Residual pancreatic function after pancreaticoduodenectomy is better preserved with pancreaticojejunostomy than pancreaticogastrostomy: A long-term analysis.

BACKGROUND: Pancreatico-enteric anastomosis after pancreaticoduodenectomy can be performed using either a pancreaticojejunostomy (PJ) or pancreaticogastrostomy (PG). Differences in surgical outcomes are still a matter of debate, and less is known about long-term functional outcomes. METHODS: Twelve years after the conclusion of a comparative study evaluating the surgical outcomes of PJ and PG (Bassi et al., Ann Surg 2005), available patients underwent morphological and functional pancreatic assessment: pancreatic volume and duct diameter measured by MRI, impaired secretion after secretin, fecal fat, fecal elastase-1 (FE-1), serum vitamin D and endocrine function. Quality of life and symptom scores were evaluated with the EORTC QLQ-C30 questionnaire. RESULTS: Only 34 patients were available for assessment. No differences were found in terms of BMI variation, endocrine function, quality of life or symptoms. Exocrine function was more severely impaired after PG than after PJ (fecal fats 26.6 ±â€¯4.1 vs 18.2 ±â€¯3.6 g/day; FE-1 121.4 ±â€¯6.7 vs 170.2 ±â€¯25.5 µg/g, vitamin D 18.1 ±â€¯1.8 vs. 23.2 ±â€¯3.1 ng/mL). MRI assessment identified a lower pancreatic volume (26 ±â€¯3.1 vs. 36 ±â€¯4.1 cm3) and a more dilated pancreatic duct (4.6 ±â€¯0.92 vs. 2.4 ±â€¯0.18 mm) in patients with PG compared to those with PJ. CONCLUSION: Compared to PJ, PG is associated with a more severely impaired exocrine function long-term, but they result similar endocrine function and quality of life. In patients with a long life expectancy, this should be taken into account.

Solitary rectal ulcer syndrome in a patient with anorexia nervosa: A case report.

This case report describes the clinical presentation, diagnosis, and management of a 26-year-old patient with anorexia nervosa (AN) diagnosed with Solitary Rectal Ulcer Syndrome (SRUS). To our knowledge, this is the first case report to document SRUS in AN, whose pathogenesis in this case seems to have been determined by the patient's malnourished and underweight state. Furthermore, SRUS symptoms appear to have interacted with the eating disorder psychopathology, increasing the need to exert control over eating. Cognitive behavioral strategies and procedures were accordingly used to address the eating disorder psychopathology and to promote complete weight restoration, which brought about a significant reduction in the size of the ulcer and the complete resolution of SRUS symptoms. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:731-735).

Randomised controlled trial of mesalazine in IBS.

OBJECTIVE: Low-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS. DESIGN: We conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 weeks, and were followed for additional 12 weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or >75% of time. RESULTS: A total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI -12.8 to 15.1). In explorative analyses, with the 75% rule or >75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI -2.7% to 26.0%) and 5.9% (p=0.404; 95% CI -7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the >75% rule. CONCLUSIONS: Mesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy. TRIAL REGISTRATION NUMBER: ClincialTrials.gov number, NCT00626288.

Role of Amylase-α2A Autoantibodies in the Diagnosis of Autoimmune Pancreatitis.

OBJECTIVES: Several serological markers have been reported in autoimmune pancreatitis (AIP) patients. However, only serum IgG4 (sIgG4) is available in clinical practice for AIP diagnosis. Antiamylase α antibodies (AMY-α Abs) have been proposed to diagnose AIP. This study evaluates the utility of AMY-α Abs and sIgG4 for AIP diagnosis. METHODS: Twenty-five AIP patients, 84 disease control groups (31 chronic pancreatitis, 30 acute pancreatitis, 23 pancreatic adenocarcinoma), and 59 healthy donors were prospectively studied. The AMY-α Abs were determined by homemade enzyme-linked immunosorbent assay and sIgG4 by nephelometry. RESULTS: Increased sIgG4 were detected to be present in 52% of AIP, 5% in control groups, and 0% in healthy donors, and AMY-α Abs, respectively, in 76%, 36%, and 2%. sIgG4 was elevated in 92% of the 13 patients with type 1 AIP, but in none of 3 with type 2 and of 8 with not otherwise specified AIP. The AMY-α Abs were present in 79%, 67%, and 75% of type 1, type 2, and not otherwise specified AIP, respectively. Sensitivity and specificity of AMY-α Abs were 76% and 78%, and of sIgG4 50% and 94%. By combining the 2 serological markers, sensitivity was 41%, and specificity was 99%. CONCLUSIONS: The AMY-α Abs may help to diagnosis of AIP and to differentiate AIP subtypes.

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.

Impedance pH Monitoring: Intra-observer and Inter-observer Agreement and Usefulness of a Rapid Analysis of Symptom Reflux Association.

BACKGROUND/AIMS: Symptom reflux association analysis is especially helpful for evaluation and management of proton pump inhibitor (PPI) re-fractory patients. An accurate calculation requires manual editing of 24-hour multichannel intraluminal impedance-pH (MII-pH) tracings after automatic analysis. Intra- and inter-observer agreement as well as reliability of rapid editing confined to the time around symptomatic episodes are unknown. Aim of this study was to explore these topics in a prospective multicenter study. METHODS: Forty consecutive patients who were off PPI therapy underwent MII-pH recordings. After automatic analysis, their tracings were anonymized and randomized. Three experienced observers, each one trained in a different European center, independently per-formed manual editing of 24-hour tracings on 2 separate occasions. Values of symptom index and symptom association proba-bility for acid and non acid reflux were transformed into binary response (i.e., positive or negative). RESULTS: Intra-observer agreement on symptom reflux association was 92.5% to 100.0% for acid and 85.0% to 97.5% for non-acid reflux. Inter-observer agreement was 100.0% for acid and 82.5% to 95.0% for non-acid reflux. Values for symptom index and symptom association probability were similar. Concordance between 24-hour and rapid (2 minutes-window before each symp-tomatic episode) editings for symptom reflux association occured in 39 to 40 patients (acid) and in 37 to 40 (non-acid), de-pending on the observer. CONCLUSIONS: Intra- and inter-observer agreement in classifying patients with or without symptom reflux association at manual editing of 24-hour tracings was high, especially for acid reflux. Classifying patients according to a rapid editing showed excellent con-cordance with the 24-hour one and can be adopted in clinical practice.

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.

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.

Prebiotic potential and gastrointestinal effects of immature wheat grain (IWG) biscuits.

In this study the effects of immature wheat grains (IWG), a natural source of fructo-oligosaccharides (FOS), on intestinal microbiota and gastrointestinal function were evaluated. Ileal effluents from three ileostomates were collected for 8 h after IWG-enriched or Control biscuit administration, and then fermented in vitro with human faecal inoculum. On fermentation broths, microbial counts and SCFA were measured. Moreover, we investigated the effect of IWG biscuits on gastric emptying. Twelve healthy volunteers underwent ultrasound measurement of gastric emptying of a standard meal consumed 5 h after a breakfast composed by lactose-free milk and IWG or Control biscuits; hunger and satiety sensations were also evaluated in this period. Bifidobacteria and lactic acid bacteria counts were higher (P < 0.05) in IWG than in Control cultures, supporting the prebiotic effects of IWG, probably linked to its FOS content; moreover IWG fermentation produced more acetate. In vivo IWG biscuits delayed gastric emptying of the next meal (P < 0.05), decreased hunger (P < 0.001) and increased satiety (P < 0.005). Therefore in vitro results substantiate the potential of IWG as a prebiotic ingredient and in vivo data suggest an effect of IWG on gastric emptying and on persistent satiety. These preliminary data tend to support the use of IWG in formulating functional prebiotic products suitable to promote satiety.

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.

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.

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.

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.

Identification of a Btk mutation in a dysgammaglobulinemic patient with reduced B cells: XLA diagnosis or not?

The identification of a Btk mutation in a male patient with <2% CD19(+) B cells warrants making the diagnosis of X-linked Agammaglobulinemia (XLA). Herein we report the case of a 31 year-old male with a gradual decline of peripheral B lymphocytes and low IgA and IgM but normal IgG levels. His clinical history revealed recurrent respiratory and skin infections, sclerosing cholangitis and chronic obstructive pancreatitis. Molecular studies revealed a novel aminoacidic substitution in Btk protein (T316A). His mother, maternal aunts and a maternal female cousin were heterozygotes for the same Btk mutation and were variably affected with pulmonary emphysema. This is a puzzling case where the patient's clinical history and laboratory findings divorce molecular genetics. Either this case confirms the variable expressivity of XLA disease or the T316A change in Btk SH2 domain is a novel non-pathogenic mutation and another unknown gene alteration is responsible for the disease.

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.