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With face-to-face interaction proving beneficial for mental health, there is still a paucity of research on the correlation between ground floor features (GFFs), defined here as the features of the ground floor of buildings overlooking a street, and public open space face-to-face interaction density (POSFTFID), defined as the density of human face-to-face interactions in the public open space (POS) adjacent to each building. Is there a correlation between GFFs and POSFTFID? This study aims to answer this question gaining empirical evidence from a Chinese village in the city (ViC). Behavioural mapping and statistical analysis were employed and the following GFFs were tested: Ground floor area, indoor visible space, presence of stairs, POS adjacent area, and land use. Results show an association between POSFTFID and: (1) The area of the POS adjacent to each building, (2) the degree of visibility (ratio of indoor visible space to total internal space) of the ground floor, (3) the presence of stairs. Moreover, food appears to be an important attribute fostering social interaction. Results can provide insights on future implications in urban design strategies and planning policies aiming at enhancing mental health conditions in contemporary cities., Competing Interests: The authors declare no conflict of interest.

Objectives: To prospectively evaluate acoustic radiation force impulse (ARFI) imaging of the kidneys in children with and without chronic renal disease., Methods: Twenty-eight children (age range 9-16 years) with primary or secondary vesicoureteral reflux (≥ grade III) underwent scintigraphy and ultrasound with ARFI. Kidneys were divided-according to scintigraphy-into "affected" and "contralateral"; the results were compared with 16 age-matched healthy subjects. An ARFI value, expressed as speed (m/s) of wave propagation through the tissue, was calculated for each kidney through the mean of the values obtained at the upper, middle and lower third. The Wilcoxon test was used; P values <0.05 were considered statistically significant., Results: The mean ARFI values obtained in the "affected" kidneys (5.70 ± 1.71 m/s) were significantly higher than those measured in both "contralateral" (4.09 ± 0.97, P < 0.0001) and "healthy" kidneys (3.13 ± 0.09, P < 0.0001). The difference between values in the "contralateral" kidneys and "healthy" ones was significant (P < 0.0001). The "affected" kidneys with secondary reflux had mean ARFI values (6.59 ± 1.45) significantly higher than those with primary reflux (5.35 ± 1.72)., Conclusions: ARFI values decrease from kidneys with secondary vesicoureteral reflux to kidneys with primary reflux to unaffected kidneys contralateral to reflux to normal kidneys.

Limited data exist about cancer prognosis and the development of second cancers in renal transplant recipients. In a retrospective cohort study on 3537 patients incidence rates of the first and, if any, of a second cancer, and standardized incidence ratios [SIR (95% CI)] were computed. Two hundred and sixty-three (7.5%) patients developed a NMSC, and 253 (7.2%) another type of cancer after a median follow-up of 6.5 and 9.0 years, respectively. A statistically significant excess risk, if compared to an age- and sex-matched reference general population, was observed for Kaposi sarcoma and NMSC, followed by non-Hodgkin lymphoma and carcinoma of cervix uteri; a small number of unusual cancers such as tumors of the salivary glands, small intestine and thyroid also were detected at a level worthy of additional scrutiny. Ten-year survival rate of all noncutaneous cancers was 71.3%, with lower rates for lung carcinoma and non-Hodgkin lymphoma (0% and 41.7%, respectively). Patients with NMSC had an increased risk of developing a second NMSC [SIR 8.3 (7.0-10.0)], and patients with a primary noncutaneous cancer had increased risk of developing a second noncutaneous cancer [SIR 1.8 (1.2-2.8)], if compared to the whole cohort. Our study underscore that the high risk of primary and second cancer in renal transplant recipients, including unusual cancers., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: To evaluate the usefulness of fistulography as a diagnostic and management tool for clinically suspected pancreatic fistulas (PF) after pancreaticoduodenectomy (PD)., Methods: 84 consecutive fistulographies were performed for clinical suspicion of PF and retrospectively analysed. We radiologically defined two types of PF by means of fistulography, PF1 in the case of primary filling with contrast agent of the jejunal loop or stomach and PF2 in the case of secondary filling of the jejunal loop or stomach through a fistulous tract or a fluid collection., Results: In 35/84 (41.7%) of the fistulograms, a PF1 was demonstrated owing to an instantaneous opacification of the intestinal lumen or the stomach, without evidence of a fistulous tract or fluid collection. In 49/84 (58.3%) fistulograms, a PF2 was demonstrated by the depiction of a fluid collection and/or a fistulous tract and a communication with the intestinal loop or the stomach anastomised with the pancreas. The mean healing time of a PF after PD was 2.7 days for PF1, and 9.8 days for PF2., Conclusion: Fistulography helps in the confirmation of clinically suspect PF, and can distinguish PF1 and PF2, thus decreasing post-operative morbidity significantly.

Background: Kinases represent potential therapeutic targets in pancreatic endocrine tumours (PETs)., Patients and Methods: Thirty-five kinase genes were sequenced in 36 primary PETs and three PET cell lines: (i) 4 receptor tyrosine kinases (RTK), epithelial growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), tyrosine-protein kinase KIT (KIT), platelet-derived growth factor receptor alpha (PDGFRalpha); (ii) 6 belonging to the Akt/mTOR pathway; and (iii) 25 frequently mutated in cancers. The immunohistochemical expression of the four RTKs and the copy number of EGFR and HER2 were assessed in 140 PETs., Results: Somatic mutations were found in KIT in one and ATM in two primary neoplasms. Among 140 PETs, EGFR was immunopositive in 18 (13%), HER2 in 3 (2%), KIT in 16 (11%), and PDGFRalpha in 135 (96%). HER2 amplification was found in 2/130 (1.5%) PETs. KIT membrane immunostaining was significantly associated with tumour aggressiveness and shorter patient survival. PET cell lines QGP1, CM and BON harboured mutations in FGFR3, FLT1/VEGFR1 and PIK3CA, respectively., Conclusions: Only rare PET cases, harbouring either HER2 amplification or KIT mutation, might benefit from targeted drugs. KIT membrane expression deserves further attention as a prognostic marker. ATM mutation is involved in a proportion of PET. The finding of specific mutations in PET cell lines renders these models useful for preclinical studies involving pathway-specific therapies.

Background: The urokinase plasminogen activator receptor is highly expressed and its gene is amplified in about 50% of pancreatic ductal adenocarcinomas; this last feature is associated with worse prognosis. It is unknown whether the level of its soluble form (suPAR) in urine may be a diagnostic-prognostic marker in these patients., Methods: The urinary level of suPAR was measured in 146 patients, 94 pancreatic ductal adenocarcinoma and 52 chronic pancreatitis. Urine from 104 healthy subjects with similar age and gender distribution served as controls. suPAR levels were normalized with creatinine levels (suPAR/creatinine, ng/mg) to remove urine dilution effect., Results: Urinary suPAR/creatinine values of pancreatic ductal adenocarcinoma patients were significantly higher (median 9.8; 25th-75th percentiles 5.3-20.7) than those of either healthy donors (median 0; 0-0.5) or chronic pancreatitis patients (median 2.7; 0.9-4.7). The distribution of values among cancer patients was widespread and asymmetric, 53% subjects having values beyond the 95th percentile of healthy donors. The values of suPAR/creatinine did not correlate with tumour stage, Ca19-9 or CEA levels. Higher values correlated with poor prognosis among non-resected patients at univariate analysis; multivariate Cox regression identified high urinary suPAR/creatinine as an independent predictor of poor survival among all cancer patients (odds ratio 2.10, p = 0.0023), together with tumour stage (stage III odds ratio 2.65, p = 0.0017; stage IV odds ratio 4.61, p < 0.0001) and female gender (odds ratio 1.85, p = 0.01)., Conclusions: A high urinary suPAR/creatinine ratio represents a useful marker for the identification of a subset of patients with poorer outcome.

Aim: The aim of our study was to compare the function and volumes of kidneys of very low birth-weight (VLBW) and of extremely low birth-weight (ELBW) infants at pre-school ages., Patients and Methods: We did a revision of the neonatal records of infants born in our hospital that weighed < or =1500 g at birth. The children were divided into two groups according to their weight at birth: ELBW (<1000 g) and VLBW (1000-1500 g). At the age of 5.7 +/- 1.4 years, the children underwent clinical, laboratory and ultrasound renal assessments., Results: Sixty-nine children fulfilled the requirements for the study. The rate of neonatal treatment with aminoglycosides was higher in ELBW preterms. Renal function parameters, i.e. estimated glomerular filtration rate and albuminuria, did not differ between the two groups of children. Urinary alpha1-microglobulin excretion was significantly higher and kidneys were significantly smaller in the ELBW group than in the VLBW group., Conclusion: No impairment or differences in renal parameters were found in pre-school children born ELBW compared with those born with VLBW, except for differences in kidney volume, renal cortical thickness and urinary alpha1-microglobulin excretion. Thus, patients born with ELBW would require a longer follow-up period.

Objectives: Prospective studies have identified a number of patient- and procedure-related independent risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, with different conclusions, so various questions are still open. The endoscopist's expertise, case volume, and case mix can all significantly influence the outcome of ERCP procedures, but have been investigated little to date., Methods: We identified patient- and procedure-related risk factors for post-ERCP pancreatitis and the impact of the endoscopist's experience and the center's case volume, using univariate and multivariate analysis, in a multicenter, prospective study involving low- and high-volume centers, over a 6-month period., Results: A total of 3,635 ERCP procedures were included; 2,838 (78%) ERCPs were performed in the 11 high-volume centers (median 257 each) and 797 in the 10 low-volume centers (median 45 each). Overall, 3,331 ERCPs were carried out by expert operators and 304 by less-skilled operators. There were significantly more grade 3 difficulty procedures in high-volume centers than in low-volume ones (P<0.0001). Post-ERCP pancreatitis occurred in 137 patients (3.8%); the rates did not differ between high- and low-volume centers (3.9% vs. 3.1%) and expert and non-expert operators (3.8% vs. 5.5%). However, in high-volume centers, there were 25% more patients with patient- and procedure-related risk factors, and the pancreatitis rate was one-third higher among non-expert operators. Univariate analysis found a significant association with pancreatitis for history of acute pancreatitis, either non-ERCP- or ERCP-related and recurrent, young age, absence of bile duct stones, and biliary pain among patient-related risk factors, and >10 attempts to cannulate the Vater's papilla, pancreatic duct cannulation, contrast injection of the pancreatic ductal system, pre-cut technique, and pancreatic sphincterotomy, among procedure-related risk factors. Multivariate analysis also showed that a history of post-ERCP pancreatitis, biliary pain, >10 attempts to cannulate the Vater's papilla, main pancreatic duct cannulation, and pre-cut technique were significantly associated with the complication., Conclusions: A history of pancreatitis among patient-related factors, and multiple attempts at cannulation among procedure-related factors, were associated with the highest rates of post-ERCP pancreatitis. Pre-cut sphincterotomy, although identified as another significant risk factor, appeared safer when done early (fewer than 10 attempts at cannulating), compared with repeated multiple cannulation. The risk of post-ERCP pancreatitis was not associated with the case volume of either the single endoscopist or the center; however, high-volume centers treated a larger proportion of patients at high risk of pancreatitis and did a significantly greater number of difficult procedures.

Summary of Background Data: The role of surgically placed intra-abdominal drainages after pancreatic resections has not been clearly established. In particular, their effect on morbidity rates and the optimal timing for their removal remains controversial., Methods: A total of 114 eligible patients who underwent standard pancreatic resections and at low risk of postoperative pancreatic fistula according to our institutional protocol (amylase value in drains < or =5000 U/L on postoperative day [POD] 1) were randomized on POD 3 to receive either early (POD 3) or standard drain removal (POD 5 or beyond). The primary end point of the study was the incidence of pancreatic fistula. Secondary endpoints included abdominal complications, pulmonary complications, in-hospital stay, and perioperative mortality. Cost-analysis between the 2 groups was also made., Results: Early drain removal was associated with a decreased rate of pancreatic fistula (P = 0.0001), abdominal complications (P = 0.002), and pulmonary complications (P = 0.007). Median in-hospital stay was shorter (P = 0.018), and hospital costs decreased (P = 0.02). Mortality was nil. A significant association with pancreatic fistula was found for timing of drain removal (P < 0.001), unintentional weight decrease before surgery (P = 0.022), type of pancreas texture (P = 0.015), serum amylase levels on POD 1 (P = 0.001), and albumin levels on POD 1 (P = 0.039). Multivariate analysis showed that timing of drain removal (P = 0.0003) and unintentional weight decrease before surgery (P = 0.02) were independent risk factors of pancreatic fistula., Conclusions: In patients at low risk of pancreatic fistula, intra-abdominal drains can be safely removed on POD 3 after standard pancreatic resections. A prolonged period of drain insertion is associated with a higher rate of postoperative complications with increased hospital stay and costs. The manuscript is a randomized trial, registered in the NLM database as NCT00931554.

A method based on selective sequential dissolutions is proposed to determine total vanadium(V) in particulate matter of emissions and working areas at concentrations 1,000 times lower than the threshold limit of 0.05 mg m(-3). Separation and preconcentration of vanadium(V) has been achieved by solid-phase extraction on Chelex 100 resin. Possible influence of the matrix has been investigated for two standard reference materials (SRMs), NIST SRM 1648 and BCR-038, before and after spiking, with vanadium(V) recovery in the range 97-103%.

Objective: To compare the long-term risk of primary nonmelanoma skin cancer (NMSC) and the risk of subsequent NMSC in kidney and heart transplant recipients., Design: Partially retrospective cohort study., Setting: Two Italian transplantation centers., Patients: The study included 1934 patients: 1476 renal transplant recipients and 458 heart transplant recipients., Main Outcome Measures: Cumulative incidences and risk factors of the first and subsequent NMSCs., Results: Two hundred patients developed a first NMSC after a median follow-up of 6.8 years after transplantation. The 3-year risk of the primary NMSC was 2.1%. Of the 200 patients with a primary NMSC, 91 (45.5%) had a second NMSC after a median follow-up after the first NMSC of 1.4 years (range, 3 months to 10 years). The 3-year risk of a second NMSC was 32.2%, and it was 49 times higher than that in patients with no previous NMSC. In a Cox proportional hazards regression model, age older than 50 years at the time of transplantation and male sex were significantly related to the first NMSC. Occurrence of the subsequent NMSC was not related to any risk factor considered, including sex, age at transplantation, type of transplanted organ, type of immunosuppressive therapy, histologic type of the first NMSC, and time since diagnosis of the first NMSC. Histologic type of the first NMSC strongly predicted the type of the subsequent NMSC., Conclusions: Development of a first NMSC confers a high risk of a subsequent NMSC in transplant recipients. Intensive long-term dermatologic follow-up of these patients is advisable.

Objectives: The present study examined the cross-talk between prostanoids and nitric oxide (NO) in human gastric biopsies during Helicobacter pylori infection., Subjects and Methods: A pool of 1 or 2 biopsies per patient (11 H. pylori positive and 9 H. pylori negative) were incubated in the medium with/without drugs, 1400W and NS-398, inhibitors of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), respectively. Levels of NO and prostaglandin E(2) (PGE(2)), predominant products of activity of NOS and COX enzymes, were measured in the medium whereas the expressions of iNOS and COX protein, examined by Western blotting, were measured in the biopsies., Results: The 11 patients with H. pylori infection showed a marked expression of COX-2 and iNOS proteins and high levels of PGE(2) and NO, as a consequence of iNOS and COX-2 activation, while proteins were absent and the level of nitrite and PGE(2) was low in the 9 noninfected patients. The COX-2 inhibitor decreased both NO and PGE(2). The iNOS-specific inhibitor decreased NO but did not have any effect on the increase in gastric mucosal PGE(2). Both inhibitors had no effect on the protein level of these two enzymes., Conclusions: The data showed that COX-2 inhibitor might modulate the iNOS pathway, suggesting that COX-2 activity and/or its products may be related to the functional activation of iNOS but not to the expression of iNOS protein., (Copyright 2009 S. Karger AG, Basel.)

Background: Over the past few years, major changes have taken place in the treatment of gastroduodenal peptic ulcer., Aim: To evaluate risk factors associated with the incidence of peptic ulcer in inpatients., Methods: From 2001 to 2004, the number of prescriptions of H2-antagonists and proton pump inhibitors (PPIs) in each department of Verona University Hospital was monitored. Over the same period we prospectively recorded the number of upper endoscopies per department for inpatients with a diagnosis of peptic ulcer., Results: We analyzed 4943 inpatients. A significantly decreasing trend in H(2)-antagonist prescriptions (r=-0,88; P<0.001) and an increasing trend in PPI prescriptions (r=0.97; P<0.001) were observed. The endoscopic incidence of duodenal ulcers decreased linearly from 2001 to 2004 as follows: 6.5% (94/1439) in 2001, 5.6% (82/1473) in 2002, 4.5% (63/1411) in 2003, and 3.1% (22/702) (P<0.001) in 2004. Gastric ulcer incidence, sex, age, indication for endoscopy, use of nonsteroidal anti-inflammatory drugs (NSAIDs), presence of Helicobacter pylori (32%), and smoking and drinking habits showed no significant changes over the study period. Considering time-dependent variables, multivariate regression analysis identified only PPI use and NSAID use as factors predictive of duodenal ulcer but not of gastric ulcer., Conclusions: In inpatients, PPIs are associated with a reduced risk of duodenal ulcer, whereas NSAIDs are associated with an increased risk. Gastric ulcer was not associated with any increased or degreased risk with the 2 above-mentioned variables.

Objective: To determine whether using a combination of body mass index (BMI) and waist circumference (WC) or waist-to-height ratio (W/Hr) is clinically helpful in identifying children with high metabolic and cardiovascular risks., Study Design: Caucasian children (M/F: 740/739; n = 1479; ages 5 to 15 years) were studied. Anthropometry, blood pressure, and venous fasting blood samples tested for triacylglycerol, HDL cholesterol, and glucose were measured., Results: Overweight children with a large waist (>90(th) percentile) or high W/Hr (>0.5) but not obese or normal-weight children had significantly greater chances of being at high metabolic and cardiovascular risk than normal-weight children (OR: 7; 95% CI: 3.63-13.48; P < .001, OR: 8.16; 95% CI: 3.87-17.23; P < .001, respectively) with a low waist measurement (

Objective: Cigarette smoking is associated with a higher risk of developing chronic pancreatitis (CP) and increases the likelihood of developing pancreatic calcifications. The aim of this study was to know whether smoking cessation modifies the course of the disease., Methods: Patients with CP who had been followed up for more than 6 years from clinical onset and who had not developed calcifications after 5 years were analyzed. We studied smokers, never-smokers, and patients who had given up smoking within 5 years. For actuarial analysis, the sixth year was considered as time 0., Results: Of the 360 patients, there were 43 women and 317 men (88.1%) with a mean age of 38.7 years. The median follow-up was 19.0 years. Chronic pancreatitis was alcohol-associated in 255 patients, hereditary in 10, obstructive in 54, and idiopathic in 41. There were 317 smokers (88.1%) and 259 alcohol drinkers (71.9%). At the end of the follow-up, 212 patients (59.8%) developed calcifications. Concerning the risk of calcifications, never-smokers and ex-smokers had similar actuarial curves, and these were significantly different from the curve for smokers (P < 0.003). Considering never-smokers as the reference class, ex-smokers had an odds ratio (OR) of 0.56 (95.0% confidence interval [CI], 0.2-1.4; P = not significant), patients smoking 1 to 10 cigarettes per day had an OR of 1.95 (95.0% CI, 1.1-3.4; P < 0.019), patients smoking 11 to 20 cigarettes per day had an OR of 1.76 (95.0% CI, 1.1-2.8; P < 0.0018), and those smoking more than 20 cigarettes per day had an OR of 1.79 (95.0% CI, 1.1-2.9; P < 0.019). Alcohol cessation seems to have no influence., Conclusions: Smoking cessation in the first years from the clinical onset of CP reduces the risk of developing pancreatic calcifications.

Background: The correlation of the amylase value in drains (AVD) with the development of pancreatic fistula (PF) is still unclear., Aim: The purpose of this study was to identify within the first postoperative day (POD1) the predictive role of different risks factors, including AVD, in the development of PF., Patients and Methods: We prospectively investigated 137 patients who underwent major pancreatic resections. PF was defined and graded in accordance with the International Study Group on PF., Results: We considered 101 pancreaticoduodenectomies and 36 distal resections. The overall incidence of PF (A, B, and C grades) was 19.7% and it was 14.8% after pancreaticoduodenectomy and 33.3% after distal resection. All PF occurred in "soft" remnant pancreas. The PF developed in patients with a POD1 median AVD of 10,000 U/L, whereas patients without PF had a median AVD of 1222 U/L (P < 0.001). We established a cut-off of 5000 U/L POD1 AVD for univariate and multivariate analysis. The area under the receiver operating characteristic (ROC) curve was 0.922 (P < 0.001). The predicting risk factors selected in the univariate setting were "soft" pancreas (P = 0.005; odds ratio [OR]: 1.54; 95% CI: 1.32-1.79) and AVD (P < 0.001; OR: 5.66; 95% CI: 3.6-8.7; positive predictive value 59%; negative predictive value 98%), whereas in multivariate analysis the predicting risk factor was the POD1 AVD (P < 0.001; OR: 68.4; 95% CI: 14.8-315). Only 2 PFs were detected with AVD <5000 U/L and both were in pancreatogastric anastomosis (P = 0.053)., Conclusions: AVD in POD1 > or =5000 U/L is the only significant predictive factor of PF development.

Background: Despite the widespread use of fractional exhaled nitric oxide (FENO) as a biomarker of airways inflammation, there are no published papers describing normal FENO values in a large group of healthy adults., Objective: The aim of this study was to establish adult FENO reference values according to the international guidelines., Methods: FENO was measured in 204 healthy, non-smoking adults with normal spirometry values using the on-line single-breath technique, and the results were analysed chemiluminescently., Results: The main result of the study was the significant difference in FENO values between men and women, thus indicating that gender-based reference FENO values are necessary. The FENO levels obtained at expiratory flows of 50 ml/s ranged from 2.6 to 28.8 ppb in men, and from 1.6 to 21.5 ppb in women., Conclusion: We propose reference FENO values for healthy adult men and women that could be used for clinical and research purposes.

Background: Intraductal papillary mucinous neoplasms (IPMNs) may present with clinical and radiological pictures resembling those of chronic pancreatitis (CP)., Aims: To compare the clinical and epidemiological characteristics of patients suffering from CP with those of patients suffering from IPMN. To assess whether CP is associated with an increased risk of developing IPMN., Methods: In our departments, from 1981 to 1998, we prospectively followed 473 patients suffering from CP, including 93 cases of chronic obstructive pancreatitis (COP), and 45 patients with a histologically confirmed diagnosis of IPMN. Another 6 patients had an initial diagnosis of CP and a subsequent diagnosis of IPMN., Results: Patients with IPMN were more often female (females 53 vs. 15%; p < 0.001), were older (mean age 63.1 vs. 42.8 years; p < 0.001), drank less alcohol (19 vs. 107 g/day; p < 0.001) and smoked fewer cigarettes (mean 8 vs. 21 cigarettes/day) than CP patients. These results were also confirmed when considering only patients with COP. The 6 patients with a subsequent diagnosis of IPMN were males (p n.s.) with a mean age of 51.4 years (p < 0.05). Only 1 patient was a drinker (p < 0.05) and 4 were smokers (p n.s.). Comparing CP and IPMN, logistic regression analysis selected sex, age, alcohol and smoking, whereas only sex and age were selected when comparing COP vs. IPMN., Conclusions: In general patients with IPMN present different epidemiological characteristics than those with CP and the subgroup with COP. The clinical and pathological features suggest that in most cases IPMN is the cause of CP and not vice versa., (Copyright 2006 S. Karger AG, Basel and IAP.)

Background: The authors report on the prevalence of, and risk factors for, hepatitis A virus (HAV) in a group of drug users in Italy., Methods: 404 heroin users were recruited and compared with a control group of 107 subjects in the general population., Results: Drug users born in north-eastern Italy have a prevalence of anti-HAV similar to the control group. A much higher prevalence was found in drug users born in southern Italy., Conclusion: The similar prevalence of anti-HAV in drug users born in north-eastern Italy and in the general population, suggests that their lifestyle does not involve a substantial additional risk of HAV. The much higher prevalence found in drug users born in southern Italy is more likely to be related to infection during infancy.

Background: In the light of the recent hypothesis that one cause of pancreatic damage may be related to the toxic action of oxygen free radicals [Braganza JM. The pathogenesis of pancreatitis. Manchester: Manchester University Press; 1991; Braganza JM. A framework for the aetiogenesis of chronic pancreatitis. Digestion 1998;59(Suppl. 4):1-12], we were prompted to assess the role of selenium in pancreatic disease., Objective: The objective of the study was to establish whether or not there is any correlation between selenium levels and the degree of impairment of exocrine pancreatic function in patients suffering from chronic pancreatitis., Patients: Two groups of subjects were recruited, the first consisting of 38 patients with clinically quiescent chronic pancreatitis of alcoholic origin and the second of 48 control subjects selected from among healthy volunteers attending our Transfusion Centre., Methods: Body mass index, smoking and drinking habits were evaluated and selenium serum levels were assayed in all subjects. The patients with pancreatic disease were subdivided into three groups on the basis of lipase output assayed with a duodenal probe. RESULTS.: Selenium serum levels in the chronic pancreatitis group as a whole were found to be significantly lower than in the control group, but when they were analysed in the three distinct subgroups, a significant difference was found against control group only in the groups with severe and moderate exocrine pancreatic insufficiency., Conclusions: The mean serum selenium levels were lower in chronic pancreatitis patients than control.

In this study we evaluated the clinical usefulness of identifying urothelial cells with increased DNA damage with the alkaline comet assay and compare it with voided urine cytology for the assessment of markers indicative of bladder cancer. The analysis was carried out on 105 subjects having clinical suspicion of bladder cancer, and who had undergone cytology for the first time. Urine cytology and alkaline comet assay were performed on the same fresh urine samples obtained from each patient. The subjects were divided according to negative or positive cytology. The Mann-Whitney U-test showed that the comet parameters (tail moment, tail length, and % of DNA in the tail) and the numbers of comets (cells with an arbitrary cut-off value of head intensity <90% of DNA content) in subjects positive in both tests were significantly higher than in the negative group. Sensitivity, specificity, and positive and negative predictive value of the comet assay were compared with those of cytology, which is regarded as the gold standard. Sensitivity was 71.4%, specificity was 91.8%, positive and negative predictive values were 38.5 and 97.8, respectively. Two subjects negative in the comet assay were positive in cytology. Eight patients were positive in the comet assay and negative for cytology. Interestingly, one of these eight patients was later found positive for cytology. Logistic regression analysis indicates that the tail moment is significantly associated with an increased risk for positive cytology.

Experimental data suggest that oxidative stress might be enhanced in hypertension and contribute to platelet activation. We hypothesized that both oxidative stress and platelet activation could be related to the clinical characteristics of hypertensive patients. The urinary excretion of 11-dehydrothromboxane (TX) B2, reflecting in vivo platelet activation, was measured in 75 patients with mild to severe essential hypertension and 75 pair-matched, healthy controls. The urinary excretion of 8-iso-prostaglandin (PG) F2alpha was determined as an index of in vivo lipid peroxidation. Urinary 11-dehydro-TXB2 was significantly higher in essential hypertensives compared with controls. Although no statistically significant difference in urinary 8-iso-PGF2alpha was observed between patients and controls, plasma vitamin C was lower and plasma homocysteine higher in hypertensive patients than in controls. Both urinary 11-dehydro-TXB2 and 8-iso-PGF2alpha were higher in patients with advanced hypertensive retinopathy compared with patients without retinopathy. Multivariate linear regression analysis identified urinary 8-iso-PGF2alpha, plasma fibrinogen, homocysteine, and vitamin E as the only variables independently correlated with urinary 11-dehydro-TXB2. Logistic regression analysis showed that high urinary 8-iso-PGF2alpha, plasma fibrinogen, and homocysteine, as well as low plasma vitamin E, advanced retinopathy, elevated diastolic blood pressure, and the absence of antihypertensive treatment, were predictors of high urinary 11-dehydro-TXB2. We demonstrated increased oxidative stress and persistent platelet activation in essential hypertensives with advanced vascular lesions. These findings might help identify hypertensive patients who are at increased risk of cardiovascular events and who might benefit from long-term antiplatelet therapy.

Background: Intestinal failure impairs nutritional status and survival expectance. Though intestinal adaptation and enteral independence may be achieved, artificial nutrition is needed in about half of the patients., Aims: This study is aimed at assessing the causes of death, survival rate, enteral independence in time, and factors affecting the clinical outcome in a group of patients with intestinal insufficiency., Patients: Sixty-eight patients with intestinal insufficiency, due to major intestinal resection in 60 cases (short bowel syndrome) (remnant intestine length 101-150 cm in 31 cases, 50-100 cm in 23 cases, <50 cm in 6 cases), and due to chronic idiopathic pseudo-obstruction in 8 cases, were enrolled and followed-up for (median) 36 months (25th and 75th percentile in 12 and 60 months, respectively). In 60 short bowel syndrome patients, the main conditions that led to intestinal failure were ischemic bowel (28), major surgery complications or severe adhesions (17), radiation enteritis (10), Chron's disease, intestinal tuberculosis, small bowel lymphoma and trauma (others)., Methods: Seventeen variables age, underlying disorders, length of remnant bowel, type of surgery, hospital stay, type of nutrition (hospital and home) and its variations in time, causes of death, survival rate and time were considered. Statistical analysis was carried out by Mann-Whitney U-test, Pearson chi2, Spearman correlation test, Kaplan-Meyer method and Cox's proportion hazards regression model., Results: At the time of admission to the hospital, none of the patients had nutritional independence, 54 (79.4%) were on parenteral nutrition and 14 (20.6%) were on enteral nutrition. At the time of discharge, 23 (33.8%) patients showed enteral independence, 39 were on home parenteral nutrition, 3 on enteral nutrition + i.v. feeding, 1 on enteral nutrition, and 2 needed oral supplementation with hydroelectrolyte solutions only. After a median value of 36 months, 30 and 2 patients were on home parenteral nutrition and enteral nutrition + i.v. feeding, respectively, 2 on enteral nutrition, 2 on oral supplementation with hydroelectrolyte solutions, and 26 cases reached enteral independence. A significant relationship was detected between the length of remnant bowel and types of nutrition at both admission (r = 0.38; P = 0.001) and discharge (r = 0.48; P = 0.001), parenteral nutrition being more frequent in patients with very short bowel. Twenty-two patients (32.4%) died (4 from newly occurring malignancies), 40 (58.8%) survived, and 6 (8.8%) were lost to the follow-up. Eleven of 22 patients died from conditions related to intestinal failure (8 cases) and/or home parenteral nutrition complications (3 cases). At 12, 24, 36, 48, 60 and 72 months, survival rates were 95.4, 93.3, 88.1, 78.6, 78.6 and 65.5%, respectively, but it was significantly lower for patients with <50 cm of remnant bowel than those with longer residual intestine (P < 0.05), and in patients who started home parenteral nutrition above the age of 45 years (P < 0.02). Survival rate was higher in patients with enteral independence than those with enteral dependence (P < 0.05). Better survival rates were registered in patients with chronic obstructive intestinal pseudo-obstruction and major surgery complications, whereas ischemic bowel and even more radiation enteritis were associated with a lower survival expectance., Conclusions: Actuarial survival rate of patients with intestinal failure quotes 88 and 78% at 3 and 5 years, respectively. It is influenced by the length of remnant intestine, age at the start of home parenteral nutrition, enteral independence and, to some extent at least, by the primary disorder. Enteral independence can be achieved in time by about 40% of the patients with intestinal insufficiency, but for home parenteral nutrition-dependent cases, intravenous feeding can be stopped in less than one out of five patients during a median 3-year period.

Recent data suggest that SEL1L may play an important role in pancreatic carcinoma, similar to breast cancer, where the expression of SEL1L has been associated with a reduction in both proliferative activity in vitro and clinical tumor aggressiveness. To investigate this possibility, we examined the expression of Sel1L in a series of primary pancreatic carcinomas by immunohistochemistry and characterized the effects of Sel1L overexpression both in vitro and in vivo. In 74 pancreatic cancers analysed, 36% lacked Sel1L expression, although there was no significant correlation between the expression of Sel1L and any clinicopathologic parameter, including survival. However, immunohistochemical reactivity for Sel1L and Dpc4/Smad4 was concordant in 69% of cases (chi(2) test P&<0.004). Overexpression of SEL1L in stably transfected pancreatic cancer cells caused both a decrease in clonogenicity and anchorage-independent growth as well as a significant increase in the levels of activin A and SMAD4. When implanted in nude mice, Suit-2-SEL1L-overexpressing clones displayed a considerably reduced rate of tumor growth. Thus, it can be hypothesized that Sel1L plays an important function in the growth and aggressiveness of pancreatic carcinoma. Moreover, our data provide evidence that SEL1L has an impact on the expression of genes involved in regulation of cellular growth, possibly through the TGF-beta signaling pathway.

The study assessed rates and predictor variables of hepatitis C virus (HCV) infection among drug users receiving pharmacological treatment for opiates addiction. There was a large cohort study in 16 public centres for drug users in north-eastern Italy, with data collected by standardized face-to-face interviews between February 2001 and August 2001. Of 1095 participants, 74.2% were HCV seropositive. Anti-HCV status was independently associated with duration of drug use of over 10 years, injecting as a route of drug administration, and hepatitis B virus (HBV) and human immunodeficiency virus (HIV) seropositivity. Further statistical analysis was conducted by dividing the subjects on the basis of the duration of heroin use: more or <10 years. In the multivariate analyses, route of drug administration and HBV status were associated with HCV seropositivity among both groups. Less education was associated with HCV among the shorter term drug users. HIV status and having a sexual partner with a history of drug use were associated with HCV seropositivity among the longer term drug users. Half of the short-term heroin users were still HCV seronegative when starting treatment, suggesting opportunities for reducing new HCV infections. Remarkable was the relationship between vaccination for hepatitis B and HCV serostatus. Being HBV seropositive was strongly associated with being HCV seropositive. But heroin users who had been vaccinated for HBV were not significantly more likely to be HCV seropositive than heroin users who were HBV seronegative. HBV vaccination does not provide biological protection against HCV; however, vaccinating heroin users against HBV may help to create a stronger pro-health attitude among heroin users, leading to a reduction in HCV risk behaviour.

We describe the prevalence of hepatitis C virus (HCV) infection among noninjection users of heroin in Italy and compare the prevalence of HCV infection among noninjection drug users (NIDUs) and injection drug users (IDUs). Multiple logistic regression analysis of data from NIDUs showed that hepatitis B virus (HBV) infection status was the only independent predictor of HCV seroprevalence. Among IDUs, the number of years of drug use and HBV and human immunodeficiency virus infection status were independent predictors of HCV seropositivity. We found an HCV infection prevalence of 20% among NIDUs. This rate was much lower than that for IDUs, who are 11 times more likely to have antibodies against HCV. The prevalence of HCV infection was much higher than that of HBV infection among the IDUs. In contrast, the prevalence of HBV infection was slightly higher than that of HCV infection among unvaccinated NIDUs. The prevalence of HCV infection among long-term IDUs approached true population saturation; among long-term NIDUs, however, it appeared to plateau at approximately 40%. Additional research on HCV infection among NIDUs is needed to develop a strategic prevention program for this patient subgroup.

Background and Aim of Study: The aim of the present study is to assess whether or not there has been improvement in the therapeutic strategy for body-tail pancreatic carcinoma over the past decade., Patients and Methods: A total of 215 patients suffering from cytologically and histologically documented ductal carcinoma in the pancreatic body-tail, observed from 1990 to 1999, were analysed. Changes in tumour stage at diagnosis, in the percentage of patients treated surgically, in resectability rates and in the use of anticancer therapies over the years were sought. Survival curves were evaluated in relation to the treatments adopted., Results: Over the 10-year period, no significant differences were observed with respect to the stage at diagnosis, resectability or type of surgery adopted. There was a significant increase in the percentage of unoperated patients (p < 0.0001) and, as expected, in the percentages of patients submitted to chemo- and/or radiotherapy (p < 0.0001). With the sole exception of tumour stage in the case of patients undergoing radiotherapy, a comparison between groups revealed no element of patient selection bias other than time. The survival of patients undergoing chemotherapy is significantly better, also at multivariate analysis, than that of patients not undergoing such therapy (13 vs. 5.8 months; p < 0.0001)., Conclusions: There has been no change over the years in the direction of earlier diagnosis and the prognosis remains distinctly poor. More extensive use of anticancer therapies, however, has led to a significant increase in median survival. Radical resection, when possible, assures the longest survival.

Aims: To investigate the feasibility of hepatitis B vaccination among heroin users, assessing adherence to the vaccination schedules and identifying factors associated with antibody response., Design and Participants: A large cohort study in nine public centres for drug users (PCDUs) in north-eastern Italy, with data collected between January 1989 and December 1998. A total of 1175 heroin users were selected and vaccinated with a recombinant vaccine using two schedules (0-1-6 months and 0-1-2 months)., Findings: Eighty-eight per cent of patients completed the vaccination series and a protective antibody response occurred in 77% of subjects. Completion of the vaccination series was not related to the length of the vaccination schedule or whether the patient was still in drug abuse treatment at the end of the series, but was related strongly to the number of patients enrolled at each PCDU (Spearman correlation = - 0.93, P < 0.001). Four variables were significantly associated with lack of seroconversion in response to vaccination: older age (AOR = 0.91 per year, 95% CI 0.88-0.94, P < 0.001), 2-month vaccination schedule (AOR = 3.10, 95% CI 2.06-4.68, P < 0.001), HCV seropositivity (AOR = 0.69, 95% CI 0.47-0.99, P = 0.04), HIV seropositivity (AOR = 0.27, 95% CI 0.10-0.77, P = 0.01)., Conclusions: A large-scale, multi-site hepatitis B vaccination programme for heroin users proved feasible and effective. The factors associated with a lack of antibody response may be useful in identifying patients who would benefit most from routine post-vaccination testing, with booster doses for non-responders. These results suggest that hepatitis B vaccination for drug users should become a routine public health practice.

Loss of immunohistochemical expression of Dpc4 occurs in about 50% of pancreatic ductal cancers and its loss correlates with DPC4/Smad4 gene inactivation. Dpc4 expression was also lost in 6 of 16 (37%) ampulla of Vater cancers (AVCs) previously analyzed. Furthermore, chromosomal losses involving 18q, where DPC4 is located, have been observed in 34% of AVCs and are associated with decreased survival. To evaluate the possibility that expression of Dpc4 may be correlated with survival, we analyzed 89 AVCs for inactivation of DPC4 by immunohistochemical staining. Thirty-seven cases showed no expression of Dpc4 (41%). Multivariate survival analysis was performed including age, sex, tumor size, histological subtype (intestinal or pancreatobiliary), grade of differentiation, T-stage, lymph-node metastases and Dpc4 status. T-stage and histological subtype were selected as independent prognostic factors, while Dpc4 immunostaining was not significantly associated with any clinicopathological variable, including histological subtype. Although Dpc4 expression is of no clinical relevance, its involvement in AVC gives additional weight to the hypothesis that, among all pancreatic exocrine and endocrine tumors, only AVC and common ductal adenocarcinomas have similar molecular fingerprints. Moreover, comparison of the frequencies of allelic loss on chromosomal arm 18q and the loss of Dpc4 expression (34% and 41%, respectively) is highly suggestive that DPC4 is the major target of these losses.

Gabexate mesilate is an antiprotease drug, which reduced the severity of pancreatitis and frequency of post-ERCP pancreatitis. In dogs gabexate inhibits sphincter of Oddi motility but no data are available in humans. The aim of this study was to verify by manometry the action of gabexate on human sphincter of Oddi motility. We enrolled 12 patients with idiopathic recurrent pancreatitis (eight males, five females, mean age 46 +/- 8 years). Standard preendoscopic sphincter of Oddi manometry was done in basal conditions and during infusion of gabexate 20 mg/min: basal pressure, amplitude and frequency of phasic contractions, and motility index (amplitude per frequency) were calculated before and after gabexate injection. Statistical analysis was performed by using Wilcoxon rank test for paired data. Six patients had a manometric diagnosis of stenosis (basal pressure greater than 40 mm Hg); six had normal findings. Phasic activity was not evaluable in five patients with stenosis. Basal pressure was unaffected by drug infusion, while gabexate caused a significant reduction of phasic activity, both in terms of frequency (4.5 +/- 1 vs 3.6 +/- 1; P < 0.05) and amplitude (157.4 +/- 44 vs 80.0 +/- 32; P < 0.05) of contractions. Motility index was reduced on average by 49%. In conclusion, this pilot study confirms, in patients with acute recurrent pancreatitis, the inhibitory action of gabexate on sphincter of Oddi motility already described in dogs. This action needs to be revaluated at therapeutic dosages. On the other hand, prophylactic use of the drug should be avoided during sphincter of Oddi manometry, in order to avoid false negative results.

Lead and lead compounds play a significant role in modern industry; a wide variety of population is at risk of occupational exposure and lead is suspected to be a human carcinogen. The biochemical and molecular mechanisms of lead toxicity are poorly understood, but emerging data suggest that some of the effects of lead may be due to its interference with calcium in the activation of protein kinase C (PKC) and/or through production of reactive oxygen species (ROS). Many of these results are conducted in vitro on cell lines or ex vivo on human lymphocytes treated in vitro. We, therefore, performed a study on the induction of DNA damage, using the alkaline comet assay, in lymphocytes of battery plant workers. To elucidate in vivo the mechanism(s) responsible for this effect, we determined ROS production, and glutathione (GSH) levels in living cells using the fluorescent probe (2',7'-dichlorofluorescein and monochlorobimane, respectively). Subcellular fractions were obtained from sonicated lymphocytes; cytosolic and membrane expression of PKC isoforms (alpha, and zeta) was evaluated after electrophoresis by immunoblot analysis. The results indicate that lead-exposed workers have significantly elevated levels of DNA breaks compared to the unexposed group. A multivariate analysis of variance (ANOVA) shows that the most common confounding factors (smoking, drinking and age) have no synergistic effects with lead-exposure on the comet parameters or on GSH levels and ROS production. The logistic regression analysis distinguishing the exposed and non-exposed indicates that only GSH with tail moment are selected as significant risk factors. There is a significant positive correlation with ROS production and negative correlation with GSH levels. The content of PKC alpha in cytosol and membranes is decreased 40% (indicating a down-regulation of protein), whereas PKC zeta isoform is not modified in an evident manner. Our results suggest that lead-exposure induces an increase of DNA breakage with an alternate cellular redox state and a significant down-regulation of PKC alpha, suggesting that this metal may act as a tumor promoter.

In order to determine the prevalence of latent infection due to Mycobacterium tuberculosis in drug users and to provide centres for drug users with a practical tool for tuberculosis screening, 237 drug users were subjected to the Monotest and, for reference purposes, to the Mantoux test. The overall prevalence of subjects with a tuberculin skin reaction size > or = 5 mm in the Mantoux test was 25.7%; utilizing a cut-off of > or = 10 mm, the prevalence was 11.4%. Irrespective of cut-off, the Monotest showed a sensitivity of > 90% and a specificity of > 80%. At a prevalence of 25.7%, and with cut-offs of > or = 5 or > or = 10 mm, the positive predictive value was 83% or 62.2%, respectively. Irrespective of cut-off, the negative predictive value was > 97%. In conclusion, the Monotest proved satisfactory as a tool for epidemiological screening in a population with a high prevalence for latent tuberculosis, namely drug users.

Introduction: In the general population, cholecystectomy, diabetes, and chronic pancreatitis seem to be associated with an increased risk of developing pancreatic cancer., Aims: We assessed whether previous cholecystectomy, gastrectomy, or diabetes mellitus may be risk factors for pancreatic cancer in patients with chronic pancreatitis., Methodology: We analyzed 853 patients with chronic pancreatitis (110 women, 743 men) with a median follow-up period of 14 years with particular reference to establishing which patients had previously undergone cholecystectomy or distal gastric resection (Billroth II anastomosis) or had diabetes or gallstone disease and the respective time scales involved., Results: Pancreatic cancer developed in 17 patients with chronic pancreatitis after a median period of 8 years from onset of pancreatitis symptoms (range, 3-38 years). Excluding two cholecystectomies performed 1 year before diagnosis of cancer, cholecystectomy was performed in 7/17 (41%) patients with pancreatic cancer and in 381/836 (46%) of the other patients with chronic pancreatitis. Forty-nine (10%) patients with chronic pancreatitis and no pancreatic cancer had undergone cholecystectomy during the years before the onset of chronic pancreatitis, whereas none of the patients in whom a pancreatic malignancy developed had undergone cholecystectomy before the onset of chronic pancreatitis symptoms. Gastrectomies were performed in 116 patients (14%), 47 before the onset of chronic pancreatitis. Only 2/17 patients with pancreatic cancer had undergone previous gastrectomy, though in both cases only shortly before diagnosis of the cancer. Diabetes was diagnosed in 353 patients, but only in 30 (4%) before onset of chronic pancreatitis. Only 1/17 patients (6%) with pancreatic cancer had long-standing diabetes, whereas diabetes developed in 3/17 shortly before diagnosis of pancreatic cancer., Conclusions: Cholecystectomy, gastrectomy, and diabetes are not major risk factors for the development of pancreatic cancer in patients with chronic pancreatitis.

Aims: To ascertain the causes of deaths among a very large cohort of heroin injecting drug users (IDUs) who, from 1985 to 1998, attended 36 Public Health Authority Centres for Drug Users (PCDUs) in north-eastern Italy., Design: Retrospective analysis of data, obtained from the Annual Register of each Centre and the Municipal Registry Office of each local health district., Setting: Thirty-six PCDUs in north-eastern Italy and Medical Service for Addictive Disorders of the University of Verona., Participants: All IDUs who had sought medical care at least once in the PCDUs during the study period., Findings: Of 2708 deaths, overdose was found to be the major cause (37%), followed by AIDS (32.5%) and road accidents (9.4%). The percentage of deaths due to AIDS increased steadily from 2.7% in 1985 to 42.2% in 1996, and then decreased to 16.9% in 1998. Deaths due to overdose remained almost constant. The average age of death per year rose from 26 in the mid eighties to 34 in 1998. The mortality rate among IDUs proved much higher compared to the general population of the same age (13-fold, 95% CI, 11.3-14.6). The proportion of all deaths attributable to regular use of illegal opiates in the 15-34 age group in the general population in 1991 was 16%. HIV prevalence was not a significant factor in suicides and deaths by overdose., Conclusions: The mortality rate was 13 times greater than in the general population. To be female and to have dropped out of any kind of treatment proved an important risk factor for overdose. The fall in deaths from AIDS enhances the problem to prevent and treat HCV infection. Decisions in drug projects, in research and in training should be influenced by the strikingly high percentage of deaths due to drug use.

Background: Tumour stage is the only reliable prognostic factor for gastric cancer. The molecular anomalies involved in this process have the potential to serve as additional prognostic markers., Methods: Forty-four gastric cancers, treated by surgery alone, have been analysed for chromosome 17p and 18q allelic loss and for the presence of microsatellite instability (MSI), using microsatellite markers and DNA from paraffin-embedded tumours., Results: Eight cancers showed a MSI-positive (MSI+) phenotype. Among the 36 MSI-negative cancers, chromosome 17p and 18q allelic losses were found in 22 of 34 and 19 of 33 informative cases respectively. Multivariate survival analysis indicated MSI status to be an independent prognostic factor along with the tumour stage. MSI+ cancers were associated with longer patient survival, whereas MSI-negative cancers had a significantly poorer prognosis (P = 0.007), with a median actuarial survival of 24 months., Conclusion: MSI status is an independent prognostic factor among gastric cancers at the same stage. Chromosome 17p and 18q status added no additional prognostic information to that of tumour stage. The combined use of tumour stage and MSI status may help in deciding whether patients with advanced gastric cancer require additional therapy other than surgery alone.

Background: The surgical strategy in patients with a pancreatic intraductal papillary mucinous tumour (IPMT) is still controversial. In this study the pathological findings in a series of patients were used to rationalize surgical choice., Methods: Fifty-one patients with IPMT were observed between 1988 and 1998 and treated by pancreatic resection. Factors evaluated included symptoms, tumour site, type of operation, histological findings and resection margins, tumour stage, follow-up and survival., Results: Pancreaticoduodenectomy was the most frequent surgical treatment (33 patients; 65 per cent), followed by left pancreatectomy (ten), total pancreatectomy (five) and middle pancreatectomy (three). Histological assessment revealed the tumour to be an adenoma in 13 patients (25 per cent), a borderline tumour in ten (20 per cent) and a carcinoma in 28 (55 per cent), 19 of which were invasive. Mild to moderate dysplasia was present at the resection margin in 20 specimens (41 per cent), and carcinoma in one. Local recurrence was observed in four patients (8 per cent), all of whom underwent a second resection. The 3-year actuarial survival rate for benign and malignant disease was 94 and 69 per cent respectively (P = 0.03)., Conclusion: These results suggest that resection should be the treatment for IPMT. Management of the resection margin could be crucial in avoiding tumour recurrence.

Background: Abdominal pain is the most challenging symptom of hereditary pancreatitis. No specific and proven therapy is yet available; analgesics, often in large doses, are required also in children and young patients., Patients and Methods: We performed an open-label, pilot study on three young patients, coming from the same kindred, with hereditary pancreatitis. The study period lasted two years (July 1997-July 1999) and was divided into four sub-periods of six months each. In the first and third period the patients took only oral analgesics, if necessary; in the second and fourth period, an antioxidant regimen per os was added. This treatment consisted of sulphadenosyl-methionine (800 mg per day), Vitamin C (180 mg per day), Vitamin E (30 mg per day), Vitamin A (2,400 microg per day), and selenium (75 microg per day)., Results: Compliance of patients to the treatment schedule was satisfactory and no important side-effects were observed. Antioxidant treatment led to a significant reduction (p<0.05) in the number of days with abdominal pain experienced by the three patients and this was verified for both periods of treatment. Albeit, consumption of analgesics was lower in the antioxidant treatment periods., Conclusions: Oxidative stress may be one of the principle contributors to pain in hereditary pancreatitis and orally administered antioxidant treatment appears to be effective for control of the condition, in young patients, suffering from this rare disease.

A high resolution allelotype for nonfunctional pancreatic endocrine tumors (NF-PETs) has been generated by microsatellite analysis of DNA from 16 frozen cases, each probed with 394 markers. Two subgroups of NF-PETs were found. Seven cases showed frequent, large allelic deletions [loss of heterozygosity (LOH)] with an average fractional allelic loss (FAL) of 0.55, whereas nine cases showed a small number of random losses with a FAL of 0.15. Designated high or low FAL, respectively, these genetic phenotypes showed correlation with the ploidy status: high-FAL tumors were aneuploid, low-FAL were diploid. Chromosomes 6q and 11q showed LOH in >60% of cases. About 50% of cases had losses on 11p, 20q, and 21. Selected LOH analysis on an additional 16 paraffin-embedded NF-PETs confirmed the high frequency of 6q and 11q LOH. The allelotype of NF-PET is markedly different from that of either ductal or acinar tumors of the pancreas as well as from that of functional-PETs. Moreover, whereas deletions involving chromosome 11 also are a feature of functional-PETs, the involvement of chromosome 6q is characteristic of NF-PETs. Survival analysis showed that none of the single chromosomal alterations was associated with outcome, whereas ploidy status is an independent factor adding prognostic information to that furnished by the proliferative index measured by Ki-67 immunohistochemistry.

Background: Pancreatitis is defined as an inflammatory disease of the pancreas, leading to morphological and pathological changes. Recently, an autoimmune pathogenesis of this disease has been proposed. This type of pancreatitis should be differentiated from other pancreatic diseases, since appropriate therapy is effective and morphological changes and pancreatic function can recover to normal levels., Aim of the Study: To assess the possibility of distinguishing autoimmune pancreatitis from other pancreatic diseases with an analogous clinical presentation on the basis of CT findings alone., Methods: The CT images of 7 patients with proven autoimmune pancreatitis, along with those of 20 patients with other pancreatic diseases, but with an analogous clinical presentation, were retrospectively evaluated in a blinded fashion by 2 radiologists. In particular, the radiologists had to search for the typical signs of autoimmune pancreatitis. Discordant cases were further analyzed in the presence of a 3rd radiologist. The final diagnosis was acquired by means of a majority or overall consensus. The sensitivity, specificity, positive and negative predictive values of CT were calculated against each of the diseases (autoimmune pancreatitis; other pancreatic diseases), in order to evaluate the diagnostic value of the scan., Results: After the consensus evaluation, the correct diagnosis was reached in 25/27 (92.5%) cases, with only 2/27 wrong diagnoses (autoimmune pancreatitis diagnosed as another pancreatic disease and vice versa). The sensitivity and specificity of CT against autoimmune pancreatitis were 86 and 95%, respectively. The positive and negative predictive values were 89 and 93%, respectively., Conclusion: Patients with autoimmune pancreatitis demonstrate imaging findings that enable the correct diagnosis by dynamic CT, even in the presence of nonspecific clinical symptoms. The precise classification of the disease is extremely important, since simple steroid therapy then represents the correct treatment, and leads to complete recovery.

Background: Octreotide has been found to be effective in the prevention of postoperative complications of pancreatic surgery, but the benefit of preoperative octreotide administration has not been assessed., Aims: To evaluate the ability of octreotide in reducing the amount of digestive enzymes in the pancreas before surgery, a morphometric ultrastructural study of the gland was undertaken in patients undergoing demolitive pancreatic surgery., Methods: Twenty-three inpatients received saline (n = 8) or octreotide (100 micrograms s.c.) before surgery either once (n = 5), or three (n = 5) or six (n = 5) times at 8-hour intervals. At surgery, biopsies of the pancreas were taken and processed for electron microscopy. Several parameters were assessed in exocrine cells by means of ultrastructural morphometry., Results: A single administration of octreotide significantly reduced the exocrine granule number and the mean and total granular surface sectional area, and the ratio between granule area and cytoplasmic area. Repeated octreotide administrations were associated with partial (3 administrations) and complete (6 administrations) recovery of all parameters to control values., Conclusion: Preoperative administration of octreotide, the synthetic analogue of somatostatin, acutely reduces exocrine granule number and size in the pancreatic cell. This finding can partially explain the prophylactic effect of the drug on early complications of pancreatic surgery. Such an effect is not maintained over multiple administrations of the somatostatin analogue. Possible explanations for this latter finding are discussed.

About 90% of patients suffering from pancreatic carcinoma are diagnosed with disease that is not amenable to surgical intervention due to local infiltration or the presence of hepatic metastases. Palliative intra-arterial chemotherapy was developed to improve the response in these patients by increasing the antiblastic dose and minimizing the side effects. The aim of this study is to evaluate the efficacy of this treatment comparison to a control group. From December 1994 to February 1997, 135 patients with ductal carcinoma, in whom 68 were stage III and 67 stage IV, with a median age of 63.3 years (range 38.4-79), were enrolled in an open study. Sixty four patients were subjected to a median of 3.5 cycles, according to intra-arterial FLEC protocol. Four patients had a partial response (6.3%), 27 enjoyed a stabilization of their disease (42.2%) and 13 showed disease progression (20.3%). The toxicity was mild. The overall survival was 8.3 months, better in the treated group (9.6 months) in respect to the control one (7.1 months), although this was not statistically significant. The treatment reported here, therefore, does not seem to change the prognosis of patients affected by no resectable pancreatic carcinoma, but it may demonstrate good tolerability and minimal toxicity.

The differential diagnosis between acute and chronic alcohol-associated pancreatitis is often difficult or impossible at onset of the disease. A study was conducted to determine possible relationships between patients suffering from a first episode of acute alcoholic pancreatitis and patients with unequivocal chronic alcoholic pancreatitis, comparing age, drinking and smoking habits, and body mass index (BMI). Two groups of men were considered. The first group consisted of 67 patients with a diagnosis of acute alcohol-associated pancreatitis in the absence of other potential pathogenic factors; in this group, 48 of the 56 patients surviving the acute attack were submitted to imaging studies for a median period of 9 years. The second group consisted of 396 patients with chronic alcoholic pancreatitis with a median follow-up period of 12 years. The variables that differed significantly in the two groups were BMI (p < 0.009) and number of smokers (p < 0.001). Logistic regression analysis selected only BMI with an odds ratio of 1.19 (95% CI, 1.07-1.33; p < 0.00015) in favor of acute alcoholic pancreatitis. In male patients, from an epidemiologic standpoint, only smoking habits and BMI are significant differences at clinical onset between the two types of pancreatitis.

Nowadays the availability of reliable, efficacious methods of assessing the outcome of chronic pancreatitis is mandatory, especially in view of the several new procedures developed to relieve the symptoms of the disease. Together with the traditional evaluation of postoperative morbidity and mortality and the assessment of exo/endocrine function in patient follow-up, we currently consider the patient's perception of his or her health status as a priority. This information is obtained by administering quality of life questionnaires along with reliable physical and psychometric evaluation.

The clinical efficacy of local nasal immunotherapy (LNIT) in patients with allergic rhinitis is amply documented. The aim of the study was to determine the effect on bronchial hyperresponsiveness (BHR) assessed at baseline and after 3 years of LNIT or pharmacological treatment alone. Forty-three randomized patients with allergic oculorhinitis were enrolled (26 positive to Graminaceae and 17 to Parietaria judaica pollens). All patients were asked whether they were willing to follow a 3-year treatment course involving preseasonal LNIT with a powder extract of Graminaceae or Parietaria pollens. Twenty-four patients (16 allergic to Graminaceae and eight to Parietaria) selected LNIT and the other 19 opted for symptomatic pharmacological treatment only. The latter was considered the control group. On the basis of positive or negative bronchial hyperresponsiveness and the LNIT, four subgroups were established and followed in open conditions, during which a record was kept of symptom scores, drug use, spirometry and methacholine test findings. After 3 years, patients treated with LNIT had a significant reduction of symptoms and drug intake. In the controls, symptoms worsened, thus requiring more drugs to control them. Bronchial hyperresponsiveness significantly improved in hyperreactive patients receiving LN7IT 10 of whom were no longer hyperreactive and one at a higher threshold. Among controls, bronchial hyperresponsiveness did not change, with the exception of three nonreactive patients who became hyperreactive, one of them with asthma. These findings confirm the efficacy of LNIT in allergic rhinitis suggesting that it might have systemic activity interfering with bronchial hyperresponsiveness and hence the onset of bronchial asthma.

Esophageal papilloma, an infrequent benign tumor, and esophageal squamous-cell carcinoma sometimes appear to be associated with human papillomavirus (HPV) infection, HPV being implicated in anogenital carcinogenesis. Our aim was to assess whether there is any epidemiological difference in terms of risk factors for papilloma and cancer. From 1989 to 1996, a total of 12,011 patients (53% male, median age 52.7 years) were submitted to esophagogastroduodenoscopy by our Digestive Endoscopy Service. The genome of HPV was sought by PCR using 2 different primer sets. Of the total, 42 subjects (0.35%), 50% male with a mean age of 45.1 years, were suffering from esophageal squamous-cell papilloma and 45 (0.37%), 91% male with a mean age of 63.0 years, from esophageal squamous-cell carcinoma. Of these patients, only 2 with papilloma were HPV(+). Compared with the general endoscopic population, patients with papilloma do not present significantly different characteristics (even in terms of frequency of esophagitis and hiatal hernia). Those with carcinoma differ significantly both from the general endoscopic population and from those with papilloma in that they are more often male (p < 0. 0001), older (p < 0.0001) and drinkers (p < 0.0001); they differ significantly only from the general population, but not from the papilloma patients, in smoking habits. Papilloma appears to be neither a lesion involving a risk of development into a malignancy nor a marker for any such risk. Environmental factors, such as alcohol and smoking, appear to play a decisive role in esophageal carcinogenesis in northern Italy., (Copyright 2000 Wiley-Liss, Inc.)