In Vitro and In Vivo Effects of the Urokinase Plasminogen Activator Inhibitor WX-340 on Anaplastic Thyroid Cancer Cell Lines.

Increased expression of the urokinase-type plasminogen activator (uPA) system is associated with tumor invasion, neo-angiogenesis, and metastatic spread, and has been shown to positively correlate with a poor prognosis in several cancer types, including thyroid carcinomas. In recent years, several uPA inhibitors were found to have anticancer effects in preclinical studies and in some phase II clinical trials, which prompted us to evaluate uPA as a potential therapeutic target for the treatment of patients affected by the most aggressive form of thyroid cancer, the anaplastic thyroid carcinoma (ATC). In this study, we evaluated the in vitro and in vivo effects of WX-340, a highly specific and selective uPA inhibitor, on two ATC-derived cell lines, CAL-62 and BHT-101. The results obtained indicated that WX-340 was able to reduce cell adhesion and invasiveness in a dose-dependent manner in both cell lines. In addition, WX-340 increased uPA receptor (uPAR) protein levels without affecting its plasma membrane concentration. However, this compound was unable to significantly reduce ATC growth in a xenograft model, indicating that uPA inhibition alone may not have the expected therapeutic effects.

Papillary Thyroid Cancer Prognosis: An Evolving Field.

Over the last few years, a great advance has been made in the comprehension of the molecular pathogenesis underlying thyroid cancer progression, particularly for the papillary thyroid cancer (PTC), which represents the most common thyroid malignancy. Putative cancer driver mutations have been identified in more than 98% of PTC, and a new PTC classification into molecular subtypes has been proposed in order to resolve clinical uncertainties still present in the clinical management of patients. Additionally, the prognostic stratification systems have been profoundly modified over the last decade, with a view to refine patients' staging and being able to choose a clinical approach tailored on single patient's needs. Here, we will briefly discuss the recent changes in the clinical management of thyroid nodules, and review the current staging systems of thyroid cancer patients by analyzing promising clinicopathological features (i.e., gender, thyroid auto-immunity, multifocality, PTC histological variants, and vascular invasion) as well as new molecular markers (i.e., BRAF/TERT promoter mutations, miRNAs, and components of the plasminogen activating system) potentially capable of ameliorating the prognosis of PTC patients.

Expression and Clinical Utility of Transcription Factors Involved in Epithelial-Mesenchymal Transition during Thyroid Cancer Progression.

The transcription factors involved in epithelial-mesenchymal transition (EMT-TFs) silence the genes expressed in epithelial cells (e.g., E-cadherin) while inducing those typical of mesenchymal cells (e.g., vimentin). The core set of EMT-TFs comprises Zeb1, Zeb2, Snail1, Snail2, and Twist1. To date, information concerning their expression profile and clinical utility during thyroid cancer (TC) progression is still incomplete. We evaluated the EMT-TF, E-cadherin, and vimentin mRNA levels in 95 papillary TC (PTC) and 12 anaplastic TC (ATC) tissues and correlated them with patients' clinicopathological parameters. Afterwards, we corroborated our findings by analyzing the data provided by a case study of the TGCA network. Compared with normal tissues, the expression of E-cadherin was found reduced in PTC and more strongly in ATC, while the vimentin expression did not vary. Among the EMT-TFs analyzed, Twist1 seems to exert a prominent role in EMT, being significantly associated with a number of PTC high-risk clinicopathological features and upregulated in ATC. Nonetheless, in the multivariate analysis, none of the EMT-TFs displayed a prognostic value. These data suggest that TC progression is characterized by an incomplete EMT and that Twist1 may represent a valuable therapeutic target warranting further investigation for the treatment of more aggressive thyroid cancers.

Evaluation of Clinicopathological and Molecular Parameters on Disease Recurrence of Papillary Thyroid Cancer Patient: A Retrospective Observational Study.

The American Joint Committee on Cancer has revised the Tumor-Node-Metastasis (TNM) staging system for papillary thyroid cancer (PTC) patients. We examined the impact of this new classification (TNM-8) on patient stratification and estimated the prognostic value of clinicopathological features for the disease-free interval (DFI) in a cohort of 1148 PTC patients. Kaplan-Meier analyses showed that all clinicopathological parameters analyzed, except age and multifocality, were associated significantly with DFI. Cox regression identified tall cell PTC variant and stage as independent risk factors for DFI. When the stage was replaced with age, tumor size, and lymph node (LN) metastases in the set of covariates, the lateral LN metastases stood out as the strongest independent predictor of DFI, followed by tall cell variant and age. A noteworthy result emerging from these analyzes is that regression models had lower Akaike and Bayesian information criterions if variables were categorized based on the TNM-7. In addition, we examined data from a different PTC patient cohort, acquired from The Cancer Genome Atlas database, to verify whether the DFI prediction could be enhanced by further clinicopathological and molecular parameters. However, none of these was found to be a significant predictor of DFI in the Cox model.

PD-1 Ligand Expression in Epithelial Thyroid Cancers: Potential Clinical Implications.

The new immunotherapy targeting the programmed cell death 1 (PD-1) receptor and its cognate ligand PD-L1 has renewed hopes of eradicating the most difficult human cancers to treat. Among these, there are the poorly differentiated and anaplastic thyroid cancers, unresponsive to all the therapies currently in use. In the present review we will summarize information regarding the expression of PD-L1 in the different thyroid cancer histotypes, its correlation with clinicopathological features, and its potential prognostic value. Then, we will evaluate the available data indicating the PD-1/PD-L1 axis as a promising target for thyroid cancer therapy.

CTLA-4 and PD-1 Ligand Gene Expression in Epithelial Thyroid Cancers.

The dysregulation of PD-1 ligands (PD-L1 and PD-L2) and CTLA-4 ligands (CD80 and CD86) represents a tumor strategy to escape the immune surveillance. Here, the expression of PD-L1, PD-L2, CD80, and CD86 was evaluated at the mRNA level in 94 patients affected by papillary thyroid carcinoma (PTC) and 11 patients affected by anaplastic thyroid carcinoma (ATC). Variations in the mRNAs in PTC patients were then correlated with clinicopathological features. The expression of all genes was deregulated in PTC and ATC tissues compared to normal tissues. In particular, the downregulation of CD80 was observed above all in ATC. In addition, the increased expression of CD80 associated with longer disease-free survival in PTC. Higher expression of PD-L1 associated with the classical histological variant and with the presence of BRAFV600E mutation in PTC. The increased PD-L2 expression correlated with BRAFV600E mutation and lymph node metastasis, while its lower expression correlated with the follicular PTC variant. The latter was also associated with the CD80 downregulation, which was also related to the absence of lymph node metastasis. In conclusion, we documented the overall dysregulation of PD-1 and CTLA-4 ligands in PTC and ATC tissues and a possible prognostic value for CD80 gene expression in PTC.

Thyroid diseases and skin autoimmunity.

The skin is the largest organ of the body, at the boundary with the outside environment. Primarily, it provides a physical and chemical barrier against external insults, but it can act also as immune organ because it contains a whole host of immune-competent cells of both the innate and the adaptive immune systems, which cooperate in eliminating invading pathogens following tissue injury. On the other hand, improper skin immune responses lead to autoimmune skin diseases (AISD), such as pemphigus, bullous pemphigoid, vitiligo, and alopecia. Although the interplay among genetic, epigenetic, and environmental factors has been shown to play a major role in AISD etiology and progression, the molecular mechanisms underlying disease development are far from being fully elucidated. In this context, epidemiological studies aimed at defining the association of different AISD with other autoimmune pathologies revealed possible shared molecular mechanism(s) responsible for disease progression. In particular, over the last decades, a number of reports have highlighted a significant association between thyroid diseases (TD), mainly autoimmune ones (AITD), and AISD. Here, we will recapitulate the epidemiology, clinical manifestations, and pathogenesis of the main AISD, and we will summarize the epidemiological evidence showing the associations with TD as well as possible molecular mechanism(s) underlying TD and AISD pathological manifestations.

Iodine deficiency in pregnancy: Still a health issue for the women of Cassino city, Italy.

OBJECTIVE: The World Health Organization, the United Nations Children's Fund, and the International Council for the Control of Iodine Deficiency Disorders recommend a median urinary iodine concentration (UIC) in pregnant women between 150 µg/L and 249 µg/L. In the present study, we evaluated whether in the urban area of Cassino (central Italy), after a national salt iodination program (30 mg/kg) was introduced in 2005, the increased demand of iodine during pregnancy was satisfied. METHODS: Between January 2016 and April 2017, 99 pregnant women were enrolled to evaluate UIC in spot urine samples, serum level of thyrotropin, free thyroxine, antithyroglobulin and antithyroperoxidase autoantibodies, and thyroid volume by ultrasonography. Eighty clinically healthy non-pregnant women were evaluated as controls. RESULTS: The median UIC was of 97.7 µg/L and 110.3 µg/L, respectively, in control and pregnant women. A significant increase (P < 0.001) of median thyroid volume was found in pregnant women, relative to control women, being, respectively, 10.4 mL (range 3.68-19.49 mL) and 7.16 mL (range 2.57-14.00 mL). A positive correlation was found between thyroid volume and anthropometric parameters, and an inverse correlation was identified between free thyroxine serum levels and anthropometric parameters. CONCLUSIONS: This observational study found that the majority of pregnant women and their fetuses appear not to be protected from the detrimental consequences of iodine deficiency. Therefore, the identification of new strategies to increase the knowledge and awareness of the general population regarding the beneficial effects of iodine supplementation during pregnancy is highly required.

Vitiligo and Autoimmune Thyroid Disorders.

Vitiligo represents the most common cause of acquired skin, hair, and oral depigmentation, affecting 0.5-1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated with other rare systemic disorders due to the presence of melanocytes in other body districts, such as in eyes, auditory, nervous, and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves' disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s).

New perspectives in the diagnosis of thyroid follicular lesions.

Thyroid nodules are very common, affecting 19%-67% of the adult population. However, about 10% of them harbor a malignant lesion. Consequently, the first aim in their clinical evaluation is to exclude malignancy. Fine-needle aspiration cytology (FNAC) represents the main diagnostic tool for the evaluation of thyroid nodules. However, FNAC has a main diagnostic limit, namely cellular atypias of indeterminate significance, which require surgical excision and histological examination to differentiate benign from malignant lesions. Histology reports show that approximately 80% of these patients harbor a benign lesion. Therefore, in order to reduce unnecessary thyroidectomy, over the last years, the cytological classification of thyroid nodules has been revised and a number of new instrumental and molecular approaches have been proposed. In the present article, we will attempt to summarize the most recent cytological, molecular and echographic strategies to enhance the diagnostic accuracy of preoperative thyroid follicular lesions. In particular, we will discuss the new cytological classifications from the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), the British Thyroid Association-Royal College of Pathologists (PTA-RCPath) and the new Italian Society for Anatomic Pathology and Cytology (SIAPEC 2014. We will review molecular tests evaluated to ameliorate follicular lesion diagnosis as well as the clinical utility of the new echographic Thyroid Imaging Reporting and Data System (TI-RADS) score.

Thyroid Imaging Reporting and Data System Score Combined with the New Italian Classification for Thyroid Cytology Improves the Clinical Management of Indeterminate Nodules.

The new Italian cytological classification (2014) of thyroid nodules replaced the TIR3 category of the old classification (2007) with two subclasses, TIR3A and TIR3B, with the aim of reducing the rate of surgery for benign diseases. Moreover, thyroid imaging reporting and data system (TI-RADS) score appears to ameliorate the stratification of the malignancy risk. We evaluated whether the new Italian classification has improved diagnostic accuracy and whether its association with TI-RADS score could improve malignancy prediction. We retrospectively analyzed 70 nodules from 70 patients classified as TIR3 according to the old Italian classification who underwent surgery for histological diagnosis. Of these, 51 were available for cytological revision according to the new Italian cytological classification. Risk of malignancy was determined for TIR3A and TIR3B, TI-RADS score, and their combination. A different rate of malignancy (p = 0.0286) between TIR3A (13.04%) and TIR3B (44.44%) was observed. Also TI-RADS score is significantly (p = 0.003) associated with malignancy. By combining cytology and TI-RADS score, patients could be divided into three groups with low (8.3%), intermediate (21.4%), and high (80%) risk of malignancy. In conclusion, the new Italian cytological classification has an improved diagnostic accuracy. Interestingly, the combination of cytology and TI-RADS score offers a better stratification of the malignancy risk.

Deregulated expression of VHL mRNA variants in papillary thyroid cancer.

Recent findings demonstrated that a subset of papillary thyroid cancers (PTCs) is characterized by reduced expression of the von Hippel-Lindau (VHL) tumor suppressor gene, and that lowest levels associated with more aggressive PTCs. In the present study, the levels of the two VHL mRNA splicing variants, VHL-213 (V1) and VHL-172 (V2), were measured in a series of 96 PTC and corresponding normal matched tissues by means of quantitative RT-PCR. Variations in the mRNA levels were correlated with patients' clinicopathological parameters and disease-free interval (DFI). The analysis of VHL mRNA in tumor tissues, compared to normal matched tissues, revealed that its expression was either up- or down-regulated in the majority of PTC. In particular, V1 and V2 mRNA levels were altered, respectively, in 78 (81.3%) and 65 (67.7%) out of the 96 PTCs analyzed. A significant positive correlation between the two mRNA variants was observed (p < 0.001). Univariate analysis documented the lack of association between each variant and clinicopathological parameters such as age, tumor size, histology, TNM stage, lymph node metastases, and BRAF mutational status. However, a strong correlation was found between altered V1 or V2 mRNA levels and DFI. Multivariate regression analysis indicated higher V1 mRNA values, along with lymph node metastases at diagnosis, as independent prognostic factors predicting DFI. In conclusion, the data reported demonstrate that VHL gene expression is deregulated in the majority of PTC tissues. Of particular interest is the apparent protective role exerted by VHL transcripts against PTC recurrences.

Endoscopic mucosal resection in elderly patients.

BACKGROUND: Endoscopic mucosal resection (EMR) of early superficial colorectal carcinomas is nowadays accepted as the gold standard treatment for this type of neoplasia. AIM: This study aims to evaluate the efficacy and safety of mucosectomy in elderly patients considering the predictive value of submucosal infiltration. METHODS: A retrospective study of all patients referred for EMR of sessile colorectal polyps classified IIa by the Paris classification between April 2013 and April 2015. A total of 50 patients (30 males (60 %); age range = 44-86; mean age = 67.7) were enrolled. Patients were divided in two groups considering 65 years as cutoff to individuate the elderly patients. RESULTS: EMR was performed in 53 lesions: 39 were performed en bloc and 14 by piecemeal technique. 30 % of lesions were in the rectum; 11 % in the sigmoid colon; 15 % in the descending colon; 6 % in the transverse colon; 24 % in the ascendant colon; and 14 % in the cecum. The mean size of the resected specimens was 20 mm (range 8-80 mm). The rate of complete resection was 79.2 %, incomplete 13.2 %, not estimable 7 %. Ten patients underwent surgery because of an incomplete resection and/or histological evaluation. CONCLUSIONS: Colon EMR is safe and effective in elderly patients. Endoscopy is still helped in the correct indication for surgery in high-risk surgical patients.

Total fistulectomy, sphincteroplasty and closure of the residual cavity for trans-sphincteric perianal fistula in the elderly patient.

BACKGROUND: Perianal fistula is a complex and frequent disease. At present, no treatment nor technique has shown an absolute superiority in terms of efficacy and recurrence rate. The technique has to be chosen considering the balance between faecal continence preservation and disease eradication. Rarely concomitant perianal abscess and fistula are treated at the same time, and often time to complete recovery is long. AIMS: The aim of this study was to evaluate the possibility of treating the abscess and the fistula tract in one procedure with total fistulectomy, sphincteroplasty and an almost complete closure of the residual cavity, thus reducing the healing time in older patients. METHODS: A non-randomized single-centre series of 86 patients from 2007 to 2012 with low-medium trans-sphincteric perianal fistula (< 30% of external sphincter involvement) with or without synchronous perianal abscess were treated with total fistulectomy, sphincteroplasty and closure of the residual cavity technique. RESULTS: Success rate was 97.7% with a healing time of 4 weeks; overall morbidity was 16.2%; recurrence rate was 2.3%; no major alterations of continence were observed. DISCUSSION: Fistulectomy, sphincteroplasty and closure of the residual cavity are associated with a low rate of recurrence and good faecal continence preservation in older patients. This technique can be safely used even with a concomitant perianal abscess, with reduction in healing time and in the number of surgical procedures needed. CONCLUSIONS: Total fistulectomy with sphincteroplasty and partial closure of the residual cavity, as described, is a safe procedure but has to be performed by dedicated colorectal surgeons.

Nodular thyroid disease in the elderly: novel molecular approaches for the diagnosis of malignancy.

Epithelial thyroid cancers (TC) comprise two differentiated histotypes (DTC), the papillary (PTC) and the follicular (FTC) thyroid carcinomas which, following dedifferentiation, are assumed to give rise to the poorly differentiated thyroid carcinomas and the rare, but highly aggressive and invariably fatal, anaplastic thyroid carcinomas. Although thyroid cancer mortality has not been changed, its annual incidence has increased over the last two decades, mainly because of the improved ability to diagnose malignant transformation in small non-palpable thyroid nodules. Despite DTC patients have a favorable prognosis, aggressive disease is more frequently observed in the elderly showing a higher disease-specific mortality. Of relevance is the high prevalence of nodular thyroid disease in aged patients being higher than 90%, in women older than 60 year, and 60% in men older than 80 year. This implies a careful evaluation of thyroid nodules in this group of patients in order to exclude malignancy. In fact, despite the tremendous progress in the comprehension of the underlying molecular mechanisms deregulated in DTC progression, several aspects of their clinical management remain to be solved and novel diagnostic strategies are sorely needed. Here, we will attempt to review new molecular approaches, which are currently being exploited in order to ameliorate the diagnosis of thyroid nodules.

Preclinical testing of selective Aurora kinase inhibitors on a medullary thyroid carcinoma-derived cell line.

Deregulated expression of the Aurora kinases (Aurora-A, B, and C) is thought to be involved in cell malignant transformation and genomic instability in several cancer types. Over the last decade, a number of small-molecule inhibitors of Aurora kinases have been developed, which have proved to efficiently restrain malignant cell growth and tumorigenicity. Regarding medullary thyroid carcinoma (MTC), we previously showed the efficacy of a pan-Aurora kinase inhibitor (MK-0457) in impairing growth and survival of the MTC-derived cell line TT. In the present study, we sought to establish if one of the Aurora kinases might represent a preferential target for MTC therapy. The effects of selective inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) were analyzed on TT cell proliferation, apoptosis, cell cycle, and ploidy. The two inhibitors reduced TT cell proliferation in a time- and dose-dependent manner, with IC50 of 19.0 ± 2.4 nM for MLN8237 and 401.6 ± 44.1 nM for AZD1152. Immunofluorescence experiments confirmed that AZD1152 inhibited phosphorylation of histone H3 (Ser10) by Aurora-B, while it did not affect Aurora-A autophosphorylation. MLN8237 inhibited Aurora-A autophosphorylation as expected, but at concentrations required to achieve the maximum antiproliferative effects it also abolished H3 (Ser10) phosphorylation. Cytofluorimetry experiments showed that both inhibitors induced accumulation of cells in G2/M phase and increased the subG0/G1 fraction and polyploidy. Finally, both inhibitors triggered apoptosis. We demonstrated that inhibition of either Aurora-A or Aurora-B has antiproliferative effects on TT cells, and thus it would be worthwhile to further investigate the therapeutical potential of Aurora kinase inhibitors in MTC treatment.

Association of thyroid diseases with primary extra-thyroidal malignancies in women: results of a cross-sectional study of 6,386 patients.

We here analyzed the prevalence of extra-thyroidal malignancies (EM) in 6,386 female patients affected by different thyroid disease (TD). At first, an age-matched analysis of EM in all patients was performed. We then evaluated EM prevalence in four TD diagnostic categories: non-nodular TD (n = 2,159); solitary nodule (n = 905); multinodular TD (n = 2,871); differentiated thyroid cancers (n = 451). Finally, patients were grouped based on the absence (n = 3,820) or presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase (TPOAb) (n = 2,369), or anti-Thyroid Stmulating Hormone (TSH) receptor autoantibodies (n = 197). A total of 673 EM were recorded. EM prevalence in TD patients was higher compared to the general population (Odds Ratio, OR 3.21) and the most frequent EM was breast cancer (OR 3.94), followed by colorectal (OR 2.18), melanoma (OR 6.71), hematological (OR 8.57), uterus (OR 2.52), kidney (OR 3.40) and ovary (OR 2.62) neoplasms. Age-matched analysis demonstrated that the risk of EM was maximal at age 0-44 yr (OR 11.28), remaining lower, but significantly higher that in the general population, in the 45-59 and 60-74 year age range. Breast and hematological malignancies showed an increased OR in all TD, while other cancers associated with specific TD. An increased OR for melanoma, breast and hematological malignancies was observed in both TPOAb and/or TgAb autoantibody negative and positive patients, while colorectal, uterus, kidney and ovary cancers showed an increased OR only in thyroid autoantibody negative patients. In conclusions, women affected by both benign and malignant TD, especially at a younger age and in absence of thyroid autoimmunity, have an increased risk of developing primary EM, thus requiring a careful follow-up and surveillance.

Deregulated expression of Aurora kinases is not a prognostic biomarker in papillary thyroid cancer patients.

A number of reports indicated that Aurora-A or Aurora-B overexpression represented a negative prognostic factor in several human malignancies. In thyroid cancer tissues a deregulated expression of Aurora kinases has been also demonstrated, but no information regarding its possible prognostic role in differentiated thyroid cancer is available. Here, we evaluated Aurora-A and Aurora-B mRNA expression and its prognostic relevance in a series of 87 papillary thyroid cancers (PTC), with a median follow-up of 63 months. The analysis of Aurora-A and Aurora-B mRNA levels in PTC tissues, compared to normal matched tissues, revealed that their expression was either up- or down-regulated in the majority of cancer tissues. In particular, Aurora-A and Aurora-B mRNA levels were altered, respectively, in 55 (63.2%) and 79 (90.8%) out of the 87 PTC analyzed.A significant positive correlation between Aurora-A and Aurora-B mRNAs was observed (p=0.001). The expression of both Aurora genes was not affected by the BRAFV600E mutation. Univariate, multivariate and Kaplan-Mayer analyses documented the lack of association between Aurora-A or Aurora-B expression and clinicopathological parameters such as gender, age, tumor size, histology, TNM stage, lymph node metastasis and BRAF status as well as disease recurrences or disease-free interval. Only Aurora-B mRNA was significantly higher in T(3-4) tissues, with respect to T(1-2) PTC tissues. The data reported here demonstrate that the expression of Aurora kinases is deregulated in the majority of PTC tissues, likely contributing to PTC progression. However, differently from other human solid cancers, detection of Aurora-A or Aurora-B mRNAs is not a prognostic biomarker in PTC patients.

Internet-based versus traditional teaching and learning methods.

BACKGROUND: The rapid and dramatic incursion of the Internet and social networks in everyday life has revolutionised the methods of exchanging data. Web 2.0 represents the evolution of the Internet as we know it. Internet users are no longer passive receivers, and actively participate in the delivery of information. Medical education cannot evade this process. Increasingly, students are using tablets and smartphones to instantly retrieve medical information on the web or are exchanging materials on their Facebook pages. Medical educators cannot ignore this continuing revolution, and therefore the traditional academic schedules and didactic schemes should be questioned. Analysing opinions collected from medical students regarding old and new teaching methods and tools has become mandatory, with a view towards renovating the process of medical education. METHODS: A cross-sectional online survey was created with Google® docs and administrated to all students of our medical school. Students were asked to express their opinion on their favourite teaching methods, learning tools, Internet websites and Internet delivery devices. Data analysis was performed using spss. RESULTS: The online survey was completed by 368 students. Although textbooks remain a cornerstone for training, students also identified Internet websites, multimedia non-online material, such as the Encyclopaedia on CD-ROM, and other non-online computer resources as being useful. DISCUSSION: The Internet represented an important aid to support students' learning needs, but textbooks are still their resource of choice. Among the websites noted, Google and Wikipedia significantly surpassed the peer-reviewed medical databases, and access to the Internet was primarily through personal computers in preference to other Internet access devices, such as mobile phones and tablet computers. Increasingly, students are using tablets and smartphones to instantly retrieve medical information.