Genetic profiling using plasma-derived cell-free DNA in therapy-naïve hepatocellular carcinoma patients: a pilot study.

Background: Hepatocellular carcinomas (HCCs) are not routinely biopsied, resulting in a lack of tumor materials for molecular profiling. Here we sought to determine whether plasma-derived cell-free DNA (cfDNA) captures the genetic alterations of HCC in patients who have not undergone systemic therapy. Patients and methods: Frozen biopsies from the primary tumor and plasma were synchronously collected from 30 prospectively recruited, systemic treatment-naïve HCC patients. Deep sequencing of the DNA from the biopsies, plasma-derived cfDNA and matched germline was carried out using a panel targeting 46 coding and non-coding genes frequently altered in HCCs. Results: In 26/30 patients, at least one somatic mutation was detected in biopsy and/or cfDNA. Somatic mutations in HCC-associated genes were present in the cfDNA of 63% (19/30) of the patients and could be detected 'de novo' without prior knowledge of the mutations present in the biopsy in 27% (8/30) of the patients. Mutational load and the variant allele fraction of the mutations detected in the cfDNA positively correlated with tumor size and Edmondson grade. Crucially, among the seven patients in whom the largest tumor was ≥5 cm or was associated with metastasis, at least one mutation was detected 'de novo' in the cfDNA of 86% (6/7) of the cases. In these patients, cfDNA and tumor DNA captured 87% (80/92) and 95% (87/92) of the mutations, suggesting that cfDNA and tumor DNA captured similar proportions of somatic mutations. Conclusion: In patients with high disease burden, the use of cfDNA for genetic profiling when biopsy is unavailable may be feasible. Our results support further investigations into the clinical utility of cfDNA in a larger cohort of patients.

A link between inflammation and metastasis: serum amyloid A1 and A3 induce metastasis, and are targets of metastasis-inducing S100A4.

S100A4 is implicated in metastasis and chronic inflammation, but its function remains uncertain. Here we establish an S100A4-dependent link between inflammation and metastatic tumor progression. We found that the acute-phase response proteins serum amyloid A (SAA) 1 and SAA3 are transcriptional targets of S100A4 via Toll-like receptor 4 (TLR4)/nuclear factor-κB signaling. SAA proteins stimulated the transcription of RANTES (regulated upon activation normal T-cell expressed and presumably secreted), G-CSF (granulocyte-colony-stimulating factor) and MMP2 (matrix metalloproteinase 2), MMP3, MMP9 and MMP13. We have also shown for the first time that SAA stimulate their own transcription as well as that of proinflammatory S100A8 and S100A9 proteins. Moreover, they strongly enhanced tumor cell adhesion to fibronectin, and stimulated migration and invasion of human and mouse tumor cells. Intravenously injected S100A4 protein induced expression of SAA proteins and cytokines in an organ-specific manner. In a breast cancer animal model, ectopic expression of SAA1 or SAA3 in tumor cells potently promoted widespread metastasis formation accompanied by a massive infiltration of immune cells. Furthermore, coordinate expression of S100A4 and SAA in tumor samples from colorectal carcinoma patients significantly correlated with reduced overall survival. These data show that SAA proteins are effectors for the metastasis-promoting functions of S100A4, and serve as a link between inflammation and tumor progression.

[Informed consent forms in medical practice: the results of a knowledge survey]. / Il consenso informato scritto nella pratica medica: i risultati di una indagine conoscitiva.

"Federico II" University of Naples Hospital Management's Staff considered 47 informed consent forms in order to evaluate quality and quantity of the information transmitted to patients. Every form, distinguished by procedure (surgical, pharmacological, anesthesiologic or related to blood transfusions) was evaluated for the accuracy and validity of information related to: diagnosis, prognosis, diagnostic and therapeutic opportunities, expected benefits, adverse-side effects, iatrogenic risks, privacy policy on personal data. The forms were judged by information completeness criteria "conformed" or "not conformed" with standards. Our analysis demonstrate that physicians often are unaware of legal and ethical topics related to constructing informed consent forms. They usually omit crucial information or would use strict technical language. So far, we conclude Hospital Management's Staff definitively has a role in improving informed consent forms by establishing guidelines and promoting ethical issues. Final result could be to deserve stronger patient confidence in medical institutions.

Antenatal and perinatal care in southern Italy. I. The mothers' reports.

A population-based cross-sectional study of antenatal and perinatal care was performed in Campania, a region of southern Italy. One thousand three hundred women who had given birth in 1982 were interviewed. The number of antenatal visits was very low, less than 1% of the mothers having attended more than three times during pregnancy. The women at high obstetric risk did not attend more than those at low risk and certain aspects of their antenatal care were unsatisfactory. The place of birth was similar for high risk and low risk mothers, with 40% delivering in small private facilities (with few neonatal resuscitation facilities and often with inadequate infant transport services). The labour was induced or accelerated in 60% of the mothers. The organisation of perinatal care did not take into account many of the needs of the mothers such as presence of a relative at delivery, ambulation during labour, early relationship with the newborn, rooming-in, or encouragement to breastfeed.

Antenatal and perinatal care in southern Italy. II. The clinicians' reactions.

One hundred obstetricians and 50 paediatricians engaged in public antenatal and perinatal care in southern Italy were interviewed about the provision of care in their facilities: 93% of the obstetricians judged the coverage of the target population to be insufficient and 53% of them considered the use of the risk approach to be unsatisfactory in public clinics. For example, no initiative was taken by 60% of public clinics when a woman at high risk failed to attend a booked antenatal visit. Bed rest during labour was prescribed by 72% of the obstetricians, a supporting relative was admitted to only 18% of the births and routine episiotomy was performed in 77% of primigravidae. Only 56% of the paediatricians interviewed allowed early contact between mother and baby. In public hospitals, 80% of paediatricians were present in the delivery room for the births. Screening for congenital hypothyroidism and phenylketonuria was executed in only 37% of the public hospitals. Newborn transport system adequate to national standards was available in only 33% of the hospitals. Antenatal and perinatal care need to be rapidly improved to meet population needs in southern Italy.

Hepatitis B virus infection among health care workers at an urban teaching hospital in southern Italy: a low occupational hazard?

A prevalence study of HBV serologic markers was carried out among hospital employees of ten departments of the Second School of Medicine in Naples, an urban area with a high prevalence of HBV infection. Departments and occupational categories were selected to represent a spectrum of different exposure to B virus infection. Workers in a large electronic plant in the same geographical area were screened as controls. HBsAg prevalence was 4.8% in the hospital community and 4.0% in control group. It rises to 4.3% in the Campania Region, where all screened workers live, and in some specific areas of the same region it rises to 12%. But no significant difference among seropositivities for at least 1 marker of HBV, considered to be a better indicator of occupational hazard, was found among personnel of different departments or belonging to different occupational categories. None of the occupational and non-occupational risk factors studied was found to be significantly associated with HBV infection. Two years later, an incidence study was carried out among susceptible subjects. Seropositivity for 1 marker was 2.2% among hospital workers and 2.8% in the control group. These figures are lower than the annual attack rate (5%) required for an acceptable cost-benefit ratio of vaccination against hepatitis B. Our results indicate that in a geographical area with HBV endemicity the occupational hazard for B virus infection is low in hospital workers because of the high number of the high number of immunized subjects and the contacts with infected people out of the hospital.

Perinatal mortality in southern Italy.

Perinatal deaths occurring in the Campania region of southern Italy in 1982 were analysed. The perinatal mortality rate was 17.6 per thousand (stillbirth rate 8.3, early neonatal mortality rate 9.3). Compared with Swedish data, our deaths excess does not seem attributable to an unfavourable birthweight distribution, but to high birthweight mortality rates in every birthweight category and particularly in the normal birthweight group (greater than 2500 g). This group of newborns, representing about 94% of the births, contributes 45.4% of perinatal deaths; this situation is not common in developed countries, where the normal birthweight newborns form a much smaller proportion of perinatal deaths. The analysis of the causes of perinatal mortality, even though autopsies are rarely executed in Campania, shows a high prevalence of events which should be prevented by good antenatal and perinatal care.