Prenatal diagnosis of absent pulmonary valve syndrome from first trimester onwards: novel insights into pathophysiology, associated conditions and outcome.

OBJECTIVE: To assess the spectrum of associated anomalies, intrauterine course and outcome in fetuses with absent pulmonary valve syndrome (APVS). METHODS: All cases with a prenatal diagnosis of APVS at two centers over a period of 13 years were analyzed retrospectively. APVS was diagnosed in the presence of rudimentary or dysplastic pulmonary valve leaflets with to-and-fro blood flow in the pulmonary trunk on color and pulsed-wave Doppler ultrasound. Data on demographic characteristics, presence of associated conditions, Doppler studies and pregnancy outcome were reviewed. RESULTS: During the study period, 40 cases of APVS were diagnosed prenatally. Thirty-seven (92.5%) cases were associated with tetralogy of Fallot (TOF) and three (7.5%) had an intact ventricular septum. Patency of the ductus arteriosus (DA) was found in 17/37 (45.9%) TOF cases and in all three cases with an intact ventricular septum. Mean gestational age at diagnosis was 19.7 (range, 12-34) weeks with 10 (25.0%) cases (all with TOF) diagnosed in the first trimester. TOF was an isolated finding in 15 (37.5%) cases. Chromosomal anomalies, cardiac defects and extracardiac anomalies were present in 18 (45.0%), four (10.0%) and three (7.5%) cases, respectively. Among the 40 cases, there were 19 (47.5%) terminations of pregnancy, six (15.0%) intrauterine deaths, four (10.0%) neonatal deaths and 11 (27.5%) survivors. Patency of the DA, reversed flow during atrial contraction in the ductus venosus, umbilical artery or fetal middle cerebral artery, and hydrops/increased nuchal translucency thickness were significantly associated with non-survival. All 10 cases diagnosed in the first trimester had a patent DA and abnormal Doppler parameters, eight had hydrops and/or increased nuchal translucency, six were associated with trisomy 13 or 18 and none survived. CONCLUSION: APVS diagnosed in the first trimester is significantly associated with TOF, patency of the DA, abnormal Doppler parameters, lethal trisomies and intrauterine mortality. Cases of APVS with isolated TOF and agenesis of the DA have a better outcome than those with additional anomalies, with > 80% survival. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Fatal disseminated varicella zoster infection following zoster vaccination in an immunocompromised patient.

A 79-year-old man with chronic lymphocytic leukaemia presented with fever and a widespread vesicular rash on 19 November 2014. The patient had not been under immunosuppressive regime for 6 months. He had received a shingles vaccine on 14th October and developed flu-like symptoms after 2 weeks. Intravenous antimicrobial therapy including aciclovir was started. He remained stable with no evidence of systemic involvement. On day 5, he developed respiratory and renal failure that required transfer to intensive care unit. Vesicle fluid, bronchoalveolar lavage and plasma were positive for varicella zoster virus by PCR. Slight clinical improvement allowed extubation on day 16. He subsequently deteriorated and died on day 25. Multiorgan failure was considered the immediate cause of death whereas disseminated varicella zoster infection was stated in the medical certificate as the other condition leading to this outcome. Varicella zoster Oka vaccine strain was detected in vesicle fluid, using PCR.

The differences in short- and long-term varicella-zoster virus (VZV) immunoglobulin G levels following varicella vaccination of healthcare workers measured by VZV fluorescent-antibody-to-membrane-antigen assay (FAMA), VZV time-resolved fluorescence immunoassay and a VZV purified glycoprotein enzyme immunoassay.

Healthcare workers (HCWs) reporting no history of varicella frequently receive varicella vaccination (vOka) if they test varicella-zoster virus (VZV) immunoglobulin G (IgG) negative. In this study, the utilities of VZV-IgG time-resolved fluorescence immunoassay (VZV-TRFIA) and a commercial VZV-IgG purified glycoprotein enzyme immunoassay (gpEIA) currently used in England for confirming VZV immunity have been compared to the fluorescent-antibody-to-membrane-antigen assay (FAMA). A total of 110 HCWs received two doses of vOka vaccine spaced 6 weeks apart and sera collected pre-vaccination (n = 100), at 6 weeks post-completion of vaccination (n = 86) and at 12-18 months follow-up (n = 73) were analysed. Pre-vaccination, by FAMA, 61·0% sera were VZV IgG negative, and compared to FAMA the sensitivities of VZV-TRFIA and gpEIA were 74·4% [95% confidence interval (CI) 57·9-87·0] and 46·2% (95% CI 30·1-62·8), respectively. Post-completion of vaccination the seroconversion rate by FAMA was 93·7% compared to rates of 95·8% and 70·8% determined by VZV-TRFIA and gpEIA, respectively. At 12-18 months follow-up seropositivity rates by FAMA, VZV-TRFIA and gpEIA were 78·1%, 74·0% and 47·9%, respectively. Compared to FAMA the sensitivities of VZV-TRFIA and gpEIA for measuring VZV IgG following vaccination were 96·4% (95% CI 91·7-98·8) and 74·6% (95% CI 66·5-81·6), respectively. Using both FAMA and VZV-TRFIA to identify healthy adult VZV susceptibles and measure seroconversion showed that vOka vaccination of HCWs is highly immunogenic.

[Clinical nutrition in surgery. Guidelines of the German Society for Nutritional Medicine]. / Klinische Ernährung in der Chirurgie. S3-Leitlinie der Deutschen Gesellschaft für Ernährungsmedizin e. V.

BACKGROUND: While enhanced recovery after surgery (ERAS) programs are the standard for perioperative management, special nutritional care has to be administered to malnourished patients and those at metabolic risk with special regard to patients with postoperative complications. METHODS: Existing guidelines of the German and European societies of nutritional medicine (DGEM and ESPEN) on enteral and parenteral nutrition in surgery were merged and in accordance with the principles of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF, German Association of the Scientific Medical Societies) and Ärztliches Zentrum für Qualität in der Medizin (AeZQ, German Agency for Quality in Medicine) revised and extended. RESULTS AND DISCUSSION: The working group developed 41 consensus-based recommendations for perioperative nutrition. The recommendation strength is: 9x A (recommendation based on significant good quality literature containing at least one randomized controlled trial), 12x B (recommendation based on well-designed trial without randomization), 13x C (recommendation based on expert opinions and/or clinical experience of respected authorities) and 7x CCP (clinical consensus point). CONCLUSION: Even in patients without obvious malnutrition perioperative nutritional support is indicated when oral food intake is not feasible or inadequate for a longer period of time.

Subclinical VZV reactivation in immunocompetent children hospitalized in the ICU associated with prolonged fever duration.

A prospective observational study was conducted to examine whether asymptomatic VZV reactivation occurs in immunocompetent children hospitalized in an ICU and its impact on clinical outcome. A secondary aim was to test the hypothesis that vaccinated children have a lower risk of reactivation than naturally infected children. Forty immunocompetent paediatric ICU patients and healthy controls were enrolled. Patients were prospectively followed for 28 days. Clinical data were collected and varicella exposure was recorded. Admission serum levels of TNF-a, cortisol and VZV-IgG were measured. Blood and saliva samples were collected for VZV-DNA detection via real-time PCR. As a comparison, the detection of HSV-DNA was also examined. Healthy children matched for age and varicella exposure type (infection or vaccination) were also included. VZV reactivation was observed in 17% (7/39) of children. Children with VZV reactivation had extended duration of fever (OR = 1.17; 95% CI, 1.02-1.34). None of the varicella-vaccinated children or healthy controls had detectable VZV-DNA in any blood or saliva samples examined. HSV-DNA was detected in saliva from 33% of ICU children and 2.6% of healthy controls. Among children with viral reactivation, typing revealed wild-type VZV and HSV-1. In conclusion, VZV reactivation occurs in immunocompetent children under severe stress and is associated with prolonged duration of fever.

[Perioperative nutrition - a nationwide web-based survey of German surgery departments]. / Perioperative Ernährung aus Sicht von Chirurgen - Eine deutschlandweite Online-Umfragen.

BACKGROUND: Insufficient nutrition in surgical patients increases perioperative morbidity, mortality, length of stay and therapy costs. Therefore, guidelines declare the integration of nutrition into the overall management as one of the key aspects of perioperative care. This study was conducted to evaluate the current clinical practice of clinical nutrition in surgical departments in Germany. METHODS: In 2009 German Surgical Society (DGCH) members in leading positions were surveyed with a standardised online questionnaire concerning their perioperative nutritional routines in elective surgery. RESULTS: From the addressed physicians n = 156 (6.24 %) answered. Of those, 86.9 % consider the nutritional status of their patients. Only 6 % use standardised nutritional screening tools. Short preoperative fasting for solid and liquid food is practiced by 65 % and 40 %, respectively. After the operation, 65 % allow intake of clear fluids on the day of surgery and 78 % initiate solid food on the day of surgery or the first postoperative day. Oral nutritional supplements are given only "sometimes" or "rarely" by 53.9 % of the respondents. CONCLUSION: The low response rate may imply the dilemma that the evidence-based benefit of perioperative nutrition does not meet sufficient interest. Even in case of a positive selection of "pro-nutrition respondents", standardised preoperative malnutrition screening is also rare. Aspects such as shorter perioperative fasting are already practiced more progressively. However, still greater efforts are needed to promote guideline-based clinical nutrition in surgical care in Germany.

Impact of viral reactivations in the era of pre-emptive antiviral drug therapy following allogeneic haematopoietic SCT in paediatric recipients.

While pre-emptive rituximab therapy for EBV has substantially reduced the incidence of post-transplant lymphoproliferative disorder, following allogeneic haematopoietic SCT (HSCT), cytomegalovirus (CMV) and adenovirus (ADV) still contribute to significant morbidity and mortality after HSCT. We therefore aimed to identify high-risk children who could benefit from recent advances in virus-specific immunotherapy, define the impact of viral reactivations on survival and estimate the economic burden of pre-emptive antiviral drug therapy. Between 2005 and 2010, prospective monitoring of 291 paediatric HSCT procedures revealed that reactivation of CMV (16%), ADV (15%) and EBV (11%) was frequent during period of CD4 T-cell lymphopenia (0.15 × 10(9) L(-1); P<0.05). We report significant risk factors for reactivation, most notably the use of serotherapy and development of GVHD (grade II) in the presence of pre-existing infection (ADV) or donor and/or recipient seropositivity (CMV, EBV). Most interestingly, CMV and ADV viraemia were the major independent predictors of mortality (P<0.05). CMV, ADV or EBV viral reactivation caused prolonged hospitalization (P<0.05), accounted for 15% of all mortality and substantially increased the cost of transplantation by ∼£22 500 ($34 000). This provides an economic rationale for targeting high-risk HSCT recipients with interventions such as virus-specific cell therapy.

Comparison of a commercial Varicella Zoster glycoprotein IgG enzyme immunoassay with a reference time resolved fluorescence immunoassay (VZV TRFIA) for measuring VZV IgG in sera from pregnant women, sera sent for confirmatory testing and pre and post vOka vaccination sera from healthcare workers.

BACKGROUND: Recently, a commercial, standardised VZV IgG glycoprotein EIA, Binding Site VaccZyme™VZV glycoprotein IgG low level EIA (VaccZyme™EIA) has become available. The VaccZyme™EIA is more robust and user friendly than the reference VZV time-resolved fluorescence immunoassay (VZV TRFIA). OBJECTIVES: To assess the usefulness of the VaccZyme™EIA in the diagnostic laboratory by comparing VZV IgG levels generated by both assays on serum panels representing, non-vaccinated, and vOka vaccinated populations. STUDY DESIGN: Sera from non-vaccinated individuals were tested; 248 from pregnant women, 117 from various patient groups referred to the Virus Reference Department for confirmatory VZV IgG testing and 102 from healthcare workers enrolled in a study (ROVE) of antibody/IgG response to vOka. From the ROVE study, 282 post vaccination sera were tested; 108 and 101 collected at six weeks post first and second doses of vOka, respectively, and 73 collected at 18 month follow-up. RESULTS: Sensitivities and specificities (equivocals treated as negatives) of the VaccZyme™EIA for sera from pregnant women were 97.8% (95% CI: [94.6%, 99.4%]) and 96.8% (95% CI: [89.0%, 99.6%]), respectively, and for sera referred for confirmatory testing were 81.2% (95% CI: [71.2%, 88.8%]) and 96.9% (95% CI: [83.8%, 99.9%]), respectively, and for ROVE baseline sera were 54.2% (95% CI: [32.8%, 74.4%]) and 100% (95% CI: [95.4%, 100.0%]), respectively. For the post vOka serum panels sensitivities of the VaccZyme™EIA ranged from 65.3% (95% CI: [50.4%, 78.3%]) to 80.4% (95% CI: [71.1%, 87.8%]). Specificities were all 100%. Correlation with VZV TRFIA was high and agreement varied between the serum panels tested. CONCLUSIONS: VaccZyme™EIA is recommended for detecting VZV IgG in sera from non-vaccinated populations; however, caution is advised when measuring post vOka VZV IgG levels.

Balloon valvuloplasty in the treatment of congenital aortic valve stenosis--a retrospective multicenter survey of more than 1000 patients.

BACKGROUND: The value of balloon valvuloplasty of the aortic valve in childhood is still under debate. OBJECTIVE: To evaluate the results of the procedure in a retrospective multicenter survey of a large cohort over a long time interval. METHODS: Retrospective analysis of 1004 patients with balloon valvuloplasty of the aortic valve performed between 9/1985 and 10/2006 at 20 centers in Germany, Austria and Switzerland. Amongst others, the following parameters were evaluated before and after the procedure as well as at the end of follow-up or before surgery: clinical status, left ventricular function, transaortic pressure gradient, degree of aortic regurgitation, freedom from re-intervention or surgery. PATIENTS: Patients from 1 day to 18 years of age with aortic valve stenosis were divided into four groups: 334 newborns (1-28 days); 249 infants (29-365 days); 211 children (1-10 years), and 210 adolescents (10-18 years). RESULTS: Median follow-up was 32 months (0 days to 17.5 years). After dilatation the pressure gradient decreased from 65 (± 24)mm Hg to 26 (± 16)mm Hg and remained stable during follow-up. The newborns were the most affected patients. Approximately 60% of them had clinical symptoms and impaired left ventricular function before intervention. Complication rate was 15% in newborns, 11% in infants and 6% in older children. Independently of age, 50% of all patients were free from surgery 10 years after intervention. CONCLUSIONS: In this retrospective multicenter study, balloon valvuloplasty of the aortic valve has effectively postponed the need for surgery in infants, children and adolescents up to 18 years of age.

Analysis of pesticides and PCBs in waste wood and house dust.

The use of the pesticides - DDT (1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane) and lindane (gamma-hexachlorocyclohexane) - and of PCBs (polychlorinated biphenyls) has been limited or forbidden for several decades. Nevertheless, due to their persistence and bioaccumulative potentials they are still ubiquitous in the environment. Therefore, the main objective of this study was to determine analytical methods to analyse the pesticides lindane and DDT, its metabolites DDD (1,1-dichloro-2,2-bis(4-chlorophenyl)ethane) and DDE (1,1-dichloro-2,2-bis(4-chlorophenyl)ethene), and PCBs in waste wood and house dust. An ultrasonic extraction was performed followed by a sample clean up by filtration or silica gel column. The prepared samples were measured by GC/MS. Quantification through internal standard calibration delivered low limits of detection. Specific amounts of the target compounds were detected in all analysed dust samples. The comparison of the contamination between dust samples of eastern Germany (former German Democratic Republic - GDR) and western Germany partly revealed significant differences of the contamination levels. Furthermore, it was examined whether older wooden material might cause a constant volatilisation of pesticides in apartments. Waste wood samples of different contamination categories were analysed. Apparently, these samples are potentially responsible for a constant DDX (Σ(DDT, DDD, DDE)) and lindane volatilisation, but not for PCBs.

[Reduced preoperative fasting periods. Current status after a survey of patients and colleagues]. / Verkürzte präoperative Nüchternheit. Erhebung eines Istzustands nach Analyse von Patienten- und Mitarbeiteraussagen.

BACKGROUND: Since October 2004 German Anaesthesiology Societies have officially recommended a decreased fasting period of 2 h for clear fluids and 6 h for solid food before elective surgery. A survey of patients and health care workers was carried out in our university clinic to assess the implementation of the new fasting recommendations. METHODS: Surgical patients (n=865) as well as physicians and nurses specialized in anaesthesia and surgery (n=2,355) were invited to complete a written questionnaire. The survey inquired about prescribed and practiced duration of fasting, attitudes towards reduced preoperative fasting and knowledge of the new guidelines. RESULTS: Data from 784 patients (91%) and 557 health care workers (24%) were analysed. Patients reported mean fasting times of 10+/-5 h for fluids and 15+/-4 h for solid food. Of the patients 52% and 16% would have preferred to drink and eat before surgery, respectively and 10% were informed about the new recommendations of shorter preoperative fluid and solid fasting. Such patients reported significantly reduced fasting times for fluids compared with those who were recommended to fast for the traditional longer periods (8+/-6 versus 12+/-4 h, p<0.001). Preoperative fasting advice remembered by the patients significantly differed from the prescribed recommendations (2 h fluid fasting, 22 versus 53%, p<0.001). Anaesthesiologists were significantly more knowledgeable of the new guidelines (90 versus 32-42%, p<0.001) and significantly more willing to recommend the new short preoperative fasting times (75 versus 15-19%, p<0.001) than other health care workers. Of all health care workers 82% and 32% reported patients' frequent desire to drink and eat before surgery, respectively, 92% considered reduced preoperative fasting to be positive, 76% feared increased risks for patients and 42% expected a decreased flexibility in their daily work. CONCLUSION: The current guidelines for preoperative fasting have not been widely implemented. Besides a knowledge discrepancy, remarkable concerns remain regarding higher risk for patients which may be important barriers to implementation. Nevertheless, health care workers are aware of patients' desire for shorter preoperative fasting. If the new guidelines are recommended patients will make use of them. Further training of staff and adequate implementation tools are needed.

Pre-operative fasting: a nationwide survey of German anaesthesia departments.

BACKGROUND: Shorter pre-operative fasting improves clinical outcome without an increased risk. Since October 2004, German Anaesthesiology Societies have officially recommended a fast of 2 h for clear fluids and 6 h for solid food before elective surgery. We conducted a nationwide survey to evaluate the current clinical practice in Germany. METHODS: Between July 2006 and January 2007, standardized questionnaires were mailed to 3751 Anaesthesiology Society members in leading positions requesting anonymous response. RESULTS: The overall response rate was 66% (n=2418). Of those, 2148 (92%) claimed familiarity with the new guidelines. About a third (n=806, 34%) reported full adherence to the new recommendations, whereas 1043 (45%) reported an eased fasting practice. Traditional Nil per os after midnight was still recommended by 157 (7%). Commonest reasons reported for adopting the new guidelines were: 'improved pre-operative comfort' (84%), and 'increased patient satisfaction' (83%); reasons against were: 'low flexibility in operation room management' (19%), and 'increased risk of aspiration' (13%). CONCLUSION: Despite the apparent understanding of the benefits from reduced pre-operative fasting, full implementation of the guidelines remains poor in German anaesthesiology departments.

Health-economic evaluation of three imaging strategies in patients with suspected colorectal liver metastases: Gd-EOB-DTPA-enhanced MRI vs. extracellular contrast media-enhanced MRI and 3-phase MDCT in Germany, Italy and Sweden.

The purpose of this study was to perform an economic evaluation of hepatocyte-specific Gd-EOB-DTPA enhanced MRI (PV-MRI) compared to extracellular contrast-media-enhanced MRI (ECCM-MRI) and three-phase-MDCT as initial modalities in the work-up of patients with metachronous colorectal liver metastases. The economic evaluation was performed with a decision-tree model designed to estimate all aggregated costs depending on the initial investigation. Probabilities on the need for further imaging to come to a treatment decision were collected through interviews with 13 pairs of each a radiologist and a liver surgeon in Germany, Italy and Sweden. The rate of further imaging needed was 8.6% after initial PV-MRI, 18.5% after ECCM-MRI and 23.5% after MDCT. Considering the cost of all diagnostic work-up, intra-operative treatment changes and unnecessary surgery, a strategy starting with PV-MRI with 959 Euro was cost-saving compared to ECCM-MRI (1,123 Euro) and MDCT (1,044 Euro) in Sweden. In Italy and Germany, PV-MRI was cost-saving compared to ECCM-MRI and had total costs similar to MDCT. In conclusion, our results indicate that PV-MRI can lead to cost savings by improving pre-operative planning and decreasing intra-operative changes. The higher cost of imaging with PV-MRI is offset in such a scenario by lower costs for additional imaging and less intra-operative changes.

Beta-papillomaviruses and psoriasis: an intra-patient comparison of human papillomavirus carriage in skin and hair.

BACKGROUND: Human papillomaviruses (HPVs) of the beta genus (beta-PV), especially HPV5 and HPV36, are proposed to play a pathogenic role in psoriasis, but many previous studies have failed to control for potential confounders, including treatment. OBJECTIVES: To re-examine the relationship between beta-PV and psoriasis addressing limitations present in previous studies and analyse intra-patient concordance for carriage of HPV. METHODS: Plucked eyebrow hairs and forearm skin scrapes were collected from 20 newly diagnosed, previously untreated adult patients with psoriasis and 23 normal controls. A combination of type-specific and degenerate polymerase chain reaction methods was used to achieve comprehensive HPV DNA detection. RESULTS: The prevalence of HPV in hair and skin from psoriasis patients was higher than in controls (83.3% vs. 46.7%, respectively, P < 0.03 corrected for age and clustering). HPV5 or HPV36 were not over-represented. The profile of diverse beta-PV types was comparable in the two groups. Intra-patient concordance for HPV DNA at separate sites was high (P < 0.00001). CONCLUSIONS: Our data do not support a specific causal role for HPV5 or HPV36 in psoriasis, but suggest that psoriatic skin may be more permissive for viral presence than normal skin. High intra-patient concordance for specific HPV types at separate sites, together with the ubiquity of HPV DNA in normal human skin, suggests that an individual becomes colonized with a particular beta-PV profile presumably to the exclusion of other types. To what extent this HPV profile is then causal in the subsequent development of hyperproliferative skin disease is unknown.

Influence of vaccination and surgery on HLA-DR expression in patients with upper aerodigestive tract cancer.

Major surgery is associated with an increased risk of post-operative immunosuppression and infections. We investigated the influence of influenza vaccination on cell-mediated immune responses in cancer patients undergoing either surgical or conservative therapy. Forty patients with an upper aerodigestive tract tumour were allocated to either a surgical or non-surgical treatment course. Patients within each group were randomized to the vaccination or non-vaccination group. Vaccination was performed twice before surgery or conservative treatment. Human leucocyte antigen receptor (HLA-DR) expression on monocytes was analysed by flow cytometry. In the surgical patients, HLA-DR expression on day 1 after surgery decreased in both the vaccinated and non-vaccinated groups. Vaccinated non-surgical patients showed significantly increased HLA-DR expression levels compared with the non-vaccinated patients. This pilot study demonstrated that vaccination increased monocyte HLA-DR expression in conservatively-treated cancer patients whereas surgery abrogated this response. Vaccination before surgery, therefore, might not help to maintain immune reactivity after surgery.

Inactivation of the CDKN2A and the p53 tumour suppressor genes in external genital carcinomas and their precursors.

BACKGROUND: p53 has been extensively studied in external genital carcinoma (EGC), and is frequently inactivated, but little is known about the role of the CDKN2A tumour suppressor gene in the oncogenesis of EGC. OBJECTIVES: To investigate the role of CDKN2A and p53 in the pathogenesis of EGCs and their precursor lesions vulval intraepithelial neoplasia (VIN3), penile intraepithelial neoplasia and lichen sclerosus (LS). METHODS: By means of CDKN2A and p53 mutation screening (single-strand conformational polymorphism analysis and sequencing), methylation analysis of alternative CDKN2A promoters (methylation-specific polymerase chain reaction) and p53 immununochemistry, we analysed eight invasive EGCs (five from vulva and three from penis) and 25 precancerous lesions (two undifferentiated VIN3 and 23 vulval/penile lesions of LS) from 33 patients. RESULTS: p53 mutations (mainly transversions) and CDKN2A mutations (including one hot spot) were present in 75% and 50% of invasive tumours, respectively, but were absent in all precancerous lesions. Remarkably, all CDKN2A-mutated tumours also harboured a p53 mutation. CDKN2A or p53 mutations were observed more frequently in LS-derived EGCs than in human papillomavirus-derived EGCs (P = 0.053). A positive anti-p53 staining, but without p53 mutations, was also detected in 30% of LS lesions, suggesting a p53 stabilization in response to inflammation and carcinogenic insult. Methylation of p16(INK4a) and p14(ARF) promoters was not a frequent mechanism of CDKN2A inactivation. CONCLUSIONS: Our study shows a high prevalence of co-inactivating mutations of p53 and/or CDKN2A genes in EGC, that seem to occur preferentially in LS-derived tumours and late in oncogenesis.

Intrapericardial teratoma in the newborn--3D-echocardiography and course of disease.

Intrapericardial teratoma is a rare tumour which may become life threatening when it causes mediastinal compression. Early sonographic detection and careful evaluation is necessary for further management. In this paper, we present a case with a large intrapericardial teratoma diagnosed in utero (25 + 0 weeks). After birth, 3D-echocardiography was particularly helpful in obtaining a comprehensive view of the three-dimensional structure of this complex tumour, in order to determine tumour extension and attachment before surgical excision. This case illustrates the opportunities which new, noninvasive echocardiographic tools create to aid therapeutic management and surgical therapy of critically ill patients.