Long-term outcomes after pancreatoduodenectomy for ampullary cancer: The influence of the histological subtypes and comparison with the other periampullary neoplasms.

BACKGROUND: Ampullary carcinoma (AC) is histologically classified as intestinal (In-AC), pancreaticobiliary (Pb-AC) or mixed-AC. The prognostic role of AC subtypes has been debated and remains unclear. The aims of this study were to evaluate outcomes after pancreatoduodenectomy (PD) for each subtype of AC and to compare these with pancreatic ductal adenocarcinoma [PDAC] and distal cholangiocarcinoma [DCC]. METHODS: PDs performed for AC between 2010 and 2018 were retrospectively evaluated. Histological subtype was obtained for all patients. One-year, 3-year and 5-year disease-free-survival (DFS) and overall survival (OS) rates were calculated. Kaplan-Meier survival analysis was performed to compare Pb-AC, In-AC and mixed-AC. Comparison with PDs performed for PDAC and DCC during the same period was also performed. RESULTS: A total of 97 patients undergoing PD for AC were evaluated: 34 (35.1%) In-AC, 54 (55.7%) Pb-AC and 9 mixed-AC (9.3%). DFS and OS rates for Pb-AC were significantly lower compared to In-AC (p < 0.05 and p < 0.01), but similar to mixed-AC (p = 0.3 and p = 0.4). Adjuvant therapy was not associated with increased survival, regardless of the histological subtype (p > 0.05). During the same period, 337 and 53 PDs for PDAC and DCC, respectively, were performed. In-AC was associated with significantly better outcomes compared to PDAC and DCC (p < 0.001); DFS and OS rates for Pb-AC and mixed AC were significantly higher compared to PDAC (p < 0.001), but similar to DCC (p > 0.05). CONCLUSIONS: Pb-AC has significantly worse survival compared to In-AC. Moreover, mixed-AC should be considered as Pb-AC. Pb-AC and mixed-AC seem to have better prognosis compared to PDAC, but similar to DCC.

Surgical margins for duodenopancreatectomy.

Microscopic residual tumor (R1) affects prognosis of resected pancreatic head cancer patients. Surgeon's ability, caseload and accuracy of pathological staging affect the rate of R1 resections. The goal of this study was to verify if a standardized histopathological workup of the specimen affects the rate of microscopic residual tumor after PD for cancer. Two groups of specimens were managed with (Group 1, Standardized Group, SG) or without (Group 2, Non Standardized Group, NSG) a standardized histopathological workup reported by the Royal College of Pathologists. Group 1 included 50 cases of PD for periampullary cancer treated between October 2010 and July 2012. Group 2 included 50 cases of PD for periampullary cancer treated between September 2005 and September 2010. The primary endpoint of the study was to verify the differences in terms of R1 rate in the two groups. Correlation between presence/absence of microscopic residual tumor status and local recurrence was also evaluated. The cohort of 100 patients consisted of 66 pancreatic ductal adenocarcinoma (PDAC) (SG: 35; NSG: 31), 15 distal common bile duct cancer (SG: 9; NSG: 6) and 19 cancer of the ampulla of Vater (SG: 6; NSG: 13). The rate of R1 resections resulted higher in the SG (66% vs 10%, p < 0.05). The rate of local recurrence did not differ in the two groups (NSG 23.4%, SG 27.6%). No relationships were found between R1 status and development of local recurrence in both groups. Local recurrence occurred in 20% of R1-NSG and in 34.3% of R1-SG. Our study showed that the standardized method determines a significant increase of R1 resection if compared with other non-standardized methods. This difference is due to the different definition of minimum clearance (0-mm- vs 1-mm rule). Even if not significantly, the standardized method seems to better discriminate the patients in terms of local recurrence risk after R1 vs R0 in SG (34 vs 11%) in comparison with R1 vs R0 in NSG (20 vs 27%).

Compensatory role of saccule in deaf children and adults: novel hypotheses.

The aim of the present study is to measure sound sensitivity of the saccule for low frequencies in a population of both young and adult prelingual deaf patients using cervical Vestibular Evoked Myogenic Potentials (cVEMPs) and to correlate the findings obtained with the phonological features. The sensitivity of the saccule to sound stimuli is well known in previous studies. The functional role of the human saccule in responding to sound stimuli is still unclear. The study was conducted on a control population of young and adults with normal hearing. The outcomes showed that the amplitude of myogenic vestibular evoked potentials resulted the most significant parameter, indicating the degree of saccular response. We found in the group of deaf adults that the saccule retained an unaltered responsiveness to sound stimuli, without suffering the age-related functional decrease as demonstrated in normal hearing patients. We assumed that the high saccular response in deaf patients is determined by a constant somatosensory stimulation (rehabilitation) of the saccule, represented by the phonetic training. We correlated the phonetic features typical of the deaf with the sensitivity of the saccule to low frequencies. Such sensitivity makes this organ the ending point of the phonetic information (perception) but also the starting point of its regulation (production). Our experience demonstrates the phonetic role of saccule in the regulation of the human voice and provides the basis for further development of this topic. Thus we strongly believe that in the deaf the saccule plays a compensatory role. The high response of the saccule allows phonemic self-regulation, compensating the low/absent tone-verbal feedback. The saccule would come rightfully to be the accessory inner ear in deaf patients. We recommend the cVEMPs in the audio-phonological assessment before starting the speech therapy or during treatment to assess the degree of responsiveness of the saccule. The resulting data would give an extremely useful information that could be ignored by the pure tone audiometry. The presence of the cVEMPs in the deaf patient may improve the expectation of the performance of speech therapy.

Intercellular space diameters of the oesophageal epithelium in NERD patients: head to head comparison between light and electron microscopy analysis.

BACKGROUND: Dilation of intercellular space diameters of oesophageal epithelium detected at transmission electron microscopy morphometry is a marker of tissue injury in non-erosive reflux disease patients. Semi-quantitative evaluation of intercellular space diameters using light microscopy seems to provide promising results. AIM/METHODS: To comparatively evaluate intercellular space diameters in the same patients, by means of morphometry and semi-quantitative analysis, both on light microscopy and transmission electron microscopy microphotographs, biopsies were taken in 29 non-erosive reflux disease patients at distal and proximal oesophagus. Twelve asymptomatic controls underwent the same protocol. RESULTS: Morphometric analysis on transmission electron microscopy microphotographs showed mean intercellular space diameter values of patients, at distal and proximal oesophagus, 3- and 2-fold, respectively, higher than those in controls (p<0.001). On light microscopy microphotographs, mean intercellular space diameter values of patients at distal oesophagus were higher than those in controls, an overlap between patients and controls being observed. The semi-quantitative score was positive in 79% of patients and in 25% of controls at distal esophagus. CONCLUSIONS: Intercellular space diameter morphometric analysis at light microscopy is widely available, allows intercellular space diameter to be quantitatively measured with good sensitivity and specificity and could represent a useful tool in non-erosive reflux disease diagnosis. Despite satisfactory sensitivity, the semi-quantitative score at light microscopy is hampered by much lower specificity than transmission electron microscopy- and light microscopy-morphometry.

Presence of gas in the refluxate enhances reflux perception in non-erosive patients with physiological acid exposure of the oesophagus.

OBJECTIVE: The mechanisms underlying symptoms in gastro-oesophageal reflux disease, particularly in non-erosive reflux disease (NERD), remain to be fully elucidated. Weakly acidic reflux and the presence of gas in the refluxate could be relevant in the pathogenesis of symptoms. METHODS: To assess the relationship between symptoms and weakly acidic, acid and mixed (liquid-gas) reflux, 24 h oesophageal pH-impedance monitoring was performed in 32 NERD and in 20 oesophagitis patients. In 12 NERD patients the study was repeated following 4 weeks treatment with a proton pump inhibitor (PPI). Impedance-pH data were compared with those of 10 asymptomatic controls. Heartburn and acid regurgitation were considered in the analysis of symptoms. RESULTS: 15 NERD patients showed a physiological acid exposure time (pH-negative). Weakly acidic reflux was significantly less frequent in patients (25% (2%), mean (SE)) than in controls (54% (4%), p<0.01). Gas was present in 45-55% of reflux events in patient groups and controls, and decreased following PPI treatment. In NERD pH-negative patients, weakly acidic reflux accounted for 32% (10%) (vs 22% (6%) in NERD pH-positive and 12% (8%) in oesophagitis patients) and mixed reflux for more than two-thirds of all symptom-related refluxes. Multivariate logistic analysis showed that in NERD pH-negative patients, the risk of reflux perception was significantly higher when gas was present in the refluxate (odds ratio, 3.2; 95% CI, 1.2 to 10; p<0.01). CONCLUSIONS: The large majority of symptoms, in all patients, are related to acid reflux. In NERD patients, the presence of gas in the refluxate significantly enhances the probability of reflux perception. These patients are also more sensitive to less acidic reflux than oesophagitis patients.

Systematic review and meta-analysis of randomised clinical trials on topical treatments for vernal keratoconjunctivitis.

AIMS: The aim of this study was to assess the efficacy of currently available topical drugs for vernal keratoconjunctivitis (VKC) through a meta-analysis of randomised clinical trials (RCTs). METHODS: Twenty-seven RCTs (n = 2184 eyes) that had evaluated the efficacy of topical drugs for the treatment of VKC were selected according to the set criteria; 10 of these trials were suitable for statistical analysis and were enrolled in the meta-analysis. Articles published up to December 2005 were identified from the following DATA SOURCES: Medline, Embase, Lilacs, the Cochrane Controlled Trials Register, and references from relevant articles. Articles in any language published with an English abstract, were screened, and those selected for inclusion were written in English, French, German, Italian, Portuguese or Spanish. The quality of the trials was assessed by the Delphi list. Statistical analysis was performed using STATA software. RESULTS: A significant improvement in all signs and symptoms, except photophobia, was observed after topical treatment for active VKC, independent of the type of treatment. Comparison of the efficacy of different drugs was not possible due to a lack of standardised criteria among studies. CONCLUSION: The currently available topical drugs are effective in treating acute phases of VKC. However, there is a lack of evidence to support the recommendation of one specific type of medication for treating this disorder. There is a need for standard criteria to assess diagnosis and therapy based on severity. There is also a need for RCTs assessing long-term effects of single drugs to control the disease and to prevent complications.

Dilated intercellular spaces and acid reflux at the distal and proximal oesophagus in patients with non-erosive gastro-oesophageal reflux disease.

BACKGROUND: Acid exposure of proximal oesophagus and dilated intercellular space diameters of oesophageal epithelium are relevant in the perception of gastro-oesophageal reflux. AIM: To explain the relationship between gastro-oesophageal reflux disease symptoms, acid exposure and intercellular space diameter along the oesophageal epithelium and to assess time-related variability of intercellular space diameter. METHODS: Thirty-three non-erosive reflux disease (NERD), six erosive oesophagitis patients and 12 asymptomatic controls underwent oesophageal manometry and 24-h dual-channel oesophageal pH-monitoring following endoscopy. Biopsies were taken 5 cm above the LES and 10 cm below the UES, at comparable levels, as pH sensors. A total of 100 intercellular space diameters per patient/control were measured blindly at transmission electron microscopy. In 15 patients, the investigation was repeated after 1 year. RESULTS: In all NERD patients, acid exposure was higher at mid-proximal oesophagus (P < 0.01) and mean intercellular space diameters, at distal and mid-proximal oesophagus, was three- and twofold higher (1.5 and 0.82 micro m, respectively) compared with controls. Intra-patient intercellular space diameter values were stable over time, not overlapping with those of controls. CONCLUSIONS: Dilation of intercellular space diameter occurs along the distal and proximal oesophageal epithelium in NERD patients and could be responsible for the enhanced perception of proximal acid reflux. This finding appears to be time-reproducible and to represent a sensitive, histopathological marker of NERD.

Effect of hiatal hernia on proximal oesophageal acid clearance in gastro-oesophageal reflux disease patients.

BACKGROUND: Proximal acid reflux is common in gastro-oesophageal reflux disease and is a determinant of symptoms. Patients with hiatal hernia complain of more symptoms than those without and are less responsive to proton-pump inhibitors. AIM: To evaluate the role of hiatal hernia on spatiotemporal characteristics of acid reflux. METHODS: Thirty seven consecutive gastro-oesophageal reflux disease patients underwent endoscopy, videofluoroscopy, manometry and multichannel 24-h pH test. Data were compared with those of 15 asymptomatic controls. Multivariate linear regression was used for statistical analysis. RESULTS: At videofluoroscopy, hiatal hernia was found in 16 of 37 patients. The mean size of hiatal hernia was 3.4 cm. Patients showed significantly prolonged acid clearance time, both at proximal and distal oesophagus, compared with controls. Hiatal hernia patients showed a significantly delayed acid clearance, along the oesophageal body, compared with non-hiatal hernia patients. The prolonged acid exposure was maintained during upright and supine position. The presence of hiatal hernia significantly predicted acid clearance delay in the distal and proximal oesophagus [at 10 cm below upper oesophageal sphincter: Delta + 2.5 min (95% confidence interval: 0.4-4.5); P < 0.02]. CONCLUSIONS: The presence of hiatal hernia is a strong predictor of more prolonged proximal oesophageal acid exposure and clearance. Hiatal hernia is likely to play a role in the pathophysiology of gastro-oesophageal reflux disease symptoms, and should be taken into greater consideration in the treatment strategies of the disease.

[A serious complication in colorectal surgery: anastomotic leakage. Our experience]. / Una grave complicanza in chirurgia colorettale: la fistola anastomotica. Nostra esperienza.

Anastomotic leakage is a severe complication in colorectal surgery with a lot of generic and specific risk factors. There are still controversies about the possibility to prevent it or to limit its severity with the use of faecal diversions. We report our experience on 189 patients operated in five years on colon-rectum, in election and emergency, with manual or mechanical anastomoses in the last 20 cm from the anal verge. We have had 21 anastomotic leakages (11%), symptomatic in 10 cases (5.5%), and 5 deaths (2.6%), 3 directly correlated to the leakage. In the patients (n 98) with loop-ileostomy there wasn't anastomotic leakages reduction, but only of clinical impact. We prefer loop-ileostomy in cases of extraperitoneal anastomoses, always in emergency and in anastomoses at risk.

Nasal surgery and eustachian tube function: effects on middle ear ventilation.

OBJECTIVES: To investigate the effect of nasal obstruction surgery on eustachian tube function and middle ear ventilation. DESIGN: Prospective study. SETTING: University Campus Bio-Medico of Rome. PARTICIPANTS: Forty consecutive patients who underwent nasal surgery were evaluated for middle ear ventilation and tubal function. MAIN OUTCOME MEASURES: Pre- and postoperative Valsalva and Toynbee tubal function tests, tympanometry and ear fullness sensation were evaluated for both ears of each patient. RESULTS: Results of postoperative tubal function tests were significantly better than preoperative ones (90% versus 46%; P<0.001). No significant difference in tympanometric values was found. The majority (95%) of the patients reported a postoperative improvement of ear fullness sensation compared with preoperative (25%; P<0.001). CONCLUSIONS: Surgery for chronic nasal obstruction significantly improves clinical tubal function but 1-month postoperative tympanometric findings remain almost the same.

Infliximab reverses growth hormone resistance associated with inflammatory bowel disease.

BACKGROUND: Increasing evidence shows that inflammation plays a major role in the aetiology of catabolism and wasting observed in inflammatory bowel disease via growth hormone resistance. AIM: To evaluate the effect of infliximab treatment on the growth hormone/insulin-like growth factor-1 axis. METHODS: Fourteen adults with active Crohn's disease or ulcerative colitis underwent three infliximab infusions at a dose of 5 mg/kg for induction of remission, plus two maintenance infusions 8 weeks apart. Blood samples were collected for the analysis of serum growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein-3 and acid labile subunit. RESULTS: Serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 concentrations, which were significantly lower in inflammatory bowel disease patients before treatment compared with controls (P < 0.01), significantly increased during the induction phase (+58% and +29%, respectively, after the second infusion, P < 0.01), and dropped to baseline levels during maintenance therapy. Both insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 showed significant negative correlations with C-reactive protein (rho = -0.37, P = 0.002; rho = -0.35, P = 0.01, respectively). Growth hormone and acid labile subunit levels were not statistically different between controls and inflammatory bowel disease patients either at baseline or during treatment. CONCLUSIONS: Infliximab induction treatment reverses growth hormone resistance observed in active inflammatory bowel disease through the suppression of systemic inflammation. The restored growth hormone/insulin-like growth factor-1 axis is impaired again following the prolonged interval between maintenance infusions, possibly because of the subclinical reactivation of the inflammatory process.

[The reciprocal evaluation in the Learning Organization]. / La valutazione reciproca nel contesto di una Learning Organization.

INTRODUCTION: The culture of the appraisal was introduced in the Italian Universities only five years ago and the collected data come from the evaluation nuclei in the university on the basis of grills structured, proposed from the national Observatory for the Appraisal, where data are dealt in comparative key. MATERIALS AND METHODS: The Medicine faculty of the University Campus Bio Medico every year carries out an evaluation survey where the judgments from the students are compared with their didactic results. We utilise questionnaires to both inquire into the quality of the logistic and organizational aspects and into the didactic teacher competences and tutors, taking them in consideration singularly and as a whole, through the integrated course's analysis. RESULTS: This study represents one further development regarding those already published in the previous years, because it compares every teacher's results of the last the five years and every student's academic career from the first moment the student entered into the faculty. The two evaluative lines have been discussed in meetings with students, teacher and administrative staff. CONCLUSIONS: From the quantitative type of data gained through questionnaires, through the curves of performance of the students and through the interpretation that are in question observations for the improvement of the didactic quality are obtained.

[Malnutrition detected by "bioelectrical status" of total and segmental body mass to nutritional management of patients]. / Rilevazione del tipo e grado di Malnutrizione con l'esame dello "Stato bioelettrico" della Massa Corporea Segmentaria e "a tutto corpo".

We examined 182 controls with Body Mass Index (BMI) between 20 and 25 kg/m2 and 246 hospitalised patients divided into 3 groups: the first one consisted of 70 severe malnourished with (BMI) < 20 kg/m2, the second one of 43 light malnourished with BMI between 20 and 25 kg/m2 and the last one of 133 obese with BMI > 25 kg/m2. The Resistance (Rs) and Reactance (Xc), with the Phase angle ((phi), are detected from total and segmental (Arm and "Trunk + Leg") body. We analysed electric parameters plotting them on 4 different graphs which reported the values of: 1) total Rs vs total Xc; 2) segmental Rs vs segmental Xc; 3) total Rs/height vs weight/ height; 4) total Xc/height vs weight/height. Rs and Xc were different in all groups: the severe malnourished patients (1st group) gave evidence of a paradoxical increase of Rs and a decrease of phi. The mean values decreased for the patient of the 2nd and 3rd group (the (phi reduced especially for the 2nd group). Referring to the segmental measures, "Trunk + Leg" biases total Rs and Xc much more than Arm. In addition the phi of "Trunk + Leg" is more similar to the total o than the Arm one. If compared with the total, this last one highly decreases in the patients of the 1st and 2nd group. We conclude that segmental bioelectrical values (Rs, Xc, phi) integrate the total one, because they allow to find out the correlation between total parameters and a specific body segment. Total and segmental Rs, Xc (and phi) values and segmental phi ratio are related to the malnutrition. The approach together with the analysis of the Graphics result to a prompt inspection of the individual bioelectrical status in subjects.

[Laparoscopic cholecystectomy for acute cholecystitis: our experience]. / La colecistectomia videolaparoscopica nella colecistite acuta: nostra esperienza.

Laparoscopic cholecystectomy (LC) is now the gold standard in the treatment of cholelithiasis. LC is safe even in patients with acute cholecystitis. In our 118 cases there was 4 major complications as bile duct injuries (3%) and 13 minor complications (11%); conversion rate was 21% (24 patients), without mortality. Our experience confirms the validity of early LC in the treatment of acute cholecystitis, but laparoscopic procedure is associated with higher conversion rate (21% versus 3%) and complication rates compared to the treatment in non-acute patients.

[Endocrine obesity: bioelectric profiles (biotypes) detected in the body composition]. / Obesità "endocrina": alterazioni della composizione corporea con l'esame dei profili bioelettrici (biotipi).

136 patients were selected (16 men and 120 women with non-specific menstrual disturbances) with a BMI (Body Mass Index) between 25 and 45 kg/m2, which were diagnosed with "disendocrinia" (GH deficit, hyperadrenocorticism, hypothyroidsm, hyperandrogenism, menstrual cycle disorders). The proposed approach, based on the visualization of the value distribution of the electric measures in different graphics, is able to immediately explain the bioelectric state of the individual's lean-mass. Subjects with hypothyroidism present, along with their overweight, less bio-conducting mass, with an altered fluid intra/extra-cellular distribution. Patients with hyperadrenocorticism show instead an hyperhydratation of the body mass, especially in the extracellular level. Patients with menstrual disorders (amenorrea, polycystic ovary syndrome, anovulatory cycle etc...) present a lean mass reduction (elevated Rs) and an increase of the intra-cellular compartment (elevated-Xc). Patients with hyper-androgenism (and hirsutism) show a characteristic bioelectric "pattern", with low Rs levels and high Xc levels. Subjects with GH deficit (men and women), has a trend of documenting bioelectric measures with lower lean mass and higher fat-mass. Different electric biotypes seem to characterize the body composition in the several endocrine disorders.

[Radiology investment planning using the Break Even Point (BEP) method]. / Pianificazione di un investimento di radiologia mediante la metodica del Break Even Point (BEP).

The health care financing decision are becoming increasingly complex in all health care environments. As a managed care becomes a greater percentage of overall business, accurate financial planning and decision making will be key components of viable organization. Therefore, the priority for health care systems is to manage their costs at the same time as maintaining the relationships they have with patients, providers, payors, and communities in order to have long term success and short term survival. Principal wedge to value an investment is to define a planning in order to identify the activities, to attribute costs to the activities, to fix a full cost for every performances and to examine fixed costs and variable costs. This is the key to achieve a economic balance.

Intra-oesophageal distribution and perception of acid reflux in patients with non-erosive gastro-oesophageal reflux disease.

BACKGROUND: The majority of patients with gastro-oesophageal reflux disease do not present with erosive oesophagitis and make up a heterogeneous group. Patients with non-erosive gastro-oesophageal reflux disease are less responsive than patients with oesophagitis to acid-suppressive therapy. AIM: To assess the role of acid reflux in gastro-oesophageal reflux disease symptoms. METHODS: The spatio-temporal characteristics of reflux events were analysed and related to reflux perception in 45 patients with non-erosive gastro-oesophageal reflux disease and 20 patients with erosive oesophagitis. RESULTS: Compared with healthy controls, all patients showed a higher intra-oesophageal proximal spread of acid, which was prominent in patients with non-erosive gastro-oesophageal reflux disease (> 50% of events lasting for 1-2 min). Irrespective of mucosal injury, the risk of reflux perception was very high when acid reached proximal sensors (odds ratio, 7.6; 95% confidence interval, 4.6-12.5), being maximal in patients with non-erosive gastro-oesophageal reflux disease with normal acid exposure time (odds ratio, 11; 95% confidence interval, 5.2-22.3). CONCLUSIONS: Patients with non-erosive gastro-oesophageal reflux disease are characterized by a significantly higher proportion of proximal acid refluxes and a higher sensitivity to short-lasting refluxes when compared with patients with oesophagitis. The highest proximal acid exposure and highest perception occurred in patients with non-erosive gastro-oesophageal reflux disease presenting with a normal pH-metric profile. The assessment of acid distribution and its perception in the oesophageal body can better identify reflux patients who should benefit from acid-suppressive treatment.

[Manual colonic anastomosis with continuous single layer suture. Our experience]. / Anastomosi coliche manuali con sutura continua monostrato. La nostra esperienza.

The use of staplers has produced a reduction on operative times in the colorectal surgery without reduction of anastomotic complications. We present our experience about colonic anastomoses (ileo-colic, colo-colic and colo-rectal intraperitoneal anastomoses) with extramucosal one-layer continuous suture in synthetic slow absorbable one-filament. In the period January 2000-January 2003 we performed 157 operations on the large bowel, with 113 manual colonic anastomoses. Our results are similar to the best series of literature. The hand-sewn suture actually represents our common technique for the anastomoses of the large bowel.

[Teachers' education goes through students' evaluation as well]. / La formazione dei docenti passa anche attraverso la valutazione degli studenti.

OBJECTIVE: Students' opinion on the quality of the educational methods can represent an interesting factor useful to encourage teachers to reconsider their educational methodologies in view of the new planning required by changes in the study curricula. MATERIALS AND METHODS: The paper considers the evaluation expressed by medical students of the "Campus Bio-Medico" University during three consecutive years, in order to perceive the dynamic sense and the evolving prospective of the educational quality as a whole. From a methodological point of view the evaluation of each year and of each course are related to a general median line. This is a significant indicator of the variations of educational methodologies considered as a whole. The relation between the general median line and the course one allows taking into consideration the relative and the absolute variation of the quality. RESULTS: To be relevant the analysis of each course has to be put in relation with the progress of the previous year and with the overall state of the educational activities. While in the first case students evaluating the same course are not the same, in the second one the group of students is substantially stable and allows a better control of the evaluators' variable. CONCLUSIONS: Students' judgements on the educational quality have to be put always into a constructive frame. They have to be involved in the process of improving the educational methodologies by means of orienting teachers' education, pointing out possible critical aspects or stressing each time the results they expect. The dynamic aspect of evaluation allows constant confrontation of the results obtained during a course with the criteria of the expected quality growth. That is, a course apparently static or even dropping, can be considered as such only because the students expectations have grown.

Expression of AP-2 transcription factor and of its downstream target genes c-kit, E-cadherin and p21 in human cutaneous melanoma.

The AP-2 transcription factor plays a pivotal role in regulating the expression of several genes involved in tumor growth and progression of melanoma. We determined, by Western blot, variation in the level of expression of AP-2 and three of its downstream targets, c-kit, E-cadherin, and p21 in several human melanoma cell lines and, by immunohistochemistry, in a group of 99 histological samples including benign and malignant melanocytic lesions. A significant negative correlation between AP-2 expression level and tumor thickness was found. Moreover, AP-2 expression was positively associated with E-cadherin and c-kit expression. In contrast, there was a significant negative association between AP-2 and p21 expression levels. These findings suggest that p21 is independent of AP-2 transactivator function during the latest phases of melanoma progression. Finally, AP-2, c-kit, E-cadherin, and p21 expression levels did not show to be able to distinguish between dysplastic nevi and nevi without dysplasia. We conclude that changes in the expression of these proteins are involved in the later phases of melanoma progression, and may be responsible for the transition from local invasive melanoma to metastasis.