. There was no association between COX-2 expression and clinicopathological variables.The high level of COX-2 expression in PanIN lesions suggests that this enzyme could be a therapeutic target at a non-invasive stage of pancreatic carcinogenesis and feasible for chemoprevention in CP.

Altered expression of the genes that control apoptosis and proliferation may influence the response of cancer cells to cytotoxic agents. The primary aim of this study was to determine the role of the novel antiapoptotic and cell cycle gene, survivin, in apoptotsis and proliferation in esophageal cancer and to evaluate whether the survivin, p53, and bcl-2 status were able to predict a patient's response to neoadjuvant therapy. A total of 104 patients with esophageal tumors were studied. Tumor tissue was immunostained for survivin, p53, and bcl-2 proteins. Proliferative and apoptotic activity was measured using ki-67 immunohistochemical analysis and the TUNEL method, respectively. Forty-eight patients whose pretreatment biopsies were analyzed received neoadjuvant chemoradiation therapy or chemotherapy followed by surgery. Outcome was graded as a complete response, a partial response, or no response according to the results of histologic examination and CT imaging. Expression of survivin was found to correlate significantly with the proliferative index but not the apoptotic index. Patients who received neoadjuvant treatment were more likely to achieve a complete response if their tumors had high proliferative activity, and p53 positive tumors were more likely to contain residual tumor after treatment. In conclusion, survivin expression appears to foster proliferative activity in esophageal cancer, and tumors with a high proliferative index or a functioning p53 gene are more responsive to neoadjuvant chemoradiation therapy.

s / Pancreatology 14 (2014) S1eS129 S88 overall pancreatic arteriovenous malformation were bleeding (50.6%), pancreatitis (16.9%), portal hypertension (6.7%), and pseudocyst (3.4%). The most common presenting symptom of pancreatic arteriovenous malformation was gastrointestinal bleeding (47.2%), followed by epigastric pain (46.1%). Surgery (43.8%) was the most common treatment for pancreatic arteriovenous malformation cases, followed by transarterial embolization (11.2%), a combination of surgery and transarterial embolization (10.1%), and radiotherapy (2.2%). No intervention was done for 29.2% of the cases of pancreatic arteriovenous malformation. Conclusion: Pancreatic arteriovenous malformation occurs most commonly in the pancreatic head; gastrointestinal bleeding is the main symptom. Surgical resection of the pancreatic arteriovenous malformation is recommended whenever feasible.

s / Pancreatology 14 (2014) S1eS129 S79 Results: Sequencing analysis of the discovery cohort revealed four common mutations: intronic mutations c.23+71_23+103del, c.183-4C>A and c.1134+32C>A; and exonic missense mutation p.V206M. . These four mutations were found in linkage disequilibrium indicating a conserved haplotype. We found this haplotype in 18 heterozygous and 2 homozygous cases, and in 24 heterozygous and 2 homozygous controls (allele frequency 11.4% and 14.1% respectively). A synonymous mutation p.P397P was also detected in a single case. Conclusion:We found a novel, commonhaplotype in the SLC26A6 gene, which did not show association with CP. Supported by T AMOP and OTKA.

G A A b st ra ct s papillary mucinous neoplasm and to assess the impact on the diagnosis of IPMN. Methods: We retrospectively analysed the clinicopathological factors of 177 patients (114 men, median age 63 yr) undergoing resection for branch duct type IPMNs at 15 tertiary hospitals in korea that had the diameter of main pancreatic duct less than 5 mm for identifying malignant predictors of this neoplasm. For the analysis, Br-IPMN with adenoma (n=72), borderline neoplasm (n=66) were grouped as benign and Br-IPMNs with carcinoma in situ(n=10), and invasive carcinoma (n=29) as malignant. Malignant IPMNs were defined as those with noninvasive (n=10 noninvasive carcinoma, and 29 invasive carcinoma). and invasive IPMN. Results: Among 177 patients with branch duct IPMN, we found significant predictors for malignancy in these patients in a univariate analysis; cyst size > 3cm, presence of a mural nodule in the cyst at abdominal CT, the history of acute pancreatitis, serum CA19-9. In a multivariate analysis among 177 patients, a mural nodule on CT imaging, cyst size>3cm, and serum CA19-9 were independent factors associated with malignancy. In patients (n= 110) who had endoscopic ultrasonography (EUS), cyst size > 3cm (odd ratio=10.6, CI= 2.812-40.199) and mural nodule larger than 5mm (odd ratio=14.9, CI=4.027-55.418) on EUS imaging is strongly associated with Malignant Br-IPMNs (p 5mm used instead of definitive mural nodule on EUS imaging in the 2012 international consensus guideline for IPMNs, the sensitivity and specificity was 84% and 85%. Conclusions: We identified useful predictive factors for malignancy in pure branch duct IPMN ; the presence of mural nodule and cyst size > 3cm on abdominal CT imaging, and the mural nodule larger than 5 mm on EUS imaging. In the worrisome features of 2012 international guideline for surgical indication of IPMNs, using the mural nodule larger than 5 mm instead of definitive mural nodule on EUS imaging may be reasonable.

Purpose Active cellular therapy (ACT) using ex-vivo expanded T cells from patients with cancer, obtained by apheresis, can represent a viable source for anti-cancer directed cellular therapy. We established a T cell expansion protocol using 2 rounds of re-stimulation with TAA peptides along with IL-2, IL-15 and IL-21. In order to gauge the ex-vivo cellular reactivity as well as the potential to successful expand antigen-specific T cells from patients with pancreatic cancer, we established a screening assay using whole-heparin blood, to gauge for TAA reactivity (NY-ESO-1, survivin and mesothelin) and control antigens (EBNA-1, EBNA-3, CMVpp65). Methods Fresh blood samples were obtained from 24 patients with pancreatic cancer and from 6 individuals with pre-malignant lesions and tested for anti-TAA reactivity. T cells were expanded without cytokines, with IL-2 and IL-7, or with IL-2, IL-15 and IL-21 and tested for CD4/ 8 expansion by flow cytometry and for IFN-gamma production. PBMCs were expanded by cytokines and TAA peptides. CD3, CD4, CD8, CD45RA and CCR7 was determined by flow cytometry and TAA-reactive T cells were identified by ICS (IL-2, TNF, IFN and IL-17). Results We could detect IFN-gamma responses in 90% (27 in 30) in blood samples for mesothelin, 55,3% (16 in 30) for survivin and 43,3% (13 in 30) for NY-ESO-1. Cellular responses could be augmented by adding cytokines, i.e. IL-2 and IL-7 could favored CD4+ T cell proliferation, IL-2, IL-15 and IL-21 favored CD8+ T cell proliferation. TAAs-reactive T cells could be successfully expanded in vitro and exhibited TAA-specific production of IFNgamma and TNFalpha and a CD8+CD45RA-CCR7+ phenotype. Conclusion A TAA-specific WBA (whole blood assay) can be used to gauge the potential for expansion of TAA-reactive T cells in peripheral blood from patients with pancreatic cancer. TAA-reactive T cells can be successfully expanded in IL-2, IL-15 and IL-21 and could represent a viable source for the cellular therapy of patients with pancreatic cancer. Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Survivin is unique for its expression in human malignancies but not in normal adult cells. It has been implicated in sensitisation to chemotherapy and as a prognostic marker in several common cancers. Immunohistochemistry for Survivin, P53 and BCL-2 expression as well as cell proliferative index (Ki-67) and apoptosis index (TUNEL) was conducted on 52 pancreatic and 12 ampullary adenocarcinomas. Survivin was detected in the cytoplasm of carcinoma cells in 46 (88%) of pancreatic tumours. P53 and BCL-2 were detected in 54% and 12% of pancreatic tumours, respectively. Proliferative index was 26.2±10.5% and apoptosis index was 1.38±0.69%. Prevalence of Survivin expression was significantly higher in P53-positive than in P53-negative cases (P=0.05) but was not associated with BCL-2 expression. Incrementally higher weighted scores of Survivin expression were associated with increased proliferative index (P=0.001). Furthermore, there was linear correlation between increased proliferative index and higher apoptosis index (P

The MAGE gene family encodes antigens that are recognized by cytotoxic T-cells. The expression of MAGE antigens has been linked to tumor stage, and MAGE peptides are under investigation as possible vaccines. Seminomas are tumors that are typically accompanied by a heavy inflammatory infiltrate, but have not been studied with regard to their MAGE antigen expression and its correlation with the inflammatory infiltrate. We investigated, therefore, MAGE protein expression, the amount of cytotoxic T-cells, clonality of the lymphocytic infiltrate, apoptotic activity and occurrence of necrosis. Specimens of 27 patients with classical seminoma were examined by immunohistochemistry for CD4, CD8, CD56, CD45R0, beta2-microglobulin and HLA-DR. MAGE expression was detected with the monoclonal antibody 57B, reactive with MAGE-1, -3, -4, -6 and -12. Clonality of the inflammatory infiltrate was examined by multiplex polymerase chain reaction (PCR) analysis of the T-cell receptor rearrangement. Apoptotic cells were detected by DNA nick-end labeling of fragmented DNA, and the apoptotic index was determined semi-quantitatively. Expression of 57B was found in 19 (70%) of 27 seminomas. In all cases, more than 70% of T-cells expressed CD45R0. In four cases, a predominant infiltration of CD8-positive cytotoxic T-cells (CD4/CD8 ratio1) was present. However, 15 seminomas showed a CD4/CD8 ratio1. In all cases, infiltration of CD56-positive natural killer cells was only focal. HLA-DR expression was not detectable in tumor tissue; beta2-microglobulin was only focal in three cases. Analysis of the T-cell clonality revealed a polyclonal population. The apoptotic index was not significantly different in 57B-positive seminomas (4.15%) compared with 57B negative seminomas (3.80%). Also, no correlation between the 57B expression and the occurrence of necrosis was found. MAGE antigens are homogeneously expressed in most seminomas, but their presence does not appear to represent a dominant epitope responsible for the lymphocytic infiltrate.

SUMMARY Infectious mononucleosis (IM), a manifestation of primary infection with EBV, is characterized by a massive expansion of the T cell population. In this study we examined this expanded T cell population regarding its EBV status, its proliferative and apoptotic activity, and its expression of apoptosis-related genes. Whereas previous studies were performed on ex vivo cultures or on peripheral blood, our investigations included in vivo analysis of IM tonsillectomy specimens (14 cases) by in situ hybridization for viral RNA (EBERs) combined with immunohistochemistry (IHC; CD3, CD45RO, CD20, CD79a, Ki-67, Bcl-2, Bax, Fas, FasL) and the TUNEL method. Of the EBER+ cells 50–70% showed expression of the B cell markers CD20/CD79a. The remainder of the EBER+ cells expressed neither B nor T cell antigens. No co-expression of EBERs and T cell antigens was detected in any of the specimens. In accordance with a high rate of apoptosis (up to 2.37%) within the expanded T cell population, Bcl-2 expression was drastically reduced and FasL expression remarkably increased. The levels of Bax and Fas expression showed no or moderate up-regulation. In conclusion, the massive expansion of IM T cells is not caused by EBV infection of these cells but merely represents an intense immune reaction. Through altered expression of Bcl-2/Bax and Fas/FasL, the activated T cells are subject to enhanced apoptosis while residing within the lymphoid tissue, which eventually allows the efficient silencing of this potentially damaging T cell response.

Despite the continuous progress in molecular methodology, the genetic events involved in the initiation and progression of ductal adenocarcinoma of the pancreas remain largely unknown. In this study, 33 pancreatic ductal adenocarcinomas were screened for genomic alterations by comparative genomic hybridization (CGH). To date, most CGH studies of pancreatic cancer have been based on cell lines. To emphasize genetic imbalances that are involved in the in vivo development and progression of pancreatic carcinoma only fresh-frozen or paraffin-embedded tumour samples were analysed in the present study. Twenty-two tumours (67%) showed genomic alterations involving up to three (12%) or more (55%) chromosomal regions. The number and nature of the genetic imbalances did not, however, correlate with tumour stage or grade. Chromosome 18 was preferentially altered in the tumours analysed. Frequent chromosomal losses were found at 18q, 10q, 8p, and 13q. Commonly gained regions were located on 8q and 3q. Moreover, high copy number amplifications of the chromosomal regions 5p, 8q22-ter, 12p12-cen, 19q12-13.2, and 20q were identified. These data provide evidence for the occurrence of characteristic genomic alterations which are of biological relevance for the genesis of pancreatic cancer. The identified altered chromosomal regions may harbour tumour genes which involved in the multistep process of pancreatic carcinogenesis.

We have recently reported that abnormal acid reflux persists in up to 50% of patients with long segment Barrett’s oesophagus, despite good control of symptoms of gastro-oesophageal reflux disease (GORD) with proton pump inhibitor (PPI) therapy.1 The critical question is whether such persistence of abnormal acid reflux alters the risk of progression to adenocarcinoma. We investigated this issue by studying cellular proliferation and expression of cyclin D1, which is an important marker of neoplastic progression,2,3 in patients with Barrett’s oesophagus on PPI therapy. A prospective cross-sectional survey of 20 patients with long segment Barrett’s oesophagus (defined as a length ⩾3 cm and presence of specialised intestinal epithelium containing alcian blue staining goblet cells) was conducted. In all cases, GORD symptoms had been well controlled with PPI therapy (omeprazole n = 13 patients, median dose 20 mg (range 10–40); lansoprazole n = 5, 30 mg; or rabeprazole n = 2, 20 mg). Patients had received PPI …