[Medical advance directives as instruments of patient self-determination]. / Patientenverfügungen als Instrument der Patientenselbstbestimmung.

Medical advance directives and durable powers of attorney for health care increasingly gain importance and recognition as instruments of patient self-determination. This article explores the various possibilities for advance directives as well as their ethical legal background. Furthermore, results of a current patient and population survey are presented, showing how (potential) patients think about the possibilities of advance directives. Finally, practical recommendations on how to deal with medical advance directives are given.

Elderly patients with acute myeloid leukaemia: characteristics in biology, patients and treatment. Recommendations of the Working Group Geriatric Oncology of the German Society for Haematology and Oncology (DGHO), the Austrian Society for Haematology and Oncology (OGHO) and the German Society for Geriatrics (DGG).

While the incidence rate of acute myeloid leukaemia (AML) is increasing with the age of the patients, the 5-year-survival rates are decreasing in an age-dependent manner. Patients with AML are considered to be old when they have reached the age of 60. This consideration is due to patient- and disease-specific parameters, which reveal differences between older and younger patients with AML. Standard of therapy is a dose-intensive chemotherapy aiming at the induction of complete remission, followed by different kinds of post-remission therapies. A small percentage of patients can be cured by this approach. However, most patients will die within the first 2 years after diagnosis due to resistance or relapse of the disease or therapy-related complications. The improvements achieved in the treatment of patients with AML are mainly restricted to the group of younger patients. The small percentage of patients who are cured, and the high rate of treatment-related mortality in elderly patients with AML give rise to the question which patients benefit from a primarily curative approach, and which should be treated with a palliative approach. The value of a palliative approach has not yet been consistently assessed in clinical trials. Geriatric assessment will be an important tool in clinical trials for elderly patients with AML to be used in the decision making process. There is hope that new classes of drugs and treatment modalities such as inhibitors of signal transduction, monoclonal antibodies, inhibitors of angiogenesis, or allogenic blood stem cell therapy after non-myeloablative conditioning regimens will improve the therapy of elderly patients with AML in the near future.

Consent and equipoise, the crucial ethical issues in randomised clinical trials.

Randomised clinical trials are widely accepted as the gold standard of clinical research. They seem to be the only means of conclusively establishing a relationship between an intervention and an observed outcome. However, randomisation by definition rules out individual choice of a treatment option. The justification of randomising is that the different options are in equipoise, and therefore no patient is at a disadvantage in the trial. There is concern whether equipoise, in a strict sense, is at all possible. This would require that there is no evidence as to the comparative efficacy of the treatments to be tested. This condition is in contrast to an honest null hypothesis. Several suggestions have been made to solve the tension of the equipoise requirement and are discussed in this paper. The second important condition for randomised clinical trials is to obtain informed consent from the patient. Valid consent requires that it is given voluntarily by a competent person who is adequately informed.

[Psychosomatic medicine--historical models and current theories]. / Psychosomatische Medizin--historische Modelle und aktuelle Theorien.

The term psychosomatic medicine has two meanings: first it represents a specific scientific approach in medicine that encompasses methodologies from natural sciences as well as social and human sciences. Second it denotes a clinical speciality that aims at applying this complex scientific background to diagnostic and therapeutic procedures. In this review partly contrasting concepts in medicine are outlined in order to discuss current psychosomatic theories and models. This reflection based on philosophy of science shows that the heterogeneity of the concepts in medicine expresses differences in the predominance of phenomenologic, dialectic, empiric-analytic and hermeneutic methodology. In psychosomatic medicine a critical evaluation and integration of the applied methodologies is regarded as scientific prerequisite and ethical demand. These hypotheses are also shared by medical anthropology (v. Weizsäcker), theoretical pathology (Doerr and Schipperges), and by the concepts of Uexküll (Situationskreis) and Hahn (Methodenkreis); they also serve as the fundamental basis for this article.

[Conceptual and ethical questions in geriatric oncology]. / Konzeptuelle und ethische Fragen der geriatrischen Onkologie.

Geriatric oncology concentrates on the field of cancer in the expanding aging population. Therapeutic goals are based on individual risk-assessment, comorbidities, and the specific tumor-biology. Good management of older cancer patients requires a multidimensional risk profile. Shared decision-making in geriatric oncology has to recognize a sometimes impaired autonomy. Possible conflicts between beneficence and autonomy are discussed and specific problems of the elderly patients are given. Informed consent requires competence, which might be lacking to some degree. It is the task of a responsible physician to promote autonomous decision-making as far as possible.

[Patient education and informed consent in hemato-oncology--limits and problems from the physician's viewpoint]. / Aufklärung und Einwilligung in der Hämato-Onkologie--Grenzen und Probleme aus ärztlicher Sicht.

Patients' information implies a complex communication process and includes more than simply giving neutral information about cancer and therapy. The goal of shared decision-making is based on the therapeutic relationship, which is rooted in the trust between doctor and patient. At the beginning of the conversation it seems paramount to optimise the setting, consisting of sufficient time, suitable space and empathy. The information should be phase-adapted and patient-centered to arrive at an informed consent about a therapeutic perspective. It seems wrong to give a plain diagnosis without therapeutic options. If possible, the next of kin should be included in the accompaniment.

Mapping of leukaemia-associated breakpoints in chromosome band 3q21 using a newly established PAC contig.

Chromosome aberrations affecting band 3q21 are associated with a particularly poor prognosis in patients with acute myeloid leukaemia. To facilitate the molecular characterization of such rearrangements, we established a PAC contig covering the relevant genomic region. Using these PACs as probes in fluorescence in situ hybridization (FISH) experiments, we showed that a number of 3q21 breakpoints in patient samples map to a previously defined 'breakpoint cluster region'. Others, however, are located at varying distances centromeric of it. These results have important implications in the search for genes affected by 3q21 rearrangements.

Molecular detection of c-mpl thrombopoietin receptor gene expression in chronic myeloproliferative disorders.

BACKGROUND: Chronic myeloproliferative disorders (CMPD) originate from a pluripotent haematopoietic progenitor cell but show a marked degree of heterogeneity, especially between Philadelphia chromosome positive and negative disease entities. Abnormal megakaryopoiesis is a frequent finding in CMPD, often associated with thrombocythaemic cell counts. Recent experimental data have suggested that the c-Mpl thrombopoietin receptor, together with its ligand thrombopoietin, are not only the major physiological regulators of megakaryopoiesis and platelet production, but also play a crucial role in chronic myeloproliferation. METHODS: A total of 18 peripheral blood mononuclear cell samples obtained from patients with CMPD (chronic myelocytic leukaemia (CML), n = 10; polycythaemia vera (PV), n = 6; and primary thrombocythaemia (PTH), n = 2) were analysed for c-mpl mRNA using the reverse transcriptase polymerase chain reaction (RTPCR). In another 20 patients (CML, n = 10; chronic megakaryocytic granulocytic myelosis (CMGM), n = 3; PV, n = 3; PTH, n = 4), we compared the number of haematopoietic progenitors expressing c-Mpl, as characterised by coexpression with the CD34 antigen, in the bone marrow using double immunofluorescence staining. RESULTS: c-mpl mRNA was detected in all samples from patients with CML analysed, whereas only two of six PV and one of two PTH samples were positive (p < or = 0.008; chi 2 test). Expression of the c-mpl receptor gene was absent in healthy subjects used as controls. Similarly, an increase of c-Mpl expressing CD34 positive haematopoietic cells was detected in seven of 10 bone marrow aspirates obtained from patients with CML. Increased numbers of c-Mpl positive CD34 positive cells were found in only one of four patients with PTH, whereas in PV and CMGM the numbers of c-Mpl positive CD34 positive cells did not exceed normal values, despite thrombocythaemic cell counts. CONCLUSIONS: These data confirm recent findings showing an impaired expression of the c-mpl thrombopoietin receptor gene in Philadelphia chromosome negative CMPD when compared with patients with Philadelphia chromosome positive CML. The relevance of this observation to the functional and morphological characteristics of abnormal megakaryopoiesis remains unclear. Thrombocythaemic cell counts and a mature phenotype in megakaryocytes occur frequently in Philadelphia chromosome negative CMPD but require an intact c-Mpl receptor under physiological conditions. Therefore, further studies are warranted to elucidate the mechanisms contributing to megakaryopoiesis in CMPD disease entities with decreased c-mpl gene expression.

Trisomy 13 is associated with poor prognosis in idiopathic myelofibrosis with myeloid metaplasia.

We report a case of idiopathic myelofibrosis with trisomy 13 as the sole clonal aberration, as demonstrated by metaphase cytogenetics. The clinical course was especially poor in this case, with death in blast crisis occurring within two weeks from diagnosis. The dismal outcome bears striking similarity to two previous cases of idiopathic myelofibrosis and trisomy 13 reported in the literature. Therefore trisomy 13 may be a predictor of a rapidly fatal outcome in this otherwise indolent disease. Fluorescence in situ hybridisation (FISH) with a chromosome 13 specific probe may enhance the detection of this aberration, since only 50% of cases of idiopathic myelofibrosis are karyotyped successfully using conventional techniques.

Fluorescence in situ hybridization and surface markers of fine needle aspiration specimen confirm extramedullary myeloblastoma in a patient with chronic myeloid leukemia.

We report on a patient with chronic myeloid leukemia (CML) with a rapidly growing left cervical tumor 5 months after the initial diagnosis of CML. This tumor was diagnosed as a very early manifestation of extramedullary myeloblastoma by a minimally invasive method. A fine needle aspirate (26-gauge needle) was obtained from the tumor. Morphological and cytochemical analysis of the aspirate revealed 19% undifferentiated blasts. The immunophenotype was suggestive of a myeloid differentiation of the blasts (CD33+). The CML origin of the blasts was confirmed by the detection of the bcr-abl gene rearrangement in the blasts by two-color fluorescence in situ hybridization (FISH). We conclude that fine needle aspiration in combination with immunophenotyping and FISH analysis of the aspirate is a minimally invasive and rapid diagnostic tool to confirm extramedullary manifestation in CML. To our knowledge, this is the first case of extramedullary myeloblastoma confirmed by this combined technique.

[To what extent is it possible to integrated quality of life as a normative, subjective evaluation into scientific medicine?]. / Inwieweit ist Lebensqualität als normative, wertende Grösse in die wissenschaftliche Medizin integrierbar?

Quality of Life is an increasingly popular concept, often associated with a wish to organize therapy along patient-oriented lines. However, determining the quality of life goes beyond a purely descriptive and objective assessment. It is based on subjective evaluation and is influenced by the ability to adapt to miserable conditions. Further conceptual problems consist in the structure of questionnaires and in the fact that there is no consensus about a clear definition of quality of life. The ideal of multidimensionality is restricted by practical limits of acceptable time and tolerable number of questions. Nevertheless most of the modern instruments focus on the patient's well-being and promote the realisation of their individual preferences. The hope is that quality of life will be an additional scale to enhance the established criteria of treatment success like survival time and remission duration. There is the risk to set value-thresholds on life, which appears to be inappropriate. Quality of life assessment may refine the choices of therapeutic aids, but can never solve the difficult moral questions that appertain to the value of life.

[Possibilities and limits of ambulatory supportive measures in oncology exemplified by antibiotic therapy of febrile neutropenia]. / Möglichkeiten und Grenzen ambulanter supportiver Massnahmen in der Onkologie am Beispiel der Antibiotikatherapie febriler Neutropenien.

Neutropenia is common after intensive chemotherapy. Hospitalization and intravenous broad-spectrum antibiotics are the standard of care for febrile neutropenic patients because of the risk of serious complications and associated mortality. Short neutropenic periods (< 7 days) are considered to be at a low-risk in cases when fever occurs in clinically stable patients. Recent work suggests that such a low-risk population of febrile neutropenic patients might benefit from alternatives to inpatient care. The agents that best qualify for outpatient treatment include quinolones i.v./p.o., glycopeptides, ceftriaxone and aminoglycosides, particularly if the latter are given once daily. Response rates to antimicrobial therapy range from 80 to 95% in low-risk febrile neutropenia episodes. Treating these patients in an outpatient setting avoids hospitalization in 75 to 95%. There is no doubt that outpatient therapy may have several advantages, including lower costs and an improved quality of live. Outpatient antibiotic therapy for febrile low-risk neutropenia should be considered as an acceptable alternative to inpatient treatment.

[Advance directives from the medical viewpoint]. / Patientenverfügungen aus ärztlicher Sicht.

Advance directives, enabling patients to declare their wishes and preferences for future situations, when they no longer are able to communicate, appear to be attractive. The concept, however, is based on two important presuppositions: First on the recognition of the right of self-determination. Second, it is assumed that a patient can direct medical care not only hic et nunc, but can advance autonomy into future incompetent states. It is the second presupposition that causes most of the ethical concerns and practical problems. Some of the limitations can possibly be overcome, or at least minimized, by careful drafting, frequent revision and the appointment of a proxy. However, advance directives should be integrated into the process of patient information and care.

[Patient education--support--help with decisions: ethical aspects in treatment of amyotrophic lateral sclerosis]. / Aufklärung-Begleitung-Entscheidungshilfe: Ethische Aspekte bei der Behandlung der amyotrophen Lateralsklerose.

Patients with amyotrophic lateral sclerosis (ALS) develop progressive, degenerative loss of muscle function while retaining mental capacity. This implies special problems of patient information, which should be phase-adapted and patient centered. The difficult task of the physicians requires to provide sufficient information, to enable shared decision-making, without leaving the patient alone. Respiratory failure due to loss of muscle function is often the limiting problem. However, the possible option of ventilatory support opens the question when to stop treatment. It is most important to differentiate between intended mercy-killing and foregoing treatment due to the patient's wish. Discontinuation of treatment is morally justifiable, even required, if the patient refuses further treatment. Advance directives may be helpful to make decisions according to patients' preferences in time.