Search

A frequent side effect of the multikinase inhibitor regorafenib is fatigue. Physical activity has shown potential in reducing cancer-related fatigue. This non-interventional pilot study assessed physical activity levels of metastatic colorectal cancer (mCRC) patients treated with regorafenib based on median daily step counts measured at 1‑week intervals using a pedometer. The study further evaluated relations between physical activity levels and fatigue, quality of life (QoL) and progression-free survival. Pedometer data were available for 22 out of 25 enrolled patients. The numbers of days with available pedometer data ranged from 6 to 100 days. The overall median daily step count was 2357 (range 10–14,931), with substantial interindividual and intraindividual variations. Interindividual median weekly step counts were in the range of 5000–7000 in some, 2000–3000 in others, and several hundreds or less in a few patients. Intraindividual daily step counts also varied by several thousands of steps. Step counts in weeks in which patients reported fatigue were well within the range of or even higher than step counts in adjacent weeks, indicating a lack of correlation. The risk of disease progression was also independent of median weekly step counts; however, significant correlations were seen between QoL and step counts. Despite the severity of their disease patients showed remarkable levels of walking activity. In view of the highly individual activity levels, exercise prescriptions for seriously ill patient populations should be personalized to the specific needs and preferences of each individual patient.

446 Background: Several PD-1 immune-checkpoint inhibitors including Nivolumab (Nivo) are approved in urothelial cancer. Recently, in the front line setting, improved activity of combined PD-L1 and CTLA4 immune-checkpoint inhibition has been reported and a phase III trial with Nivolumab + Ipilimumab (Nivo+Ipi) is ongoing. Here we report a response-based tailored approach starting treatment with Nivo monotherapy using Nivo+Ipi as immunotherapeutic “boost”. Methods: Between July 2017 and April 2019 86 patients were enrolled and treated according to protocol version 3 (cohort 1). Patients started with Nivo 240 mg Q2W induction. After 4 dosings and tumor assessment at week 8 (i) responders (PR/CR) to Nivo monotherapy continued with maintenance while (ii) patients with stable (SD) or progressive disease (PD) received 2 cycles Nivo3+Ipi1 followed by another 2 cycles Nivo1+Ipi3 if not responding. Median follow-up is 8.7 months. The primary endpoint is confirmed investigator-assessed objective response rate (ORR) per RECIST1.1. Secondary endpoints include activity of Nivo monotherapy at week 8, remission rate with Nivo+Ipi “boosts”, safety, overall survival and quality of life. Results: Of the patients 42, 39 and 5 were first, second and third line, respectively. Median age was 67 years (range 45-84), 61 patients (71 %) were male and 25 female. ORR with Nivo monotherapy at first assessment (week 8) was 29 % and 23 % in first and second/third line, respectively. Of the patients 41 received Nivo+Ipi “boosts” after week 8 while 12 received later “boosts”. Best overall response (BOR) rate with Nivo induction ± Nivo+Ipi “boosts” was 48 % and 27 % in first and second/third line, respectively. In first line 7/17 (41 %) patients receiving Nivo+Ipi after week 8 had an improved response compared to 2/24 (8.3 %) in second/third line. Of the patients who continued with Nivo maintenance after week 8 and received later “boosts” 2/12 (17 %) had a PR and 2/12 (17 %) improved to SD. Treatment-related AEs will be presented. Conclusions: TITAN–TCC explores a response-driven use of Nivo+Ipi as an immunotherapeutic “boost”. In first line, this significantly improved ORR compared to the expected response rate of Nivo monotherapy, providing further evidence to the added value of Ipi in combination with Nivo. Further follow-up is ongoing to characterize duration and depth of response. Clinical trial information: NCT03219775 . Research Sponsor: Bristol-Myers Squibb[Table: see text]

Die Palliative Sedierungstherapie (PST) ist eine wichtige und ethisch akzeptierte Therapie in der Versorgung von ausgewahlten sterbenden Menschen, welche aufgrund therapierefraktarer Symptome fur sie unertragliches Leiden erleben. PST findet zunehmend Anwendung in der Betreuung Sterbender. In Ostereich gibt es keine standardisierte ethisch fundierte Leitlinie fur diese exzeptionelle Therapie, es liegen jedoch Beweise vor, dass die angewandte Praxis bundesweit sehr uneinheitlich ist. Im Auftrag der Osterreichischen Palliativgesellschaft (OPG) erarbeitete eine 16-kopfige multiprofessionelle Arbeitsgruppe aus Experten der Palliative Care und Ethikern die Nationale Leitlinie zur PST auf der Basis jungster systematischer Ubersichtsarbeiten mit dem Ziel, innerhalb der Rahmenleitlinie der Europaischen Palliativgesellschaft (EAPC) zu sein und Osterreichs nationale legale, kulturelle und strukturelle Gegebenheiten zu respektieren. Der Expertenkonsens wurde mittels eines 4‑stufigen Delphiprozesses mit anschliesenden Konferenzen etabliert. Der Delphiprozess folgte strikt der jungst entwickelten EUROIMPACT-sedation-study-checklist und war am AGREE-2-Leitlinieninstrument orientiert. Zum Abschluss wurden nationale Stakeholder eingeladen, die Ergebnisse zu reflektieren. Als Ergebnis eines rigorosen Konsensusprozesses liegt die Langversion der Nationalen Leitlinie zur Palliativen Sedierungstherapie mit 112 Aussagen, kategorisiert in 11 Domanen vor. Erganzung finden diese Aussagen in einem Exkurs einer Philosophin uber das Leiden. Wir haben mittels Delphi-Expertenkonsensus und Einbeziehung der Stakeholder eine Nationale Leitlinie zur Palliativen Sedierungstherapie entwickelt. Die Wirkung der Leitlinie auf die Praxis in Osterreich muss zukunftig evaluiert werden.

Personalized cancer treatment utilizing targeted therapies in a tailored approach is based on tumor and/or patient-specific molecular profiles. Recent clinical trials continue to look for new potential targets in heavily pretreated patients or rare disease entities. Careful selection of patients who may derive benefit from such therapies constitutes a challenge. This case report presents an experimental personalized cancer treatment in an advanced cancer patient and provides a list of issues for discussion: How can we combine treatment goals and simultaneously meet the individual needs in advanced cancer reconciling both perspectives: oncology and palliative care?

Background: Neoadjuvant chemotherapy with methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) is the standard of care for muscle-invasive urothelial bladder cancer. Gemcitabine plus cisplatin (GC) shows similar efficacy with less toxicity in the metastatic setting and has therefore often been used interchangeably with MVAC. We report on the efficacy and safety of neoadjuvant GC in patients with locally advanced urothelial cancer. Materials and Methods: We prospectively evaluated 87 patients in 2 centers. Their median age was 68 years. Treatment consisted of 3× GC prior to radical cystectomy. The primary endpoint was pathologic response. The secondary endpoints were safety, progression-free survival (PFS), and overall survival (OS). Results: In all, 83 patients finished chemotherapy; 80 patients were evaluable for the primary endpoint. Pathologic complete response (pCR) was achieved in 22.5% and near pCR was seen in 33.7% of the patients. The 1-year PFS rate was 79.5% among those patients achieving ≤pT2 versus 100% among those patients achieving pCR or near pCR (p = 0.041). Five-year OS was 61.8% (95% CI 67.6 to NA). GC was well tolerated. Grade 3/4 toxicities occurred in 38% of the patients. There was no grade 3/4 renal toxicity, febrile neutropenia, or death. Conclusion: Neoadjuvant GC is a well-tolerated regimen. Although the pathologic response is lower than that reported with MVAC, our data support GC as a feasible option in the absence of a prospective randomized comparison, particularly for older patients, since its toxicity is lower than that of MVAC.

Palliative sedation therapy (PST) is an important and ethically accepted therapy in the care of selected palliative care patients with otherwise unbearable suffering from refractory distress. PST is increasingly used in end-of-life care. Austria does not have a standardized ethical guideline for this exceptional practice near end of life, but there is evidence that practice varies throughout the country.The Austrian Palliative Society (OPG) nominated a multidisciplinary working group of 16 palliative care experts and ethicists who established the national guideline on the basis of recent review work with the aim to adhere to the Europeans Association of Palliative Care's (EAPC) framework on palliative sedation therapy respecting Austrians legal, structural and cultural background.Consensus was achieved by a four-step sequential Delphi process. The Delphi-process was strictly orientated to the recently published EUROIMPACT-sedation-study-checklist and to the AGREE-2-tool. Additionally national stakeholders participated in the reflection of the results.As a result of a rigorous consensus process the long version of the Austrian National Palliative Sedation Guideline contains 112 statements within eleven domains and is supplemented by a philosophers excursus on suffering.By establishing a national guideline for palliative sedation therapy using the Delphi technique for consensus and stakeholder involvement the Austrian Palliative Society aims to ensure nationwide good practice of palliative sedation therapy. Screening for the practicability and efficacy of this guideline will be a future task.

Non

Das Patientengesprach hat einen wesentlichen Stellenwert im medizinischen Alltag eingenommen. Patienten mochten uber Diagnosen und Prognosen ausfuhrlich informiert werden und bei Alternativen aktiv in den Entscheidungsprozess miteinbezogen werden. Daruber hinaus wird Wert auf eine informative, stilvolle und empathische Mitteilung gelegt. Die entsprechende Zeit wird von Patienten und deren Angehorige mit Recht eingefordert. Das Gesprach zwischen Arzt und Patient ist somit ein wesentliches Hilfsmittel im Alltag des Gesundheitssystems, das vom Apparaten und Laborwerten nicht geleistet werden kann, und stellt ein zutiefst menschliches Bedurfnis von Arzt und Patient dar. Der folgende Fallbericht soll eine stufenweise Aufklarung eines Patienten mit anfanglich kurativen, aber im weiteren Verlauf fortgeschrittener und metastasierter maligner Erkrankung reflektieren. Ein Patient mit Nierenzellkarzinom wurde nach Abgehen eines Tumorembolus der Niere an der Thoraxchirurgie embolektomiert, wobei die Entfernung des Tumorzapfens nur unvollstandig gelang. Wenige Monate danach wurden Lungenmetastasen diagnostiziert, und der Patient verstarb am Nierenzellkarzinom. Der Fallbericht diskutiert die Gesprache und Begleitung des Patienten.

Although it is well known that body mass index (BMI) and bone mineral density (BMD) are positively correlated, the mechanisms by which adiposity reduces the risk of osteoporotic fractures are not fully understood. The present study was initiated to gain deeper insight into the mechanisms underlying the osteoprotective effect of adiposity, and to assess particularly the relevance that BMI-associated changes in circulating hormone levels could have for the build-up of additional bone mineral density. Using data from a previous study on a large cohort of healthy adult Austrians, we analyzed correlations of BMI with (i) BMD at sites in the lumbar spine and hip region, (ii) bone resorption and formation markers, (iii) circulating levels of vitamin D, parathyroid hormone, testosterone and estrogen, and (iv) rates of daily vitamin D and calcium intake. After adjustment for age, positive correlations between BMI and BMD were highly significant (P

I am reporting on a 74-year-old female patient with primary pulmonary and hepatic metastatic colon cancer. In the course of three-and-a-half years the patient decided to receive multiple cycles of palliative chemotherapy, irradiation of the liver and of the upper body. As a result of the extended anti-tumour therapy, remissions of the advanced cancer disease could be achieved repeatedly, which lead to a substantial increase of the patient's quality of life. This case shows that even in an advanced palliative situation the goal of a multimodal treatment is to curb disease progression and to extend the life and increase quality of life of the patient.

Biomarkers as biochemical substances of collagen metabolism are produced during bone turnover and can be determined as parameters of bone metabolism not only in serum, but also in urine. These growth and decomposition products of the bone are already used to determine bone metabolism in osteoporosis and to prove efficacy of antiresorptive therapy. Metastases of the bone likewise show a higher rate of bone turnover. Nowadays detection of neoplastic bone lesions and progression of their spread are performed with x-rays, radionucleoide bone imaging and magnetic resonance imaging. In the future, biomarkers might improve early detection of bone lesions and follow-up of skeletal metastases. At present, the clinical use is documented insufficiently. In the foreseeable future the determination of the bone turnover markers and additional serum parameters of bone metabolism such as OPG, RANKL might be available for early diagnosis and follow-up in patients with bone metastatic diseases.

Das Prostatakarzinom ist die haufigste Krebserkrankung und die zweithaufigste Krebstodesursache beim Mann. Trotz zunehmender Fruherkennung wird sie oft erst in fortgeschrittenen Stadien entdeckt. Bei Annahme eines lokal begrenzten Tumors wird eine kurative Therapie angestrebt, sofern die zu erwarerwartende Lebenserwartung mindestens 10 Jahre betragt. Hierfur in Betracht kommen die radikale Prostatektomie oder die Radiatio. Zwischen einem Viertel und der Halfte der Patienten sind nach einer radikalen Prostatektomie innerhalb von 10 Jahren von einem Rezidiv betroffen. Die Therapie der Wahl in solchen Fallen ist die Hormontherapie, wobei nach anfanglicher Stabilisierung fast alle Patienten fruher oder spater eine hormonrefraktare Progression der Erkrankung entwickeln. Die primare Therapie des fortgeschrittenen Stadiums besteht in einer Hormontherapie. Dafur stehen zwei Optionen zur Verfugung: der Androgenentzug, also die chirurgische oder medikamentose Kastration mit LH-RH-Analoga sowie die Androgenblockade mit nichtsteroidalen Antiandrogenen. Steigen trotz Testosteronspiegels im Kastrationsniveau die PSA-Spiegel an und sind Masnahmen der sekundaren hormonellen Manipulation ausgeschopft, handelt es sich um ein hormonrefraktares Prostatakarzinom. Dies manifestiert sich entweder im Rahmen eines PSA-Anstiegs oder mit lokaler und/oder viszeraler Metastasierung. In diesem Stadium kann die Chemotherapie erste Erfolge aufweisen. Im weiteren Verlauf sind es die supportiven Masnahmen mit dem Ziel eine entsprechende Lebensqualitat zu erhalten. Mit neuen Substanzen wie Docetaxel (Taxotere®) und Vinorelbin (Navelbine®) zeichnet sich ein Fortschritt in der Behandlung des hormonrefraktaren Prostatakarzinoms ab.

Several effective therapies are now available to cancer patients to either prolong and/or to improve their quality of life. However, most of them wish to take part in the decision - provided they do not intend to make it their own decision - whether or not and which possibly painful diagnostic or therapeutic procedure should be performed. It is particularly important when life is drawing to its close that the patient participates on own responsibility in deciding whether or not a particular therapy should be continued or terminated, his life prolonged, or whether merely pain-relieving measures should be employed. If the patient is no longer able to say this, he may express his intent via a person of his confidence. Life-prolonging measures may thus be excluded as life is gradually waning. Such "assistance while dying” is not culpable, contrary to "actively promoting the termination of life” which may be subject to criminal prosecution.

Management and leadership are an integral part of any organisation, to optimise procedures and increase efficiency. Aims, ideals and structures first need to be defined for tasks to be carried out successfully, particularly in difficult times. A good example for the way communities can effectively and with conviction pass on their values and standpoints from generation to generation, grow in strength and also influence their surroundings is provided by religion. This paper focuses leadership provided by charismatic personalities within the Jewish and Christian religions. Monasteries have run hospitals without governmental support ever since the Middle Ages. Leadership within today's health care system calls for a variety of strategies in the different phases of development. In times of limited resources and multifarious societies, leadership implies both a scientific as well as an ethical challenge.

Auch heute gehen fortgeschrittene Larynxkarzinome in den meisten Fallen mit einer sehr schlechten Prognose und einer hochgradig eingeschrankten Lebensqualitat der Patienten einher. Die vorliegende Fallstudie beschreibt die vielfaltigen und schwerwiegenden Komplikationen nach Durchfuhrung einer totalen Laryngektomie, trotz intensiver medizinischer Betreuung. Die Entwicklung und Einfuhrung neuer organerhaltender Verfahren bei fortgeschrittenen Larynxkarzinomen, ohne Einbusen fur das onkologisch- prognostische Ergebnis, stellen gegenwartig eines der aktuellsten klinisch onkologischen Forschungsgebiete bei den Kopf- Halstumoren dar. Anhand des vorliegenden Patientenbeispiels werden die aktuellen Therapiemoglichkeiten bei Patienten mit fortgeschrittenem Larynxkarzinom kritisch hinterfragt. Nach Meinung der Autorin ist es zur Erzielung der besten Lebensqualitat der Patienten erforderlich, die Wahl der Therapie im Rahmen einer intensiven interdisziplinaren Therapieplanung unter Einbeziehung aller zur Verfugung stehenden Therapieoptionen zu treffen.

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.

Patientenverfugungen, die Direktiven zur medizinischen Versorgung in zukunftigen Situationen geben, in denen ein Patient nicht mehr entscheidungsfahig ist, erscheinen als attraktives Konzept. Sie konnten viele schwierige Fragen im Zusammenhang mit der Fortsetzung, Beendigung oder Modifikation der Behandlung in solchen Situationen losen. Das Konzept hat jedoch zwei wichtige Voraussetzungen: Erstens die grundsatzliche Anerkennung des Selbstbestimmungsrechtes und zweitens, wird vorausgesetzt, das ein Patient medizinische Behandlung nicht nur hic et nunc bestimmen kann, sondern das seine Autonomie auch in spatere bewustlose, inkompetente Zustande hineinreicht. Diese zweite Bedingung verursacht die meisten ethischen Fragen und praktischen Probleme. Einige Probleme lassen sich durch sorgfaltige Erstellung der Verfugung, haufige Erneuerung und durch die Bestellung eines Sachwalters reduzieren. Der Deutsche Bundesgerichtshof hat in einer heftig diskutierten Entscheidung der Patientenverfugung eine wichtige Rolle in der Ermittlung des mutmaslichen Willen zugesprochen und gefordert, dass darauf Bedacht zu nehmen ist. Wir meinen, das die Patientenverfugung als nutzliches Instrument zur Verbesserung der Kommunikation bereits vor dem Verlust der Entscheidungsfahigkeit eingesetzt werden kann. Daher sollte das Angebot dazu bestehen und in den Prozes von Aufklarung, Begleitung und Entscheidungsfindung eingebunden werden.

qEpidemiologie: Die Inzidenzrate der akuten myeloischen Leukamie (AML) steigt altersabhangig deutlich an, die 5-Jahres-Uberlebensrate sinkt mit zunehmendem Alter des Patienten. qBiologie und Patient: Patienten mit AML werden ab einem Alter von 60 Jahren als alt angesehen. Diese Charakterisierung beruht auf patienten- und krankheitsspezifischen Parametern, die Unterschiede zwischen alten und jungen AML-Patienten zeigen. qTherapie: Standardtherapie ist eine dosisintensive Chemotherapie zur Induktion einer kompletten Remission, in deren Anschluss verschiedene Postremissionstherapien eingesetzt werden. Ein kleiner Teil der Patienten kann durch solch eine dosisintensive Chemotherapie geheilt werden. Die uberwiegende Zahl der Patienten verstirbt jedoch binnen 2 Jahren nach Diagnosestellung an ihrer Erkrankung oder an therapiebedingten Komplikationen. Die in den letzten Jahren im Rahmen der AML-Behandlung erreichten Verbesserungen der Behandlungsergebnisse sind uberwiegend bei jungeren Patienten erzielt worden. Aufgrund der geringen Heilungsrate und hoher therapieassoziierter Mortalitat stellt sich bei alteren Patienten mit AML die Frage, welche Patienten kurativ und welche eher mit einem palliativen, nebenwirkungsarmeren Konzept behandelt werden sollen. Die Wertigkeit palliativer Therapiekonzepte ist bisher wissenschaftlich nicht ausreichend uberpruft worden. Gerade bei geriatrischen Patienten mit AML wird daher einem multimodalen Assessment grose Bedeutung in der Planung von Studien zukommen. qAusblick: Verbesserungen der Behandlung lassen sich in Zukunft moglicherweise durch neue Substanzen, wie z.B. Signaltransduktionsinhibitoren, Antikorper und Angiogeneseinhibitoren, oder durch den Einsatz allogener Blutstammzellen nach nicht myeloablativer Konditionierungstherapie erreichen.

Die Hospizbewegung hat das wichtigste Ziel jeder arztlichen Arbeit wieder neu in Erinnerung gerufen. € Arztliche Kunst ist begrenzt, doch die Begleitung und Bemuhung um Lebensqualitat darf nicht an medizintechnischen Grenzen stehen bleiben. Im Gegenteil, die grosten Herausforderungen bestehen darin, menschliche Warme und Empathie mit modernster Medizintechnik gerade in den existentiellen Situationen in Harmonie zu bringen. Fachkompetenz des Arztes bedeutet im Angesicht des Sterbenden auch den Mut zu haben, die Grenzen scheinbar ohnmachtig auszuhalten. Gerade dann nicht davonzulaufen, wenn allemedizinischen Bemuhungen versagen, sondern die neuen Ziele der Begleitung physisch, psychisch, spirituell zu entdecken, Beschwerden kompetent zu lindern und zuletzt einfach den Patienten nicht alleine zu lassen. Denn nur wer die Erfahrung macht angenommen zu sein, wird sein Leid annehmen konnen. Der 3. Universitatslehrgang Palliativmedizin hat sich wiederum der Aufgabe gestellt, interdisziplinare Konzepte der Palliativmedizin in praxisorientierter Weise zu unterrichten. Die wissenschaftlich bewahrte Methode des Lernens durch Patientengeschichten (case-reports), die unterschiedliche Situationen und Herausforderungen systematisch anhand eines konkreten Beispiels beleuchtet, erlaubt einen praxisnahen Zugang zu dem Thema. Es wird dabei besonders deutlich, wie komplex und interdisziplinar palliative Medizin ist – und fast immer sogar weit uber die fachlich medizinische Ebene hinausgeht. Ein besonderes Anliegen der Kursleitung ist es,mit Unterstutzung von inlandischen und auslandischen Experten die neuesten wissenschaftlichen Erkenntnisse in die tagliche Praxis zu stellen. Die Aufbruchsstimmung – auch anspruchsvolle wissenschaftliche Fragestellungen neben der grosen Starke der Palliative Care im Sinne der psychosozialen Kompetenz einzubringen – ist in diesem Jahr sehr gut gelungen. Die vorliegenden Arbeiten sind ausgewahlte Beispiele, die unseren Ansatz verdeutlichen. Sinnhaftigkeit und Dauer einer Chemotherapie sind Fragen, die sich in der palliativen Chemotherapie fruher oder spater immer stellen und die Kenntnis der neuesten Studiendaten ebenso erfordern, wie eine einfuhlsame Kommunikation mit den Patienten, um den richtigen therapeutischen Weg zu finden. Die Arbeit von Heidemarie Seemann geht dieser Frage unter dem Leitziel der Lebensqualitat nach. Tumorschmerzen sind meist die wichtigste Storung der Lebensqualitat. Trotz Einsatzes aller konventioneller Mitteln bleiben manchmal Extremsituationen, die nicht ausreichend behandelbar sind. In solchen Fallen ist die invasive Schmerztherapie eine hilfreiche Erweiterung unseres Spektrums, wie die Arbeit vonOfenschussl zeigen kann. Interdisziplinaritat ist Kennzeichen einer gut funktionierenden Palliativmedizin. Gerade die Strahlentherapie erlaubt Behandlungsansatze in schwierigen Situationen und ist die wichtigste Masnahme bei Korrespondenz: Prim. Univ.-Prof. Dr. Johannes G. Meran, MA, Medizinische Abteilung, Krankenhaus der Barmherzigen Bruder Wien, Johannes von Gott Platz 1, 1020 Wien, Osterreich. Fax: þþ43-1-21121-2103, E-Mail: johannes.meran@bbwien.at editorial

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.

"Breaking Bad News" outlines a pathway for medical and other professional staff to deliver bad news to patients, clients, their families and carers. Bad news can mean different things to different people. Basically, it means any information which adversely and seriously affects an individual point of view of future or situations without any feeling of hope. The way a doctor or other health or social care professionals deliver bad news places an indelible mark on the doctor/professional-patient relationship. The debate about the levels of truth given to patients about their diagnosis has developed significantly over the last few years. While doctors and professionals now increasingly share information it has been the practice to withhold information because it was believed to be in the best interests of the patient. We discuss the situation of a patient with renal cancer who developed metastases after surgery. Unfortunately a tumour embolism from the kidney flashed into the pulmonary arteries. First it was not for sure if there were any metastases beside the tumour embolus. Months after embolectomy by thoracic surgery there was certain evidence of multiple pulmonary nodal lesions. First and second line chemotherapies failed and the patient died within several months after start of pharmacologic treatment. The case report discusses diagnosis and procedures, how the patient was supported and the way he got information at any critical date.

Jede arztliche Tatigkeit geht uber naturwissenschaftliche Probleme weit hinaus und erfordert immer wieder moralische Bewertungen. Ethik ist die »Theorie der Moral«, also die argumentative Auseinandersetzung mit Moral, die ihrerseits soziokulturell gepragte Regeln widerspiegelt (Schockenhoff 2007). Aufgabe der Ethik ist daher die Begrundung des sittlichen, guten Handelns. Der verantwortliche Arzt in Klinik und Praxis steht taglich vor wertenden Entscheidungen, bei denen er neben den rein medizinisch- physiologischen Daten vor allem Nutzen und Risiko, Wirkungen und Nebenwirkungen im Interesse der ihm anvertrauten Patienten abwagen muss. Eine medizinische Ethik kann dem Arzt keine Entscheidungen abnehmen, aber Grundlagen liefern um schwierige Entscheidungsprozesse konsistent, durchdacht und letztlich nach bestem Wissen und Gewissen zu gestalten.

I am reporting on a 74-year-old female patient with primary pulmonary and hepatic metastatic colon cancer. In the course of three-and-a-half years the patient decided to receive multiple cycles of palliative chemotherapy, irradiation of the liver and of the upper body. As a result of the extended anti-tumour therapy, remissions of the advanced cancer disease could be achieved repeatedly, which lead to a substantial increase of the patient's quality of life. This case shows that even in an advanced palliative situation the goal of a multimodal treatment is to curb disease progression and to extend the life and increase quality of life of the patient.

Optimal care for elderly cancer patients requires empathy and alertness about impaired autonomy and an exceptional quality of care. Specific to geriatric oncology is the particular need of attention and care for the patients. Most important from a conceptual point of view is to identify that this will result in additional demands. To care for these patients will require more time as any intervention must be adapted to age specific capabilities. The difficult task of shared decision-making should be preferably based on the quality of life assessment of the individual patient and their needs. The process of assessing quality of life is in itself already an act of enhancing autonomy, because it respects the individual's subjectivity. Many ethical questions arise between the contradictory contexts of paternalism and autonomy. There are conditions to be met and limits of autonomy to be considered, which differ for the elderly patients because of their vulnerability and particular dependencies. As the elderly patient is closer to death and dying, questions of care in these situations are frequently more pressing. It is important to distinguish actively intended euthanasia from the goals and concerns of modern palliative care in order to enable dying with dignity.

Paraprotein induced renal failure is a frequent complication of multiple myeloma and is associated with poor survival. Previously, reversal of renal function has been hampered by the lack of fast acting and highly effective myeloma therapy and most patients remained or became dependent on hemodialysis. Here we show reversal of acute paraprotein-induced renal failure by bortezomib-based therapy in 5 out of 8 patients. Improvement of renal function was preceded by a significant reduction in paraprotein concentration in all patients, with improvement in renal function.

Prostate cancer is the second-leading cause of cancer-related death among men and the seventh most common cause of death in the United States overall. As prostatic carcinoma is a slowly growing cancer depending on the tumor burden, use of PSA results in early cancer detection. pT2 tumors can be cured with low morbidity by radical prostatectomy. Five years after operation only few patients will experience further PSA recurrences. Adjuvant radiation therapy is effective in about half of patients with pT3 tumors in case of PSA recurrence. Most prostate cancers are androgen-dependent, meaning that they respond to androgen-ablation therapy. However, these tumors eventually become androgen-independent and grow despite androgen ablation. Since androgens are essential to the survival of prostate cells, a major question is how a prostate cell survives after androgen-ablation therapy. The mechanisms by which a prostate cancer cell survives after androgen-ablation therapy are conflicting. Specific targeting of genes involved in such pathways may further increase the chance of inventing new therapeutic options. So far, chemotherapy with docetaxel has been proved to prolong survival time and minimize cancer induced side effects in patients with hormone refractory prostate cancer.

Biomarkers as biochemical substances of collagen metabolism are produced during bone turnover and can be determined as parameters of bone metabolism not only in serum, but also in urine. These growth and decomposition products of the bone are already used to determine bone metabolism in osteoporosis and to prove efficacy of antiresorptive therapy. Metastases of the bone likewise show a higher rate of bone turnover. Nowadays detection of neoplastic bone lesions and progression of their spread are performed with x-rays, radionucleoide bone imaging and magnetic resonance imaging. In the future, biomarkers might improve early detection of bone lesions and follow-up of skeletal metastases. At present, the clinical use is documented insufficiently. In the foreseeable future the determination of the bone turnover markers and additional serum parameters of bone metabolism such as OPG, RANKL might be available for early diagnosis and follow-up in patients with bone metastatic diseases.

Management and leadership are an integral part of any organisation, to optimise procedures and increase efficiency. Aims, ideals and structures first need to be defined for tasks to be carried out successfully, particularly in difficult times. A good example for the way communities can effectively and with conviction pass on their values and standpoints from generation to generation, grow in strength and also influence their surroundings is provided by religion. This paper focuses leadership provided by charismatic personalities within the Jewish and Christian religions. Monasteries have run hospitals without governmental support ever since the Middle Ages. Leadership within today's health care system calls for a variety of strategies in the different phases of development. In times of limited resources and multifarious societies, leadership implies both a scientific as well as an ethical challenge.

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.

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.

296 Background: Urothelial cancer (UC) is a common tumor with a peak in the seventh decade. Locally advanced disease has a significant risk for developing metastases. Neoadjuvant, platinum-containing, combination chemotherapy improves survival over radical cystectomy (RC). Chemotherapy with gemcitabine plus cisplatin (GC) shows equivalent efficacy with less toxicity to methotrexate-vinblastine-doxorubicin- cisplatin (MVAC) in metastatic setting. Methods: We prospectively evaluated 23 elderly pts (8 female, 15 male) with a median age of 72 years, WHO performance status 0/1, with muscle invasive UC who received neoadjuvant GC (gemcitabine 1,000 mg/m2 days 1, 8, 15 and cisplatin 70 mg/m2, day 2 q28) for 3 cycles between 2006 and 2010 prior to RC. Assessments included toxicity of GC, pathologic response, progression free survival (PFS) and overall survival (OS). Results: 21 (91.3%) out of 23 pts finished intended chemotherapy. Two refused chemotherapy due to personal reasons. According to CTCAE guidelines 43.5% developed grade 3 hematologic toxicities; 13% developed grade 4 thrombopenia. Grade 3 non-hematologic toxicities included nausea in 2 patients. In 2 (8.7%) pts grade 4 thromboembolic events occurred. There was no treatment related febrile neutropenia or death. 15 (71.4%) of the pts underwent RC. 5 (23.8%) pts refused RC due to personal reasons. 1 of them agreed second look TURB. 1 patient underwent palliative radiotherapy due to progression of disease. Out of the 16 pts 43.75% achieved pathological response (18.75% pT0 stage and 25% pT1 stage). 56.25% had muscle invasive UC. 18.75% of them nodal positive disease. All 7 pts achieving < pT2 pathologic stage remained progression-free at a median follow up of 16 months. Pts > pT2 stage had a median PFS of 14 months. Median OS was not reached yet. Conclusions: Neoadjuvant GC is a well tolerated regiment in elderly pts and it seems to be less toxic than MVAC. Prophylactic anticoagulation during treatment should be considered. Although pathologic response is lower than in previously published retrospective data we recommend neoadjuvant treatment with GC in elderly pts. [Table: see text]