[Compliance of patients undergoing thromboprophylaxis with enoxaparin: the COMFORT study]. / Patientencompliance unter einer Thromboseprophylaxe mit Enoxaparin: die COMFORT-Studie.

Venous thromboembolism and subsequent pulmonary embolism are frequent and sometimes fatal complications in patients after surgical interventions. To prevent thromboembolisms an effective prophylaxis is necessary and outpatients in particular need adequate compliance. The aim of the prospective non-interventional study COMFORT was to analyze 8,091 outpatients after surgical and orthopedic interventions with different risk profiles with respect to factors affecting patient compliance in a positive or negative way. The follow-up period was 14 days and 92.5 % of the patients took the medication for the prescribed duration, 2.1 % (n = 166) terminated the medication too early and no information was available for 5.9 % (n = 442) of the patients. The reasons given for the premature termination of the injections were no more need for prophylaxis and end of medication by order of the physician due to mobilization or adverse events. Of the patients 73 % stated that the administartion was simple and without any problems and the majority of patients recognized injection as the administration mode of low molecular weight heparin to be the most important medication. The findings of this study can contribute to a better understanding of patient compliance.

Prenatal sonographic diagnosis of an oropharyngeal teratoma (epignathus) on a stillborn infant: a case report.

Oropharyngeal teratomas are rare congenital malformations that arise from all three basic germinal layers and form a high risk situation for the neonate. Their incidence is only sporadic and they are not associated with a high recurrence risk, although some cases of associated chromosomal aberrations have been described. In this case report we present the clinical course and the histopathological findings of a prenatal diagnosed stillborn infant with an oropharyngeal teratoma of the left maxilla by a 33-year-old primigravida woman at 40 weeks 5 days' gestation. Moreover we emphasize on the relevance of the prenatal diagnosis and visualisation of such fetal tumors not only because of their great importance on the obstetrical management but also for their critical contribution to the optimal treatment of the affected newborn.

Activation of the HIF pathway in childhood ALL, prognostic implications of VEGF.

Hypoxia-inducible factor 1 (HIF-1) controls angiogenesis and glycolysis, two leading characteristics of solid tumor invasion, metastasis, and lethality. Increased angiogenesis is also found in the bone marrow (BM) of leukemias. Less is known in leukemia about the role of HIF-1 and vascular endothelial growth factor (VEGF), the most important proangiogenic target gene of HIF-1. We show by immunohistochemistry that the oxygen-regulated component of HIF-1 (HIF-1alpha) is overexpressed in clusters of leukemic cells in BM specimens of childhood acute lymphoblastic leukemia (ALL) and absent in biopsies of normal BM. Half the HIF-1alpha-positive ALL biopsies exhibited VEGF coexpression. Among 96 children with relapsed ALL, diagnostic BM aspirates with high VEGF mRNA levels were associated with a significantly lower probability of event-free survival at 3 years (0.31+/-0.08 vs 0.65+/-0.07, P=0.003). Those with poor molecular response to therapy (evaluated by MRD assessment) had 2.2-fold higher VEGF levels than those responding well to chemotherapy (P=0.005). In conclusion, the data demonstrate activation of the HIF pathway in the BM of ALL patients and indicate that the expression of HIF target genes, such as VEGF, play an important role in leukemia progression, therapy response, and outcome.

[Rare mesenchymal lesions in siblings. Two case reports]. / Seltene mesenchymale Läsionen bei Geschwisterkindern. Zwei Fallberichte.

We report on a 15-month-old boy presenting a juvenile active ossifying fibroma in the right nasal cavity and the sibling, a 9-month-old girl with a mesenchymal hamartoma of the chest wall. The two lesions showed many similarities. Both lesions are present at the time of birth or in early life with local obstructive or compressive effects. The lesions have a similar mixture of mature and immature mesenchymal tissue with areas of ossification. The entities present a tumor-like development with an abnormal mixture of tissue indigenous to the specific area of the body without notable atypical cytologic features. These features are typical criteria for hamartoma lesions.

[Incidental chorangiocarcinoma. Case report, immunohistochemistry and theories of possible histogenesis]. / Inzidentelles Chorangiokarzinom. Fallbericht, Immunhistochemie und Theorien zur möglichen Histogenese.

We describe the third case world-wide of a chorangiocarcinoma, a tumour with an abnormal trophoblast proliferation in combination with a hypervascular chorangiosis of the villous stroma. The lesion was an incidential finding by a healthy 31-year-old woman, gravida 1, para 1 when the pregnancy was terminated at 34 weeks gestation because of fetal distress and intrauterine growth restriction. Hormonal levels were within the normal range. Mother and infant had an uneventful postpartum course. Immunohistochemical studies of the abnormal trophoblasts demonstrated strong immunoreactivity for HCG and in 80% for Ki 67. The semiquantitative expression of angiogenic growth factors (VEGF, bFGF, Ang-1 und Ang-2, PDGF) in the tumour trophoblasts was similar to that seen in the normal villi. The pathogenesis of this tumour with a villous vascular response is curious and unclear. Possibilities include the occurrence of a variant of a chorion carcinoma, the occurrence of a new tumour entity or of two separate lesions, a chorangioma and incidential chorion carcinoma, present together as a "collision" tumour. Another possibility is a composition tumour or a reactive lesion of trophoblasts and the villous vascular tree.

[Solitary and multiple chorangiomas--clinical consequences, expression of growth factors and differences in the growth rate]. / Solitäre und multiple Chorangiome--Klinische Konsequenzen, Expression von Wachstumsfaktoren und Differenzen in der Wachstumsrate.

BACKGROUND: Chorangiomas are regarded as hamartous lesions of the placenta which may complicate a pregnancy if they grow large. The etiology of these lesion is still unclear. We suspected a link between the development of chorangiomas and an increase of the expression of the angiogenic growth factor bfgf and angiopoietin-1 within the tumour. MATERIAL AND METHODS: We examined 20 placentas without tumour, 19 placentas with solitary chorangiomas and 10 placentas with multiple chorangiomas (chorangiomatosis) with respect of the difference in clinical complications, regarding the expression of bfgf and angiopoietin-1 and with regard to the proliferation rate. RESULTS: The expression of the growth factors in solitary chorangiomas did not differ from that in the normal placental tissue. Both groups showed moderate expression of growth factors. In placentas with multiple chorangiomas all cases were associated with a strong expression of bfgf and angiopoietin-1. Proliferating cells and fibroblasts were seen more often in placentas with chorangiomatosis. There were clinical differences with regard to the maternal age. The mean age in case of normal placentas was 24 years, in placentas with solitary chorangiomas 32 years and for placentas with multiple chorangiomas 28 years. There were more complications such as HELLP-syndrome, diabetes, preterm birth and additional maturational arrest of the placenta in case of chorangiomas. CONCLUSION: There is a link between the development of multiple chorangiomas and an increase of the expression of bfgf and angiopoietin-1 in the placenta. In our study there is no correlation between multiple tumours and complications of pregnancy.

Autosomal recessive type of Adams-Oliver syndrome: prenatal diagnosis.

We report on three pregnancies complicated by Adams-Oliver syndrome in a consanguineous Turkish couple. Two cases were correctly diagnosed prenatally at 22+3 and 13+0 weeks gestation following the first case of Adams-Oliver syndrome in which severe anomalies of the extremities were observed at 26+5 weeks' gestation. In this first case, the diagnosis of Adams-Oliver syndrome was made following termination of pregnancy at 27+2 weeks' gestation. In all three cases, autopsy was performed. All fetuses showed anomalies of the extremities, aplasia cutis and symmetric defects of the skull, with bone being replaced by collagenous tissue. Although there have been numerous cases of the postnatal diagnosis of Adams-Oliver syndrome following termination of pregnancy, this is the first description of the prenatal diagnosis of this disorder.

[Growth factors and apoptosis rate in an unusual chorangioma]. / Wachstumsfaktoren und Apoptoserate in einem ungewöhnlichen Chorangiom.

We describe an unusual type of cellular chorangioma with a high rate of proliferating cells and mitosis and high expression of the growth factor BFGF. The tumor was observed in the placenta of a 26-year-old gravida 1 with help syndrome. The pregnancy was terminated at 35+5 weeks by elective caesarean section. Chorangiomas are hamartoma malformations of the placenta which in some cases may be large enough to influence the course of pregnancy and associated complications are hydramnion, gestosis or hemorrhage. Complications for the fetus are due to hemodynamic alterations caused by the formation of an arteriovenous shunt. Because the histogenesis of the tumor is still unknown, we examined the expression of the growth factors VEGF and BFGF. The number of cells with an expression of VEGF in placental tissue and in the chorangioma was uniform, but the number of cells with an expression of BFGF was much higher in the chorangioma than in the placenta. We conclude that BFGF may have an influence on the growth of chorangiomas. There was no difference between the chorangioma and the placenta in the rate of apoptosis-inhibited cells.

Rare mesenchymal lesions: Hamartoma of the chest wall and juvenile active ossifying fibroma in siblings.

Mesenchymal hamartomas of the thorax are known as rare dysontogenetic tumorous non-neoplastic lesions. The juvenile active ossifying fibroma (JAOF) also is considered as a benign tumor like lesion of the mesenchymal connective tissue. The authors report the cases of 2 siblings-a 2-year-old girl with a hamartoma of the chest wall and her 4-year-old brother with a JAOF. The girl had bilocular mesenchymal hamartoma in the area of the 8(th) rib diagnosed in the first year of life, which was surgically removed completely. Her brother had been treated for JAOF of the right nasal sinus area diagnosed at the age of 15 months. Both lesions are extremely rare mutations of the local tissue, which occur typically in early childhood and continue benignly after surgical resection, but such a familial occurrence in siblings has not yet been reported. Furthermore, according to the histologic findings, the JAOF also could be seen as a hamartomatous lesion.

[Intestinal polyp of the umbilical cord]. / Der intestinale Nabelschnurpolyp.

The morphology, pathogenesis, complications and differential diagnosis of an intestinal polyp of the umbilical cord are presented. The polyp were detected postnatal on the umbilical cord in an healthy male newborn. The presents of intestinal tissue upon the umbilical cord ist possible about the persistence from remnants of the ductus omphalomesentericus with prolapse and differentiation of the intestinal cells. The ductus omphalomesentericus is a tubular structure, a communication between the developing embryonic gut and the yolk sac, forming during the early embryonic life. Obliteration of the omphalomesenteric duct is usually complete by the 10(th) week of gestation. Various portions of the duct may persist, however, giving rise to polyps, fistulas or cysts of the umbilical cord with potentially dangerous clinical consequences. Other tumors of the umbilical cord are myxoma, angioma and teratoma are differential diagnosis.

[Femur-fibula-ulna (FFU) complex in the 33rd week of gestation: ultrasonography, radiology, pathology and differential diagnosis. Case report]. / Femur-Fibula-Ulna(FFU)-Komplex in der 33. SSW - Sonographie, Radiologie, Pathologie und Differentialdiagnose anhand eines Fallberichtes -

We present a case of a 27 year old I. gravida, I. para. Despite of regular ultrasonographic examination the diagnosis of skeletal malformation at the fetus was not before 33. weeks of gestation. It was the rare type of a bothside femur-fibula-ulna (FFU) complex. The FFU-complex is a no lethal malformation with typical unilateral combination from defects of femur and fibula, with contralateral defect of ulna. Dependent to involvement of malformated limbs the FFU-complex is classifiable in four groups. Only in 10 % all limbs are affected. Our case (type IV) showed a peromelia of both upper limbs with stumps of humeri, bothside aplasia of fibula and missing from 4. and 5. toes. There fetus were without nonlimb congenital abnormalities. The etiology of FFU-complex is unknown, the occurrence sporadic. There are never found genetic abnormalities. Familial recurrence is not described. There is no maternal or paternal age effect on FFU-complex. The differential diagnosis must include malformations with reduction anomalies of extremities, like thalidomide syndrome, splenogonadal fusion with limb malformations, Roberts syndrome, oroacral complex or acheiropodia. Mark off are amniotic band too.

Mesomelic campomelia, polydactyly and Dandy-Walker cyst in siblings.

The present report describes two fetuses, one female and one male, with thus far undescribed skeletal malformations. The mother was a gravida 2, para 0. Both pregnancies were terminated in the second trimester because of multiple congenital anomalies diagnosed ultrasonographically resembling a short rib-polydactyly syndrome. Both fetuses were found to have postaxial hexadactyly of the hands and feet, marked bilateral campomelia of the forearm and shank bones, and a Dandy-Walker cyst. In addition, the fourth ventricle was dilated in the first sibling and the second sibling had an inverse intestinal malrotation. A literature search failed to reveal similar observations.

Prenatal diagnosis of familial absent pulmonary valve syndrome: case report and review of the literature.

We report on a case of absent pulmonary valve syndrome in a woman with a history of one healthy child and one child with tetralogy of Fallot with absent pulmonary valve. The diagnosis was missed at the first ultrasound examination performed at 13 + 5 weeks of gestation and correctly diagnosed at 21 + 5 weeks. Re-evaluation of the ultrasound examination recorded at 13 + 5 weeks exhibited severe insufficiency of the pulmonary valve at this time. However, neither dilatation of the right and left pulmonary arteries nor asymmetry of the ventricles were present at that time. The pregnancy was terminated at 22 + 1 weeks of gestation when autopsy confirmed the diagnosis of absent pulmonary valve syndrome. Karyotyping of the fetus after termination of pregnancy revealed normal chromosomes. Echocardiography of the parents and the healthy sibling revealed normal results.

Addison-disease - an unusual clinical manifestation of CMV-end organ disease in pediatric AIDS.

CMV infection is common in pediatric HIV-1 infected patients. We present a case report, to our knowledge the first pediatric patient, in which Addison-disease due to CMV was suspected during lifetime. We want to point out the importance of routine clinical and laboratory follow up once a HIV-1 infected child is shown to be infected with CMV.

Adrenal tissue in the placenta: a heterotopia caused by migration and embolism?

Heterotopic adrenal tissue is not uncommon, especially in the urogenital system. Adrenocortical tissue in the placenta, however, is presumably very rare. To our knowledge, four cases have been published. There are several different theories to explain such a heterotopia. According to our findings, an embolic spread of adrenal precursor cells via fetal vascular shortcuts is the most likely mechanism. Apart from that hypothesis, the possibility of a monodermal teratoma as well as of an aberrant differentiation of cells of the extraembryonic mesoderm are considered in the literature.

Immunohistochemical assessment of the tumour-associated epitopes CD44v6 and E48 in tumour-free lymph nodes from patients with squamous cell carcinoma in the head-neck region.

We examined immunohistochemically 370 tumour-free lymph nodes from 41 patients with a head and neck squamous cell carcinoma (HNSCC) to clarify whether the tumour-associated epitopes CD44v6 and E48 are suitable for adjuvant postoperative immunotherapy. All the positively immunostained cells found were single cells. CD44v6+ cells were found in 55% of the lymph nodes, with their numbers increasing in pN>0-patients (62%). Only pN>0-patients had abundant to massive CD44v6+ cells. A comparison with mononuclear cells in lymphatic tissue from control patients suggested a similarity with activated T-cells. In the 41 cancer patients there were significantly fewer lymph nodes with E48+ cells (11%), but the number of E48+ cells increased in pN> 1-patients (29%) with predominantly abundant E48+ cells. We conclude from the comparison with the epithelial marker EMA that the E48+ single cells are epithelial in origin. Only a specific E48 peptide sequence appears suitable for adjuvant immunotherapy in patients with head-neck tumours.

Ellis-van Creveld syndrome: examination at 15 weeks' gestation.

In 1940, Ellis and van Creveld defined a syndrome they referred to as chondro-ectodermal dysplasia. This autosomal recessive condition, now usually referred to as Ellis-van Creveld syndrome (EVC), comprises bilateral postaxial polydactyly, a chondrodysplasia, characterized by shortness of limbs, and ectodermal dysplasia. Congenital heart defects are also common. There are many reports in medical literature describing affected newborns and even, older children. Here, we report the clinical, radiological and histological findings in a 15-week-old affected fetus. The diagnosis of Ellis-van Creveld syndrome in this fetus is based on a positive family history (an affected sib) and shortness of long bones as well as hexadactyly diagnosed by prenatal ultrasonography. On post-mortem examination, bilateral postaxial hexadactyly and symmetrical shortness of the long bones was noted. Histologically, there was too short a zone of cartilagineous columns in the metaphyses, a reduced number of chondrocytes and an irregularly structured spongiosa within the ossification zone. In addition, the fetus was found to have an atrio-ventricular canal. This heart defect is presumably rare in this syndrome. Other characteristic features such as small and dysplastic nails, sparse hair and abnormalities of the teeth were, of course, not yet present in this early developmental stage. In addition to EVC, the fetus had a 47,XXY chromosome constitution.

Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations.

We investigated 17 children with nephrotic syndrome (NS) of early onset (14 aged < 1 year) and rapid progression to end-stage renal disease for the presence of mutations in the Wilms' tumor suppressor gene WT1 on chromosome 11. In eight children (7 genotypic males) an association with Wilms' tumor and/or ambiguous genitalia (Denys-Drash syndrome) was observed. In these eight and two additional female patients with NS only constitutional missense mutations in the WT1 gene were detected; four children presented the so-called hot spot mutation in exon 9 (R394N) and six had different mutations in exons 8 and 9 (4 not previously described). Renal biopsy showed diffuse mesangial sclerosis in eight and focal segmental sclerosis in two cases. End-stage renal disease was reached either concomitantly or within four months after onset of NS in seven of ten patients. A unilateral Wilms' tumor was found before or concomitant with NS in four children (3 males, 1 female). From the seven genotypic males with WT1 mutations, five presented ambiguous genitalia and two a female phenotype. No mutation of the WT1 gene was found in seven other children with isolated congenital or infantile NS with or without DMS who appeared to have a slower progression than the first group. It is proposed that patients with early onset, rapidly progressive NS and diffuse mesangial or focal segmental sclerosis should be tested for WT1 mutations to identify those at risk for developing Wilms' tumor.

[Primary leiomyosarcoma in the left atrium--a rarity. Case report and literature review]. / Primäres Leiomyosarkom im linken Herzen--eine Rarität. Fallbeschreibung und Literaturübersicht.

The case presents a 61 year old woman which came into the hospital with left heart failure. After an unsuccessful trial to treat the heart failure in an habitual method the echocardiographic showed a mass lesion which had filled out mostly of the left atrium. Histological features demonstrated a leiomyosarcoma with an origin from the wall of the left atrium. Immunohistochemical preparations revealed a positivity for actin, desmin and vimentin. Despite an operative resection and an attach of polychemotherapy it developed a local relapse and multiple lymph node metastases. Within the scope of this case report apart from an detailed bibliography it ought to be discussed the origin of the tumor into the atrium and the differential diagnosis from other sarcoma.