The prevalence of celiac disease and the appropriateness of the diagnosis in family medicine setting could be lower than expected.

OBJECTIVE: To assess the prevalence of celiac disease (CD) and the appropriateness of this diagnosis in the family medicine setting in Italy. PATIENTS AND METHODS: The electronic databases of 16 general practitioners working in Rome (Italy) were analyzed. The prevalence of CD according to the Italian pathology identification code issued by the Italian National Health System was assessed. In addition, patients registered as having celiac disease without being assigned a pathology identification code were interviewed. RESULTS: Overall, a population of 22,064 patients was analyzed. 91 patients had a diagnosis of CD (0.41%), 60 of whom had a pathology identification code (0.27%), and 31 did not (0.14%). 29 of these patients were interviewed, 16 (17.58% of the CD recorded patients) of whom reported being on a gluten-free or gluten restricted diet, with reported improvement in their clinical symptoms. Half of them further stated that they would not agree to resume a restriction free diet in order to make a definitive CD diagnosis, due to the risk of symptom recurrence. CONCLUSIONS: In a family medicine setting, the prevalence of CD seems to be lower than expected, and one third of patients diagnosed with CD do not fulfill all diagnostic criteria. Any effort to improve the diagnostic work-up for CD should also be made in this setting.

A systematic review of FOLFOXIRI chemotherapy for the first-line treatment of metastatic colorectal cancer: improved efficacy at the cost of increased toxicity.

AIM: The simultaneous administration of irinotecan, 5-fluorouracil, folinic acid and oxaliplatin (FOLFOXIRI) has been compared with standard 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) in randomized trials in metastatic colorectal cancer patients. A superior efficacy of FOLFOXIRI has been reported by some authors, but others have failed to show any differences and do not recommend its use because of greater cost and toxicity. We performed a systematic review of the literature to analyse efficacy and toxicity of FOLFOXIRI. METHOD: Odds ratios (OR) with 95% confidence intervals (CI) were used to analyse dichotomous variables. Hazard ratios (HR) for progression and death were combined with an inverse variance method based on logarithmic conversion. A fixed-effect model and Mantel-Haenszel's method were used. Heterogeneity was tested with Cochrane's Q test and I(2) test. RESULTS: A significant increase in response rate (OR 2.04; P < 0.01) was associated with treatment by FOLFOXIRI and a benefit was also shown by the HR for progression (HR 0.72; P < 0.01) and death (HR 0.71; P < 0.01). Analysis for toxicity found a significant increase associated with FOLFOXIRI except for anaemia, fatigue and febrile neutropenia. CONCLUSION: FOLFOXIRI confers significant benefit in progression-free survival, survival, response and R0 resection rates but is more toxic compared with FOLFIRI.

BRCA1 expression and molecular alterations in familial breast cancer.

The aim of the study was to evaluate the performance of immunohistochemical MS110 expression in a series of familial and sporadic breast cancer patients. An immunohistochemical study was performed on TMA samples from 93 sporadic and 94 familial breast cancer patients with (7/94) and without BRCA1 germline mutations. BRCA1 protein expression level was evaluated using the monoclonal MS110 antibody. Immunohistochemistry, performed on TMA samples, showed positive nuclear staining for BRCA1 in 34 sporadic and 37 familial breast tumours, respectively. All the tumours from patients carrying BRCA1 mutations showed complete loss of both BRCA1 and ERalpha expression, regardless of the type of mutation. The percentage of MS110 positive cases was significantly lower in mutated versus wild type BRCA1 familial cases (p=0.02) while the percentage of patients with higher ERalpha expression was significantly lower in BRCA1-mutated versus BRCA1-wild type familial patients (p=0.05). Interestingly, the presence of the E1038G polymorphism in BRCA1 exon 11 was significantly associated with protein expression (p=0.029). The frequency of MS110 negative cases also detected in BRCA1-wild type tumours, points to the inability of the BRCA1 IHC expression in discriminating between familial and sporadic breast cancer.

Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer.

BACKGROUND: Several studies looked for tumor biomarkers predictive for paclitaxel sensitivity but till now no reliable biomarkers are available. The aim of this study was to verify the potential predictive value of beta-tubulin III and IV, vascular endothelial growth factor-receptor (VEGFR-1), HER2/neu and microvessel density (mVD), in a group of 70 patients with advanced breast cancer (ABC) treated with paclitaxel-based chemotherapy. PATIENTS AND METHODS: Immunohistochemical analysis (ICA) of HER2, VEGFR-1, mVd, beta-tubulin III and beta-tubulin IV expression were performed in a series of 72 advanced breast cancer. Furthermore apoptotic fraction with TUNEL analysis was evaluated. RESULTS: beta-tubulin III ICA expression was predictive of progression after chemotherapy. In fact only 2% of the patients with low beta-tubulin III expression progressed after paclitaxel chemotherapy vs 38% of those with high beta-tubulin III tumor expression (P=0.000; by chi(2)). This evidence was confirmed by a logistic regression analysis (OR 28.789; 95% CI 3.212-258,072; P=0.004). There was not a significant association between other biomarkers' characteristics and clinical response to chemotherapy. A Cox multivariate analysis, with overall survival as a dependent variable, showed that only HER2 expression was independently associated (OR 2.39; 95% CI 1.09-5.23; P=0.03) with overall survival. CONCLUSIONS: We suggest that class III beta-tubulin immunohistochemical expression analysis could be a potentially relevant tumor biomarker for paclitaxel resistance in advanced breast cancer patients.

Symptom-based approach to colorectal cancer: survey of primary care physicians in Italy.

BACKGROUND: Colorectal cancer is a frequent cause of mortality in Western countries, including Italy, where a definite screening policy has not yet been adopted. It is likely that most patients with colorectal cancer refer, first of all, to their primary care physician at onset of symptoms. AIM: To perform a survey on the approach, of primary care physicians, to patients with symptoms suggesting the presence of colorectal cancer. METHODS: A total of 280 consecutive symptomatic patients without previous diagnosis of organic colon disease or recent colon investigation in whom, after consulting, 159 primary care physicians in Lazio (Italy) prescribed colonoscopy or double-contrast barium enema. RESULTS: Most frequent presenting symptoms were lower abdominal pain (79.6%), bloating (59.6%), constipation (47.8%), diarrhoea (30.3%), iron deficiency anaemia (24.6%), change in bowel habits (20.3%) and weight loss (15%). Colonoscopy and barium enema were equally advised by physicians to rule out the presence of cancer (56% versus 44%, P = ns). Cancer was found in 14.6% of patients. Age > 50 years and iron deficiency anaemia were the only independent variables associated with colorectal cancer (Odds ratios 9.0 and 8.8 at multivariate analysis, respectively). CONCLUSION: The symptom-based selection criteria used by primary care physicians have been shown to be scarcely effective. Colonic investigation should be requested, irrespective to the symptoms, in patients aged > 50 years with iron deficiency anaemia.