Frequency and characterization of benign lesions in patients undergoing surgery for the suspicion of solid pancreatic neoplasm.

OBJECTIVES: A diagnosis of benign lesions (BLs) is reported in 5% to 21% of pancreatoduodenectomies performed for neoplasms; no data for body-tail resections are available. The aims were to investigate the frequency and characterize the BLs mimicking cancer in the head and the body-tail of the pancreas. METHODS: This study is a retrospective review of pancreatic specimenscollected from 2005 to 2011 in the pathology database of Mainz (Germany). Patients with final diagnosis excluding malignancy were analyzed by histology, imaging, and clinical aspects. RESULTS: Among 373 patients, 33 patients (8.8%) were diagnosed with a benign disease: 25 (8.4%) of 298 in the pancreatic head and 8 (10.7%) of 75 in the body-tail resections. Paraduodenal pancreatitis was diagnosed in 13 (3.5%) of 373 patients; autoimmune pancreatitis (AIP), in 11 (2.9%); "ordinary" chronic pancreatitis, in 6 (1.6%); and accessory spleen, in 3 (0.8%). In pancreatic head resections, the most frequent diagnoses were paraduodenal pancreatitis (13/298, 4.4%) and AIP (9/298, 3%), whereas in the body-tail, the most frequent diagnoses were accessory spleen (3/75, 4%), chronic pancreatitis (3/75, 4%), and AIP (2/75, 2.7%). CONCLUSIONS: Benign lesions are observed with the same frequency inspecimens of the head or the body-tail of the pancreas.

Retrospective comparison between preoperative diagnosis by International Consensus Diagnostic Criteria and histological diagnosis in patients with focal autoimmune pancreatitis who underwent surgery with suspicion of cancer.

OBJECTIVE: The objective of this study was to compare the preoperative diagnosis by International Consensus Diagnostic Criteria (ICDC) with histological diagnosis in patients with focal autoimmune pancreatitis (AIP) who underwent surgery. METHODS: Thirty patients (type 1 AIP in 23 and type 2 AIP in 7) with a diagnosis of AIP based on histology of surgical specimens were classified according to ICDC based on their preoperative data. RESULTS: Pancreatic core biopsies and diagnostic steroid trial were not preoperatively performed in any of the patients. Based on preoperative data, ICDC diagnosed 6 patients (20%) as having type 1 AIP and 24 (80%) as probable AIP. Assuming all patients had responded to a steroid trial preoperatively, ICDC would have diagnosed 8 patients (27%) as having type 1 AIP, 4 (13%) as type 2 AIP, 10 as AIP-not otherwise specified (33%), and 8 (27%) as probable AIP. In the hypothetical situation, 7 of 8 type 1 AIP patients and 3 of 3 type 2 AIP patients would have been classified into the correct subtype of AIP. CONCLUSIONS: A steroid trial enhances the possibility of correctly diagnosing AIP by ICDC despite the lack of histology. However, some patients cannot be diagnosed as having AIP or be classified into the correct subtype without histology.

Validation of the balloon evacuation test: reproducibility and agreement with findings from anorectal manometry and electromyography.

BACKGROUND & AIMS: The balloon evacuation test (BET) measures the time required to evacuate a balloon filled with 50 mL water; it has been incorporated into many algorithms for diagnosis of pelvic floor dyssynergia. We aimed to assess the reproducibility of the BET, determine the upper limit of normal, and assess its concordance with evaluation of pelvic floor dyssynergia by anorectal manometry (ARM) and pelvic floor surface electromyography (EMG). METHODS: The BET was tested in 286 consecutive patients with chronic constipation (mean age, 44 years; 91% female) before and after 30 days of conservative treatment at a tertiary gastroenterology clinic in Italy from March 2010 through May 2012. The BET was tested twice, 7 days apart, in 40 healthy individuals (controls: mean age, 38 years; 92% female). The 238 constipated patients who responded incompletely to conservative therapy were examined by ARM, EMG, and digital rectal examination. Forty-seven patients with conflicting ARM and BET results underwent defecography. RESULTS: The balloon was evacuated within 1 minute by 37 controls (93%; 3 individuals required 1-2 minutes). Among patients with constipation, 148 (52%) passed the balloon within 5 minutes (110 passed the balloon in 1 minute, 35 passed it in 1-2 minutes, and 3 passed it in 2-5 minutes). The BET showed perfect reproducibility in 280 of the patients with constipation (98%) when a time less than 2 minutes was set as abnormal. The level of agreement between BET and ARM for dyssynergia was 78%, and between BET and EMG it was 83%. Thirty-two patients had abnormal results from the BET but normal results from ARM; 31 cases had inadequate straining (n = 11) or anatomic defects (n = 20), which could account for the abnormal findings from BET. CONCLUSIONS: The BET is reliable for analysis of pelvic floor dyssynergia; the optimal upper limit of normal is 2 minutes. Findings from the BET have a high level of agreement with those from ARM and EMG.

Fecal elastase-1 is useful in the detection of steatorrhea in patients with pancreatic diseases but not after pancreatic resection.

BACKGROUND: Fecal elastase-1(FE-1) has been suggested as an alternative to steatorrhea quantification to evaluate pancreatic insufficiency, but its diagnostic performance has not been compared with steatorrhea in chronic pancreatitis or after pancreatic resection. METHODS: The relationship between steatorrhea and FE-1 was studied in patients with chronic pancreatic disorders or pancreatic resection. Student's t test and ANOVA were used for statistical analysis, accepting 0.05 as limit for significance. RESULTS: Eighty-two patients were studied (42 non-operated; 40 previously submitted to pancreatic resection). Fat output was higher in operated than non-operated patients (29.2 ± 3.1 vs 9.9 ± 2.2 g/day, p < 0.001) FE-1 was more severely reduced in operated patients (202 ± 32.3 µg/g in non operated vs 68.6 ± 18.2 in operated patients; p < 0.001). Steatorrhea was significantly more severe in operated patients across different levels of FE-1. The relationship between FE-1 and steatorrhea was described by a power regression model, with a regression line significantly different in operated and non-operated patients (p < 0.001). A steatorrhea of 7 g (upper limit of normal range) was calculated by this regression line when FE-1 is 15 µg/g in non-operated, but as high as 225 µg/g in operated patients. CONCLUSION: FE-1 is useful to identify pancreatic insufficiency. Steatorrhea is anticipated in non-operated patients only when FE-1 is below the limit for a confident measurement of our assay. In operated patients, steatorrhea may be present even if FE-1 is only slightly reduced, that suggests a role for non pancreatic factors. FE1 is not useful to identify operated patients at risk of malabsorption.

Application of international consensus diagnostic criteria to an Italian series of autoimmune pancreatitis.

BACKGROUND: International consensus diagnostic criteria (ICDC) have been proposed to classify autoimmune pancreatitis (AIP) in type 1, type 2, or not otherwise specified. OBJECTIVE: Aim was to apply the ICDC to an Italian series of patients to evaluate the incidence and clinical profiles among different subtypes of AIP. METHODS: we re-evaluated and classified 92 patients diagnosed by Verona criteria, according to the ICDC. RESULTS: Out of 92 patients, 59 (64%) were diagnosed as type 1, 17 (18%) as type 2, and 15 (16%) as not otherwise specified according to the ICDC. A significant difference between type 1 and type 2 were found for age (54.5 ± 14.5 vs. 34.4 ± 13.9 respectively; p < 0.0001), male sex (76 vs. 47%; p = 0.007), jaundice (66 vs. 18%; p = 0.002) and acute pancreatitis (9 vs. 47%; p < 0.0001), elevated serum IgG4 levels (85 vs. 7%; p < 0.0001), inflammatory bowel disease (8 vs. 82%; < 0.0001), and relapse of the disease (34 vs. 6%; p = 0.058). Imaging and response to steroids in the not-otherwise-specified group were similar to type 1 and 2. CONCLUSIONS: Type 1 has a different clinical profile from type 2 autoimmune pancreatitis. The not-otherwise-specified group has peculiar clinical features which are shared both with type 1 or type 2 groups.

Prospective evaluation of subjects with chronic asymptomatic pancreatic hyperenzymemia.

OBJECTIVES: Chronic asymptomatic pancreatic hyperenzymemia (CAPH) has been described since 1996 as a benign disease. Recent studies described pathological findings at magnetic resonance cholangiopancreatography with secretin stimulation (s-MRCP) in more than half of the CAPH subjects. The aim of this study was to investigate the frequency and clinical relevance of s-MRCP findings in patients with CAPH. METHODS: Subjects prospectively enrolled from January 2005 to December 2010 underwent s-MRCP and biochemical tests routinely performed. RESULTS: Data relative to 160 subjects (94 males, 66 females, age 49.6±13.6 years) were analyzed. In all, 51 (32%) subjects had hyperamylasemia, 9 (6%) hyperlipasemia, and 100 (62%) an increase in both enzyme levels. The time between the first increased dosage of serum pancreatic enzymes and our observation was 3.3±3.9 years (range: 1-15). Familial pancreatic hyperenzymemia was observed in 26 out of 133 subjects (19.5%). Anatomic abnormalities of the pancreatic duct system at s-MRCP were found in 24 out of 160 subjects (15%). Pathological MRCP findings were present in 44 subjects (27.5%) before and in 80 subjects (50%) after secretin administration (P<0.0001). Five subjects (3.1%) underwent surgery, 3 for pancreatic endocrine tumor, 1 for pancreatic adenocarcinoma, and 1 for intraductal papillary-mucinous neoplasia (IPMN) involving the main pancreatic duct, and 18 patients (11.3%) needed a follow-up (17 for IPMN and 1 for endocrine tumor). CONCLUSIONS: Alterations of the pancreatic duct system at s-MRCP in subjects with CAPH can be observed in 50% of the subjects and are clinically relevant in 14.4% of cases.

A practical approach to the diagnosis of autoimmune pancreatitis.

Autoimmune pancreatitis is a disease characterized by specific pathological features, different from those of other forms of pancreatitis, that responds dramatically to steroid therapy. The pancreatic parenchyma may be diffusely or focally involved with the possibility of a low-density mass being present at imaging, mimicking pancreatic cancer. Clinically, the most relevant problems lie in the diagnosis of autoimmune pancreatitis and in distinguishing autoimmune pancreatitis from pancreatic cancer. Since in the presence of a pancreatic mass the probability of tumour is much higher than that of pancreatitis, the physician should be aware that in focal autoimmune pancreatitis the first step before using steroids is to exclude pancreatic adenocarcinoma. In this review, we briefly analyse the strategies to be followed for a correct diagnosis of autoimmune pancreatitis.

Italian consensus guidelines for chronic pancreatitis.

This paper gives practical guidelines for diagnosis and treatment of chronic pancreatitis. Statements have been elaborated by working teams of experts, by searching for and analysing the literature, and submitted to a consensus process by using a Delphi modified procedure. The statements report recommendations on clinical and nutritional approach, assessment of pancreatic function, treatment of exocrine pancreatic failure and of secondary diabetes, treatment of pain and prevention of painful relapses. Moreover, the role of endoscopy in approaching pancreatic pain, pancreatic stones, duct narrowing and dilation, and complications was considered. Recommendations for most appropriate use of various imaging techniques and of ultrasound endoscopy are reported. Finally, a group of recommendations are addressed to the surgical treatment, with definition of right indications, timing, most appropriate procedures and techniques in different clinical conditions and targets, and clinical and functional outcomes following surgery.

Smoking as a cofactor for causation of chronic pancreatitis: a meta-analysis.

OBJECTIVES: To assess the evidence for tobacco smoking as a risk factor for the causation of chronic pancreatitis. METHODS: We performed a meta-analysis with random-effects models to estimate pooled relative risks (RRs) of chronic pancreatitis for current, former, and ever smokers, in comparison to never smokers. We also performed dose-response, heterogeneity, publication bias, and sensitivity analyses. RESULTS: Ten case-control studies and 2 cohort studies that evaluated, overall, 1705 patients with chronic pancreatitis satisfied the inclusion criteria. When contrasted to never smokers, the pooled risk estimates for current smokers was 2.8 (95% confidence interval [CI], 1.8-4.2) overall and 2.5 (95% CI, 1.3-4.6) when data were adjusted for alcohol consumption. A dose-response effect of tobacco use on the risk was ascertained: the RR for subjects smoking less than 1 pack per day was 2.4 (95% CI, 0.9-6.6) and increased to 3.3 (95% CI, 1.4-7.9) in those smoking 1 or more packs per day. The risk diminished significantly after smoking cessation, as the RR estimate for former smokers dropped to a value of 1.4 (95% CI, 1.1-1.9). CONCLUSIONS: Tobacco smoking may enhance the risk of developing chronic pancreatitis. Recommendation for smoking cessation, besides alcohol abstinence, should be incorporated in the management of patients with chronic pancreatitis.

Altered intestinal function precedes the appearance of bacterial DNA in serum and ascites in patients with cirrhosis: a pilot study.

OBJECTIVES: Bacterial translocation seems to precede the occurrence of overt bacterial infection in patients with cirrhosis. The presence of bacterial DNA in blood and ascites correlates with bacterial translocation and is frequent in patients with advanced cirrhosis without overt infection. Our aim was to search for bacterial DNA in patients with cirrhosis both with and without ascites, and to study its correlation with abnormal intestinal motility or permeability and the presence of bacterial overgrowth. METHODS: Blood and ascites samples were obtained on day 1, and blood samples were taken twice a day for the following 3 days. Bacterial DNA was assayed by polymerase chain reaction using universal primers for rRNA 16 s. Oro-caecal transit time and bacterial overgrowth were assessed with Lactulose H(2) breath testing. Intestinal permeability was assessed by determining urinary lactulose and mannitol excretion with high performance liquid chromatography. RESULTS: We studied seven patients (six were male, age range was 42-78 years). Aetiology was alcohol in four, HCV in two, HBV in one; ascites was present in four and Child-Pugh grade was A in four and B in three. All patients had increased intestinal permeability, six had decreased transit time and one had bacterial overgrowth. In only one patient (with ascites), polymerase chain reaction was positive for bacterial DNA both in ascites and serum for all 4 days on which samples were taken. CONCLUSION: Increased intestinal permeability and abnormal motility were frequent without evidence of bacterial translocation in cirrhosis even without ascites. They are likely to be facilitators for bacterial translocation and thus precede it.

Exocrine and endocrine pancreatic function in 21 patients suffering from autoimmune pancreatitis before and after steroid treatment.

BACKGROUND/AIM: Autoimmune pancreatitis (AIP) responds rapidly and dramatically to steroid therapy. The aim of this study was to evaluate pancreatic exocrine and endocrine function in patients suffering from AIP both before and after steroid therapy. PATIENTS AND METHODS: Fecal elastase 1 and diabetes were evaluated before steroid therapy and within 1 month of its suspension in 21 patients (13 males and 8 females, mean age 43 +/- 16.5 years) diagnosed as having AIP between 2006 and 2008. RESULTS: At clinical onset, fecal elastase 1 was 107 +/- 126 microg/g stool. Thirteen patients (62%) showed severe pancreatic insufficiency (<100 microg/g stool), 4 (19%) had mild insufficiency (100-200 microg/g stool), while 4 (19%) had normal pancreatic function (>200 microg/g stool). Before steroids, diabetes was diagnosed in 5 patients (24%), all of whom had very low levels of fecal elastase 1 (<19 microg/g stool). Following steroids, fecal elastase 1 increased in all patients (237 +/- 193 microg/g stool) and observed levels were significantly higher than those seen before steroids (p = 0.001). CONCLUSIONS: Patients suffering from AIP display exocrine and/or endocrine pancreatic insufficiency at clinical onset. These insufficiencies improve after steroid therapy.

Esophageal motility and symptoms in restricting and binge-eating/purging anorexia.

BACKGROUND: Esophageal symptoms are common in anorexia nervosa, but it is not known whether they are associated with motility disorders, with different forms of the disease, and whether they respond to nutritional rehabilitation. METHODS: To clarify these points, 23 patients with anorexia nervosa (12 binge-eating/purging, "purgers"; 11 restricting type, "restricters") were studied by esophageal manometry before and after 22 weeks rehabilitation. Manometric parameters of 35 age and sex-matched patients were used as controls. Patients with anorexia also filled questionnaires on eating disorder psychopathology, psychopathological distress and esophageal, gastric and colonic symptoms before and after 4 and 22 weeks of a rehabilitation program. RESULTS: Symptoms were more severe in patients than in controls. Gastric and colonic, but not esophageal symptoms improved with treatment. LES basal pressure was higher in restricters (restricters 32.1±4.6; purgers 14.9±2.2; controls 17.1±1.1 mmHg, p<0.005), but still within normal range; this difference disappeared after treatment. Postdeglutitive body waves were normally propagated. Their amplitude was significantly higher in anorexia than in controls. No correlation was found between results of psychopathological tests (improved after treatment), esophageal symptoms and manometry. CONCLUSIONS: In anorexia, esophageal symptoms are frequent and severe. They are not adequately explained by psychological or manometric derangements.

Biofeedback is superior to electrogalvanic stimulation and massage for treatment of levator ani syndrome.

BACKGROUND & AIMS: Levator ani syndrome (LAS) might be treated using biofeedback to teach pelvic floor relaxation, electrogalvanic stimulation (EGS), or massage of levator muscles. We performed a prospective, randomized controlled trial to compare the effectiveness of these techniques and assess physiologic mechanisms for treatment. METHODS: Inclusion criteria were Rome II symptoms plus weekly pain. Patients were categorized as "highly likely" to have LAS if they reported tenderness with traction on the levator muscles or as "possible" LAS if they did not. All 157 patients received 9 sessions including psychologic counseling plus biofeedback, EGS, or massage. Outcomes were reassessed at 1, 3, 6, and 12 months. RESULTS: Among patients with "highly likely" LAS, adequate relief was reported by 87% for biofeedback, 45% for EGS, and 22% for massage. Pain days per month decreased from 14.7 at baseline to 3.3 after biofeedback, 8.9 after EGS, and 13.3 after massage. Pain intensity decreased from 6.8 (0-10 scale) at baseline to 1.8 after biofeedback, 4.7 after EGS, and 6.0 after massage. Improvements were maintained for 12 months. Patients with only a "possible" diagnosis of LAS did not benefit from any treatment. Biofeedback and EGS improved LAS by increasing the ability to relax pelvic floor muscles and evacuate a water-filled balloon and by reducing the urge and pain thresholds. CONCLUSIONS: Biofeedback is the most effective of these treatments, and EGS is somewhat effective. Only patients with tenderness on rectal examination benefit. The pathophysiology of LAS is similar to that of dyssynergic defecation.

Identification of a novel antibody associated with autoimmune pancreatitis.

BACKGROUND: Autoimmune pancreatitis is characterized by an inflammatory process that leads to organ dysfunction. The cause of the disease is unknown. Its autoimmune origin has been suggested but never proved, and little is known about the pathogenesis of this condition. METHODS: To identify pathogenetically relevant autoantigen targets, we screened a random peptide library with pooled IgG obtained from 20 patients with autoimmune pancreatitis. Peptide-specific antibodies were detected in serum specimens obtained from the patients. RESULTS: Among the detected peptides, peptide AIP(1-7) was recognized by the serum specimens from 18 of 20 patients with autoimmune pancreatitis and by serum specimens from 4 of 40 patients with pancreatic cancer, but not by serum specimens from healthy controls. The peptide showed homology with an amino acid sequence of plasminogen-binding protein (PBP) of Helicobacter pylori and with ubiquitin-protein ligase E3 component n-recognin 2 (UBR2), an enzyme highly expressed in acinar cells of the pancreas. Antibodies against the PBP peptide were detected in 19 of 20 patients with autoimmune pancreatitis (95%) and in 4 of 40 patients with pancreatic cancer (10%). Such reactivity was not detected in patients with alcohol-induced chronic pancreatitis or intraductal papillary mucinous neoplasm. The results were validated in another series of patients with autoimmune pancreatitis or pancreatic cancer: 14 of 15 patients with autoimmune pancreatitis (93%) and 1 of 70 patients with pancreatic cancer (1%) had a positive test for anti-PBP peptide antibodies. When the training and validation groups were combined, the test was positive in 33 of 35 patients with autoimmune pancreatitis (94%) and in 5 of 110 patients with pancreatic cancer (5%). CONCLUSIONS: The antibody that we identified was detected in most patients with autoimmune pancreatitis but also in some patients with pancreatic cancer, making it an imperfect test to distinguish between these two conditions.

Reduced serum hepcidin levels in patients with chronic hepatitis C.

BACKGROUND/AIMS: Patients with chronic hepatitis C (CHC) often have increased liver iron, a condition associated with reduced sustained response to antiviral therapy, more rapid progression to cirrhosis, and development of hepatocellular carcinoma. The hepatic hormone hepcidin is the major regulator of iron metabolism and inhibits iron absorption and recycling from erythrophagocytosis. Hepcidin decrease is a possible pathophysiological mechanism of iron overload in CHC, but studies in humans have been hampered so far by the lack of reliable quantitative assays for the 25-amino acid bioactive peptide in serum (s-hepcidin). METHODS: Using a recently validated immunoassay, we measured s-hepcidin levels in 81 untreated CHC patients and 57 controls with rigorous definition of normal iron status. All CHC patients underwent liver biopsy with histological iron score. RESULTS: s-hepcidin was significantly lower in CHC patients than in controls (geometric means with 95% confidence intervals: 33.7, 21.5-52.9 versus 90.9, 76.1-108.4 ng/mL, respectively; p<0.001). In CHC patients, s-hepcidin significantly correlated with serum ferritin and histological total iron score, but not with s-interleukin-6. After stratification for ferritin quartiles, s-hepcidin increased significantly across quartiles in both controls and CHC patients (chi for trend, p<0.001). However, in CHC patients, s-hepcidin was significantly lower than in controls for each corresponding quartile (analysis of variance, p<0.001). CONCLUSIONS: These results, together with very recent studies in animal and cellular models, indicate that although hepcidin regulation by iron stores is maintained in CHC, the suppression of this hormone by hepatitis C virus is likely an important factor in liver iron accumulation in this condition.

Autoimmune pancreatitis: differences between the focal and diffuse forms in 87 patients.

OBJECTIVES: Autoimmune pancreatitis (AIP) is a particular type of chronic pancreatitis that can be classified into diffuse and focal forms. The aim of this study was to analyze clinical and instrumental features of patients suffering from the diffuse and focal forms of AIP. METHODS: AIP patients diagnosed between 1995-2008 were studied. RESULTS: A total of 87 AIP patients (54 male and 33 female patients, mean age 43.4+/-15.3 years) were studied. Focal-type AIP was diagnosed in 63% and diffuse-type in 37%. Association with autoimmune diseases was observed in 53% of cases, the most common being ulcerative colitis (30%). Serum levels of IgG4 exceeded the upper normal limits (135 mg/dl) in 66% of focal AIP and in 27% of diffuse AIP (P=0.006). All patients responded to steroids. At recurrence non-steroid immunosuppressive drugs were successfully used in six patients. Recurrences were observed in 25% of cases, and were more frequent in focal AIP (33%) than in diffuse AIP (12%) (P=0.043), in smokers than in non-smokers (41% vs. 15%; P=0.011), and in patients with pathological serum levels of IgG4 compared to those with normal serum levels (50% vs. 12%; P=0.009). In all, 23% of the patients underwent pancreatic resections. Among patients with focal AIP, recurrences were observed in 30% of operated and in 34% of not operated patients. CONCLUSIONS: Focal-type and diffuse-type AIP differ as regards clinical symptoms and signs. Recurrences occur more frequently in focal AIP than in diffuse AIP. The use of non-steroid immunosuppressants may be a therapeutic option in relapsing AIP.

Clinical and radiological outcome of patients suffering from chronic pancreatitis associated with gene mutations.

OBJECTIVES: Cystic fibrosis transmembrane conductance regulator (CFTR), cationic trypsinogen gene (PRSS1), and serine protease inhibitor kazal type 1 (SPINK1) gene mutations have been associated with chronic pancreatitis (CP). The aim of this study was to compare clinical and radiological findings in sporadic CP with (CPgm) and without (CPwt) gene mutations. METHODS: Data from patients observed between 2001 and 2006 were collected. All patients were tested for 25 CFTR gene mutations, for R122H and N29I on the PRSS1 gene, and for N34S mutation on the SPINK1 gene. RESULTS: We found 34 (17.2%) of 198 patients with CPgm, 23 (11.6%) of them on the CFTR gene, 11 (5.6%) on the SPINK1, and none on the PRSS1 gene. The age at clinical onset was younger in CPgm (36.2 +/- 17.2 years) than in CPwt (44 +/- 12.6 years; P = 0.005). There were more heavy drinkers among CPwt (33%) than among CPgm (9%; P = 0.003), and the same applied to smokers (69% vs 33%, respectively; P < 0.0001). In CPgm group, the onset of pancreatic calcifications was observed more frequently in drinkers and/or smokers. Exocrine and endocrine insufficiency occurred less frequently and later in CPgm than in CPwt patients. CONCLUSIONS: Clinical and radiological outcome differ in CPgm compared with CPwt. Alcohol, even in small quantities, and cigarette smoking influence the onset of pancreatic calcifications.

Models of learning, training and progress evaluation of medical students.

Medical education has changed during the last century. Teachercentred medical education has been replaced by a studentcentred one. Some general educational principles have been adopted in medicine faculties, leading to more active students involved in learning, and interactive methods have been introduced, and the role of experience has been focused. Disciplinebased medical education is inadequate for developing comprehensive competence and doctoring. Integrated multidisciplinary learning, together with new clerkship approaches and organization, represent the future of medical education. Continuing, comprehensive, assessment can measure progression in knowledge, skills, attitudes and values. Progress test have recently been introduced in some medical school as a reliable tool for assessing the progressive performance of students in time and monitoring the entire learning process.

Risk factors of peptic ulcer in 4943 inpatients.

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.