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Testicular germ cell tumours (GCTs) are the most frequent solid malignancy in younger males aged 15-40. The differentiation between seminomas and non-seminomas impacts prognosis, clinical management and follow-up procedures. With stage- and risk-adapted multimodal treatment approaches, GCTs have an exceptionally good prognosis. Therefore, avoiding overtreatment to reduce treatment-related long-term side effects is of utmost importance. Clinical and histopathological risk factors aid in treatment decision-making.Discussion of (histo-)pathological characteristics that directly influence treatment decision-making by urologists and oncologists.Non-systematic literature review to describe histopathological features for interdisciplinary treatment planning.Key histopathological characteristics for clinicians are: (i) identification of a GCT, if necessary by 12p aberration analysis, (ii) description of the different subtypes, and (iii) risk factors, including lymphovascular invasion and/or rete testis infiltration and size of the primary tumour. Molecular pathological analyses, that is, genomic sequencing, is not part of routine diagnostics due to the lack of prognostic/predictive markers and effective targeted treatment approaches.Detailed histopathology reporting, ideally with a synoptic template, is the basis for planning and conducting guideline-endorsed, risk-adapted, multi-disciplinary management of GCTs. Along with radiographic imaging and assessment of the serum tumour markers AFP and β‑HCG (especially in non-seminomas), histopathology is crucial to maintain success and reduce the burden of GCT treatment.HINTERGRUND: Keimzelltumoren des Hodens sind die häufigste maligne Tumorerkrankung bei Männern im Alter von 15–40 Jahren. Die Unterscheidung von Seminomen und Nichtseminomen hat prognostische Bedeutung und ist für Therapieplanung und Nachsorge essenziell. Durch interdisziplinäre, stadiengerechte Therapie haben Keimzelltumoren generell eine sehr gute Prognose. Eine Übertherapie sollte wegen möglicher Langzeitfolgen vermieden werden. Hierbei hilft die Risikobeurteilung anhand klinischer und pathologischer Faktoren.Darstellung der (histo-)pathologischen Charakteristika, die die uroonkologische Therapieplanung maßgeblich beeinflussen.Nichtsystematischer Übersichtsartikel über die relevanten (histo-)pathologischen Befunde für die klinische Therapieplanung im interdisziplinären Kontext.Zentrale Pathologiebefunde für Kliniker:Innen sind: (i) Identifikation eines Keimzelltumors, ggf. durch Nachweis eines Chromosom-12p-Zugewinns, (ii) Subtypenspezifizierung und (iii) Angabe von Risikofaktoren (insbesondere Invasion von Lymphgefäßen und/oder Rete testis und Tumorgröße). Molekularpathologische Untersuchungen i. S. von Mutationsanalysen sind angesichts einer sehr geringen Mutationslast und bislang fehlender prädiktiver Marker und zielgerichteter Therapieoptionen nicht Teil der Routinediagnostik.Ein detaillierter, idealerweise synoptischer histopathologischer Befundbericht ist Grundlage der Planung und Durchführung einer leitlinienkonformen, risikoadaptierten Therapie und neben der bildgebenden Diagnostik und der Bestimmung der Serumtumormarker AFP und β‑HCG (letztere insbesondere bei Nichtseminomen) mitentscheidend, um die guten Heilungsaussichten zu wahren und eine Übertherapie zu vermeiden.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer death worldwide. The incidence continues to rise and only a detailed surveillance of patients with chronic liver disease can allow an early assessment. Diagnosis is made by imaging techniques, such as contrast-enhanced ultrasound (CEUS), computed tomography (CT), magnetic resonance imaging (MRI) and also histopathological examination of biopsy material. The determination of the tumor marker alpha fetoprotein (AFP) is no longer established for early detection but can be used as a supplement in addition in HCC history progressio.

Painless scrotal swelling must always be considered as a potential malignant testicular tumour until proven otherwise. Prepubertal testicular tumours are seldom entities, for their differential diagnosis testicular sonography is gaining increasing importance. Although, according to national and international tumour registries, most patients tend to have malignant tumours, some clinical series from paediatric centres confirm that prepubertal testicular tumours are mainly benign lesions, especially up to the age of 12 years. Testis-sparing procedures are favoured when AFP is in a normal range and testicular parenchyma is detected sonographically. Oncological principles should be applied to paediatric patients consequently, staging examinations should be requested when a definite histology is proven. Cases should be reported to national tumour registries and, in addition to close surveillance, in some cases adjuvant therapy is necessary. In addition to the clinical guidelines from the tumour registries, differential diagnosis, testis-sparing surgery and the presence of TIN in the paediatric population should be discussed.

Testicular cancer is the most frequent cancer in patients between 20 and 40 years of age. Cure rates are very high due to standardised operative treatment as well as additional chemotherapy and radiotherapy according to -histological subtype and tumour stage. Histological subtypes are seminoma, non-seminoma and mixed tumours (partly seminoma and partly non-seminoma). The aim of this study was to determine the value of different tumour markers in the primary diagnosis of testicular cancer.In a retrospective study we investigated 152 consecutive patients with testicular cancer as well as 75 patients with benign scrotal conditions. In all patients the tumour markers human alkaline phosphatase (hPLAP), alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and the enzyme lactate dehydrogenase (LDH) were measured. Statistical analyses included descriptive analysis, boxplots, fourfold table, receiver operating characteristic (ROC), calculation of confidence intervals and analysis of variance (ANOVA).145 patients with a mean age of 34.3 years were eligible. There were 72 seminomas, 33 non-seminomas and 40 mixed tumours with 69% of patients being in Lugano stage I, 19% in stage II and 11% in stage III. hPLAP, AFP and hCG were statistically significantly higher in patients with testicular cancer compared to patients with benign scrotal conditions (p0.005). hPLAP showed the best sensitivity/specificity (51.1%/84.0%) followed by AFP (35.7%/97.1%), hCG (32.6%/98.6%) and LDH (31.4%/97.8%). ROC analysis demonstrated no difference between hPLAP, AFP and hCG in the specificity range of 80-100%. However, a combination of hPLAP, AFP and hCG provided statistically significantly better results than single markers (p0.001).hPLAP is the most often elevated marker in the serum of patients with testicular cancer and potentially demonstrates a significant benefit for therapy monitoring. In our opinion there is a need to debate the consideration of hPLAP in the usual guide-lines of the cancer societies. The unspecific elevation in smokers must be considered. In this regard, reference values of hPLAP depending on smoking habits could be a solution, but valid data are not yet available.

The prognosis of untreated advanced hepatocellular carcinoma (HCC) is grim with a median survival of less than 6 months. Spontaneous regression of HCC has been defined as the disappearance of the hepatic lesions in the absence of any specific therapy. The spontaneous regression of a very large HCC is very rare and limited data is available in the English literature. We describe spontaneous regression of hepatocellular carcinoma in a 65-year-old male who presented to our clinic with vague abdominal pain and weight loss of two months duration. He was found to have multiple hepatic lesions with elevation of serum alpha-fetoprotein (AFP) level to 6,500 µg/L (normal, GMS German Medical Science; 9:Doc07; ISSN 1612-3174

A high rate of recurrence after primary resection is common to all tumor entities discussed here. However, there is no scientific evidence that regular surveillance after primary surgery changes the natural course of disease. Nevertheless, patients with hepatocellular carcinoma and a subgroup of patients suffering from other non-colorectal gastrointestinal tumors may benefit from selected follow-up examinations. This manuscript gives some practical guidance on how to individually follow these patients after primary tumor resection.

Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed tumour diseases throughout the world. In the vast majority of cases those affected are high-risk patients with chronic viral hepatitis and/or liver cirrhosis, which means there is a clearly identifiable target group for HCC screening. With resection, transplantation, and interventional procedures for local ablation, following early diagnosis curative treatment options are available with which 5-year survival rates of over 60% can be reached. Such early diagnosis is a reality only in a minority of patients, however, and in the majority of cases the disease is already in an advanced stage at diagnosis. One of the objects of HCC screening is diagnosis in an early stage when curative treatment is still possible. Precisely this is achieved by screening, so that the proportion of patients treated with curative intent is decisively higher. There is not yet any clear evidence as to whether this leads to a lowering of the mortality of HCC. As lower mortality is the decisive indicator of success for a screening programme the benefit of HCC screening has so far been neither documented nor refuted. Nonetheless, in large regions of the world it is the practice for high-risk patients to undergo HCC screening in the form of twice-yearly ultrasound examination and determination of AFP.

Sertoli cell tumors of the testis are extremely rare (0.4-1.5% of all testicular neoplasms) and have a heterogeneous pathology. Histopathologically classic, large cell calcifying and sclerosing subtypes are differentiated.Up to now, 14 cases of sclerosing Sertoli cell tumor are known. This article presents a new case and compares the three subtypes. The subtypes differ in particular in age of onset, malignant potential, prognosis, and therapy. While no cases of sclerosing Sertoli cell tumor with a malignant course have been reported, both other subtypes have been found to be potentially malignant. In the case of malignancy the prognosis is very poor, and it is difficult to select the best treatment because there is so little experience with this type of tumor. Once the diagnosis of a Sertoli cell tumor has been confirmed, exact determination of the histological subtype is essential to allow appropriate risk-adapted therapy. The various histological subtypes are presented with the clinical features, prognosis and treatment of each.

In cases of penetrating stab wounds by different knives it is highly relevant to prove which knife caused which injury, especially if one of the injuries was lethal. This is possible by immunocytochemical examination of cellular material remaining on the injuring blade because some organs have organ-specific antigen determinants such as alpha-l-fetoprotein in the liver cells or cardiac troponin I in the heart muscle cells, to which antibodies can bind. Even when penetrations occur through several layers of clothing, enough cells from the injured organ remain on the blade of a knife to allow immunohistochemical examination. These cells can be collected by means of adhesive film or wiping the blade and can be stained immunocytochemically. The organ specificity of the examined proteins allows proof of their origin. The present study shows that immunocytochemical alpha-l-fetoprotein and cardiac troponin I staining of the cells remaining on a knife blade enables proof of whether the knife blade injured the heart or the liver, or both.

Calcific aortic valve disease is present in more than 25% of patients65 years of age and is associated with a 50% increased risk of cardiovascular events. The clinical significance of aortic valve calcification detected incidentally by radiologic examinations, especially on CT scans of the chest, was unknown. Concerning the multifactorial pathogenesis of aortic valve calcification, recent data indicate that, besides other factors, also the regulators of calcification play a key role in the disease process.This study aims to give an overview of the prevalence and clinical significance of incidentally detected aortic valve calcifications. Moreover, the role calcification inhibitors in the pathogenesis of aortic valve calcification is discussed.

Despite the introduction of NTBC into the treatment of tyrosinaemia type I (TT1) and a considerable improvement in the outcome of these patients, the principal risk of developing hepatocellular carcinoma (HCC) in this metabolic disorder remains mainly in those children with late introduction of NBTC after the second year of life. Serial total alpha-Fetoprotein (AFP) levels are used to evaluate the individual risk to develop malignant changes. A failure of AFP to decrease on adaequate treatment or a secondary increase after a period of falling levels have been an indication for liver transplantation. Lectin-reactive alpha-Fetoprotein is a recently described marker to distinguish hepatocellular carcinoma from benign liver disease in adult cirrhotic patients.To investigate if the analysis for Lectin-reactive alpha-Fetoprotein would lead to earlier detection of HCC compared to a judgement based on the evolution of standard total AFP alone.We report the analysis of 12 patients with TTI and histologically proven HCC. There of 5 were diagnosed under one year of age, but NTBC treatment was started between 2 years 3 month and 7 years of age except in one case in which NTBC was introduced when the diagnosis of TTI was made. The remainder of the patients cover up to the age of 15 years. All patients had been treated with NTBC.Lectin containing agarose gel for AFP electrophoresis leads to AFP separation according to different affinities of the varying carbohydrate chains of AFP to lectins.AFP subfractions could be identified in all 12 patients. In 6 patients the L3-AFP rose before the total AFP. In 3 patients the rise in L3-AFP was consistent with the rise of the total AFP and in 3 patients the L3-AFP was raised after the total AFP or did not increase at all.We were able to identify 6 out of 12 patients who had an early increase of L3-AFP before they developed a change in total AFP levels. The clinical significance of these early changes need to be determined. Lectin-affinity electrophoresis may have a potential role as an additional tool that may help to discriminate benign liver disease from HCC in TTI.We suggest the further evaluation of lectin-reactive AFP in TTI.

The sonographic measurement of the nuchal translucency is already regarded as the most valuable screening parameter for chromosomal anomalies. Beside standardised examinations profound information and counselling of the pregnant women should be emphasised. With the improvement of the specific maternal risk calculation using the sonographic measurement of the nuchal translucency, the biochemical markers and the maternal age, unnecessary invasive examinations may be prevented and their overall number can be reduced significantly.

To assess the ability of [(18)F]FDG-PET, CT/MRI and serum tumor marker (TM) for the early prediction of response in patients with metastatic germ cell tumors (GCT) undergoing salvage high-dose chemotherapy (HD-CTX).Before commencement of HD-CTX, 19 patients with metastases from GCT were evaluated with [(18)F]FDG-PET, CT or MRI and TM after 2-3 cycles of induction chemotherapy and the results compared with those of the baseline examinations. PET was analyzed visually and quantitatively by calculating the standard uptake value (SUV). CT or MRI was evaluated for changes in tumor size (progressive disease/stable disease PD/SD = viable lesion; partial remission/complete remission PR/CR = nonviable lesion), density or signal intensity, homogeneity and contrast enhancement. For the prognosis, the worse case, i.e., the most vital lesion detected in a patient, was considered. The reference standard was the result of the histology after resection of any residual masses (N = 10) and/or the clinical-radiological follow-up for at least 6 months after completion of the treatment (N = 9).Six of nineteen patients (32 %) remained progression-free for over 6 months following treatment, whereas 13 (68 %) progressed. The outcome of HD-CTX was correctly predicted by PET, CT and TM in 89 %, 67 % and 88 %, respectively. In 5 of 6 patients with successful HD-CTX, PET was negative (mean SUV = 1.8), with CT or MRI showing a partial regression of the tumor in 4 of 5 patients. Of the 13 patients not cured by HD-CTX, the PET data were positive in all (mean SUV = 2.7), and the CT/MRI results were true positive (PD or SD) in 8 and false negative (PR) in 5 patients. The combined assessment of CT and TM corrected 3 false negative prognoses and 1 false positive CT prognosis. Two patients with unfavorable outcome despite a favorable response by CT and TM criteria were exclusively identified by PET. The resultant sensitivities and specificities for the prediction of therapy response are as follows: PET 100% and 67%; CT/MRI 62% and 80%; TM 83% and 100%; CT+TM 85% and 83%.FDG-PET has a high prognostic value for predicting the response to chemotherapy in patients with metastatic GCT early in the course of treatment and may improve patient selection for subsequent HD-CTX protocols. Especially in patients with response to induction chemotherapy according to CT or TM evaluation, PET offers additional information to detect patients with an overall unfavorable outcome.

A 27-year-old, previously healthy man with abdominal discomfort was diagnosed with a small gastric tumor of the cardia by means of gastroscopy. Further staging revealed diffuse hepatic metastases and enlarged mediastinal lymph nodes. Serum alpha-fetoprotein (AFP) was grossly increased (7179 micro g/l). Biopsies taken from the gastric tumor and one of the hepatic metastases revealed a poorly differentiated adenocarcinoma (grade 3) with papillary and small solid areas and frequent clear cells. Cytoplasmic hyaline droplets were positive with PAS staining (diastase-resistant). Immunohistochemistry revealed focal tumor cells strongly positive for AFP and there was luminal expression of CEA. The diagnosis of an AFP-producing adenocarcinoma of the stomach was made. In spite of intensive combination chemotherapy the patient succumbed to his disease 3 months after diagnosis. The rare AFP-producing adenocarcinoma of the stomach is characterised by a distinct morphology and immunohistochemistry. A hepatoid differentiation may occur but is not obligatory as this case shows. In differential diagnosis, a metastasising germ cell tumor should be excluded. The prognosis for an AFP-positive adenocarcinoma is poor.

The recent discovery of heretofore unknown, multipotential stem cells within the embryonic and adult islets of Langerhans suggests new therapeutic options for the treatment of diabetes mellitus type 1. These cells are characterised by the expression of the neural stem cell marker nestin and by their ability to differentiate ex vivo into pancreatic endocrine, exocrine and hepatic phenotypes with the expression of insulin, glucagon, amylase, cytokeratin-19 as well as liver specific proteins such as alpha-fetoprotein. The insulinotropic hormone glucagon-like peptide-1 enhances the differentiation of these nestin positive islet derived progenitor (NIP) cells into insulin secreting cells by activation of IDX-1, the key transcription factor for the differentiation into a beta-cell.

The failure to reduce the mortality of patients with malignant liver tumors (hepatocellular carcinoma, cholangiocarcinoma) is probably a result of the early dissemination of cancer cells to secondary sites, which is usually missed by conventional diagnostic procedures used for tumor staging. Recent developments in the field of molecular biology enable us to detect tumor cells at a submicroscopic level. Therefore, over the past 10 years, sensitive assays have been developed to detect individual carcinoma cells disseminated to regional lymph nodes or distant organs. In contrast to colorectal and also breast cancer where disseminated tumor cells may be of additional prognostic value, few data exist for hepatocellular carcinomas. Until now, no relevant studies have been reported for cholangiocarcinoma. Alpha-fetoprotein and also albumin mRNA have been used for the detection of circulating micrometastatic tumor foci of hepatocellular carcinoma (HCC); however, the interpretation of the results has been equivocal. If hepatocyte-specific mRNAs are detected in the circulation, it is possible to infer the presence of circulating, presumably malignant, liver cells. The literature about the incidence of "micrometastases" and specificity of different assays for hepatocellular carcinomas varies tremendously. This clearly indicates the need for uniformity in protocols. For hepatocellular carcinoma, mRNA for alpha-fetoprotein and albumin is not a specific marker of circulating micrometastases, but may serve for treatment monitoring. Nevertheless, PCR-based techniques are a powerful tool in the therapeutical monitoring of hepatocellular carcinoma and will find their way into the daily practice of diagnostic histopathologists in the near future.

High AFP level (386.9 ng/ml) at the 16th gestational week in a 23-year old pregnant woman was observed. Fetal malformations or maternal causes could not be detected. Monitoring of fetal development and that of the fetal heart rate showed a worsening intrauterine growth retardation (IUGR). Due to the chronic hypoxia and IUGR cesarean section was performed in the 32nd gestational week and a 960 g female newborn was delivered. Histological examination of the placenta showed signs of maternal floor infarct (MFI): intervillous fibrin netlike deposition with the increase of extravillous trophoblast (X cells) and septal cystic formation. High unexplained AFP level and IUGR can draw attention to the possibility of intrauterine fetal demise, which indicates intensive intrauterine fetal monitoring.

Elevation of alphafetoprotein in pregnancy warrants a thorough diagnostic workup. In most cases, no pathologic result in the fetus will be obtained.A case report is presented on a hepatocellular carcinoma (HCC) during pregnancy, in which a massive increase of alpha-fetoprotein (AFP) was found during a routine screening for neural tube defects in the 17th week of gestation. The amniocentesis revealed a normal AFP value in the amniotic fluid. Liver sonography in the 21st week of gestation showed a 5 cm tumor, which was interpreted as nodular focal hyperplasia. In the control sonography in the 32nd week of gestation, there was a growth to 12 cm. The subsequently performed magnetic resonance imaging (MRI) and fine needle aspiration led to the diagnosis of a HCC. Delivery was performed in the 34th week of gestation by cesarean section followed by surgical therapy of the HCC.Unexplained cases of alphafetoproteinelevation in pregnancy can be caused by maternal disease and should prompt a directed amnamnestic and diagnostic search for maternal causes. Nuclear magnetic resonance beyond the first trimester of gestation can help to clarify the diagnosis in liver tumors.

We analyzed 33 patients with disseminated germ cell tumors (GCT) who underwent residual tumor resection (RTR) during the period from 1991-1997. The patients were marker positive prior to surgery were analyzed. The histopathological examination of the resected masses, the marker dynamics and the relapse-free respectively the progression free survival, were evaluated. The status differed at primary diagnosis: minimal disease n = 1, moderate disease n = 15, advanced disease n = 17. The patients received at average 8.5 cisplatin-containing cycles of polychemotherapy. Only 11 patients underwent surgery after first-line-chemotherapy. The remaining received second- or third-line-chemotherapy prior to surgery. In 12 of 31 evaluable patients, a durable CR was achieved. The median follow-up for this group is 30 months (2-58 months). The histopathologic examination of the resected specimen and the tumor marker level prior to RTR do not permit determination of prognostic outcome. After operation 44% of the AFP-positive and 30% of the beta-HCG-positive patients had a durable remission. If tumor marker levels at time of RTR are within normal range, disease-free survival is 72%; in case of elevated markers 39% will survive. If intensive chemotherapy fails to normalize markers, RTR remains the only option to change the fatal course of the disease.

Primary intracranial germ cell tumors are rare neurological diseases. Secreting germ cell tumors that predominantly appear in the pineal region are characterized by elevated levels of beta-HCG and AFP in CSF. Adequate diagnostic and therapeutic regimens of these tumors are still under debate. We present the case of a patient suffering from spinal metastasis of a secreting germ cell tumor with raised levels of beta-HCG in CSF. Six years before, a pineocytoma of intermediate differentiation had been diagnosed by stereotaxic biopsy. This demonstrates the importance of an early detection of a germ cell neoplasm in case of midline-sized brain-tumors by evaluation of beta-HCG and AFP in CSF and serum. Today, different therapeutic strategies depending on the histological diagnosis are available and justify a high priority of a surgical tumor biopsy. However, the value of stereotaxic procedures remains controversial. Recently published data gave evidence of a definite improved prognosis of secreting CNS germ cell tumors following combined treatment with high-dose polychemotherapy, surgical resection and radiation of the tumor area. beta-HCG and AFP may serve as useful markers to enable follow-up of the disease.

Chronic hepatitis C and B are the main causes of hepatocellular carcinoma (HCC) worldwide. Little is known about the etiology of HCC in Germany which is regarded as a low-prevalence area for viral hepatitis C (HCV) and B (HBV). To assess the etiologic factors of HCC in Germany we have retrospectively analyzed the records of 100 consecutive patients with hepatocellular carcinoma in our clinic. HCC-patients with documented status on HCV/HBV-infection and daily alcohol intake (n = 55) had HCV antibodies in 53%, HBs-Ag in 20%, isolated chronic alcohol abuse in 11% and genetic hemochromatosis in 2%. In 13% of the HCC-patients no risk factor could be identified. Coinfections with HCV and HBV were not observed. Liver cirrhosis was present in 90% of the HCC-patients. In histologically confirmed HCC (n = 71) serum alpha-fetoprotein level was normal (8.5 ng/ml) in 20%, moderately elevated (8.5-300 ng/ml) in 48% and considerably elevated (300 ng/ml) in 32% of the patients. Only 31% of all patients presented with small single lesions (or = 5 cm) without evidence for extrahepatic metastases or portal vein thrombosis. Only 30% of the HCC-patients could be treated with a curative intention (28 hepatic resections, one orthotopic liver transplantation). Patients who underwent resection had cumulative 6-month, 1-year, 2-year and 3-year survival rates of 83.8%, 65.9%, 54.3% and 24.8% respectively. Median survival time after resection was 24.8 months compared with 5.8 months in symptomatically treated patients with unresectable HCC (n = 39). Patients with hepatitis C-associated HCC were significantly older than patients with hepatitis B-associated HCC (mean values: 63.2 vs. 54.2 years). Frequency of cirrhosis, tumor stage, alpha-fetoprotein level and prognosis did not differ between groups. In conclusion hepatocellular carcinoma was predominantly associated with chronic HCV-infection. Most patients presented with normal or moderately elevated serum AFP-levels. Prognosis was poor even after hepatic resection.

Since 1991 the measurement of 3 biochemical parameters for the risk assessment of trisomy 21 pregnancy (AFPplus, Alpha-check) is also offered by private laboratories in Switzerland. This work aimed at the proof of reliability of this risk analysis in the hands of practitioners and private laboratories. The investigated cohort included 2,641 pregnant women. An anonymous questionnaire on the outcome of pregnancy furnished informations in 97% of cases (2,561 cases). At a trisomy 21 risk cutoff of one to 380, 9% of the pregnant women had conspicuous AFPplus results (trisomy 21-risk1 to 380; age distribution at term: 17 to 45 years; median 29.4 years). Among the conspicuous cases were 8 with trisomy 21, 1 with trisomy 18, 5 spontaneous abortions and 3 special cases. Seven of a total of 9 trisomies were detected by the screening. From these data the following diagnostic parameters for AFPplus have been calculated: specificity 91.0%, sensitivity 77.8%, positive predictive value 99.9%, false positive rate 9.0%, false negative rate 22.2%. The use of AFPplus by a practitioner cooperating with a private laboratory thus reveals a detection rate comparable to that known from larger centers. AFPplus by a practitioner cooperating with a private laboratory thus reveals a detection rate comparable to that known from larger centers. AFPplus allows to individualize the statistical age-related risk of a pregnant women before age 35. Above age 35 AFPplus may support the indication for cases suitable for cytogenetic investigation. Thorough personal information of the patient before the 16th pregnancy week by the practitioner or by genetic counseling has without any doubt first priority.

The association of increased maternal serum alpha-fetoprotein levels (MS-AFP) with certain morphologic anomalies of the fetus is fully established. These anomalies are abdominal wall defects (e.g. omphalocele, gastroschisis, complete eventration), neural tube defects (anencephalus, spina bifida, encepalocele) and other malformations (e.g. coccygeal teratoma). The present study compares MS-AFP levels with amniotic fluid alpha-fetoprotein (AF-AFP) and acetylcholinesterase activity, the results of ultrasound, genetic and morphologic examination. Between April 1992 and November 1995 60 patients were referred to our clinic for further diagnosis after detection of elevated MS-AFP. After an ultrasound examination was carried out amniocentesis (AC) was performed in 54 cases, AC + placentesis (PC) in 3 patients and PC only in 3 cases with anhydramnion. Mean maternal age was 29 years (range 20-37 years). Punction was performed at a median of 19 + 1 weeks of gestation (15 + 2-23 + 2 weeks of gestation). MS-AFP, AF-AFP and acetylcholinesterase activity was measured. MS-AFP and AF-AFP were given as multiples of the median (MoM). Valuesor = 1-2.0 MoM were considered normal. Elevated levels were defined to be greater than 2 MoM. In all cases the chromosomal finding was normal or norm variant. Sonographical anomalies were detected in 7 fetuses (3 cases with spina bifida, 1 case with omphalocele and 3 cases with abdominal wall defects in connection with other malformations). All sonographic diagnoses were confirmed post partum. The MS-AFP varied between 0.9-6.0 MoM. In 7 cases MS-AFP previously (referring center) evaluated as increased was found to be within normal range in our department. This cases included normal values were found in 30 cases and 25 findings were pathological. 2 out of 7 structurally abnormal fetuses had normal values, 5 of them had elevated MS-AFP. In the group of normal fetuses the highest MS-AFP we found was 6.6 MoM. In the AC-group the AF-AFP ranged between 0.7-8.7 MoM, it was within normal range in 50 and pathological in 8 cases. In the group of fetuses without structural anomalies the highest AF-AFP was 7.5 MoM. In the group of fetuses with structural anomalies the AF-AFP values were 1x normal and 3x pathological (3.5 MoM). Acetylcholinesterase activity in the amniotic fluid was negative in 51 cases, positive in 4 cases and faint positive in 2 cases. In all fetuses with structural anomalies in which an AC could be performed, acetylcholinesterase activity was positive. On the other hand we found only 1 of the structurally normal fetuses with positive acetylcholinesterase activity. Elevated MS-AFP and AF-AFP may be an indicator for morphological anomalies. Yet there were many positive results without any sonographical findings. The determination of a positive acetylcholinesterase activity in the amniotic fluid is more specific. All malformations have been detected by ultrasound examination before the results of the AF-AFP were available.

Hepatocellular carcinoma (HCC) is a frequent complication of chronic liver disease. The major causes of chronic liver diseases are hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, as well as chronic alcohol misuse. The clinical presentations of HCC patients are unspecific, with signs and symptoms of chronic liver disease. Early diagnosis of HCC in an asymptomatic and potentially curable stage is of highest priority. The present strategy for the detection of early HCC in patients with chronic liver disease is 6-monthly determination of alpha-fetoprotein (AFP) and ultrasound study of the liver. If these are abnormal, further diagnostic steps include computer tomography, magnetic resonance tomography, lipiodol-angiography and histopathology. By this sequential diagnostic strategy it should be possible to identify HCC in patients with chronic liver disease at an early and potentially curable stage.

An age-dependent analytic program (Alpha-Software from Wald) was compared to an age-independent Index (Ulm-Index) in order to determine effectivity of detection in prenatal screening for Down's Syndrome in 7060 pregnant women. The rate of accuracy was similar in both analytic programs (6 from 7), but, the rate of false-positive results was twice as high using the Ulm-Index (14.7 versus 7.7%). The higher rate of amniocentesis necessary using the age-independent Ulm-Index apparently does not justify this method for prenatal screening of Down's Syndrome.

The aim of the study was to clarify by a cost-effectiveness analysis, if a triple-marker screening for trisomy 21 (triple test) should be established in Austria.The published triple-test results of the last years were combined with the data of the Styrian Malformation Register covering the years 1985-1992. The cost-effectiveness analysis was based on total costs of prenatal diagnosis, costs per fetus diagnosed as affected, the number of affected fetuses detected, and the number of procedure-related losses.If low costs are given priority, the triple test should be offered to women 35 years of age or older. If a high detection rate is given top priority, the test should be offered to all pregnant women.The results suggest that the present policy of maternal age screening in Austria should be replaced by maternal serum screening.

An epignathus was found by routine screening ultrasound examination in the 17th week of pregnancy. Epignathi are teratomas in the oral cavity and are rarely found. The detection of an epignathus in the first half of pregnancy was described only three times in literature. The teratoma may also invade the cerebrum and is associated with a polyhydramnios and elevated alphafetoprotein. If the diagnosis is made in the first half of pregnancy a induced abortion is to be discussed.

3.7% of the diagnoses in the Pediatric Tumour Registry (Zentrales Tumor-Register) of the German Society for Pediatric Oncology and Haematology (Gesellschaft für Pädiatrische Onkologie und Hämatologie) concern germ cell tumors. The annual incidence has increased from 0.22 in 1980 to 0.60 per 100,000 children in 1992. The most common localizations are the coccygeal region (25%), followed by the testes (20%), the ovaries (20%) or the brain (20%). Some malignant germ cell tumors tend to secret the tumour markers Alpha-1-Feto-protein and HCG, and may then be diagnosed clinically due to the increased serum or spinal fluid levels. In the cases of extensive tumors growth and secreting intracranial germ cell tumors, a preoperative chemotherapy is favourable. The latest chemotherapy regime containing Cis-Platinum allows us to achieve long term remission in 80% of cases. Risk factors for the regime include histology, localization stage, and incomplete resection of the primary tumors.

The evaluation for every new method of early diagnostics is the criterion of quality of previous methods. The Triple diagnostics in the prenatal medicine however does not fulfill the criterion of standard for example for early diagnostics in gynecological oncology. Particularly, the precision in laboratories cannot be safely assumed so that false positive as well as false negative results are possible. The consequences of this method of early diagnostics are uncertainty for patients and physicians and of high expenditure for both.

5 years ago, maternal serum markers have been established for individual risk estimation of fetal Down syndrome. Recently Benz et al. presented an arbitrary age-independent risk index. Compared to the commonly applied statistical approach a 20% increase in detection rate was obtained by using the index (85% versus 65%). We recalculated data from 19,333 prospectively investigated pregnancies without trisomy 21 and 57 pregnancies with fetal Down syndrome using the proposed risk index. At the corresponding false-positive rate (7.9%) the age-independent detection rate was only 56%. This result indicates that the sensitivity cannot be increased by the Ulm index, when compared to statistical methods of risk estimation.

The cardinal syndrome of a testicular germ cell tumour is typically scrotal enlargement. The present paper compares the group of patients with typical scrotal presentation and those who present with atypical symptoms caused by metastases. Among 284 retrospectively studied patients, 34 (12%) presented with extrascrotal symptoms. The most important were abdominal pain (n = 16) and pulmonary symptoms (n = 10). The group of patients with extrascrotal symptoms was characterized by the following parameters: percentage of pure seminoma in 35% (versus 56% in the patients with typical presentation), elevation of alpha-feto-protein in 47% (versus 27%), and elevation of beta-HCG in 61% (versus 29%). The outcome was lethal in 35% of the patients with atypical presentation, as opposed to 6% of those with typical presentation. In 22 patients with extrascrotal presenting signs a palpable testicular mass was found on clinical examination. Occult testicular tumour proved to be present in 9 patients, and burned-out tumours in 3. Unawareness of testicular cancer is a significant factor in diagnostic delay. Scrotal palpation should be part of every clinical examination in younger male patients with cancer from an unknown primary.

In a patient with elevated serum alpha-fetoprotein a little haemangioma of the umbilical cord is diagnosed by ultrasound in the 21st week of pregnancy. So far only nine reports exist of prenatal diagnosed haemangiomas of the cord. Severe complications like rupture, cord haematoma, non-immune hydrops fetalis and polyhydramnions as well as a perinatal mortality of 35% have been reported. Therefore, intensive surveillance during pregnancy is mandatory.

Between September 1st 1990 and Juli 31st 1993, 5071 pregnant women were screened prospectively by the "triple-test", including maternal serum alpha-fetoprotein, human chorionic gonadotropin and unconjugated oestriol in order to detect chromosomal anomalies and open neural tube defects. The serum samples were collected in collaboration with the obstetricians of the region of West-Mecklenburg and North-West-Brandenburg. Laboratory testing using radioimmunoassays was performed between weeks 15 and 20 of gestation, all serum specimens being investigated in only one institution. The original alpha-software from Wald et al. was the basis for calculating the statistical risk for Down's syndrome. Pregnant women with a high risk for Down's syndrome (cutoffor = 1:250) were taken care of in a special outpatient clinic including procedures like amniocentesis and fetal blood sampling. Amongst 5071 pregnant women, 21 fetal anomalies were seen. Five cases of Down's syndrome, three of trisomy 18, one trisomy 13, two cases of triploidy and four cases of open neural tube defects, one 46 xy/45 x mosaic karyotype and one case of gastroschisis could be diagnosed correctly. One case of trisomy 21, one case of trisomy 18 and two open neural tube defects showed false negative results. Using the cutoff of 1:250 for prenatal detection of Down's syndrome and performing ultrasound routinely to determine gestational age, the sensitivity of the "triple-test" was 83.33% having a specificity of 92.68%. The predictive value of a positive test for prenatal diagnosis of Down's syndrome was 1.33%.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary extragonadal germ cell tumors are a rare malignant disease in young males. They account for only 1 to 4% of all germ cell tumors.In this paper we describe three selected cases of primary extragonadal germ cell tumors. The literature is reviewed with regard to clinical features, differential diagnosis and treatment.Tumor markers alpha-fetoprotein and human chorionic gonadotropin are of considerable diagnostic value if disease distribution is considered. With cisplatin-based combination chemotherapy similar disease-free survival rates are achieved as for testicular tumors with poor-prognosis metastatic disease. Surgical procedures play a role as adjunctive modality.If young males present with a mass in the retroperitoneum or in the anterosuperior mediastinum, a primary extragonadal germ cell tumor, should be taken into consideration. Tumors of both localisations have distinct clinical features but carry a similar prognosis. Patients benefit from the cumulative experience of a specialist unit.

The need for alternatives to amniocentesis, beset by 1% abortion rate, has been increasingly voiced over the past years and also includes the under 35 age group. However, the known age-dependent screening programs such as Alpha program according to Wald (1988) and the Dermalog Program according to Norgaard-Pederson (1990) only yield a detection rate of 50 or, at best, 70% (Müller, 1992) for this age group. We tried to improve this result by index calculation. Compared to the tested age-dependent screening programs the Ulm Index achieves a 25 to 40% higher detection rate (85%). For pregnant women beyond 35 years the detection rate of Down's syndrome can even be raised to 95-100% by a combination of the Alpha or Dermalog program with the Ulm Index, without entailling an increase in the rate of false-positive results.

Information is presented on 1100 early amniocenteses between the 12th and 14th week of gestation, performed at the Evangelisches Krankenhaus Oberhausen over a two year period. In all cases, a sufficient amount of amniotic fluid was obtained. In 99.7%, the cytogenetic diagnosis was successful. In 2.6% (29 patients), an aberrant karyotype was found. The time of cultivation was in the same range as can be observed in standard amniocentesis. The AFP-median measurements correlate with other studies. The spontaneous abortion rate was 0.3%. We conclude, that early amniocentesis can be performed safely and successfully by an experienced surgeon between the 12th to 14th week of gestation.

Germ cell tumors of the central nervous system are histological identical to the extracranial tumor sites. According to the localisation germ cell tumors of the CNS are different in symptoms, diagnostic approaches, kind and location of metastases and stratification of therapy. Since 1986 patients with intracranial germ cell tumors are registered in the ongoing study for non-testicular germ cell tumors (MAKEI) of the German Society of Pediatric Oncology and Hematology, and are treated in accordance to therapy guidelines for extracranial sites. In MAKEI 89 therapy strategy was revised with a reduction of radiotherapy and an increased cumulative cisplatinum dose from 200 mg/m2 to 400 mg/m2. Patients with germinoma receive after histologic diagnosis radiotherapy consisting of 30 Gy craniospinal irradiation and 15 Gy tumorboost. Malignant non-germinoma receive after diagnosis by tumor marker in CSF and/or serum 2 courses bleomycin 15 mg/m2 day 1-3, Etoposide 150 mg/m2 day 1 + 2 and cisplatinum 20 mg/m2 days 4-8 (BEP), continued by 2 courses Vinblastine 3 mg/m2 day 1 + 2, Ifosfamide 1500 mg/m2 days 1-5 and cisplatinum 20 mg/m2 days 1-5 (VIP), followed by 30 Gy craniospinal irradiation and 20 Gy tumor boost. In teratoma first line therapy is complete resection. In incomplete resected cases adjuvant chemotherapy according to histological grading is administered. Until 31st January, 1993 101 patients (pts) were registered, containing 69 protocol pts. Diagnosis in protocol pts was teratoma in 8 cases, 2 pts died postnatal because of extended disease, 2/8 pts relapsed, but were salvaged by chemotherapy. 40 pts offered germinomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Retroperitoneal lymphadenectomy was performed in 462 patients with testicular cancer. A total of 142 patients with advanced non-seminomatous germ cell tumours underwent retroperitoneal lymphadenectomy following cisplatin-based polychemotherapy. After inductive chemotherapy all of the patients described (108/142) showed seroconversion of tumour markers. Histology following RLA revealed vital tumour in 41% and teratoma in 12%. It was not possible to distinguish preoperatively between non-malignant residual tissue and vital tumour. In addition, sonography, computed tomography, and the tumour marker results did not correlate significantly with the intraoperative histopathological findings. Although histopathological confirmed complete remission was achieved in 47% of the patients with chemotherapy alone, subsequent retroperitoneal lymphadenectomy remains mandatory in cases with residual retroperitoneal lesions and pathological partial remission.

Between 1980 and 1990, 670 testicular examinations were performed. Testicular palpation and ultrasonography were carried out. A total of 588 patients (87.8%) had malignant testicular tumors; 82 patients (12.2%) were found to have nongerminal testicular and paratesticular tumors. Intraoperative frozen section histology and tumor size determined the subsequent procedure. In cases of epidermal cysts, adenomatoid tumors and fibrous pseudotumors, the testicle was preserved in the majority of cases. Leydig's cell tumor, Sertoli's cell tumor and dermoid cysts were removed together with the testicle because it was not clear if they were benign. During the postoperative follow-up period, there was no evidence of local recurrence or metastases in any of the patients.

In Europe and North America, primary liver tumors are rare. Resection is the only means of cure, but is possible in only 20-30% of the patients affected, so that in all other patients, i.e. the vast majority, only palliative treatment is possible. In a retrospective analysis we investigated the 68 patients we had treated for hepatocellular or cholangiocellular carcinoma of the liver. In 14 patients resection was possible, while 28 patients were treated by chemoembolization and 26 by intraarterial regional chemotherapy to the liver. There was no difference in tumor stage between the two groups receiving different palliative treatments. The patients in whom resection was performed, in contrast, mostly had less advanced tumors. For chemoembolization we used a mixture of Ethibloc, mitomycin, Adriamycin and cisplatin. Up to 1986, the intraarterial chemotherapy was performed with mitomycin and 5-FU. Since 1986 we have used Adriamycin and cisplatin. The overall median survival time was 8 months: after resection 17 months, after chemoembolization 6.5 months, and after intraarterial chemotherapy 6.5 months. There was a significant difference in survival between patients with tumor stage II and those with tumor stages III and IV. On comparing the survival time achieved with our treatments and that ensuing in the natural course of patients with liver tumor we found no improvement.