Ultrasonographic diagnosis of ileo-ileal intussusception secondary to Vanek's tumor.

Intussusception is a common condition of bowel obstruction in pediatric patients. However, 5% of all cases occur in adults, mostly aged over fifty, with no difference based on sex, representing about 1% of all causes of bowel obstruction. Compared to pediatric population, it is triggered by a pathologic lead point in about 85% of cases, represented in 60% of cases by malignant and benign neoplasms. Among these neoplasms, an inflammatory fibroid polyp (IFP), a benign neoplastic submucosal lesion also known as Vanek's tumor, is considered a very uncommon cause of adult intussusception. Clinical presentation could differ by location and size of tumor, and may include abdominal pain, nausea, vomiting, diarrhea or constipation, bleeding, weight loss, palpable abdominal mass, bowel obstruction, and gastrointestinal bleeding. Considering its common and non-specific symptoms, radiologic imaging plays a key role in the diagnosis of an IFP, especially computed tomography (CT) scan, which represents the most sensitive modality to confirm intussusception. However, bowel sonography (BS) has become an accurate procedure in various pathological intestinal diseases, also including intussusception. In this paper, we report a rare case of ileo-ileal intussusception secondary to Vanek's tumor diagnosed by BS.

The non-euphoric phytocannabinoid cannabidivarin counteracts intestinal inflammation in mice and cytokine expression in biopsies from UC pediatric patients.

Patients with ulcerative colitis (UC) using marijuana have been reported to experience symptomatic benefit. Cannabidivarin (CBDV) is a safe non-psychoactive phytocannabinoid able to activate and desensitize TRPA1, a member of the TRP channels superfamily, which plays a pivotal role in intestinal inflammation. Here, we have investigated the potential intestinal anti-inflammatory effect of CBDV in mice and in biopsies from pediatric patients with active UC. Colonic inflammation was induced in mice by dinitrobenzenesulfonic acid (DNBS). The effect of orally administered CBDV on macroscopic and microscopic damage, inflammatory parameters (i.e. myeloperoxidase activity, intestinal permeability and cytokine production) and faecal microbiota composition, was evaluated 3 days after DNBS administration. TRPA1 expression was studied by RT-PCR in inflamed colons of mice as well as in mucosal colonic biopsies of children with active UC, whose response to incubation with CBDV was also investigated. CBDV attenuates, in a TRPA1-antagonist sensitive manner, DNBS-induced signs of inflammation including neutrophil infiltration, intestinal permeability, and cytokine (i.e. IL-1ß, IL-6 and the chemokine MCP-1) production. CBDV also alters the dysregulation of gut microbiota associated to colitis. Finally, CBDV lessens cytokine expression in colonic biopsies from pediatric patients with ulcerative colitis, a condition in which TRPA1 was up-regulated. Our preclinical study shows that CBDV exerts intestinal anti-inflammatory effects in mice via TRPA1, and in children with active UC. Since CBDV has a favorable safety profile in humans, it may be considered for possible clinical trials in patients with UC.

US and MR imaging findings to detect placental adhesion spectrum (PAS) in patients with placenta previa: a comparative systematic study.

PURPOSE: To compare the performance US and MR in identifying placental adhesion spectrum (PAS) in placenta previa (PP) and to establish a potential method of image interpretation. METHODS: US and MR examinations of 51 patients with PP were selected. The presence of imaging signs commonly used to detect PAS was assessed. Penalized logistic regression was performed considering histology as standard of reference; only signs statistically significant (p < 0.05) were considered for ROC and multivariate analysis. The probability of PAS according to the presence of US and/or MR signs was then assessed. RESULTS: At univariate analysis, loss of retroplacental clear space, myometrial thinning (MT) and placenta lacunar spaces on US, intraplacental dark bands (IDBs), focal interruption of myometrial border (FIMB) and abnormal vascularity (AV) on MR were statistically significant (p < 0.01). Three diagnostic methods for PAS were then developed for both US and MR when at least one (Method 1), two (Method 2) or three (Method 3) imaging signs occurred, respectively. Method 2 for MR showed a significantly (p < 0.05) higher accuracy (91%) compared to the other methods. When MR IDBs and AV as well as IDBs and FIMB were present in combination with US MT the probability of PAS increased from 75 to 90% and from 80 to 91%, respectively. CONCLUSION: MR demonstrated a higher diagnostic accuracy than US to detect PAS. However, since the combination of MR and US signs could improve the probability to detect PAS, a complementary diagnostic role of these techniques could be considered.

Diagnostic accuracy of magnetic resonance imaging in assessing placental adhesion disorder in patients with placenta previa: Correlation with histological findings.

OBJECTIVE: To evaluate MRI accuracy in assessing placental adhesion disorders (PAD) in patients with placenta previa correlating imaging results with histological findings. MATERIALS AND METHODS: Sixty-one patients who underwent abdomino-pelvic magnetic resonance imaging (MRI) for ultrasound suspicion of PAD were prospectively evaluated. T1- and T2-weighted images, with and without fat suppression, were obtained in the three conventional planes using a 1.5 T MRI scanner. MRI accuracy to evaluate the presence of PAD was assessed on the basis of the occurrence of the following abnormal MRI signs: 1) intraplacental dark bands; 2) focal interruption of myometrial border; 3) intraplacental abnormal vascularity; 4) uterine bulging; 5) tenting of the bladder and/or 6) direct visualization of adjacent tissues invasion only in case of percretism. Imaging results were classified as suggestive or not of PAD using histological data as standard of reference; two methods of imaging analysis were used represented by the presence of at least one (Method A) or two (Method B) abnormal MRI signs; the correlation between the presence of each abnormal MRI sign of PAD and the corresponding histological finding was also assessed. RESULTS: The accuracy, as the area under the receiver operating characteristic curve, was significantly (p = 0.001) higher for Method B (0.92, C.I. 95%: 0.82-0.97) compared to Method A (0.764, C.I. 95%: 0.64-0.86). Among the abnormal MRI signs, intraplacental dark bands and focal interruption of myometrial border were those highly correlated with histological proof of PAD (ρ > 0.71, p < 0.001, for both); as result, a modified version of Method B (Method C) was identified considering as criterion for PAD the combined presence of the two abnormal MRI signs highly correlated with histologically proven PAD; however, the accuracy of Method C was significantly (p = 0.005) lower (0.80, C.I. 95%: 0.67-0.89) than Method B and comparable to Method A. CONCLUSIONS: MRI is a useful imaging technique to assess PAD in patients with placenta previa; in particular, the presence of at least two among all the abnormal MRI signs represents the most accurate criterion (Method B) to identify PAD. Although intraplacental dark bands and focal interruption of myometrial border showed the highest correlation with histological proof of PAD as well as this association was the most frequent in PAD, the combination of these latter MRI signs along with other abnormal signs should be considered diagnostic for PAD.

Confocal laser endomicroscopy in ulcerative colitis: beyond endoscopic assessment of disease activity.

BACKGROUND: The aim of this study was to investigate the role of confocal laser endomicroscopy (CLE) in the assessment of disease activity in ulcerative colitis (UC). METHODS: Consecutive patients with UC referred to our inflammatory bowel disease unit for colonoscopy were enrolled. Patients without UC were used as controls. UC activity was evaluated by white light endoscopy and classified according to the Mayo Ulcerative Colitis Endoscopic Score of Severity. Endoscopic biopsies were also taken for histological assessment of disease activity and then assessed with CLE. Three parameters were evaluated; crypt architecture (crypt diameter, inter-crypt distance, presence of fused crypts, crypts regularity), microvascular pattern (regular, dilated, irregular and deformed), fluorescein leakage. RESULTS: Fifty patients with UC and 10 controls were enrolled. At colonoscopy, 11 patients (22%), 19 patients (38%), 12 patients (24%) and 8 patients (16%) presented a Mayo score of 0, 1, 2 and 3, respectively. At CLE, fused crypts were present in all the patients with UC and absent in controls. Crypt diameter and inter-crypt distance showed a parallel increase with the Mayo score. Fluorescein leakage and irregular vessels were more frequently found in case of a high level of endoscopic severity, but were also identified in about 20% of UC patients with normal mucosa. Biopsies also demonstrated the presence of histological activity in 4 patients with endoscopically inactive colitis. CONCLUSIONS: CLE might be a useful tool to determine inflammatory activity in UC. Fused crypts appeared to be a CLE marker of UC, while other abnormalities, like microvascular alteration and fluorescein leakage, have also been identified in patients with mucosal healing at endoscopy. Larger series are required to validate these results and the advantages of a CLE-based assessment of UC activity.

PAPILLARY THYROID CANCER IS CHARACTERIZED BY ALTERED EXPRESSION OF GENES INVOLVED IN THE SUMOYLATION PROCESS.

Small Ubiquitin–like MOdifier (SUMO) proteins are small protein modifiers capable of regulating cellular localization and function of target proteins. Over the last few years, a relevant role has been demonstrated for sumoylation in the modulation of important cellular processes, including gene transcription, DNA repair, cell-cycle regulation and apoptosis. Components of the sumoylation machinery have been found deregulated in different human cancers, and are thought to significantly affect cancer cell progression. In the present study we sought to analyze the expression of all the components of the sumoylation machinery in a case study comprising 77 papillary thyroid cancers (PTC) and normal matched tissues. In particular, we evaluated the expression of the SENP1 to SENP8 (SENtrin-specific proteases), SAE1 (SUMO1 activating enzyme subunit 1), UBA2 (UBiquitin-like modifier activating enzyme 2), UBC9 (UBiquitin conjugating enzyme 9), RanBP2 (RAN binding protein 2), MSMCE2 (Non- SMC element 2), CBX4 (ChromoBoX homolog 4), PIAS1 to PIAS4 (protein inhibitor of activated STAT), ZMIZ1 (zinc finger, MIZ-type containing 1) and ZMIZ2 (Zinc finger, MIZ-type containing 2) by means of quantitative RT-PCR. In most of the PTC examined we observed a significant alteration in the mRNAs of SENP8, ZMIZ1, SAE1, PIAS1 and PIAS2. These tended to be reduced in about 50 to 66% of cases, and unchanged or increased in the remaining ones. Univariate and Kaplan-Mayer analyses documented the lack of association between the expression of the above 5 genes and clinicopathological parameters. Only SAE1 was significantly higher in female PTC tissues, in respect to male PTC tissues (p=0.021), and SENP8 was significantly lower in TNM stages III-V, with respect to stages I-II (p=0.047). In conclusion, we demonstrated that the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. However, differently from other human cancers, their mRNA level does not represent a prognostic biomarker in PTC patients.

Hepatic epithelioid hemangioendothelioma: Pitfalls in the diagnosis on fine needle cytology and "small biopsy" and review of the literature.

Hepatic epithelioid hemangioendothelioma is a rare vascular neoplasm with an unpredictable malignant potential. Different therapeutic options are available, depending on the basis of disease extension and the patient's overall condition. A correct pathological diagnosis is necessary and is often based on scant material. Here, we report a case diagnosed on fine needle aspiration and on a small surgical biopsy. In addition, we will review the literature. The patient is a 54-year-old woman who presented with persistent pain in the right hypochondrium and suffered from weight loss. Ultrasound examination and CT scan showed several focal and confluent hepatic lesions. Thus, an ultrasound-guided fine-needle aspiration (US-FNA) was performed. A cytological diagnosis of vascular proliferation with epithelioid component was performed. Afterwards, a hepatic "small biopsy" (SB) was made. Histological and immunohistochemical data were consistent with a hepatic epithelioid hemangioendothelioma diagnosis. The patient, however, is in good general condition and is waiting for a hepatic transplantation; repeated total CT scan showed no signs of metastasis. The literature was reviewed in order to define the pathological features that were helpful in the cytological and histological diagnosis of hepatic epithelioid hemangioendothelioma, and to better understand if pathological data is prognostically useful.

Selective inhibitors of aurora kinases inhibit proliferation, reduce cell viability and impair cell cycle progression in papillary thyroid carcinoma cells.

The three members of the Aurora kinase family, Aurora-A, -B and -C, regulate several aspects of the mitotic process, and their aberrant expression and/or function causes mitotic abnormalities leading either to cell death or aneuploidy. They are found overexpressed in several human malignancies, including the papillary thyroid carcinoma (PTC). In the present study, we sought to establish whether Aurora kinase inhibition could be of any therapeutic value in the treatment of aggressive forms of PTC, enduring to radioactive iodide (RAI) ablation. To this end, the effects of selective inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) were analyzed on 3 human PTC cell lines expressing either wild-type (K1 and TPC1) or mutant p53 (BCPAP). The two inhibitors were capable of reducing cell proliferation in a time- and dose-dependent manner, with IC50 comprised between 65.4 and 114.9 nM for MLN8237, and between 26.6 and 484.6 nM for AZD1152. Immunofluorescence experiments confirmed that AZD1152 inhibited Aurora-B phosphorylation of histone H3 on Ser10, however, 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. Time-lapse videomicroscopy evidenced that both inhibitors prevented the completion of cytokinesis, and cytofluorimetric analysis showed accumulation of cells in G2/M phase and/or polyploidy. Apoptosis was induced in all the cells by both inhibitors independently from the p53 status. In conclusion, in the present preclinical study MLN8237 and AZD1152 have emerged as promising drug candidates for RAI-insensitive PTC.

Accuracy of neurosonography and MRI in clinical management of fetuses referred with central nervous system abnormalities.

OBJECTIVE: To assess the accuracy of expert neurosonography (two- and three-dimensional NSG) in the characterization of major fetal central nervous system (CNS) anomalies seen at a tertiary referral center and to report the differential clinical usefulness of magnetic resonance imaging (MRI) used as a second-line diagnostic procedure in the same cohort. METHODS: This was a retrospective analysis of all 773 fetuses with confirmed CNS abnormalities referred to our center between 2005 and 2012. The following variables were analyzed: gestational age at NSG and MRI, NSG and MRI diagnoses, indication for MRI (confirmation of NSG findings; diagnostic doubt; search for possible additional brain anomalies), association with other malformations, diagnostic accuracy of NSG vs MRI (no additional clinical value for either MRI or NSG; additional information with clinical/prognostic significance on MRI relative to NSG; additional information with clinical/prognostic significance on NSG relative to MRI, NSG and MRI concordant but incorrect) and final diagnosis, which was made at autopsy or postnatal MRI/surgery. RESULTS: CNS malformations were associated with other anomalies in 372/773 (48.1%) cases and were isolated in the remaining 401 (51.9%) cases. NSG alone was able to establish the diagnosis in 647/773 (83.7%) cases. MRI was performed in 126 (16.3%) cases. The indication for MRI was: confirmation of NSG diagnosis in 59 (46.8%) cases; diagnostic query (in the case of inconclusive or uncertain finding on NSG) in 20 (15.9%) cases; search for possible additional brain anomalies in 47 (37.3%) cases. NSG and MRI were concordant and correct in 109/126 (86.5%) cases. Clinically relevant findings were evident on MRI alone in 10/126 (7.9%) cases (1.3% of the whole population) and on NSG alone in 6/126 (4.8%) cases; in all six of these cases, MRI had been performed at < 24 weeks of gestation. In one case, both NSG and MRI diagnoses were incorrect. The main type of malformation in w ich MRI played an important diagnostic role was space-occupying lesions, MRI identifying clinically relevant findings in 42.9% (3/7) of these cases. CONCLUSIONS: (1) In a tertiary referral center with good NSG expertise in the assessment of fetal CNS malformations, MRI is likely to be of help in a limited proportion of cases; (2) MRI is more useful after 24 weeks of gestation; (3) the lesions whose diagnosis is most likely to benefit from MRI are gross space-occupying lesions.

The dual Aurora kinase inhibitor ZM447439 prevents anaplastic thyroid cancer cell growth and tumorigenicity.

The anaplastic thyroid cancer (ATC) is among the most aggressive human tumors which fail to respond to all the currently available therapeutic approaches. As a consequence most patients die within a few months from diagnosis. In the present preclinical study, the effects of the ZM447439, a functional inhibitor of Aurora kinases, on the growth and tumorigenicity of a panel of ATC derived cell lines (CAL-62, 8305C, 8505C and BHT-101) were evaluated. The treatment of the different ATC cells with ZM447439 inhibited proliferation in a time- and dose-dependent manner, with IC50 comprised between 0.5 mM and 5 mM. Moreover, the drug remarkably impaired the formation of colonies in soft agar of all the cell lines. Consistently with Aurora inhibition, immunofluorescence and immunoblotting experiments demonstrated that Aurora auto-phosphorylation following drug treatment was completely abrogated, and treated cells were characterized by the presence of multiple spindles with short microtubules. In the same experiments we observed the loss of histone H3 phosphorylation on Ser10, specifically due to Aurora-B, after ZM447439 treatment. Time-lapse videomicroscopy and flow cytometric analysis demonstrated that in presence of ZM447439 the cells were able to enter mitosis but not to complete it, becoming polyploid. Almost all the ATC cell lines studied showed increased apoptosis after only 48 h of treatment. In conclusion, our data demonstrate that ZM447439 is effective in reducing cell growth and tumorigenicity of different ATC derived cell lines, and further investigations are needed to exploit its potential therapeutic value for ATC treatment.

A case of extraovarian primary peritoneal carcinoma in an oophorectomized-hysterectomized patient: a diagnostic dilemma.

Extra Ovarian Primary Peritoneal Carcinoma (EOPPC) is a rare type of adenocarcinoma of the pelvic and abdominal peritoneum. The objective examination and the histological aspect of the neoplasia virtually overlaps with that of ovarian carcinoma. The reported case is that of a 72 year-old patient who had undergone a total hysterectomy with bilateral annessiectomy surgery 20 years earlier subsequently to a diagnosis for uterine leiomyomatosis. The patient came to our attention presenting recurring abdominal pain, constipation, weight loss, severe asthenia and fever. Her blood test results showed hypochromic microcytic anemia and a remarkable increase CA125 marker levels. Instrumental diagnostics with Ultrasound (US) and CT scans indicated the presence of a single peritoneal mass (10-12 cm diameter) close to the great epiploon. The patient was operated through a midline abdominal incision and the mass was removed with the great omentum. No primary tumor was found anywhere else in the abdomen and in the pelvis. The operation lasted approximately 50 minutes. The post-operative course was normal and the patient was discharged four days later. The histological exam of the neoplasia, supported by immunohistochemical analysis, showed a significant positivity for CA 125, vimentin and cytocheratin, presence of psammoma bodies, and cytoarchitectural pattern resembling that of a serous ovarian carcinoma even in absence of primitiveness, leading to a final diagnosis of EOPPC. The patient later underwent six cycles of chemotherapy with paclitaxel (135 mg/m²/24 hr) in association with cisplatin (75mg/m²). At the fourth year follow-up no sign of relapse was observed.

[Thyroid Phylogeny: from seaweeds to man]. / Filogenesi della tiroide: dalle alghe all'uomo.

Iodine uptake and production of iodine-aminoacids are evolutionarily very old phenomena. Seaweed are the first eukaryotic organism presenting these functions; they are rich in iodine and are at basis of the food chain. The monoiodotirosines, precursors of thyroxine, have been identified in a wide variety of invertebrates, such as Gorgonians and Tunicates. The structure of the thyroid appears for the first time in Cyclostomes adults (Lamprey), while in Tunicates (Ciona intestinalis) and Amphioxus is present a similar structure, the endostyle, which is an invagination of the ventral wall of the pharynx containing glandular cells that are able to concentrate iodine. This is not a true endocrine gland because the secretion is poured into the alimentary canal. In the larva of Lamprey (Ammocoetes) during the metamorphosis some of the epithelial cells persist and transform in the follicles. The cyclostomes, therefore, represent a link between the endostyle of protochordates and the thyroid gland of higher chordates. This hypothesis is confirmed by molecular genetic studies which have demonstrated the expression of Thyroid Transcription Factor (TTF-1) in the endostyle of Ciona, Lamprey and Amphioxus. The TTF-1 is an ancestral transcription factor which controls the survival of thyroid follicular cells at the beginning of organogenesis and regulates the expression of thyroid-specific genes in adult life.

Aberrant right subclavian artery: incidence and correlation with other markers of Down syndrome in second-trimester fetuses.

OBJECTIVE: To assess the incidence of aberrant right subclavian artery (ARSA) and other strong markers of Down syndrome and their correlation in a large population of second-trimester Down syndrome fetuses assessed in a tertiary referral center. METHODS: Presence or absence of ARSA and other major ultrasound markers of Down syndrome was assessed in a population of 106 second-trimester Down syndrome fetuses referred to our unit for expert assessment and/or termination of pregnancy after karyotyping performed for positive first- or second-trimester screening or advanced maternal age or on maternal request. All cases in which the diagnosis of Down syndrome followed the ultrasound detection of major anomalies or soft markers were excluded from the study, as were all cases with a gestational age less than 14 + 0 weeks. We searched for the ARSA on the three vessels and trachea view using color or power Doppler. All fetuses underwent a thorough anatomic assessment and fetal echocardiography. The other Down syndrome markers assessed were: absent or hypoplastic nasal bone (NB-), defined as length < 5(th) centile; nuchal fold ≥ 5 mm; and mild pyelectasis (> 5 mm). In addition, the presence of major cardiac and extracardiac defects was recorded. A correlation analysis was then performed in order to investigate possible associations between markers and/or major anomalies. Postmortem or postnatal diagnostic confirmation was available in all cases. RESULTS: The mean (SD) gestational age at ultrasound assessment was 20.4 (4.1) weeks. The incidence of the various variables in the population of Down syndrome fetuses was: ARSA, 25%; NB-, 43%; nuchal fold ≥ 5 mm, 16%; pyelectasis, 17%; major heart defects, 41%; atrioventricular septal defect, 25%; and extracardiac anomaly, 24%. The presence of ARSA did not correlate with any of the other variables. The only positive correlations (P < 0.05) were between NB- and pyelectasis, and between cardiac and extracardiac defects. CONCLUSIONS: This represents the largest Down syndrome population assessed for ARSA. In this series, the incidence of ARSA was 25%, lower than previously reported in much smaller series. Its presence did not correlate with the presence of any other marker or major anomaly, including heart defects.

Deregulation of Aurora kinase gene expression in human testicular germ cell tumours.

The Aurora kinases regulate chromosome segregation and cytokinesis, and alterations in their expression associate with cell malignant transformation. In this study, we demonstrated by qRT-PCR analysis of 14 seminomas that Aurora-A mRNA was, with respect to control tissues, augmented in five of 14 tumour tissues by 2.17 +/- 0.30 fold (P < 0.05) and reduced in 9 to 0.38 +/- 0.10 (P < 0.01). Aurora-B mRNA was increased in 11 tumour tissues by 4.33 +/- 0.82 fold (P < 0.01) and reduced in 3 to 0.41 +/- 0.11 fold. Aurora-C mRNA was reduced to 0.20 +/- 0.32 fold (P < 0.01) in 13 seminomas and up-regulated in one case. Western blot experiments, performed on protein extracts of nine seminomas and six normal testes, showed an up-regulation of Aurora-B protein by 10.14 +/- 3.51 fold (P < 0.05), while Aurora-A protein was found increased in four seminomas by 2.16 +/- 0.43 (P < 0.05), unchanged in three and reduced in two tumour tissues. Aurora-C protein was increased by 9.2 +/- 2.90 fold (P < 0.05), suggesting that post-transcriptional mechanisms modulate its expression. In conclusion, we demonstrated that expression of Aurora kinases is deregulated in seminomas, suggesting that they may play a role in the progression of testicular cancers.

Subclinical hyperthyroidism and sport eligibility: an exploratory study on cardiovascular pre-participation screening in subjects treated with levothyroxine for multinodular goiter.

BACKGROUND: Subclinical hyperthyroidism (sHT) affects cardiovascular (CV) morphology and function; whether such changes can impact on sport eligibility is unclear. AIM: This exploratory study evaluated the CV system and sport eligibility in athletes with levothyroxine-induced sHT, in the setting of mandatory pre-participation screening. SUBJECTS AND METHODS: A full, non-invasive CV screening (history and physical examination, 12-lead ECG, echocardiography, 24-hour Holter ECG, exercise stress test) was performed in two groups of untrained female athletes affected by non-toxic multinodular goiter. One group was taking levothyroxine at mildly suppressive doses (TG) whereas the other was untreated (UG). There was also a group of healthy controls (HC). RESULTS: In TG the following characteristics were observed: a) a higher resting heart rate (HR; p<0.01 and p<0.05, vs HC and UG respectively), b) a thicker left ventricular posterior wall (p<0.05 vs HC, and p<0.05 vs HC and UG, respectively), c) a higher mean HR during the 24-hour Holter ECG (p<0.01 and p<0.05, vs HC and UG respectively), and d) a lower achieved maximum work load (p<0.05, vs HC). No differences in the prevalence of cardiac arrhythmias among groups were observed. Sport eligibility was granted to all except one subject in the TG. CONCLUSIONS: Although some alterations were found in athletes with levothyroxine-induced mild sHT, these are probably of limited clinical relevance and they did not contraindicate sport participation in the majority of cases. Future research to address both health risks and the need for specific evaluations (e.g. free thyroxine, TSH, echocardiography) during the preparticipation screening of athletes with sHT is warranted.

[Antithyroid drugs therapy]. / Terapia con farmaci antitiroidei.

Methimazole and Propylthiouracil are the cornerstones in the management of Graves' disease. Their primary effect is to inhibit thyroid hormone synthesis at different steps, i.e. in thyroid gland and in peripheral tissues. Antithyroid drugs can be used as the primary treatment for hyperthyroidism (long term therapy: 1-2 years) or as preparative therapy before radioiodine treatment or surgery (short term therapy: weeks or months). Generally, the starting dose of methimazole is 10-30 mg, as single daily dose, while that of PTU is 100-300 mg every 6 hours. Methimazole is the drug of choice, because major side effects are less common, it can be used as single dose, it's less expensive and more available. As far as the treatment of hyperthyroidism in pregnancy, MMI and PTU have same therapeutic efficacy and are both safe for the fetus, having similar placental transfer kinetics. The use of methimazole can be associated with aplasia cutis and choanal/esophageal atresia, while there are no data supporting the association between congenital anomalies and PTU. For this reason the latter is the drug of choice in the treatment of hyperthryroidism in pregnancy. Both thionamides are present in breast milk, but there are no controindications for their use during lactation.

Neo-adjuvant treatment of rectal cancer with capecitabine and oxaliplatin in combination with radiotherapy: a phase II study.

BACKGROUND: Preoperative chemoradiation is now standard treatment for stages II-III rectal cancer. Capecitabine (CAP) and oxaliplatin (OX) are synergistic with radiotherapy (RT) and active in colorectal neoplasms. PATIENTS AND METHODS: Two cycles of CAP 825 mg/m(2) b.i.d. (days 1-14) and OX 50 mg/m(2) (days 1 and 8) every 3 weeks were given concomitantly with pelvic conformal RT (45 Gy). Patients with a > or =T3 and/or node-positive rectal tumour were eligible. The pathologic tumour response was defined according to the tumour regression grade (TRG) scale. RESULTS: Forty-six patients were enrolled. Gastrointestinal adverse events were mostly G1-G2; only two patients experienced G3 vomiting and diarrhoea and six patients had G1 peripheral neuropathy. Haematological toxicity was rare. G2 proctitis and anal pain occurred in two patients. Pathological complete response (TRG1) was observed in nine patients (20.9%; 95% CI 8.7%-33.1%); TRG2 in 19 patients (44.2%); TRG3 in 12 patients (27.9%); and TRG4 in three patients (7%). Overall, nine patients recurred: five with distant metastases, one with local recurrence, and three with both local recurrence and distant metastases. CONCLUSIONS: CAP-OX-RT as preoperative treatment for rectal cancer induces a remarkable rate of complete or near-complete pathologically documented response and is well tolerated.

Expression of Fas and Fas ligand in human testicular germ cell tumours.

In the present study, we analysed the expression of Fas ligand (FasL) and its cognate receptor Fas in 14 seminomatous testicular germ cell tumours (TGCT) and six normal testicular tissues obtained following orchiectomy. Tissue samples have been processed to prepare either total RNA or protein extracts or fixed and embedded in paraffin for immunohistochemistry (IHC) experiments. Quantitative RT-PCR experiments demonstrated in TGCT a significant (p < 0.01) increase of the FasL mRNA expression of 21.1 +/- 5.4 fold, with respect to normal tissues. On the contrary, in the same cancer tissues, the levels of Fas mRNA were significantly (p < 0.01) reduced to 0.27 +/- 0.06 fold. These observations were confirmed in western blot experiments showing a significant increase of FasL and a concomitant decrease of Fas proteins in testicular cancer tissues, with respect to normal testis. Moreover, IHC experiments showed a strong FasL immuno-reactivity in six out of eight TGCT samples analysed, while Fas immuno-positivity was found in cancer cells of only two TGCT tissues. In addition, in all tumour samples, infiltrating lymphocytes were Fas positive. However, no correlation could be observed between Fas or FasL mRNA variations and clinical parameters such as patient's age, TNM stage or tumour size. We also compared the serum levels of soluble FasL (sFasL) of 15 patients affected by seminomatous TGCT, of four patients with non-seminomatous TGCT and six age-matched healthy males. No significant differences in sFasL serum level could be identified. In conclusion, our data demonstrated that the majority of seminomas are characterized by an increased expression of FasL and a concomitant reduction of Fas, with respect to human normal testis, and that sFasL serum level is not a tumour marker for patients affected by TGCT.

The estimation of the thyroid volume before surgery--an important prerequisite for minimally invasive thyroidectomy.

INTRODUCTION: Actually, thyroid volume >25 ml, obtained by preoperative ultrasound evaluation, is a very important exclusion criteria for minimally invasive thyroidectomy. So far, among different imaging techniques, two-dimensional ultrasonography has become the more accepted method for the assessment of thyroid volume (US-TV). The aims of this study were: (1) to estimate the preoperative thyroid volume in patients undergoing minimally invasive total thyroidectomy using a mathematical formula and (2) to verify its validity by comparing it with the postsurgical TV (PS-TV). MATERIALS AND METHOD: In 53 patients who underwent minimally invasive total thyroidectomy (from January 2003 to December 2007), US-TV, obtained by ellipsoid volume formula, was compared to PS-TV determined by the Archimedes' principle. A mathematical formula able to predict the TV from the US-TV was applied in 34 cases in the last 2 years. RESULTS: Mean US-TV (14.4 +/- 5.9 ml) was significantly lower than mean PS-TV (21.7 +/- 10.3 ml). This underestimation was related to gland multinodularity and/or nodular involvement of the isthmus. A mathematical formula to reduce US-TV underestimation and predict the real TV was developed using a linear model. Mean predicted TV (16.8 +/- 3.7 ml) perfectly matched mean PS-TV, underestimating PS-TV in 19% of cases. We verified the accuracy of this mathematical model in patients' eligibility for minimally invasive total thyroidectomy, and we demonstrated that a predicted TV <25 ml was confirmed post-surgery in 94% of cases. CONCLUSIONS: We demonstrated that using a linear model, it is possible to predict from US the PS-TV with high accuracy. In fact, the mean predicted TV perfectly matched the mean PS-TV in all cases. In particular, the percentage of cases in which the predicted TV perfectly matched the PS-TV increases from 23%, estimated by US, to 43%. Moreover, the percentage of TV underestimation was reduced from 77% to 19%, as well as the range of the disagreement from up to 200% to 80%. This study shows that two-dimensional US can provide the accurate estimation of thyroid volume but that it can be improved by a mathematical model. This may contribute to a more appropriate surgical management of thyroid diseases.

Obesity and sexual dysfunction, male and female.

Obesity has become a worldwide public health problem of epidemic proportions, as it may decrease life expectancy by 7 years at the age of 40 years: excess bodyweight is now the sixth most important risk factor contributing to the overall burden of disease worldwide. Overweight and obesity may increase the risk of erectile dysfunction (ED) by 30-90% as compared with normal weight subjects. On the other hand, subjects with ED tend to be heavier and with a greater waist than subjects without ED, and also are more likely to be hypertensive and hypercholesterolemic. The metabolic syndrome, characterized by a clustering of risk factors associated with insulin resistance and abdominal obesity, associates with ED. Moreover, women with the metabolic syndrome have an increased prevalence of sexual dysfunctions as compared with matched control women. Lifestyle changes aimed at reducing body weight and increasing physical activity induce amelioration of both erectile and endothelial functions in obese men. Moreover, preliminary evidence suggests that a Mediterranean-style diet might be effective in ameliorating sexual function in women with the metabolic syndrome. Lifestyle changes, mainly focussing on regular physical activity and a healthy diet, are effective and safe ways to reduce cardiovascular diseases and premature mortality in all population groups; they may also prevent and treat sexual dysfunctions in both sexes.