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Objectives Patients in Intensive Care Units (ICU) are a high-risk population for sepsis, recognized as a major cause of admission and death. The aim of the current study was to evaluate the diagnostic accuracy and prognostication of monocyte distribution width (MDW) in sepsis for patients admitted to ICU. Methods Between January and June 2020, we conducted a prospective observational study during the hospitalization of 506 adult patients admitted to the ICU. MDW was evaluated in 2,367 consecutive samples received for routine complete blood counts (CBC) performed once a day and every day during the study. Sepsis was diagnosed according to Sepsis-3 criteria and patients enrolled were classified in the following groups: no sepsis, sepsis and septic shock. Results MDW values were significantly higher in patients with sepsis or septic shock in comparison to those within the no sepsis group [median 26.23 (IQR: 23.48–29.83); 28.97 (IQR: 21.27–37.21); 21.99 (IQR: 19.86–24.36) respectively]. ROC analysis demonstrated that AUC is 0.785 with a sensitivity of 66.88% and specificity of 77.79% at a cut-off point of 24.63. In patients that developed an ICU-acquired sepsis MDW showed an increase from 21.33 [median (IQR: 19.47–21.72)] to 29.19 [median (IQR: 27.46–31.47)]. MDW increase is not affected by the aetiology of sepsis, even in patients with COVID-19. In sepsis survivors a decrease of MDW values were found from the first time to the end of their stay [median from 29.14 (IQR: 26.22–32.52) to 25.67 (IQR: 22.93–30.28)]. Conclusions In ICU, MDW enhances the sepsis detection and is related to disease severity.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values

Objectives Preterm premature rupture of membranes (pPROM) causes preterm delivery, and increases maternal T-cell response against the fetus. Fetal inflammatory response prompts maturation of the newborn’s immunocompetent cells, and could be associated with unfavorable neonatal outcome. The aims were (1) to examine the effects of pPROM on the newborn’s and mother’s immune system and (2) to assess the predictive value of immune system changes in neonatal morbidity. Methods Mother-newborn pairs (18 mothers and 23 newborns) who experienced pPROM and controls (11 mothers and 14 newborns), were enrolled. Maternal and neonatal whole blood samples underwent flow cytometry to measure lymphocyte subpopulations. Results pPROM-newborns had fewer naïve CD4 T-cells, and more memory CD4 T-cells than control newborns. The effect was the same for increasing pPROM latency times before delivery. Gestational age and birth weight influenced maturation of the newborns’ lymphocyte subpopulations and white blood cells, notably cytotoxic T-cells, regulatory T-cells, T-helper cells (absolute count), and CD4/CD8 ratio. Among morbidities, fewer naïve CD8 T-cells were found in bronchopulmonary dysplasia (BPD) (p=0.0009), and more T-helper cells in early onset sepsis (p=0.04). Conclusions pPROM prompts maturation of the newborn’s T-cell immune system secondary to antigenic stimulation, which correlates with pPROM latency. Maternal immunity to inflammatory conditions is associated with a decrease in non-major histocompatibility complex (MHC)-restricted cytotoxic cells.

A previous trial failed to demonstrate the superiority of a demographic-genetic algorithm in predicting warfarin (W) dose over a standard clinical approach. The purpose of the present study is to re-analyse the results in subgroups of patients with differing baseline sensitivity to W, integrated with additional pharmacokinetic data. The original trial allocated 180 treatment-naive patients with non-valvular atrial fibrillation to a control arm (CTL, n = 92) or a genetic-guided arm (GEN, n = 88). Before starting anticoagulation treatment, all patients were genotyped for CYP2C9, VKORC1 and CYP4F2 variants and classified into four quartiles (Q1, Q2, Q3, Q4) according to the algorithm-predicted W maintenance dose. International normalised ratios (INR) and plasma concentrations of S-warfarin [S-W]s and R-warfarin [R-W]s were measured at baseline and on days 5, 7, 9, 12, 15 and 19 of therapy. In the lowest dose quartile (Q1), the number of INRs > 3 and mean INR values on days 5 and 7 were significantly higher in CTL than in GEN. In Q3 and Q4, the mean INR values reached therapeutic level (> 2) 2 days later in CTL than in GEN. During follow-up, the mean time courses of INRs and [S-W]s in GEN were remarkably stable in all dose quartiles. Thus, mean changes from starting to final doses were significantly smaller in GEN than in CTL. Plasma concentrations of R-W (a partially active enantiomer) steadily increased from day 5 to day 19 in all Qs in both CTL and GEN, except in the Q1 CTL group, due to the marked dose reduction required. This analysis showed that the demographic-genetic algorithm used to predict the W dose can identify patients with differing degrees of sensitivity to W and to ‘normalise’ their average anticoagulant responses. The progressive rise in [R-W]s throughout the 19-day follow-up indicates that the (partial) contribution of R-W to the W anticoagulant effect changes continually during the early phase of treatment.

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55-2.77, ptrend = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

Pancreatic neuroendocrine neoplasms (pNEN) account for less than 5% of all pancreatic neoplasms and genetic association studies on susceptibility to the disease are limited. We sought to identify possible overlap of genetic susceptibility loci between pancreatic ductal adenocarcinoma (PDAC) and pNEN; therefore, PDAC susceptibility variants (n = 23) from Caucasian genome-wide association studies (GWAS) were genotyped in 369 pNEN cases and 3277 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium to evaluate the odds associated with pNEN risk, disease onset and tumor characteristics. Main effect analyses showed four PDAC susceptibility variants-rs9854771, rs1561927, rs9543325 and rs10919791 to be associated with pNEN risk. Subsequently, only associations with rs9543325, rs10919791 and rs1561927 were noteworthy with false positive report probability (FPRP) tests. Stratified analyses considering age at onset (50-year threshold), showed rs2736098, rs16986825 and rs9854771 to be associated with risk of developing pNEN at a younger age. Stratified analyses also showed some single nucleotide polymorphisms to be associated with different degrees of tumor grade, metastatic potential and functionality. Our results identify known GWAS PDAC susceptibility loci, which may also be involved in sporadic pNEN etiology and suggest that some genetic mechanisms governing pathogenesis of these two entities may be similar, with few of these loci being more influential in younger cases or tumor subtypes.

Hepatitis C Virus (HCV) chronic infection can be associated with extrahepatic manifestations such as mixed cryoglobulinemia and lymphoproliferative disorders that are endowed with increased rates of morbidity and all-cause mortality. In this study we used flow cytometry to evaluate the effect of Interferon-free antiviral treatment on peripheral blood lymphocytes in HCV patients with or without associated lymphoproliferative disorders. Flow cytometry analysis of peripheral blood lymphocytes were performed at baseline and at the end of treatment. In HCV infecteded patients with lymphoproliferative disorders s we evaluated Immunoglobulin (Ig) light chain κ/λ ratio variations as a measure of monoclonal B-cell response to antiviral therapy. Healthy volunteers were enrolled as controls. A total of 29 patients were included, 9 with and 20 without lymphoproliferative disorders. Sustained virological response was achieved in 29/29 patients. We observed a significant reduction of the B-cell compartment (39% global reduction) in eight out of nine HCV patients with lymphoproliferative disorders after viral clearance. We recognized the same trend, even if less pronounced, in HCV patients without lymphoproliferative disorders (9% global reduction). Among HCV patients with lymphoproliferative disorders, three showed an improvement/normalization of the Ig light chain ratio, whereas in the remaining six patients monoclonal B-cells persisted to be clonally restricted even one year after the end of treatment. Our data show that DAAs treatment can be effective in reducing the frequency of pathological B-cells in the peripheral blood of HCV patients affected by HCV-associated lymphoproliferative disorders, however monoclonal populations can persist after viral eradication. This article is protected by copyright. All rights reserved.

Expression of the solute carrier (SLC) transporter SLC22A3 gene is associated with overall survival of pancreatic cancer patients. This study tested whether genetic variability in SLC22A3 associates with pancreatic cancer risk and prognosis. Twenty four single nucleotide polymorphisms (SNPs) tagging the SLC22A3 gene sequence and regulatory elements were selected for analysis. Of these, 22 were successfully evaluated in the discovery phase while six significant or suggestive variants entered the validation phase, comprising a total study number of 1,518 cases and 3,908 controls. In the discovery phase, rs2504938, rs9364554, and rs2457571 SNPs were significantly associated with pancreatic cancer risk. Moreover, rs7758229 associated with the presence of distant metastases, while rs512077 and rs2504956 correlated with overall survival of patients. Although replicated, the association for rs9364554 did not pass multiple testing corrections in the validation phase. Contrary to the discovery stage, rs2504938 associated with survival in the validation cohort, which was more pronounced in stage IV patients. In conclusion, common variation in the SLC22A3 gene is unlikely to significantly contribute to pancreatic cancer risk. The rs2504938 SNP in SLC22A3 significantly associates with an unfavorable prognosis of pancreatic cancer patients. Further investigation of this SNP effect on the molecular and clinical phenotype is warranted. National Institute of Public Health Ministry of Education Youth and Sports of the Czech Republic Italian Cancer Genome Project Ministero Salute Pancobank Heidelberger Stiftung Chirurgie EU ERA-Net TRANSCAN Italian Ministry of Health Division of Gastroenterology, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Italy

Based on the knowledge that matrix metalloproteinases (MMPs) and S100A8/A9 synergistically work in causing PDAC-associated type 2 diabetes mellitus (T2DM), we verified whether tissue and blood MMP8, MMP9, S100A8 and S100A9 expression might help in distinguishing PDAC among diabetics.Relative quantification of MMP8, MMP9, S100A8 and S100A9 mRNA was performed in tissues obtained from 8 PDAC, 4 chronic pancreatitis (ChrPa), 4 non-PDAC tumors and in PBMCs obtained from 30 controls, 43 T2DM, 41 ChrPa, 91 PDAC and 33 pancreatic-biliary tract tumors.T2DM was observed in PDAC (66%), in pancreatic-biliary tract tumors (64%) and in ChrPa (70%). In diabetics, with or without PDAC, MMP9 tissue expression was increased (p0.05). Both MMPs increased in PDAC and MMP9 increased also in pancreatic-biliary tract tumors PBMCs. In diabetics, MMP9 was independently associated with PDAC (p=0.025), but failed to enhance CA 19-9 discriminant efficacy. A highly reduced S100A9 expression, found in 7 PDAC, was significantly correlated with a reduced overall survival (p=0.015).An increased expression of tissue and blood MMP9 reflects the presence of PDAC-associated diabetes mellitus. This finding fits with the hypothesized role of MMPs as part of the complex network linking cancer to diabetes.

AimTo identify the best management strategy for improving the appropriateness of vitamin D, vitamin B12 and folate retesting.MethodsThe study was conducted between 3 November 2012 and 8 June 2015, with inpatients and outpatients being considered separately. After an observational reference period (3 November 2012 to 14 September 2013), an information technology (IT)-based permissive strategy (16 September 2013 to 27 July 2014) followed by a limiting strategy was used to manage the demand for inpatient retesting. For outpatients, an educational strategy period (28 July 2014 to 16 December 2014) with direct contact between medical personnel and general practitioners (GPs) was followed by a post-educational period without any restriction. Data from a total of 66 496 patients for vitamin D, 14 618 for vitamin B12 and 14 445 for folate were retrieved from the laboratory IT system. The main outcomes measures were inappropriate vitamin D, vitamin B12 and folate retesting. The minimal retesting intervals were 90 (vitamin D) or 180 days (vitamin B12 and folate).ResultsIn the absence of a laboratory demand strategy, the frequency of inappropriate retesting for vitamin D, vitamin B12 and folate was 60%, 94% and 93%, respectively, for inpatients, and 27%, 87% and 87%, respectively, for outpatients. A limiting IT-based demand management strategy reduced inappropriate retesting for vitamin D (36%), but not for vitamin B12 and folate. The educational strategy was followed by a reduction in inappropriate retesting among outpatients (16% for vitamin D, 72% for vitamin B12 and folate).ConclusionsLaboratory demand management based on an IT-limiting management strategy or on education of the referring physicians appears helpful in maximising appropriate retesting.

Background The identification of specific serological algorithms allowing the diagnosis of celiac disease (CD) is a new challenge for both the clinic and the laboratory. We compared the diagnostic accuracy of three new tests proposed for CD screening with that of the well established IgA tTG, and ascertained whether any combination of these tools might enhance accuracy in diagnosing CD. Methods In sera from 329 CD and 374 control children, the following were assayed: IgA tTG; IgA/IgG, which identify tTG-gliadin complexes (Aeskulisa Celi Check and CeliCheck IgGA); IgA/IgG, which identify deamidated gliadin peptides and tTG (QUANTA Lite TM h-tTG/DGP Screen). Results When specificity was set at 100%, the most sensitive index of CD was IgA tTG (75.7%, cut-off = 100 U), followed by QUANTA Lite TM h-tTG/DGP Screen (65.3%, cut-off 145 U), Aeskulisa Celi Check (62.6%, cut-off 909 U/mL) and CeliCheck IgGA (59.6%, cut-off 977 U/mL). Three algorithms were obtained by combining IgA tTG with each of the new tests. The algorithm obtained by measuring IgA tTG and QUANTA Lite TM h-tTG/DGP Screen allowed the correct identification of CD in 78.7% of cases (negative predictive value = 97.3%). Conclusions The two-test based strategy could be used for the cost effective diagnosis of CD.

Central nervous system involvement (CNS) is a serious and mostly fatal complication of aggressive lymphoma. The incidence of CNS disease in diffuse large B-cell lymphoma (DLBCL) is low (about 5%) and there are not randomised prospective trial which specifically address a decision-making process for CNS prophylaxis. Potentially two methods exist for identifying patients requiring CNS directed treatment. Surveillance lumbar puncture and brain magnetic resonance (MRI) at the time of diagnosis could identify the presence of lymphoma; another method is the identification of patients whose characteristics are indicative of a high risk of CNS disease. Several site-specific risks are described in literature such as testicular, breast, paranasal sinuses, epidural spaces, and intravascular involvement with an incidence of CNS relapse ranging from 15% to 50%. Recently a modified IPI score (CNS IPI) was described to predict risk of CNS relapse. The efficacy of different forms of CNS prophylaxis has never formally been demonstrated. In the RICOVER 60 trial, patients treated with R-CHOP-14 instead of CHOP-14 presented a lower incidence of CNS relapse while intrathecal methotrexate (MTX) has not showed a role in preventing CNS disease for patients treated with combined immunochemotherapy. Recently, combination of intrathecal MTX and high dose MTX infusion after R-CHOP treatment was considered an effective strategy of prevention of CNS relapse. In order to evaluate the efficacy and feasibility of intrathecal MTX administration and high dose MTX after first line chemotherapy, we retrospectively reviewed 27 patients (11 males and 16 females, mean age 61 yrs, range 27-79) with newly diagnosed DLBCL at high risk for CNS relapse, treated from January 2009 to April 2018 at Veneto Institute of Oncology IOV-IRCCS. In our cohort 21 (78%) patients were at advanced stage (III-IV Ann Arbor stage) and 15 (56%) belonged to intermediate-high or high risk IPI categories, two patients presented with orbital localization. Almost all patients received R-CHOP as first line treatments, two patients with paravertebral localization received HyperCVAD as front line approach. For 20 patients CNS-IPI was intermediate or high. In the other cases with low CNS-IPI, disease localization was considered at high risk of CNS relapse (breast, paravertebral, orbit, paranasal sinus). In all patients we performed brain MRI and diagnostic lumbar puncture at diagnosis (all negative at flow cytometry analysis). All 14 patients >65 yrs were evaluated with comprehensive geriatric assessment (CGA) and 8 (57%) were considered fit. Nineteen (19) patients (70%) received at least 3 lumbar punctures with MTX and 24 (89%) two courses of high dose intravenous MTX during first line therapy. At the end of planned first line treatment, 24 (89%) patients obtained a complete remission at PET scan evaluation and 3 patients (11%) presented progressive disease, 2 with CNS involvement and another with peritoneal disease; this last patient had a Double Hit lymphoma with BCL6 and c-MYC rearrangements. Another patient in complete remission after R-CHOP chemotherapy, experienced CNS relapse three year after obtaining complete remission. Among the two patients treated with Hyper CVAD regimen, one is still in complete remission 5 years after the end of treatment; another developed early CNS relapse. All the 3 patient who experienced CNS involvement after R-CHOP, didn't receive prophylaxis because were evaluated frail at CGA. So, at a median follow up of 26.2 months (3.5-100 months) all patients who received the planned treatment at full dose including CNS prophylaxis did not experience central nervous system relapse. In conclusion, CNS prophylaxis including intrathecal MTX administration and high dose MTX infusion after first line chemotherapy is feasible and effective. Larger prospective trials are needed to evaluate the most effective prophylactic therapy and the correct timing of intravenous MTX infusion. Disclosures No relevant conflicts of interest to declare.

UNLABELLED:Genotype-guided warfarin dosing have been proposed to improve patient’s management. This study is aimed to determine whether a CYP2C9- VKORC1- CYP4F2-based pharmacogenetic algorithm is superior to a standard, clinically adopted, pharmacodynamic method. Two-hundred naïve patients with non-valvular atrial fibrillation were randomized to trial arms and 180 completed the study. No significant differences were found in the number of out-of-range INRs (INR3.0) (p = 0.79) and in the mean percentage of time spent in the therapeutic range (TTR) after 19 days in the pharmacogenetic (51.9%) and in the control arm (53.2%, p = 0.71). The percentage of time spent at INR>4.0 was significantly lower in the pharmacogenetic (0.7%) than in the control arm (1.8%) (p = 0.02). Genotype-guided warfarin dosing is not superior in overall anticoagulation control when compared to accurate clinical standard of care. TRIAL REGISTRATION:ClinicalTrials.gov NCT01178034.

OBJECTIVES Anti-tissue transglutaminase antibody (anti-tTG) determination using second-generation (human antigen) enzyme-linked immunoassays (ELISAs) is a very accurate test to diagnose celiac disease (CD). In this study, we compared 2 second-generation ELISAs (Celikey tTG; Pharmacia Diagnostics GmbH & Co, Freiburg, Germany, and QuantaLite; Inova Diagnostics, San Diego, CA) and antiendomysial antibodies (EMAs) with a new indirect chemiluminescence immunoassay (LIAISON tTG; DiaSorin S.p.A., Saluggia, Italy) in diagnosing and monitoring CD in children. PATIENTS AND METHODS Antiendomysial antibodies, anti-tTGs and total immunoglobulin A were measured in the sera of 103 control children, 101 children with histologically proven CD and 31 CD children on gluten-free diet (GFD). RESULTS Anti-tissue transglutaminase antibody mean levels were significantly higher in CD with respect to control or GFD children. The sensitivity value of EMAs, LIAISON tTG, Celikey tTG and QuantaLite in diagnosing CD was 97.7%, 97.0%, 94.1% and 98.0%, respectively, and the corresponding specificity values were 91.1%, 98.1%, 97.1% and 96.1%, respectively. The degree of mucosal destruction (Marsh criteria) was correlated with EMA semiquantification (P < 0.01) and with the circulating levels of anti-tTGs measured using LIAISON (P < 0.05) or QuantaLite (P < 0.01). Twenty-six CD children were followed up from 5 to 25 months after GFD. The circulating levels of anti-tTGs measured with any of the 3 assays significantly dropped after GFD. CONCLUSIONS Anti-tissue transglutaminase antibody determination with second-generation ELISAs is as effective as EMAs for CD diagnosis. The novel chemiluminescent method described in the present paper for the detection of anti-tTGs in the diagnosis of CD had the highest sensitivity and specificity values. The anti-tTG test correlates with the degree of mucosal destruction and is suitable for verifying patient compliance to dietary treatment.

Background Our aim was to identify the pancreatic cancer diabetogenic peptide. Methods Pancreatic tumor samples from patients with (n = 15) or without (n = 7) diabetes were compared with 6 non-neoplastic pancreas samples using SDS-PAGE. Results A band measuring approximately 1500 Da was detected in tumors from diabetics, but not in neoplastic samples from non-diabetics or samples from non-neoplastic subjects. Sequence analysis revealed a 14 amino acid peptide (1589.88 Da), corresponding to the N-terminal of the S100A8. At 50 nmol/L and 2 mmol/L, this peptide significantly reduced glucose consumption and lactate production by cultured C2C12 myoblasts. The 14 amino acid peptide caused a lack of myotubular differentiation, the presence of polynucleated cells and caspase-3 activation. Conclusions The 14 amino acid peptide from S100A8 impairs the catabolism of glucose by myoblasts in vitro and may cause hyperglycemia in vivo. Its identification in biological fluids might be helpful in diagnosing pancreatic cancer in patients with recent onset diabetes mellitus.

Aim: To study in vivo whether pancreatic cancer tumour growth and metastasis can be modified by a gene construct with HSV-TK suicide gene and IL2 co-expression. Methods: Seventy-eight female SCID mice were i.p. inoculated with retrovirally transduced or control MIA PaCa 2, CAPAN-1 and PANC-1 cell lines. The animals were then randomly selected for saline or ganciclovir (GCV) treatment from the second week, for a total of two weeks. Results: Most inoculated mice developed tumour nodules and spleen metastases. The liver was colonized by control CAPAN-1 and MIA PaCa 2, but not by PANC-1. Tumours in transduced MIA PaCa 2 cell injected mice were smaller, and in transduced CAPAN-1 injected mice larger, than in control-inoculated mice. There were increased pancreatic and decreased spleen metastases from transduced CAPAN-1, and diminished liver involvement from transduced MIA PaCa 2. No differences were found between mice inoculated with transduced and control PANC-1 cell lines. GCV treatment had no effect on tumour's size or metastases. Conclusions: The HSV-TK suicide gene does not confer GCV sensitivity to pancreatic cancer in this in vivo model. Different pancreatic cancer cell lines cause different growth and metastasis patterns after inoculation in SCID mice, possibly because of variations in their inherent characteristics. The different effects of our vector on cell growth and metastasis may be attributable to the effects of the immunostimulatory cytokine IL2.

Background. The aims of our study were twofold. First, we sought to evaluate in symptomatic children the influence of the Helicobacter pylori genotype on gastritis, abdominal pain, and circulating anti–H. pylori IgG antibodies (anti–H. pylori IgG) or pepsinogen A (PGA) and C (PGC). Additionally, we sought to assess anti–H. pylori IgG, PGA, and PGC patterns in a large cohort (N = 921) of asymptomatic children. Materials and Methods. In 183 symptomatic children, H. pylori infection and the presence of gastritis were evaluated by histology. In a subgroup of 20 H. pylori–positive children, the H. pylori genotype was evaluated also by polymerase chain reaction. Nine hundred and twenty-one asymptomatic children, aged 11 to 14 years, were studied by anti–H. pylori IgG, PGA, and PGC serum determination. Results. The infection was found in 33 of 183 symptomatic children; among the 20 H. pylori–positive children for which the H. pylori genotype was available, cagA was present or absent in equal percentages. H. pylori infection was associated with more severe gastritis and higher serum levels of anti–H. pylori IgG and PGC but not with abdominal pain. In infected children, higher levels of anti–H. pylori IgG and the presence of abdominal pain were associated with infections caused by cagA-positive strains. In the cohort of 921 asymptomatic children, raised levels of anti–H. pylori IgG, PGA, and PGC were found in approximately 5% of the cases. Conclusions. Infection with cagA-positive H. pylori strains can be associated with increased frequency of reported abdominal pain and higher circulating levels of anti–H. pylori IgG. The serological assessment of H. pylori IgG using H. pylori antigens containing significant amounts of cagA protein may, therefore, underestimate the true prevalence of infection.

OBJECTIVES: To identify new biomarkers of pancreatic cancer (PaCa), we performed MALDI-TOF/MS analysis of sera from 22 controls, 51 PaCa, 37 chronic pancreatitis, 24 type II diabetes mellitus (DM), 29 gastric cancer (GC), and 24 chronic gastritis (CG). METHODS: Sera were purified by Sep-Pak C18 before MALDI-TOF/MS Anchorchip analysis. RESULTS: Features present in at least 5% of all spectra were selected (n = 160, m/z range, 1200-5000). At univariate analysis, 2 features (m/z 2049 and 2305) correlated with PaCa, 3 (m/z 1449, 1605, and 2006) with DM. No feature characterized gastric cancer or chronic gastritis. Ten-fold cross-validation binary recursive partitioning trees were obtained for patients' classification. The tree (CA 19-9, age, m/z 2006, 2599, 2753, and 4997), built considering only patients with diabetes, allowed a distinction between DM [area under the receiver operating characteristic curve (AUC), 0.997], chronic pancreatitis (AUC, 0.968), and PaCa (AUC, 0.980), with an overall correct classification rate of 89%. The tree including CA 19-9, 1550, and 2937 m/z features, achieved an AUC of 0.970 in distinguishing localized from advanced PaCa. MALDI-TOF-TOF analysis revealed the 1550 feature as a fragment of Apo-A1, which was determined as whole protein and demonstrated to be closely correlated with PaCa. CONCLUSIONS: The findings made demonstrate a role for serum peptides identified using MALDI-TOF/MS for addressing PaCa diagnosis. Copyright © 2013 Lippincott Williams & Wilkins.

Within-individual biological variation of INR (CV(B)) was assessed in 245 selected stable warfarin-treated patients monitored by three thrombosis centers. Selection criteria were: treatment period of six months or longer before the observation period; at least six consecutive INRs within the therapeutic range of 2.0 - 3.0; interval between consecutive INR measurements of two weeks or longer; no change in warfarin dose; no changes in the patient's circumstances which may influence the INR, such as intercurrent diseases, invasive procedures, starting or stopping drugs interacting with warfarin. The minimum, maximum and mean within-individual coefficient of variation CV(B) of the INR measurements in the 245 selected patients were 0.4%, 14.5%, and 9.0%, respectively Analytical performance goals for the INR measurement (imprecision) could be derived from the mean CV(B). For a therapeutic range of 2.0 - 3.0 with warfarin, the desirable and optimum imprecision of INR determination is

Pancreatic cancer is the fourth leading cause of cancer deaths in the European Union and in the USA, but little is known about its genetic susceptibility. The PANcreatic Disease ReseArch (PANDoRA) consortium was established to unite the efforts of different research groups; its aim is to create a large bio-database to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. So far 2220 cases of pancreatic adenocarcinoma, a smaller number of cases of endocrine pancreatic tumours (n = 86), chronic pancreatitis (n = 272) and 3847 healthy controls have been collected. As a collective effort of the consortium, SNPs associated with pancreatic adenocarcinoma risk from a genome-wide association study performed in Caucasians were replicated. The possibility that the same genetic polymorphisms may influence patient survival as well was also addressed. This collective effort is particularly important for pancreatic cancer because it is a relatively rare disease for which little is known about aetiopathogenesis and risk factors. The recruitment of additional collaborators and partner institutions is continuously on-going.

Of serum prostate specific antigen variability 40% depends on inherited factors. We ascertained whether the knowledge of KLK3 genetics would enhance prostate specific antigen diagnostic performance in patients with clinical suspicion of prostate cancer.We studied 1,058 men who consecutively underwent prostate biopsy for clinical suspicion of prostate cancer. At histology prostate cancer was present in 401 cases and absent in 657. Serum total prostate specific antigen and the free-to-total prostate specific antigen ratio were determined. Four polymorphisms of the KLK3 gene (rs2569733, rs2739448, rs925013 and rs2735839) and 1 polymorphism of the SRD5A2 gene (rs523349) were studied. The influence of genetics on prostate specific antigen variability was evaluated by multivariate linear regression analysis. The performance of total prostate specific antigen and the free-to-total prostate specific antigen ratio alone or combined with a genetically based patient classification were defined by ROC curve analyses.For prostate cancer diagnosis the free-to-total prostate specific antigen ratio index alone (cutoff 11%) was superior to total prostate specific antigen (cutoff 4 ng/ml) and to free-to-total prostate specific antigen ratio reflex testing (positive predictive value 61%, 43% and 54%, respectively). Prostate specific antigen correlated with KLK3 genetics (rs2735839 polymorphism p = 0.001, and rs2569733, rs2739448 and rs925013 haplotype combination p = 0.003). In patients with different KLK3 genetics 2 optimal free-to-total prostate specific antigen ratio cutoffs (11% and 14.5%) were found. For free-to-total prostate specific antigen ratio values between 11% and 14.5% the prostate cancer probability ranged from 30.0% to 47.4% according to patient genetics.The free-to-total prostate specific antigen ratio is superior to total prostate specific antigen for prostate cancer diagnosis, independent of total prostate specific antigen results. Free-to-total prostate specific antigen ratio findings below 11% are positively associated with prostate cancer and those above 14.5% are negatively associated with prostate cancer, while the interpretation of those between 11% and 14.5% is improved by patient KLK3 genetic analysis.

s / Pancreatology 12 (2012) 502–597 505 Results: During the course of the study, the average level of IL-6 was significantly (p

Backround: In pancreatic cancer (PaCa) S100A8 is highly expressed by stromal and cancer cells. Moreover S100A8 and its binding partner S100A9 are suggested to be involved in cancer progression and in cancer-associated diabetes mellitus.Our aim was to analyze S100A8 and S100A9 expression levels in peripheral blood mononuclear cells of patients with PaCa, chronic pancreatitis (ChrPa) or pancreatobiliary tract tumors (PBT) and to ascertain S100A8/S100A9 on PaCa Akt and NF-kB signalling. Methods: 55 PaCa, 12 ChrPa and 15 PBT were studied. S100A8 and S100A9 mRNA expression levels were quantified by RT-PCR (Taqman chemistry). Capan-1 and MiaPaCa2 cell lines were used to analyze S100A8, S100A9 effects on Akt (pAkt473) and NF-kB (pIkBa) signalling by western blotting. Results: S100A8 and S100A9 expression levels were correlated with each other (r=0.637, p

To evaluate beta-cell function in patients with pancreatic cancer, the glucagon stimulation test was performed in seven patients with pancreatic adenocarcinoma, seven patients with type I diabetes mellitus, seven patients with type II diabetes mellitus, and in seven healthy controls. C-peptide serum levels were determined before and after a 1-mg i.v. glucagon injection. Basal C-peptide values were normal or slightly increased in pancreatic cancer and type II diabetic patients and low in type I diabetic patients. Following glucagon stimulation, no significant increase was observed in C-peptide values of type I diabetics and pancreatic cancer patients, whereas significant increases occurred in controls and type II diabetics. It is concluded that the altered beta-cell function found in pancreatic cancer patients may lead to hyperglycemia, which is frequently associated with this tumor type.

Aim: A total of 371 patients under stable warfarin therapy were retrospectively selected to develop a pharmacogenetic algorithm to identify the individual maintenance dose. Materials & methods: The variables that were entered into the algorithm were: VKORC1, CYP2C9 and CYP4F2 polymorphisms, body surface area and age. Results: The percentage of cases whose predicted mean weekly warfarin dose was within 20% of the actual maintenance dose was 51.8% considering patients overall, and were 36.2, 66.2 and 55.4%, respectively, taking into account patients requiring low (≤25 mg/week), intermediate (25–45 mg/week) and high (≥45 mg/week) doses. The algorithm could correctly assign 73.8 and 63.2% of patients to the low- and high-dose regimens, respectively. We developed and validated a pharmacogenetic algorithm in a series of Italian patients, we then tested, in the same series of italian patients, the formulas of three published algorithms. These three algorithms were developed and validated by their authors in a series of patients different from our own. The performance of our algorithm in our patients series was slightly higher than that achieved when using the three other algorithms in our patients series. Conclusion: The high predictive accuracy of low and high warfarin requirements of our algorithm warrants its application in prospective studies for clinical validation.

Background: AGA IgA II and AGA IgG II have recently been suggested as reliable tools for celiac disease (CD) diagnosis. We compared their utility for diagnosis and monitoring CD in children with that of tTG IgA, an established CD marker.Methods: We studied a cohort of 161 CD and 129 control children in whom CD was histologically confirmed or ruled out. We followed 37 children with CD on a gluten-free diet for 12–84 months. In fasting sera, we measured AGA IgA II, AGA IgG II, and tTG IgA using ELISAs.Results: The best sensitivity (92.5%), specificity (97.6%), positive predictive value (98%), and negative predictive value (91.2%) were obtained using tTG IgA. AGA IgG II correctly identified 3 of 3 children with CD with total IgA deficiency who had negative AGA IgA II and tTG IgA results. In children Conclusions: The best available index for diagnosing CD in children was tTG IgA. In infants

Variations in urinary kallikrein in pancreatic diseases were ascertained, and possible influencing factors were investigated. Serum amylase and urinary excretion of glandular kallikrein, pancreatic ribonuclease (RNase), gamma-glutamyltransferase (GGT) and amylase were measured in 24 control subjects, 39 patients with pancreatic cancer, 49 with pancreatitis and 63 with extra-pancreatic diseases. Urinary kallikrein was found to be elevated in a substantial number of patients with pancreatitis. Higher levels were detected in patients with a relapse, which was diagnosed using clinical and biochemical examinations. RNase was also increased in a high number of patients with pancreatic diseases, but was not correlated with pancreatic damage. In patients with pancreatitis, a correlation was found between urinary kallikrein and RNase excretions. No correlations were found between kallikrein and serum or urinary amylase and GGT. We can conclude that urinary kallikrein excretion increases in pancreatitis, especially when a phlogistic involvement of the pancreas is present; this condition may lead to a release of this ultrafiltrable enzyme in the circulation. Renal tubular damage, which determines a reduced reabsorption of this enzyme, seems to play a concomitant but minor role in this process.

Background The combined evaluation of serum pepsinogens A (PGA) and C (PGC), gastrin-17 (G17) and anti- H. pylori antibodies (anti- H. pylori )(GastroPanel) has recently been proposed as a useful aid for investigating H. pylori -associated gastric mucosal inflammation. Our aim was to evaluate whether GastroPanel can correctly classify children who need or not endoscopy (EGD). Methods GastroPanel was performed in 554 consecutive children subjected to EGD. Results PGC and anti- H. pylori were sensitive (82.5% and 73.1%) and specific (58.1% and 84.0%) indices of H. pylori infection. Antral H. pylori colonization density, inflammation and activity grades were correlated with PGC. PGC and G17 were significantly higher in children with celiac disease (14.9 ± 0.88 µg/L and 5.6 ± 0.79 pmol/L) than in controls (8.5 ± 0.38 µg/L and 2.4 ± 0.24 pmol/L). The best cut-offs to distinguish H. pylori infected children from controls were 7.45 µg/L for PGC, 4.2 pmol/L for G17, 18 U for anti- H. pylori and 25 µg/L for PGA. With these cut-offs, GastroPanel had a NPV of 89.6% and a PPV of 66.8%. Conclusions A negative GastroPanel result in children with upper abdominal non alarm symptoms, should allow the paediatrician to reasonably rule out the presence of major gastro-duodenal diseases and therefore avoid EGD.

The present report focuses on the diagnosis of celiac disease and its pathogenesis, which depends on a genetic predisposition (HLA DQ2 or DQ8 haplotypes), gluten ingestion and T cell activation, type II transglutaminase (TG2), the autoantigen recognized by the antiendomysial antibody playing a key role. IgA class antibody anti-environmental (gliadin) and endogenous (TG2) antigens are present in the sera of patients with celiac disease. The anti-TG2 antibody has the best available diagnostic accuracy, especially when measured employing second generation ELISA tests, which use the human TG2 antigen, or immunochemiluminescent assay, which is highly sensitive. A diagnosis of celiac disease must always be confirmed by the histological evaluation of multiple duodenal mucosa specimens, and serology is recommended for follow-up controls.

An impaired host immunity might concur in determining the dismal prognosis of patients with pancreatic cancer (PC). Our aim was to ascertain whether the immunophenotype pattern of blood lymphocytes in PC correlates with tumor stage, grade, or survival.We studied 115 patients with PC, 44 with chronic pancreatitis (CP), 23 with tumors of the pancreatico-biliary tract, and 34 healthy controls (CS). Survival data were available for 77 patients with PC. Lymphocyte subsets were determined by fluorescent activated cell sorter (FACS) analysis.In patients with PC, total lymphocyte counts were lower than in CP or CS, and CD8 lymphocyte subset levels were higher with respect to CS. Lower circulating lymphocytes were found in advanced PC stages (IIB-IV; chi2 = 11.55, P0.05) compared with stages 0 to IIA. Cox regression analysis, made considering total lymphocyte counts and tumor stage as covariates, was found to be significant for both tumor stage (P0.001) and total lymphocyte counts (P0.05).The reduction of total lymphocytes in blood is the main immunologic change in advanced PC. The survival of these patients depends mainly on tumor stage, but it is also affected by the number of circulating lymphocytes, suggesting that the immune system plays an important role in pancreatic adenocarcinoma immunosurveillance and immunoediting.

Objectives: Our aim was to verify whether the quantitative determination of PSA mRNA in circulating cells is helpful in diagnosing and scoring localized prostate cancer (PC). Design and methods: The study included 145 patients with benign prostatic hyperplasia (BPH), 138 with localized PC and 28 healthy controls (CS). PSA cDNA was amplified by real-time PCR from circulating mononuclear cells. Serum total and free PSA were determined. Prostate cancers were histologically scored according to the Gleason criteria. Results: The most sensitive index of PC was tPSA (70%), and the most specific was f/t PSA (80%). High PSA mRNA was found more frequently in PC patients with poorly differentiated (23.1%) than in those with well (4.5%) or moderately (4.3%) differentiated tumors. Conclusions: tPSA and f/t PSA are the best available tools for discriminating between localized PC and BPH. The quantitative assessment of PSA mRNA in blood might be helpful in the biochemical grading of prostate cancer.

Objectives: (1) To compare two stool antigen EIAs (HpSA, FemtoLab) and PCR of ureaseA and cagA in feces, with 13 C-urea breath test (UBT). (2) To ascertain whether a simplified UBT (breath collection time = 10 min) is as reliable as the standard assay (30 min). Design and Methods: Helicobacter pylori status was recorded in Group 1 ( n = 187) by UBT, H. pylori stool antigen, ureA and cagA PCR in feces. UBT with 10, 20 and 30 min sampling was performed in Group 2 patients ( n = 283). Results: The sensitivity and specificity of HpSA, FemtoLab, and ureA were 67% and 99%, 90% and 96%, 35% and 98%, respectively. cagA results were positive in 16/48 H. pylori -positive, and in 5/100 H. pylori −negative patients. The results of UBT with a 10- and 30-min sampling strictly overlapped. Conclusion: UBT with 10 min breath collection and FemtoLab stool antigen assay are the most reliable non-invasive tests to diagnose H. pylori infection.

Objective: It has been suggested that the molecular identification of cancer cells in the circulation may be useful in predicting the presence of micrometastasis in several cancer types. The aim of the present study was therefore to assess the feasibility of CEA mRNA identification in blood for diagnosing and staging colorectal, gastric and pancreatic cancer. Methods: We studied 16 control subjects, 69 patients with colorectal (CRC), 30 with gastric (GC), 27 with pancreatic cancer (PC) and 8 with benign diseases of the pancreatobiliary tree. At diagnosis CEA mRNA was identified in peripheral blood by means of a RT-PCR procedure. Results: The specificity of this test in control subjects was 94%, and its sensitivity in identifying CRC, GC and PC were 34, 37 and 41%, respectively. False-positive findings were recorded in 25% patients with benign diseases. No association was found between CEA mRNA and stage in patients with GC or PC. In CRC patients, positive CEA mRNA findings were correlated with local spread (χ2 = 14.6, p < 0.01), lymph node (χ2 = 18.95, p < 0.001) and distant metastasis (χ2 = 11.3, p < 0.001). In these cases, CEA mRNA, but not CEA, was entered in stepwise discriminant analysis to classify the presence of lymph node metastasis. Conclusions: The molecular detection of micrometastasis in the blood by means of CEA mRNA identification is feasible for colorectal, but not for gastric or pancreatic cancer staging. Further studies are needed in order to define the clinical utility of this marker also in follow-up protocols.

Objectives. To ascertain when the serum determination of the free prostate-specific antigen (PSA)/total PSA (fPSA/tPSA) ratio is clinically useful, and whether the identification of PSA or prostate-specific membrane antigen (PSM) mRNA in circulating cells has diagnostic advantages over the determination of their protein product. Methods. fPSA, tPSA, and the fPSA/tPSA ratio were determined in the sera of 50 men with benign nonprostatic urologic diseases (EPD), 112 patients with prostate cancer (PCa), and 218 with benign prostatic hyperplasia (BPH). mRNA was extracted from the circulating mononuclear cells of 13 EPD samples, 25 PCa samples, and 38 BPH samples. PSA and PSM mRNA signals were identified in these samples by means of reverse transcriptase-polymerase chain reaction. Results. Overall, at a fixed specificity of 95%, the sensitivity of tPSA was 19% and that of the fPSA/tPSA ratio was 40% in distinguishing PCa from BPH. The fPSA/tPSA ratio allowed the discrimination of PCa from BPH with satisfactory sensitivity and specificity when considering patients less than 60 years of age (100% and 95%, respectively). PSA and PSM mRNA were positive in 1 and 7 of 13 EPD samples, 6 and 13 of 25 PCa samples, and 6 and 17 of 38 BPH samples. The Gleason score did not correlate with tPSA, the fPSA/tPSA ratio, PSA mRNA, or PSM mRNA. Conclusions. The serum determination of the fPSA/tPSA ratio is an excellent index of PCa for subjects younger than 60 years of age; the clinical utility of PSA mRNA identification in circulating cells needs to be validated by large follow-up studies, and the analysis of PSM mRNA seems to be of no clinical interest.

The usefulness of serum DU-PAN-2 in diagnosing pancreatic cancer and in distinguishing between this cancer and other benign and malignant diseases, and to assess the role of liver dysfunction in altering the serum levels of this marker were investigated. DU-PAN-2 was measured in the sera of 31 patients with pancreatic cancer, 32 with chronic pancreatitis, 20 with benign and 21 with malignant extra-pancreatic diseases. DU-PAN-2 was found to be above 300 U ml-1 in 21/31 patients with pancreatic cancer (sensitivity 68%). Only 3/32 patients with chronic pancreatitis had abnormal values. A substantial number of patients with both benign and malignant extra-pancreatic diseases had an elevated serum DU-PAN-2 (9/20 and 15/21, respectively). Correlations were found between DU-PAN-2 and (1) total bilirubin, (2) alanine-amino-transferase and (3) alkaline phosphatase. Of the patients with high DU-PAN-2 values, jaundice was found in: 2/3 with chronic pancreatitis, 9/10 with benign and 12/14 with malignant extra-pancreatic diseases. In conclusion, the serum DU-PAN-2 test for pancreatic malignancy is not completely satisfactory, because it is not sensitive enough. While the test for chronic pancreatitis has an acceptable specificity, the assay cannot distinguish between pancreatic cancer and other extra-pancreatic diseases, mainly of the liver and biliary tract. Liver dysfunction as well as jaundice seem to considerable affect the levels of this marker, as reported elsewhere for CA 19-9.

Interleukin 6 (IL-6), an autocrine growth factor for many tumors, seems to favour tumor spread to the liver. Our aims were first to evaluate the pattern of portal and systemic IL-6 levels in patients with pancreatic cancer (PC, n =18) and chronic pancreatitis (CP, n =22) compared with controls (CS, n =20); and second, to ascertain whether there was any relation between IL-6 levels and tumor spread or PC-associated Diabetes mellitus. For all subjects, a fasting serum sample was obtained from a cubital vein; a portal serum sample was obtained from nine PC and three CP patients. In cubital and portal sera we measured IL-6, interleukin 1 beta (IL-1b), CA 19-9, c-reactive protein (CRP) and amylase. Systemic IL-6 levels were significantly higher in PC patients than in CS. In PC, portal IL-6 levels were significantly higher than the corresponding systemic values. The same pattern was found in the three CP patients, whereas IL-1b, CA 19-9, CRP and amylase portal levels were the same as systemic values. No correlation was found between PC stage and systemic or portal IL-6 levels. Portal IL-6 levels were correlated with the corresponding fasting serum glucose values. A significant correlation was found between IL-6 values and CRP, ALT, total bilirubin, GGT and creatinine, but not amylase. In conclusion: (1) Portal IL-6, which is partly of pancreatic origin, is first metabolised in the liver; (2) Systemic IL-6 reflects hepatic and renal functions rather than local conditions in the pancreas; (3) IL-6 does not appear to influence PC spread; (4) IL-6, which is released in large amounts by the inflamed pancreas, may contribute to determining diabetes, thus interfering with the signal transducing pathways involved in glucose metabolism in liver cells.

An expansion of different myeloid derived suppressive cell (MDSC) subsets can be detected in the blood and secondary lymphoid organs of early and advanced pancreatic ductal adenocarcinoma (PDAC) patients. Double negative (CD14−HLA-DR−) MDSCs are frequently induced by PDACs. In addition, by releasing S100A8 and S100A9, advanced PDAC lesions cause an expansion of highly immunosuppressive CD33+CD14+HLA-DR− monocytic MDSCs expressing low levels of cytotoxic T lymphocyte antigen 4 (CTLA4) on the cell surface.

s / Pancreatology 13 (2013) S2–S98 S81 OR body mass index OR lean tissue loss OR fat free mass). Relevant Abstracts were read, eligible articles retrieved and a manual search of the bibliographies performed. The «related article» function in PubMed was used to identify missed studies. English language relevant clinical studies of any level of evidence were included. Unpublished data, Abstract or duplicate publications were excluded. Results: Two articles were found of 343 articles and related research. Two retrospective trials included 152 patients with inoperable pancreatic adenocarcinoma. The prevalence of sarcopenia was 62(56%) and 26(63%) patients. All had advanced cancer and underwent chemotherapy/chemoradiation. Sarcopenia was assessed by means of CT-scan skeletal muscle calculation. Sarcopenia alone was not significantly associated with poor survival. In multivariate analysis sarcopenic obesity but not sarcopenia alone was associated with significantly lower survival. Conclusion: The systematic review showed the lack of data about sarcopenia impact on survival in patients with pancreatic cancer. It justifies the need of further research. PII-96 Abstract id: 85. Liver resection for metastatic periampullary cancer: Is it (sometimes) worthwile? Nicola Zanini , Raffaele Lombardi , Luca Valeriani , Dario de Biase , Francesco Cinquantini , Adele Fornelli , Michele Masetti , Elio Jovine . Dept of Surgery, Maggiore Hospital, Bologna, Italy Dept of Clinical Nutrition, Maggiore Hospital, Bologna, Italy University of Bologna, Bologna, Italy Dept of Radiology, Maggiore Hospital, Bologna, Italy Dept of Pathology, Maggiore Hospital, Bologna, Italy Introduction: Surgery is generally not indicated for metastatic periampullary adenocarcinoma because it does not appear to improve survival. Aims: Is metastastic periampullary cancer an absolute contraindication to surgery? Could someone benefit from liver resection? Patients & methods: Our prospectively collected database (20032012) lists 21 patients who underwent liver resection for metastases from periampullary adenocarcinoma. Resection was offered to young patients who were fit for surgery and had few synchronous or metachronous metastases. Potential prognostic factors were taken into consideration to design a score that was applied to the study population to predict survival. Results: Ductal carcinoma was the primary tumor in 15 patients; the remaining patients had ampullary carcinoma or distal bile duct carcinoma. One right hepatectomy, 2 bisegmentectomies and 18 atypical resections were performed. Simultaneous liver and pancreatic resection did not significantly improve postoperative morbidity and mortality compared to standard pancreatic resection. The median overall survival from liver resection (OS) of patients with synchronous and metachronous disease was 11.4 months (95% CI: 6.0-16.9) and 28.5 months (95% CI: 1.7-55.2), respectively (p1⁄40.12). The proposed score was able to divide the subjects into three classes of prognosis, inwhich the estimated OS was significantly different. Conclusion: Surgery for liver metastases from periampullary tumors is controversial. It is not suggested for most patients, and death may occur even earlier compared to palliative cure. However, a small group of highly select patients could benefit from surgery. PII-97 Abstract id: 109. MMP9 and S100A9 expression in peripheral blood mononuclear cells (PBMC) are correlated with PDAC and with PDAC-associated diabetes mellitus Stefania Moz , Dania Bozzato , Carlo Federico Zambon , Paola Fogar , Michela Pelloso , Anna Caterina Milanetto , Andrea Padoan , Filippo Navaglia , Eliana Greco , Claudio Pasquali , Mario Plebani , Daniela Basso . Department of Medicine DIMED,University of Padova., Italy Department of Surgical, Oncological and Gastroenterological Sciences DISCOG; University of Padova, Italy Introduction: Tumor-stroma-endocrine interactions favour pancreatic adenocarcinoma (PDAC) growth/progression and PDAC-associated diabetes mellitus (DM). S100A8/A9 and the matrix methalloproteinases (MMPs) 8 and 9 are overexpressed in PDAC stroma. Aims: To verify whether S100A8, S100A9, MMP8 and MMP9 mRNA in PBMC is useful for diagnosing and staging PDAC and/or for detecting PDACassociated DM. To study the impact of S100A8/A9 and of PDAC-associated growth factors and cytokines on MMPs expression. Patients & methods: S100A8, S100A9, MMP8 e MMP9 mRNA were quantified by qRT-PCR in 62 PDAC, 37 chronic pancreatitis, 23 pancreatobiliary tract tumors (PBT) and 30 healthy controls (HC). PBMC (blood donors) were treated with insulin, EGF, TGFb1, S100A8/A9 before MMP8 and MMP9 mRNA analysis. Results:MMP8 andMMP9 were higher in PDAC and in PBT than in HC (Kruskal-Wallis Test: p

The effect of an acid-protected pancreatic enzyme preparation was evaluated in 10 patients with chronic pancreatitis and steatorrhea. (Twelve patients were enrolled but two withdrew because of poor compliance.) Fecal fat excretion and stool weight were measured, a p -aminobenzoic acid (PABA) test was performed, and gastrointestinal symptoms were assessed before and after 4 weeks of treatment with a standardized dose of pancreatic enzymes (two capsules three times daily, each capsule containing 13,000 FU [Italian Official Pharmacopeia] units of lipase). After treatment, we observed a statistically significant reduction in fecal fat excretion and stool weight as well as improved PABA test results and symptoms. This study confirmed the efficacy of this pancreatic enzyme preparation in the treatment of patients with pancreatogenic steatorrhea.

The present review focuses on the utility of serum tumor markers in screening, diagnosis, prognosis and monitoring of pancreatic cancer. Serum determination of all tumor markers studied offers no help in screening or early diagnosis of pancreatic cancer. For diagnosis, blood group-related antigens, in particular CA 19-9, are considered the best indicators of this neoplasm. However, as occurs with other glycoproteic tumor markers, the circulating levels of CA 19-9 are significantly influenced by jaundice, probably because its liver metabolism is reduced. Therefore, the finding of elevated CA 19-9 levels in jaundiced patients has to be evaluated with caution. Since pancreatic cancer recurrences are not susceptible to treatment, the clinical role of widespread use of tumor marker determination in follow-up programs is limited and calls for a critical evaluation.

We evaluated levels of insulin-like growth factor-I and interleukin-1 alpha and beta in patients with pancreatic cancer; the role of these substances in tumor spread and in hyperglycemia was also investigated. Thirty pancreatic cancer patients (21 with hyperglycemia) were compared with others with diseases causing hyperglycemia [liver cirrhosis (14 cases, 12 with hyperglycemia), chronic pancreatitis (20 cases, 12 with hyperglycemia), type I diabetes mellitus (13 cases, all hyperglycemic)]. Insulin-like growth factor-I was significantly reduced in patients with liver cirrhosis, probably due to a reduced hepatic capacity for synthesis. It was increased in 6 of 30 pancreatic cancer patients; in these subjects it was correlated with alanine aminotransferase and C-peptide, but not with tumor diameter or the presence of metastases. Interleukin-1 alpha and beta were both elevated in pancreatic cancer patients. The former was high, while the latter was low when liver metastases were present. Neither was related to glucose or C-peptide levels. In summary, insulin-like growth factor-I levels are increased in some pancreatic cancer patients but this does not seem to favor tumor spread; however IGF-I could be involved influencing glucose homeostasis. Interleukin-1 alpha increased, while interleukin-1 beta decreased in pancreatic cancer patients with metastases, suggesting a different involvement of these two substances in pancreatic cancer spread.