Increased prevalence of risk factors for cardiovascular disease in long-term survivors of acute lymphoblastic leukemia and Wilms tumor treated with radiotherapy.

BACKGROUND: Only a few studies have assessed cardiovascular risk factors (CRFs) in childhood cancer survivors. We determined the prevalence of CRFs in long-term survivors of acute lymphoblastic leukemia (ALL) and Wilms tumor. PROCEDURE: Adult survivors of ALL and Wilms tumor treated with radiotherapy and chemotherapy (RT + CT) or treated with chemotherapy alone (CT) were compared with sibling controls. CRFs (hypertension, diabetes mellitus, hypercholesterolemia, obesity, renal insufficiency) and hormonal deficiencies were assessed in each participant. Multivariate logistic regression analysis was used to evaluate the association between CRFs and treatment. RESULTS: Seventy-nine ALL, 62 Wilms tumor survivors, and 69 control subjects (mean ages 24.5, 25.9, and 26 years, respectively) were enrolled. Mean follow-up time since cancer treatment was 20.8 years. In the Wilms RT + CT group significantly more survivors had hypertension (21.6% vs. 1.4%, P < 0.001) and renal insufficiency (8.1% vs. 0%, P = 0.016) compared to controls. There were also more patients with multiple CRFs in the Wilms RT + CT group (16.2% vs. 2.9% in controls, P = 0.019). Almost 15% of ALL RT + CT survivors had growth hormone deficiency. Hypogonadism was seen in 18.9% of survivors in the Wilms RT + CT group. We observed no significant differences between CT-treated survivors of both malignancies and controls. The adjusted odds ratio for the occurrence of at least one CRF was 2.6 increased for survivors following abdominal radiotherapy. Treatment with CT alone was not associated with the occurrence of multiple CRFs. CONCLUSIONS: Long-term survivors of ALL and Wilms tumor have unfavorable CRFs due to previous RT not CT.

Models as instruments for optimizing hospital processes: a systematic review.

PURPOSE: The purpose of this article is to find decision-making models for the design and control of processes regarding patient flows, considering various problem types, and to find out how usable these models are for managerial decision making. DESIGN/METHODOLOGY/APPROACH: A systematic review of the literature was carried out. Relevant literature from three databases was selected based on inclusion and exclusion criteria and the results were analyzed. FINDINGS: A total of 68 articles were selected. Of these, 31 contained computer simulation models, ten contained descriptive models, and 27 contained analytical models. The review showed that descriptive models are only applied to process design problems, and that analytical and computer simulation models are applied to all types of problems to approximately the same extent. Only a few models have been validated in practice, and it seems that most models are not used for their intended purpose: to support management in decision making. RESEARCH LIMITATIONS/IMPLICATIONS: The comparability of the relevant databases appears to be limited and there is an insufficient number of suitable keywords and MeSH headings, which makes searching systematically within the broad field of health care management relatively hard to accomplish. PRACTICAL IMPLICATIONS: The findings give managers insight into the characteristics of various types of decision-support models and into the kinds of situations in which they are used. ORIGINALITY/VALUE: This is the first time literature on various kinds of models for supporting managerial decision making in hospitals has been systematically collected and assessed.

Proclets in healthcare.

Healthcare processes can be characterized as weakly-connected interacting light-weight workflows coping with different levels of granularity. Classical workflow notations fall short in supporting these kind of processes. Although these notations are able to describe the life-cycle of individual cases and allow for hierarchical decomposition, they primarily support monolithic processes. However, they are less suitable for healthcare processes. The Proclets framework is one formalism that provides a solution to this problem. Based on a large case study, describing the diagnostic process of the gynecological oncology care process at the Academic Medical Center (AMC), we identify the limitations of "monolithic workflows". Moreover, by using the same case study, we investigate whether healthcare processes can be described effectively using Proclets. In this way, we provide a comparison between the Proclet framework and existing workflow languages and identify research challenges.

Electromagnetic interference from radio frequency identification inducing potentially hazardous incidents in critical care medical equipment.

CONTEXT: Health care applications of autoidentification technologies, such as radio frequency identification (RFID), have been proposed to improve patient safety and also the tracking and tracing of medical equipment. However, electromagnetic interference (EMI) by RFID on medical devices has never been reported. OBJECTIVE: To assess and classify incidents of EMI by RFID on critical care equipment. DESIGN AND SETTING: Without a patient being connected, EMI by 2 RFID systems (active 125 kHz and passive 868 MHz) was assessed under controlled conditions during May 2006, in the proximity of 41 medical devices (in 17 categories, 22 different manufacturers) at the Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Assessment took place according to an international test protocol. Incidents of EMI were classified according to a critical care adverse events scale as hazardous, significant, or light. RESULTS: In 123 EMI tests (3 per medical device), RFID induced 34 EMI incidents: 22 were classified as hazardous, 2 as significant, and 10 as light. The passive 868-MHz RFID signal induced a higher number of incidents (26 incidents in 41 EMI tests; 63%) compared with the active 125-kHz RFID signal (8 incidents in 41 EMI tests; 20%); difference 44% (95% confidence interval, 27%-53%; P < .001). The passive 868-MHz RFID signal induced EMI in 26 medical devices, including 8 that were also affected by the active 125-kHz RFID signal (26 in 41 devices; 63%). The median distance between the RFID reader and the medical device in all EMI incidents was 30 cm (range, 0.1-600 cm). CONCLUSIONS: In a controlled nonclinical setting, RFID induced potentially hazardous incidents in medical devices. Implementation of RFID in the critical care environment should require on-site EMI tests and updates of international standards.

Simulation to analyse planning difficulties at the preoperative assessment clinic.

BACKGROUND: Little research has been performed on designing appointment systems for the preoperative assessment clinic (PAC). We aimed to investigate how two organizational planning difficulties, (i) long access times and (ii) long waiting times, could be analysed systematically. METHODS: Two simulation models were used to test different scenarios to reduce access time and waiting times. First, we determined the number of appointments needed to reduce the access time from 5 weeks to 10 working days for 95% of all patients. Subsequently, we determined how long the consultation time should be, taking patients' American Society Anesthesiologists (ASA) physical status into account, to reduce the maximum waiting time to 10 min for 95% of all patients. RESULTS: Although we found the actual capacity, that is, consultations per day, to be enough to meet demand, a backlog existed, as the access time for the PAC was 5 weeks. A temporary extra capacity is needed to eliminate this backlog. When the reserved consultation time is 18 min for patients with ASA class I or II and 30 min for patients with ASA class III or IV, the maximum waiting times decrease to 10 min for 95% of all patients. CONCLUSIONS: This study shows that a simulation model is a helpful tool to determine the capacity needed to achieve and to maintain a proposed service level for access times and waiting times. In addition, waiting times at the PAC can be reduced by making the reserved consultation time dependent on patients' ASA physical status.

Using computer simulation to reduce access time for outpatient departments.

AIM: To develop general applicable models for analysing the capacity needed in appointment-based hospital facilities. METHOD: A fairly simple analytical queuing model was used to obtain rapid global insight into the capacity needed to meet the norm of seeing 95% of all new patients within 2 weeks. For more detailed analysis, a simulation model was developed that could handle daily variations in demand and capacity schedules. The capacity needed to eliminate backlogs and the capacity needed to keep access time within 2 weeks was calculated. Both models were applied to two outpatient departments (neurology and gynaecology) at the Academic Medical Center in Amsterdam, the Netherlands. Model results for neurology were implemented. RESULTS: For neurology, to eliminate the 6-week backlog, 26 extra consultations per week were needed over 2 months. A permanent increase of 2-weekly consultations was required to keep access time within 2 weeks. Evaluation after implementation showed the improvements the model had predicted. The gynaecology department had sufficient capacity. With the simulation, it was calculated that the same service level could be achieved with 14% less capacity. Thus the models supported decisions made for departments with shortages of capacity as well as those for departments with adequate capacity. CONCLUSION: The analytical model provided quick insight into the extra capacity needed for the neurology department. The added value of the simulation model was the possibility of taking into account variations in demand for different weekdays and a realistic schedule for doctors' consultations. General applicability of the models was shown by applying both models to the gynaecology department.

Development of a national protocol to screen Dutch cancer survivors on late cancer treatment effects.

PURPOSES: The development of a national protocol to formalize the screening of Dutch cancer survivors on potential late cancer treatment effects and the medical terminology used in describing the patient follow up procedures. METHODS: A combined evidence-based and qualitative approach, the Glaser's State of the Art Strategy, was used to reach consensus on how to screen Dutch cancer survivors on late cancer treatment effects. A core working group set up a first proposal of a screening protocol and a handbook of medical term definitions by incorporating available research evidence (1980-2003), clinical expertise and definitions from Dutch medical dictionaries and textbooks. External experts reviewed this proposal in a cycle of two postal and two discussion rounds. The follow-up procedures and medical term definitions described in the draft screening protocol were to be accepted if consensus among external experts was > or =50%. RESULTS: A protocol for screening cancer survivors on late cancer treatment effects was developed describing the follow-up procedures for cancer survivors according to previous therapeutic exposures. Four hundred and twenty one medical terms were used in describing these follow-up procedures. One hundred and fifteen of these terms were classified as multi-interpretable and 101 of these terms were defined. No definitions could be found for the remaining 14 medical terms. CONCLUSIONS: We succeeded in reaching consensus throughout The Netherlands on a protocol to screen cancer survivors on late cancer treatment effects. This protocol is now in use by all Dutch outpatient clinics and warrants that the screening of cancer survivors is consistent across The Netherlands. The screening protocol specifies in detail how screening of cancer survivors should take place and can therefore be used by clinicians who were not involved in the consensus study.

Risk of second malignancies in long-term survivors of childhood cancer.

INTRODUCTION: Childhood cancer survivors are known to be at increased risk for second malignancies. PATIENTS AND METHODS: The risk of second malignancies was assessed in 1368 5-year survivors of childhood cancer treated in the Emma Children's Hospital AMC in Amsterdam. The median follow-up time was 16.8 years. RESULTS: Sixty two malignancies were observed against 5.4 expected, yielding a standardised incidence ratio (SIR) of 11.2 (95% confidence interval: 8.53-14.4; absolute excess risk: 3.2 per 1000 person-years). New observations were the strongly increased risks of meningiomas (SIR=40) and basal cell carcinomas (SIR=9). Patients whose treatment involved radiotherapy had a 2-fold increased second cancer risk compared to patients with chemotherapy alone. DISCUSSION: The relative risk of second malignancies does not decrease till at least 30 years of follow-up. With aging of the survivor cohort this results in a strong increase of the AER, due to the rising background risk of cancer with age.

Evidence-based re-engineering: re-engineering the evidence--a systematic review of the literature on business process redesign (BPR) in hospital care.

PURPOSE: Business process redesign (BPR) is used to implement organizational transformations towards more customer-focused and cost-effective care. Ideally, these innovations should be carefully described and evaluated so that "best practices" can be re-applied. To investigate this, available evidence was collected on patient care redesign projects. DESIGN/METHODOLOGY/APPROACH: The Ebsco Business Source Premier, Embase and Medline databases were searched. Studies on innovations related to re-engineering patient care that used before-after design as minimum prerequisites were selected. General characteristics, logistic parameters and other outcome measures to determine the objectives and results and interventions used were looked at. FINDINGS: A total of 86 studies that conformed to the criteria were found: a minority mentioned measurable parameters in their objectives. In the majority of studies, multiple interventions were combined within single studies, making it impossible to compare the effects of individual interventions. Only three randomized controlled trials were found. Furthermore, inconsistencies were noted between the study objectives and the reported results. Many more issues were reported in the results than were mentioned in the study aims. It would appear that publications were hard to find owing to a lack of specific MeSH headings. Nearly 7,500 abstracts were scanned and from these it was concluded that clear and univocal research methods, terms and reporting guidelines are advisable and must be developed in order to learn and benefit from BPR innovations in health care organizations. ORIGINALITY/VALUE: This appears to be the first time available evidence about redesign projects in hospitals has been systematically collected and assessed.

Long-term cause-specific mortality among five-year survivors of childhood cancer.

BACKGROUND: The purpose of our study was to assess long-term cause-specific mortality of 5-year childhood cancer survivors. PROCEDURE: The study population consisted of 1,378 patients who had been treated for childhood cancer in The Netherlands between 1966 and 1996 and survived at least 5 years; follow-up was complete for 99% of survivors. Cause-specific mortality was compared with general population rates to assess relative and absolute excess risks of death (standardized mortality ratio (SMR) and AER). RESULTS: After a median follow-up of 16.1 years, 120 patients had died. The overall SMR was 17-fold (95% CI: 14.3-20.6) increased compared to the general population. Our cohort experienced an excess of 7 deaths per 1,000 person-years. Patients who received combined modality treatment and were treated for at least one recurrence experienced the highest risk of death (SMR = 92.3; AER = 37.0 per 1,000 person-years). The SMR appeared to stabilize at an about 4 to 5-fold increased risk of death after 20 years of follow-up. Only after more than 20 years of follow-up excess mortality due to other causes than the primary cancer exceeded mortality from the primary childhood cancer (2.3 vs. 0.3/1,000 patients/year). The SMR for all causes other than primary cancer was 5.4 in 25-year survivors. The overall risks of death strongly decreased with increasing attained age, with an SMR of 1.6 (n.s.) and an AER of 0.3 per 1,000 person-years for survivors of 30 years or older. CONCLUSIONS: The first primary cancer contributes most to the absolute excess risk of death in 5-year survivors of childhood cancer, but after 25 years childhood cancer mortality is negligible. Relative risk of death due to other causes is still significantly increased after 25 years of follow-up.

Long-term effects of cranial irradiation for childhood malignancy on sleep in adulthood.

BACKGROUND: Cranial radiation therapy (CRT) is required for successful treatment of a variety of brain tumours in childhood. OBJECTIVE: To investigate whether childhood CRT leads to altered sleep-wakefulness organization in adulthood, and to identify the determinants of such alterations. SUBJECTS AND METHODS: Subjective (questionnaires) and objective (actigraphy) measures of circadian rhythmicity and sleep were assessed in 25 individuals, 8-29 years after CRT for medulloblastoma (n=17) or other intracranial tumours (n=8), and in a group of 34 age-matched healthy individuals. Serum GH peak during insulin-induced hypoglycaemia and serum concentrations of prolactin and leptin (expressed per fat mass) were determined in the CRT group. RESULTS: The CRT group showed a markedly increased sleep duration (8.66 h, compared with 7.66 h in controls). In addition, the sleep-wake rhythm showed greater amplitude and less fragmentation, and less tolerance for alterations in the timing of sleep. Regression analysis showed both radiation dosage and neuroendocrine status to be determinants of sleep changes, suggesting that some of the alterations may be normalized with hormone supplementation. CONCLUSION: The present study shows that high-dose cranial radiation therapy in childhood is associated with objective and subjective changes in the sleep-wake rhythm in adulthood.

Cumulative incidence and risk factors of mitoxantrone-induced cardiotoxicity in children: a systematic review.

Mitoxantrone is believed to maintain anthracycline antitumour activity but be associated with a reduced cardiotoxicity. The aim of this study was to evaluate the evidence for the cumulative incidence of and risk factors for mitoxantrone-induced cardiotoxicity (M-CT) in children treated for childhood cancers. After an extensive literature search, 17 studies were included. The cumulative incidence varied between 0 and 6.7% in the 16 studies evaluating symptomatic M-CT and between 0 and 80% in the 11 studies evaluating asymptomatic M-CT. Risk factors for developing M-CT remain unclear. All studies had serious methodological limitations. In conclusion, children treated with mitoxantrone are at risk of developing M-CT, but due to the low quality of the current evidence, the exact cumulative incidence and risk factors for M-CT remain unclear. It is too early to conclude that in children mitoxantrone is less cardiotoxic than anthracyclines. More well-designed studies are needed to reliably evaluate the incidence of M-CT and its associated risk factors.

The content and amount of information given by medical oncologists when telling patients with advanced cancer what their treatment options are. palliative chemotherapy and watchful-waiting.

This study aimed to determine the content and the amount of information given by medical oncologists when proposing palliative chemotherapy and whether this information given is influenced by patient or physician background characteristics. In a prospective study, 95 patients with incurable cancer were interviewed before they consulted their medical oncologist. Their first consultation was audiotaped, and their eventual decision scored. A coding scheme comprised six categories of information given during the consultation. Medical oncologists mentioned or explained the disease course (53%), symptoms (35%) and prognosis (39%). Most patients were told about the absence of cure (84%). Watchful-waiting was mentioned to only half of the patients, either in one sentence (23%) or explained more extensively (27%). Multilevel analysis revealed that the patients' age, patient's marital status, and consulting in an academic hospital explained 38% of the amount of information given. Most of the physicians' attention is spent on the 'active' treatment option. Older patients, married patients and patients in academic hospitals receive more information.

Palliative chemotherapy or best supportive care? A prospective study explaining patients' treatment preference and choice.

In palliative cancer treatment, the choice between palliative chemotherapy and best supportive care may be difficult. In the decision-making process, giving information as well as patients' values and preferences become important issues. Patients, however, may have a treatment preference before they even meet their medical oncologist. An insight into the patient's decision-making process can support clinicians having to inform their patients. Patients (n=207) with metastatic cancer, aged 18 years or older, able to speak Dutch, for whom palliative chemotherapy was a treatment option, were eligible for the study. We assessed the following before they consulted their medical oncologist: (1) socio-demographic characteristics, (2) disease-related variables, (3) quality-of-life indices, (4) attitudes and (5) preferences for treatment, information and participation in decision-making. The actual treatment decision, assessed after it had been made, was the main study outcome. Of 207 eligible patients, 140 patients (68%) participated in the study. At baseline, 68% preferred to undergo chemotherapy rather than wait watchfully. Eventually, 78% chose chemotherapy. Treatment preference (odds ratio (OR)=10.3, confidence interval (CI) 2.8-38.0) and a deferring style of decision-making (OR=4.9, CI 1.4-17.2) best predicted the actual treatment choice. Treatment preference (total explained variance=38.2%) was predicted, in turn, by patients' striving for length of life (29.5%), less striving for quality of life (6.1%) and experienced control over the cause of disease (2.6%). Patients' actual treatment choice was most strongly predicted by their preconsultation treatment preference. Since treatment preference is positively explained by striving for length of life, and negatively by striving for quality of life, it is questionable whether the purpose of palliative treatment is made clear. This, paradoxically, emphasises the need for further attention to the process of information giving and shared decision-making.

Palliative chemotherapy or watchful waiting? A vignettes study among oncologists.

PURPOSE: To determine the preferences of oncologists for palliative chemotherapy or watchful waiting and the factors considered important to that preference. METHODS: Sixteen vignettes (paper case descriptions), varying on eight patient and treatment characteristics, were designed to assess the oncologists' preferences. Their strength of preference was rated on a 7-point scale. An orthogonal main effects design provided a subset of all possible combinations of the characteristics, allowing estimations of the relative weights of the presented characteristics. A written questionnaire was sent to a random sample of oncologists (N = 1,235). RESULTS: The response rate was 67%, and 697 questionnaires were available for analysis. Eighty-one percent of the respondents were male. The mean age was 46 years. We found considerable variation among the oncologists. No major associations between physician characteristics and preferences were found. Of the patient and treatment characteristics affecting treatment preference, age was the strongest predictor, followed by the patient's wish to be treated and the expected survival gain. Other patient and treatment characteristics had a limited effect on preferences, except for psychologic distress, which had no independent impact. CONCLUSION: Patients will encounter different decisions depending on their oncologists' preferences and their own personal background. Therefore, to ensure adequate information for decision-making processes, decision aids are proposed.

High concentration of Daunorubicin and Daunorubicinol in human malignant astrocytomas after systemic administration of liposomal Daunorubicin.

The value of chemotherapy in patients with malignant astrocytoma remains controversial. In our laboratories in vitro experiments with organotypic spheroid cultures showed superior effectiveness of anthracyclines. Systemic administration did not provide in therapeutic concentrations so far. Because recent studies on Daunorubicin in liposomes in the treatment of Kaposi sarcoma have shown effectiveness with diminished systemic toxicity, we administered intravenously a single dose of Daunorubicin in liposomes in eight patients at different intervals prior to surgery (12-50 h). In samples taken from tumor, tumor-edge and where possible from adjacent brain, the levels of Daunorubicin and its active metabolite Daunorubicinol were assessed with high performance liquid chromatography. Here we report that high concentrations of Daunorubicin and Daunorubicinol were found in malignant gliomas after systemic administration of liposomal Daunorubicin.

Wild-type p53-function is not required for hyperthermia-enhanced cytotoxicity of cisplatin.

The objective was to test the hypothesis that wild-type p53-function is required for the enhancement of the cytotoxicity of cis-diammine-dichloroplatinum(II) (cDDP) cytotoxicity by hyperthermia (HT). Human colorectal carcinoma cells (RKO) with wild-type p53-function and transfectants with HPV16-E6 or with a dominant negative mutant p53 were used. Cells were treated with HT (60 min at 41 degrees C, 43 degrees C, 45 degrees C: HT41, HT43, HT45). with various doses of cDDP alone or with a combined treatment, simultaneously applied. Survival was determined by clonogenic assays. Levels and localization of p53 were analysed with immunocytochemistry and Western blotting. The extent of HT41-enhanced cytotoxicity of cDDP was similar in all cell lines studied. Immunocytochemistry of wild-type p53 cells showed that p53 is transferred to the nucleus within 5 h after HT43, whilst after HT41 no significant effects were observed. Cell fractionation experiments of wild-type p53 cells showed that, immediately after HT43/HT45, nuclear p53-levels increased as compared to controls, but could not be extracted from the matrix. The extractability was restored 3-5 h after treatment. No significant differences in p53-levels were observed after HT41. These results indicate that, although HT43/HT45 might shortly inactivate p53-function, probably by protein aggregation to the nuclear matrix, the HT-enhanced cDDP-cytotoxicity does not depend on p53-function.

Long term survivors of childhood brain cancer have an increased risk for cardiovascular disease.

BACKGROUND: Cranial irradiation for children with brain tumors frequently leads to neuroendocrine deficiencies. In this controlled study, the authors investigated risk factors for cardiovascular disease (CVD) for long term survivors of childhood brain cancer. They also tested whether the presence of these risk factors was related to endocrine status. METHODS: In 26 survivors of childhood brain cancer (mean age, 25.8 years; mean posttreatment interval, 16 years) and 29 healthy controls (mean age, 27.7 years), the blood pressure, smoking habits, body mass index (BMI), and waist/hip (W/H) ratio were determined. Lipids and lipoproteins were measured and endocrine function was assessed. Carotid intima-media thickness (IMT) measurements were performed by high resolution ultrasonography. RESULTS: In the survivors of childhood brain cancer, systolic blood pressure and W/H ratio were elevated compared with controls. The cholesterol/high density lipoprotein ratio (4.7 +/- 1.7 vs. 3.4 +/- 0.8 mmol/L, P = 0.0005), low density lipoprotein cholesterol level (3.3 +/- 0.9 vs. 2.8 +/- 0.6 mmol/L, P = 0.027), and apolipoprotein B level (P = 0.001) were higher in survivors of childhood brain cancer, whereas HDL cholesterol was lower (P = 0.005). The IMT was increased in the survivor group, but only in the carotid bulb (0.63 mm +/- 1.6 vs. 0.53 mm +/- 1.1, P = 0.02), not in the internal or common carotid artery. In the absolute growth hormone deficient (GHD) population (n = 9), LDL cholesterol and apolipoprotein B levels were elevated and the W/H ratio was particularly increased compared with the other survivors of childhood brain cancer. CONCLUSIONS: For long term survivors of brain cancer, the risk for CVD is strongly increased due to dyslipidemia, central obesity, and elevated systolic blood pressure, particularly for those with GHD. The first effects of this increased risk for CVD were observed in the carotic bulb, as assessed by IMT measurements. Efforts should be directed at CVD prevention by risk factor control.

The effect of p53-function on the sensitivity to paclitaxel with or without hyperthermia in human colorectal carcinoma cells.

The importance of p53-function for the sensitivity to paclitaxel with and without hyperthermia (HT) was studied in an isogenic cell line system. The inactivation of p53 decreased sensitivity to paclitaxel (1.1-2.5-fold), which correlated with a lower induction of apoptosis. The magnitude of the G2/M arrest after treatment with paclitaxel was similar in all cell lines. The cytotoxicity of paclitaxel was not enhanced by HT in either wild-type p53 or p53-inactivated cells. In conclusion, cellular sensitivity to paclitaxel depends on p53-function by its ability to induce apoptosis. Irrespective of the p53-function HT was not able to enhance the sensitivity to paclitaxel.

[Malignant intracranial germ cell tumor treated with chemotherapy and radiotherapy without histopathological confirmation]. / Maligne intracerebrale kiemceltumor behandeld met chemotherapie en radiotherapie zonder histopathologische diagnose.

In two men aged 19 and 24 years, a rare malignant intracranial germ cell tumour was diagnosed in the pineal gland region and in the second patient in a suprasellar position as well. Although histological confirmation is required in general to diagnose a malignancy, obtaining it can be difficult and potentially dangerous in case of intracranial neoplasms. The clinical picture of a young patient with an intracerebral tumour localised in the midline of the brain and increased levels of the tumour markers alpha-foetoprotein and/or human chorion gonadotrophin (beta-HCG) in blood and/or CSF makes any other diagnosis highly unlikely. There is no place for radical surgery in the first-line treatment of malignant intracerebral germ cell tumours because of the sensitivity to radio- and chemotherapy. Also, the sensitivity to chemotherapy makes it possible to reduce radiation volume and dose in an effort to avoid the serious complications of craniospinal irradiation. Both patients responded well to chemotherapy based on cisplatin followed by radiotherapy.