Human papillomavirus infection and risk factors in a cohort of Tuscan women aged 18-24: results at recruitment

<p>Abstract</p> <p>Background</p> <p>There is conclusive evidence that human papillomavirus (HPV) infections of the cervix are a necessary cause of cervical cancer. In Italy there are consistent data of HPV prevalence in women aged 25 - 64 years, but there is limited data for younger women. The objective of this on-going 3-year prospective cohort study is to investigate the prevalence, acquisition, clearance and persistence of HPV infections in young Tuscan women and the risk factors correlated with such events.</p> <p>Methods</p> <p>One thousand and sixty-six women aged between 18 and 24 years were enrolled and received an initial HPV test. They were asked to return to the clinic over the study period for further tests every 12 months, if their HPV HR result was negative, or every 6 months, if positive. Additionally, women with an HPV positive result were given a cytological examination and if the cytological diagnosis was ASC-US or more severe, only women with HPV HR, were referred for colposcopy.</p> <p>Results</p> <p>We present here data for the enrolment phase of the study. At baseline, within the study sample, just under 30% of women were infected by HPV and 19.3% of women were infected with oncogenic types. A relationship was highlighted between HPV infection, number of sexual partners (in particularly in the last 3 years) and the lifetime number of partner's partners. Condom use showed a slight protective effect in univariate analysis but these data were not statistically significant in multivariate analysis. The association between HPV infection and demographic and behavioural variables were tested by crude odds ratio (OR). Multivariate logistic regression was applied to compute the adjusted odds ratios.</p> <p>Conclusions</p> <p>The prevalence of oncogenic HPV types was high in young Tuscan women. The 3-year follow-up of this cohort may provide a better understanding of the processes of acquisition, clearance and persistence of infection and the correlated risk factors.</p

Antiangiogenic and anticolorectal cancer effects of metronomic irinotecan chemotherapy alone and in combination with semaxinib

Metronomic chemotherapy refers to the administration of chemotherapy at low, nontoxic doses on a frequent schedule with no prolonged breaks. The aim of the study is to rationally develop a CPT-11 metronomic regimen in preclinical settings of colon cancer. In vitro cell proliferation, apoptosis and thrombospondin-1/vascular endothelial growth factor (TSP-1/VEGF) expression analyses were performed on endothelial (HUVEC, HMVEC-d) and colorectal cancer (HT-29, SW620) cells exposed for 144 h to metronomic concentrations of SN-38, the active metabolite of CPT-11. HT-29 human colorectal cancer xenograft model was used, and tumour growth, microvessel density and VEGF/TSP-1 quantification was performed in tumours. In vitro and in vivo combination studies with the tyrosine inhibitor semaxinib were also performed. SN-38 preferentially inhibited endothelial cell proliferation alone and interacted synergistically with semaxinib; it induced apoptosis and increased the expression and secretion of TSP-1. Metronomic CPT-11 alone and combined with semaxinib significantly inhibits tumour growth in the absence of toxicity, which was accompanied by decreases in microvessel density and increases in TSP-1 gene expression in tumour tissues. In vitro results show the antiangiogenic properties of low-concentration SN-38, suggesting a key role of TSP-1 in this effect. In vivo, the CPT-11 metronomic schedule is effective against tumour and microvessel growth without toxic effect on mice

Loss of nuclear p27kip1 and α-dystroglycan is a frequent event and is a strong predictor of poor outcome in renal cell carcinoma

Expression levels of p27kip1, a negative regulator of the G1 phase of the cell cycle, and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were assessed by immunostaining in a series of renal cell carcinomas (RCCs) and their prognostic significance was evaluated. Expression of p27kip1 as well as of the α-subunit of the dystroglycan (DG) complex, previously reported to be altered in RCC, was also evaluated by western blot analysis. Nuclear expression of p27kip1 was reduced in a significant fraction of tumors and low p27kip1 staining correlated with higher tumor grade (P < 0.01). Recurrence and death from clear cell RCCs were significantly more frequent in p27kip1-low expressing tumors and Kaplan–Meier curves showed a significant separation between high vs low expressor groups for both disease-free (P = 0.011) and overall (P = 0.002) survival. Low nuclear expression of p27kip1 as well as loss of α-DG were confirmed to be independent prognostic parameters at a multivariate analysis and the simultaneous loss of both molecules defined a "high-risk" group of patients with increased risk of recurrence (RR = 28.7; P = 0.01) and death (RR = 12.9; P = 0.03). No significant correlation with clinical or pathological parameters was found for 8-OHdG staining. Western blot analyses suggested a post-translational mechanism for the loss of α-DG expression and demonstrated that cytoplasmic dislocation of the protein contributes to the loss of active nuclear p27kip1. Loss of nuclear p27kip1 is a frequent event in human RCCs and is a powerful predictor of poor outcome which, in combination with low DG expression, could help to identify high-risk patients with clear cell RCC. (Cancer Sci 2010; 00: 000–000

Small bowel angiodysplasia: usefulness of peroperative enteroscopy

Abstract In this report the Authors present the case of an old patient treated for chronic recurrent bleeding from small bowel angiodysplasia. The diagnosis was missed by the conventional methods: angiography and scintiscan with marked erythrocytes. Diagnosis was instead possible by using intraoperative enteroscopy. The Authors stress the usefulness of this technique that permits the exploration of the mucosal by trans-illumination to discover bleeding and vascular anomalies of the bowel

Definition of the microvascular pattern of the normal human adult mammary gland

The present report provides a detailed description of microvascularization in the normal human mammary gland, and defines two novel morphometric parameters to be used as a reference when angiogenesis in breast carcinoma is evaluated. Microvascularization was analysed by histology, immunohistochemistry and computer-assisted analysis in a set of breast tissue samples taken from nine women, during the pre-ovulatory phase of the menstrual cycle. The two parameters designed for image analysis were: vascular density (VD): [microvessel number/(microvessel area + residual stromal area)] × 10 000; and vascular area ratio (VAR): [microvessel area/(microvessel area + residual stromal area)]. In the lobules VD (mean value ± SE 2.48 ± 0.14) and VAR (0.33 ± 0.02) showed little variability and correlated significantly (P < 0.05). The areas occupied by microvessels, stroma and acini remained constant in all lobules (21.53 ± 1.87%, 42.65 ± 1.35% and 35.14 ± 1.57%, respectively). Microvascularization of the lobules was of a sinusoidal type, with large S-shaped capillaries. In the ducts VD (2.95 ± 0.16) and VAR (0.29 ± 0.03) showed little variability but did not correlate significantly. Microvascularization of the ducts was of a classic type, with capillaries normal in size and shape. The expression of oestrogen (ER) and progesterone (PR) receptors was analysed by immunohistochemistry and compared with the morphometric results. ER expression levels were in the range 20–25% (24.3 ± 2.1) and 14–18% (15.4 ± 1.5) in lobules and ducts, respectively. PR expression levels were in the range 10–13% (11.1 ± 1.6) and 14–17% (15.2 ± 1.4), respectively. No correlation was found between ER/PR expression and vascularization parameters

Focal nodular hyperplasia of the liver associated with cardial achalasia,situs viscerum inversus and gastric mucosal ectopia in the duodenum

Abstract The authors describe the clinical case of a young woman with a focal nodular hyperplasia (FNH) of the liver associated with achalasia of the cardia, situs inversus totalis and ectopy of gastric mucosa in duodenum, and discuss the etiopathogenic aspects of the hepatic lesion. The frequent association of the FNH with various malformations, as the literature and this case-report relate, seems to confirm the hypothesis of a dysgenetic hamartomatous origin. Therefore any liver single mass in a patient with a malformative syndrome must rouse the suspicion of a FNH. PMID: 1961605 [PubMed - indexed for MEDLINE

Apoptosis control and proliferation marker in human normal and noeplastic adrenocortical tissues

We evaluated by immunohistochemistry the expression of the Bcl-2 and p53 proteins, as markers of apoptosis control, and of MIB-I, as a marker of cell proliferation, in a series of normal and neoplastic adrenocortical tissues. The specimens were 13 normal adrenals, 13 aldosterone-producing adenomas, 13 non-functioning adenomas and 16 carcinomas. Results were calculated as percentage of immunostained cells by using specific antibodies. No p53 protein was detected in any of the adrenocortical adenomas (functioning and non functioning) or normal adrenals, while p53 was overexpressed in 15 out of 16 carcinomas. In particular, 10 adrenal cancer specimens (62.5%) showed strong staining in a high percentage (range 10-50%) of the malignant cells. The percentage of Bcl-2 positive cells was higher (P<0.05 or less) in non-functioning adenomas (8.1±1.9%) and in carcinomas (14.9±5.6%) than in normals (2.9±0.9%) and aldosterone-producing adenomas (5.3±1.3%) since four specimens of the non-functioning adenomas-group (30.7%) and six of the carcinomas-group (37.5%) showed over 10% positivity (cut-off for normal values, set at 90th percentile of our controls). MIB-I positivity was 0.50±0.36% in normals, 0.54±0.08% in non-functioning adenomas and 0.54±0.08% in aldosterone-producing adenomas. MIB-I was expressed in all carcinomas with values (13.7±3.1%) significantly (P<0.0006) higher than in the other groups. In conclusion, the present data indicate that the apoptosis control and proliferation activity evaluated by the p53 and MIB-I proteins are impaired in adrenal carcinomas but preserved in adenomas, independently of their functional status. Therefore, these immunohistochemical markers, overexpressed in carcinomas only, may be useful in the diagnosis of malignancy in adrenocortical tumours. Whether Bcl-2 positivity found in some carcinomas and non-functioning adenomas may constitute, in the latter, a negative prognostic marker is still unknown

Role of conventional ultrasonography and color flow-doppler sonography in predicting malignancy in 'cold' thyroid nodules

The aim of the present study was to establish the usefulness of conventional thyroid ultrasonography (US) and color flow-doppler (CFD) sonography in the assessment of 'cold' thyroid nodules. One hundred and four consecutive patients with thyroid nodules who were to undergo surgery were examined by US and CFD before thyroidectomy. Conventional US evaluated the presence of a halo sign, hypoechogenicity and microcalcifications. The vascular pattern on CFD was classified as follows: Type I, absence of blood flow; Type II, perinodular blood flow; Type III, marked intranodular blood flow. On histology, 30 nodules were diagnosed as malignant (carcinoma, CA) and 74 as benign nodules (BN). On US, the echographic pattern most predictive for malignancy was absent halo sign, which was found in 20/30 CA and in 17/72 BN (P = 0.0001; specificity 77.0%; sensitivity 66.6%). The most specific combination on US, absent halo sign/microcalcifications, was found in 8/30 CA and in 5/74 BN (P < 0.005; specificity 93.2%, sensitivity 26.6%). The Type III pattern on CFD was found in 20/30 CA and 38/74 BN (not statistically significant). The combination of absent halo sign on US with Type III pattern on CFD was found in 15/30 CA and in 8/74 BN (P < 0.0001; specificity 89.0%, sensitivity 50.0%). The combination of absent halo sign/microcalcifications on US with Type III pattern on CFD was the most specific combination of the two techniques, being found in 5/30 CA and in only 2/74 BN (P < 0.01; specificity 97.2%, sensitivity 16.6%). In conclusion, findings on US and CFD become highly predictive for malignancy only when multiple signs are simultaneously present in a thyroid nodule. Thus the predictive value of these techniques increases at the expense of their sensitivity. Only in a small proportion of patients with thyroid carcinoma is US and CFD information highly predictive of malignancy