The clinical impact of magnetic resonance imaging in fetuses with central nervous system anomalies on ultrasound scan.

OBJECTIVES: Magnetic resonance imaging (MRI) was performed on fetuses with sonographically diagnosed central nervous system (CNS) anomalies to determine frequency and type of cases in which fetal MRI adds clinically relevant information. PATIENTS AND METHODS: Forty-three cases presenting with CNS anomalies by ultrasonography were investigated by MRI. The potential effect of MRI on parental counseling and pre- or postnatal management were the main endpoints. RESULTS: Fetal MRI confirmed the sonographic diagnosis in 28 of 43 cases, showed additional findings in 14 of 43 cases, and was inferior to sonography in 1 of 43 cases. The MRI diagnosis had therapeutic consequences in 11 of 43 patients, with the fetal MRI diagnosis influencing parental counseling in 8 of these 11 patients. Prenatal patient care was not influenced by the additional investigation with fetal MRI. CONCLUSION: MRI is well suited as additional imaging method in fetuses with CNS anomalies. Additional fetal MRI is particularly indicated if the findings might have a therapeutic consequence.

Prenatal magnetic resonance imaging as a useful adjunctive to ultrasound-enhanced diagnosis in case of a giant foetal tumour of the neck.

Large cervical masses in the prenatal period are rare and can cause life threatening situations after birth. All available diagnostic techniques should therefore be used to determine the best mode of delivery in the case of such malformation. A large cervical mass was detected by ultrasound in a 41-year-old women, gravida 4, para 3, at 29 + 5 weeks of gestation. US imaging was most consistent with the diagnosis of a large cervical teratoma, but it was not possible to sufficiently evaluate the cervical anatomy of the oropharynx and trachea. An MRI scan demonstrated a distorted oropharynx and a trachea displaced to the right and posteriorly, but not detectable from the middle of the neck up to the larynx. Based on these facts, an EXIT procedure was planned and performed at 30 + 5 weeks of gestation. Foetal MRI provided valuable anatomical information for all specialists deciding on the indication and the pre-therapeutic planning of the EXIT procedure.

Prenatal diagnosis of the Meckel-Gruber syndrome from 11th to 20th gestational week.

INTRODUCTION: The Meckel-Gruber syndrome (MKS) is a rare autosomal recessive disorder that is characterized by typical sonographical findings: occipital encephalocele, postaxial polydactyly and cystic enlargement of the kidneys. Its recurrence risk of 25 % demands an exact diagnosis. METHOD: Retrospective analysis of the sonographic characteristics in relation to the gestational age in eight cases with the pathologic diagnosis of MKS. RESULTS: The sonographic characteristics depend on the gestational age. The classic trias was solely seen in the case diagnosed before 14 (th) week of gestation. In the other seven cases, diagnosed between the 17 (th) and 20 (th) week of gestational age, only two of three characteristic signs of MKS could be visualised by US. Polydactyly was missed by ultrasound in all seven cases due to the marked oligohydramnion. CONCLUSION: The Meckel-Gruber syndrome can be confidently detected and diagnosed by sonography at the 11th to 14th gestational week. Later in the pregnancy, severe oligohydramnion makes it more difficult to establish the diagnosis by US alone. In these cases a meticulous autopsy is necessary to establish the diagnosis of MKS.

Fetal skeletal deformities - the diagnostic accuracy of prenatal ultrasonography and fetal magnetic resonance imaging.

OBJECTIVE: To evaluate the diagnostic accuracy of prenatal ultrasonography and fetal magnetic resonance imaging (MRI) in fetuses with skeletal deformities (SD). METHODS: Fourteen pregnant women of 21 - 34 weeks of gestation whose fetuses had SD on prenatal ultrasound (seven fetuses with spina bifida, four with complex malformation syndrome, two with scoliosis, and one with chondrodysplasia) were additionally investigated by fetal MRI using a 1.5T superconducting system with T1-and T2-weighted sequences in three section-planes. Main outcome measures were diagnostic accuracy, potential effect on parental counselling and influence on perinatal management of the additional investigation with fetal MRI. RESULTS: In 10 cases ultrasound had a better diagnostic accuracy than MRI concerning the diagnosis of SD. In four cases with spina bifida MRI provided additional information towards preoperative evaluation for neurosurgery. In five cases parental counselling was improved. There was no influence on perinatal management. CONCLUSION: MRI may provide additional information to ultrasound scan in fetuses with spina bifida and consecutive neurosurgery; in fetuses with other skeletal deformities additional information may be expected only in rare cases.

Foetal facial clefts: prenatal evaluation of lip and primary palate by 2D and 3D ultrasound.

INTRODUCTION: To examine whether three-dimensional ultrasound (3D US) is an accurate diagnostic method of clinical use in the ability to define the location and extent of facial clefting prenatally, compared to two-dimensional ultrasound (2D US). METHODS: 18 foetuses suspected or diagnosed to suffer from a facial cleft by 2D US were examined with a targeted 3D US. 2D US and 3D US results were compared with postnatal outcome. RESULTS: Comparison of the number of foetuses with a cleft lip + primary palate diagnosed correctly with 2D US with the results of adjunctive 3D US (true positive + true negative) showed that adjunctive 3D US correctly diagnosed more cleft lips (100 %; 15/15 foetuses vs. 66 %; 12/18 foetuses) and more cleft primary palates (100 %; 12/12 foetuses vs. 58 %; 7/12 foetuses). CONCLUSION: Interactive review of standardised 3D multiplanar images allows to systematically evaluate lip defects and abnormalities of the maxillary tooth-bearing alveolar ridge. The accuracy of adjunctive 3D ultrasound is superior to 2D ultrasound alone for extensive prenatal diagnosis of cleft lip with or without cleft primary palate.

Prenatal diagnosis of a giant foetal lymphangioma and haemangiolymphoma in the second trimester using 2D and 3D ultrasound.

Lymphangiomas are benign tumours of the lymphatic system. Early prenatal diagnosis is important to permit a planned delivery and provide adequate postnatal care. It thereby improves prognosis and allows the option of terminating the pregnancy if poor outcome is predicted. We report two cases, a giant haemangiolymphoma and a lymphangioma. 2D and 3D US findings are presented and differential diagnosis, therapeutic options and prognosis are discussed.

Magnetic resonance imaging in foetuses with bilateral moderate ventriculomegaly and suspected anomaly of the corpus callosum on ultrasound scan.

OBJECTIVE: The diagnosis of anomalies of the corpus callosum (ACC) in foetuses with bilateral moderate ventriculomegaly (BMV) is difficult by means of ultrasound scan. The aim of this study was to examine the value of the additional investigation with magnetic resonance imaging (MRI) in foetuses with BMV and suspected ACC on ultrasound scan. Pathogenesis and clinical presentation of BMV and ACC are discussed. METHODS: 41 foetuses with central nervous system (CNS) anomalies on ultrasound scan were assessed by ultrasonography and MRI from 1999 to 2001. Eight of these 41 foetuses presented with BMV and suspected ACC on ultrasound scan and were prospectively included in the study. Foetal investigations with sonography and MRI were analysed with regard to diagnostic confidence; results were correlated with post partum findings. Six of these 41 foetuses presented with BMV without suspected ACC on ultrasound scan and were retrospectively analysed. RESULTS: Ultrasonography suspected ACC in 8 foetuses with BMV. MRI confirmed the presence of ACC in 4 of these 8 cases. MRI additionally showed ACC in two of the six retrospectively analysed foetuses with BMV without suspected ACC on ultrasound scan. Prenatal MRI diagnosis was confirmed after delivery in all cases. CONCLUSION: MRI is more sensitive than ultrasonography in the evaluation of ACC in foetuses with BMV. For prenatal screening ultrasound still remains the investigation of choice.

Prenatal diagnosis of a de novo inversion of chromosome (2)(p21q11).

Prenatal diagnosis of "apparently balanced" chromosomal rearrangements, if not inherited from a parent, are problematic for genetic counsellors and families. Although the parents need to be informed about the increased risk of multiple congenital anomalies, the anomalies that the fetus is at risk can not be discussed unless a similar breakpoint and accompanying phenotype have been reported in the literature. In the reported case prenatal ultrasound examination revealed a massive hydrocephalus internus and IUGR. The karyotype of the fetus was inv(2)(p21q11) de novo. Postmortem examination revealed short palpebral fissures, hypertelorism, atypical nasiolabial configuration, microgenia, extended position of the fingers, atypical proximal inserted first toe, hydrocephalus internus, hypoplasia of the cerebellum and bulbi olfactorii, bilateral hypoplastic lungs, atrial septal defect II, small right ventricle, dysplasia of the pulmonary valve, hypoplastic pulmonary artery, right proximal ureterostenosis, hypoplastic gall bladder. This is the first description of a de novo inversion (2)(p21q11) in a fetus with multiple malformations.

Fetal ovarian cysts: development and neonatal outcome.

INTRODUCTION: The aim of the study was to evaluate the outcome of fetal ovarian cysts in relation to their size and ultrasonic appearance. METHODS: We retrospectively analysed pre- and postnatal charts of 61 infants with a prenatal diagnosis of ovarian cysts between 1991 and 2000. RESULTS: In a total of 61 fetuses 65 ovarian cysts were detected by transabdominal ultrasound: 35 (57 %) cysts on the left side, 22 (36 %) on the right side and 4 fetuses (7 %) had bilateral cysts. Three patients with uncomplicated cysts were lost to follow-up and one fetus with bilateral cysts died in the 27th week of gestation. In 17 cysts treatment was necessary. 14 cysts (all complicated) were operated after delivery because of persistence or enlargement. The histological results were either follicular or theca lutein cysts in 12 cases, one lymphangioma and one teratoma. Two cysts were aspirated in utero and one after delivery. In the remaining 40 fetuses, 43 cysts where only controlled by ultrasound. 8 cysts regressed before delivery and 35 cysts after delivery independent of their sonographic appearance. The mean diameter of cysts that required treatment was significantly different from the mean diameter of cysts that resolved spontaneously (6.8 [SD 2.4] cm vs. 3.3 [SD 0.8] cm; p < 0.01). CONCLUSION: Complicated cysts which do not regress should be treated either by laparotomy or laparoscopically after delivery. Uncomplicated cysts which exceed 5 cm could be treated by in utero aspiration or aspiration after delivery to avoid further complications. Cysts smaller than 5 cm, presenting the tendency to regress, should be left untouched independent of their sonographic appearance.

Incidence and tumour stages of breast cancer in the region of Aachen, Germany.

We present epidemiological data of female breast cancer in the region of Aachen (Germany) including incidence and tumour stages for the period 1996-1997. Furthermore, we compare epidemiological data from Aachen with data from the directly neighbouring Dutch region South-Middle Limburg before and after the introduction of a national mammographic screening programme. The field study of breast cancer was undertaken at the Institute of Pathology and Comprehensive Cancer Center at the University of Aachen, supported by the Federal Ministry of Health (Germany), using data files from the Cancer Registry Aachen. The patient's consent to collect all data concerning her epidemiological and social situation as well as information on the outcome of disease was obtained in 83.4% of all cases. The remaining 16.6% of the cases without a patient's consent are based on histopathological reports. Only those patients are included who were documented as residing in the region of Aachen at the time of diagnosis. Tumour cases were counted according to International Agency for Research on Cancer rules and tumour stages are classified according to UICC guidelines. Incidence rates are calculated as crude value, adapted to the European and World Standard population (ESR, WSR), and the age specific incidence is presented in 5-year intervals. The cumulative risk is assessed for a certain life span by summarizing the age-specific incidences. The age-standardized breast cancer incidence rate in Aachen was 94 per 100 000 women in 1996 and 90 cases of invasive breast cancer per 100 000 women in 1997 according to the ESR. The cumulative risk of developing breast cancer in the life span ranging from 0 to 74 years is approximately 8%. The stage distribution of breast cancer reveals only 4% favourable carcinomata in situ, but 12% advanced T4 tumours. T1 and T2 tumour stages count for about 40% and T3 tumour stages about 4%. Incidence rates and the tumour stages of breast cancer in the region of Aachen during 1996 and 1997 are similar to the data obtained from the directly neighbouring Cancer Center of the region South-Middle Limburg, in the Netherlands, in 1989/1990 before the beginning of the national breast cancer screening programme. However, major differences are found in terms of the incidence and the tumour stages between Aachen 1996/1997 and South-Middle Limburg 1995/1996 after the introduction of the mammographic screening. The incidence of female breast cancer in Aachen, Germany, was high and in the range of the data from other cancer registries in Europe without national screening programmes. The tumour stages at diagnosis in Aachen were not very favourable, especially in elderly women. An increase of the cancer incidence and a shift of the tumour stages to more favourable ones were observed in the neighbouring Dutch region of South-Middle Limburg, comparing data from 1989/90 and 1995/96. This is probably as a result of the national mammographic screening programme. As data from Aachen were similar to Limburg's data from 1989/90 before the mammographic screening was introduced, it will be important to follow and compare the cancer incidence and the tumour stages in the future.

Inhibition of TNF-alpha induced cell death in human umbilical vein endothelial cells and Jurkat cells by protocatechuic acid.

The Chinese herb radix Salviae miltiorrhizae (RSM) is used in traditional Chinese medicine as a treatment for cardiovascular and cerebrovascular diseases. Several components of the plant extract from salvia mitorrhiza bunge have been determined previously, one of which is protocatechuic acid (PAC). It has been found, in the study, that PAC inhibited TNF-alpha-induced cell death of human umbilical vein endothelial cells (HUVECs) and Jurkat cells in a concentration of 100 microM when applied 2 h prior to TNF-alpha exposure. Molecular studies revealed that PAC activated NF-kappaB with a maximum effect after 30 min of treatment. Inhibition of NF-kappaB action by MG132 and NF-kappaB inhibitory peptide suppressed the cell-protective effect of PAC. Further, degradation of IkBalpha occurred in response to PAC treatment. The results provide evidence that activation of NF-kappaB plays an important role in mediating the cell-protecting effect of PAC on HUVECs and Jurkat cells. Further studies are required to test whether PAC, a component of radix salviae miltiorrhizae, could be useful in preventing in vivo cell death resulting from cardiovascular or cerebrovascular diseases.

[Pathology of implants]. / Pathologie der Implantate.

Progress in the surgery of implants and biomaterials can be accomplished by: 1. Painstakingly analysing and registering of defaulting implants after explantation within a "National Registry of Implant Pathology". 2. Development of a DNA-microarray named "Implantat/Chronic Wound" in order to discover the differential transcriptional activities of cells brought into contact with different foreign surfaces. 3. Predictive cell-engineering combined with custom-made implant surfaces with the aim of optimal patient care.

Benign solitary fibrous pleural tumour. Evidence of primitive features and complex genomic imbalances, including loss of 20q.

AIMS: Cytogenetic data on solitary fibrous tumours (SFT) are very limited. We studied a benign pleural SFT for its ultrastructural and immunohistochemical details, and made cytogenetic analyses for comparison with other genetic and ultrastructural studies of SFT. RESULTS: Immunohistochemistry showed strong positivities for CD34 and vimentin, but no reactions with anti-cytokeratins and epithelial membrane antigens. Electron microscopy revealed primitive desmosomes in our SFT. The results thus evinced fibroblast-like cells with intermediate epithelial-mesenchymal character. Comparative genomic hybridization of the tumour revealed losses of 1p33-->pter, 17pter q21, entire copies of chromosomes 19 and 22, and gains of 1p21-p22, 2q23-q32.3, 3pl2-q13.2, 4p14-q28, 6p12-q21, 9p21-->pter and 13q21-q31. Furthermore, there was loss of 20q, as was previously reported elsewhere in a case of benign and a case of malignant SFT. CONCLUSIONS: The results furnish further evidence of the involvement of -20q in SFT. In addition, they show that SFT may have complex genomic imbalances and primitive features, despite having a benign appearance.

[Is disease grounded in the mind, the spirit or communication? Pathology as a leading path in learning about disease]. / Ist Krankheit begründet in Materie, Geist oder Kommunikation? Die Pathologie als Wegweiserin in der Krankheitslehre.

What is the reason, why pathology could command a dominating position as a central teaching discipline in the last 150 years? Furthermore: can this position be maintained in the future? Pathology takes its definitive stand in the philosophic confrontation of "Mind" versus "Matter". It guards the dogma of Morgagni: every disease is reflected by its typical morphological substrate. As long as this dogma is guarded and defended by the discipline of pathology, we will stay at the helm of teaching in medicine. Recently information as a third reality (besides mind and matter) has come into existence. Information is defined here as genomic information specifically the differentially activated functional genomics. In extension to the old dogma of Morgagni we recognize now an extension to "functional" diseases where we do not (yet) find a pathological anatomical manifestation. In these cases "information" is defined as differences in physical states. They can be converted to information in the sense of meaning and purpose by communication. Pathology provides the bridge between functional genomics and morphological manifestations of diseases (phenomics). The future of pathology is based on the amalgamation of the old and reliable Morgagni-Virchow dogma with the new informational dogma. If pathology provides sense, meaning and significance to phenomics, morphology in relation to functional genomics it will retain and even enlarge its influence as the most important teaching discipline in medicine.

Von Willebrand's factor mediates the adherence of human tumoral cells to human endothelial cells and ticlopidine interferes with this effect.

The aim of this study was to explore whether von Willebrand's factor (vWF) plays a role in the adhesion of human colon tumor cells to human endothelial cells in our coculture system. Cell colony density was evaluated basally (endothelial plus colon tumor cells) and following the addition of: purified vWF, vWF plus vWF-blocking antibodies, antibodies against various integrins and adhesion molecules (alpha2 b integrin, beta1 integrin, beta3 integrin, intercellular adhesion molecule-I, intercellular adhesion molecule-II, vitronectin receptor CD61 CD51, laminin alpha6/beta4 receptor), and various drugs inhibiting the hemostatic system (ticlopidine, heparin, acetyl salicylic acid [ASA], defibrotide, indobuphen, dipyridamole, sulfinpyrazone). Furthermore, vWF concentration was measured in the supernatant fluid of the coculture system basally and following the addition of the above-listed drugs. Cell colony density (as measured by light absorption) increased by 33% following the addition of vWF and returned to a value similar to the basal level with antibodies against vWF, while it did not change significantly following the addition of antibodies against the other integrins or adhesion molecules tested. The same parameter was reduced by 35% following the addition of ticlopidine, while it showed a smaller or no change with the other drugs tested. Similarly, vWF concentration in the cell coculture supernatant showed the greatest reduction (from 0.22 to 0.11 mg/mL) following the addition of ticlopidine. These data suggest that vWF mediates the adherence of human tumor cells to human endothelial cells and that ticlopidine interferes with this effect.

[Expanded, radical perineal prostatectomy]. / Die erweiterte, radikale perineale Prostatektomie.

One hundred and twenty-five consecutive patients with prostate cancer underwent an extended, radical perineal prostatectomy according to the technique described by VE Weldon. This technique was modified by an initial complete mobilization of the posterior aspect of the prostate and seminal vesicles from the rectum and pelvic wall, incision of the endopelvic fascia, and partial resection of the dorsal vein complex after suture ligature. The perioperative morbidity was low. An operative revision was necessary in four (3.2%) patients because of arterial bleeding from a drainage channel (n = 1), wound infection (n = 2), and rectocutaneous fistula (n = 1). The in-dwelling catheter was removed on day 4-8 in 104 (83%) patients. Positive surgical margins were diagnosed in 22 (17.6%) patients only. These patients had pT3 (n = 17) and pT4 (n = 5) tumors with a Gleason score > or = 7 (n = 17) mostly; extensive, multifocal capsular penetration (n = 18); seminal vesicle invasion (n = 11); and lymph node metastases (n = 4). The unifocal positive margins were localized at the apex (n = 3), dorsolateral (n = 6) aspect, and bladder neck (n = 4). In nine patients, multifocal positive surgical margins were noted. The risk for a positive surgical margin depends on the serum PSA level, Gleason score, and tumor volume. In case potency preservation is not considered, the extended, radical perineal prostatectomy with the above mentioned modifications should be considered to guarantee a low rate of surgical margins.

Expression of heat shock proteins 72/73 in human peritoneal mesothelial cells in vivo and in vitro.

Leukocyte accumulation during peritonitis leads to an injurious microenvironment which is involved in the host defense reaction but is also thought to cause peritoneal damage. We tested the hypothesis that mesothelial cells (MC) respond to the injurious microenvironment during peritonitis by an increased expression of heat shock proteins (HSP 72/73), a basic way by which cells are protected against injury. Comparison of resting MC and activated MC during peritonitis in vivo by means of immunohistochemistry revealed an increased expression of HSP 72/73. As assessed by Western immunoblotting, incubation of MC in vitro with tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) caused a time-dependent induction of HSP 72/73 expression, which was maximal 6 h after stimulation. We suggest that the increased HSP 72/73 expression of MC during peritonitis is in part induced by TNF-alpha and IL-1beta and may exert a cell-protective function, lessening MC damage during peritonitis.