Recent Results in Cancer Research最新文献

LDLT covers all standard indications for liver transplantation, and the results are similar or even better than for standard DDLT. Due to the donor shortage and long waiting time, LDLT has become a relevant option for patients with liver tumors, provided the expected five-year survival rate is comparable to that of patients receiving a DDLT. Nowadays, LDLT offers the possibility to extend the standard morphometric selection by considering the biological parameters. In the setting of LDLT, we are not only faced with surgical morbidity in the donor, but long-term non-medical problems like psychological complications and financial burden also have to be considered. On the other hand, the benefits to the donor are mainly social and psychological. In LDLT, the donor's altruism is the fundamental ethical principle and it is based on the principles of (1) beneficence (doing good), (2) non-maleficence (avoiding harm), (3) respect for autonomy, and (4) respect for justice (promoting fairness). On top of that, the concept of double equipoise of living organ donation evaluates the relationship between the recipient's need, the donor's risk, and the recipient's outcome. It considers each donor-recipient pair as a unit, analyzing whether the specific recipient's benefit justifies the specific donor's risk in particular oncologic indications. In this light, it is essential to seek adequate informed consent focused on risk, benefits and outcome benefits of both donor and recipient supported by an independent living donor advocate. Finally, the transplant team must protect donors from donation if harm does not justify the expected benefit to the recipient.

Human papillomavirus (HPV) vaccination of young adolescent girls as a part of primary prevention of cervical cancer is now a routine practice in many countries. Bangladesh, a lower-middle income country, observed a successful HPV vaccination demonstration program recently. As much as the benefits of the vaccination programs are well-recorded, the ethics of administration of it is not focused highly; rather the focus tends to be on the most efficient method to get it done. In countries like Bangladesh, vaccination-related ethical issues are often overlooked. Thus, addition of HPV vaccination to the existing immunization programs calls for logical discussion and consideration to preserve the highest ethical standard in administering this vaccine to a sensitive age group of adolescence. This chapter summarizes some ethical concerns related to the HPV vaccination implementation in Bangladesh.

This article is a revised version of our proposal for the establishment of the legal concept of risk-adjusted prevention in the German healthcare system to regulate access to risk-reduction measures for persons at high and moderate genetic cancer risk (Meier et al. Risikoadaptierte Prävention'. Governance Perspective für Leistungsansprüche bei genetischen (Brustkrebs-)Risiken, Springer, Wiesbaden, 2018). The German context specifics are summarized to enable the source text to be used for other country-specific healthcare systems. Establishing such a legal concept is relevant to all universal and free healthcare systems similar to Germany's. Disease risks can be determined with increasing precision using bioinformatics and biostatistical innovations ('big data'), due to the identification of pathogenic germ line mutations in cancer risk genes as well as non-genetic factors and their interactions. These new technologies open up opportunities to adapt therapeutic and preventive measures to the individual risk profile of complex diseases in a way that was previously unknown, enabling not only adequate treatment but in the best case, prevention. Access to risk-reduction measures for carriers of genetic risks is generally not regulated in healthcare systems that guarantee universal and equal access to healthcare benefits. In many countries, including Austria, Denmark, the UK and the US, entitlement to benefits is essentially linked to the treatment of already manifest disease. Issues around claiming benefits for prophylactic measures involve not only evaluation of clinical options (genetic diagnostics, chemoprevention, risk-reduction surgery), but the financial cost and-from a social ethics perspective-the relationship between them. Section 1 of this chapter uses the specific example of hereditary breast cancer to show why from a medical, social-legal, health-economic and socio-ethical perspective, regulated entitlement to benefits is necessary for persons at high and moderate risk of cancer. Section 2 discusses the medical needs of persons with genetic cancer risks and goes on to develop the healthy sick model which is able to integrate the problems of the different disciplines into one scheme and to establish criteria for the legal acknowledgement of persons at high and moderate (breast cancer) risks. In the German context, the social-legal categories of classical therapeutic medicine do not adequately represent preventive measures as a regular service within the healthcare system. We propose risk-adjusted prevention as a new legal concept based on the heuristic healthy sick model. This category can serve as a legal framework for social law regulation in the case of persons with genetic cancer risks. Risk-adjusted prevention can be established in principle in any healthcare system. Criteria are also developed in relation to risk collectives and allocation (Sects. 3, 4, 5).

The expansion of genetic diagnostic potential in the direction of future contingencies (risks) creates temptations and compulsions for timely knowledge and responsible-sometimes radical-prevention. In the area of mamma carcinoma, the 'Angelina Jolie effect' has not only been a media topic but has had real consequences. The undisputed right to knowledge is increasingly taking on the character of a general recommendation or even norm for society as a whole, regardless of the possibly toxic consequences of discovering a predisposition. In an "enlightened knowledge society" in which health and illness increasingly "appear as products of our own actions" (Giovanni Maio), not wanting to know is difficult; thus, it is all the more significant that this concept has found widespread recognition in current law. Its legal practical implementation, however, presents several questions that have not yet been fully clarified, for example in connection with incidental medical findings or family members affected as third parties. It is also unclear how, in the age of next-generation sequencing and the standardizing digitalization of medicine and society, it will be possible to counteract the cultural bias in favour of knowledge, even outside the law.

Human papillomaviruses (HPVs) are small DNA viruses that infect basal epithelial cells and are the causative agents of cervical, anogenital, as well as oral cancers. High-risk HPVs are responsible for nearly half of all virally induced cancers. Viral replication and amplification are intimately linked to the stratified epithelium differentiation program. The E6 and E7 proteins contribute to the development of cancers in HPV positive individuals by hijacking cellular processes and causing genetic instability. This genetic instability induces a robust DNA damage response and activating both ATM and ATR repair pathways. These pathways are critical for the productive replication of high-risk HPVs, and understanding how they contribute to the viral life cycle can provide important insights into HPV's role in oncogenesis. This review will discuss the role that differentiation and the DNA damage responses play in productive replication of high-risk HPVs as well as in the development of cancer.

Medicines, including those intended for the treatment of cancer, are tightly regulated. Such regulation, historically linked to disasters due to unsafe medicines, evolved to cover all aspects of research around the quality, safety and efficacy of candidate medicines. This chapter intends to give an introduction on what regulators do and where the ethical foundations for regulating medicines might be searched. Some specific dilemmas will be explored, such as (i) whether at all, and if so subject to which conditions, research on animals is justified; (ii) what to do when potentially useful data on a medicine were collected unethically; (iii) which additional ethical challenges are posed by the fact that regulators have to make decisions on a medicine under uncertainty; and (iv) how to account for patients' preferences (and their heterogeneity) in regulatory decision-making. An overview of emerging topics such as use of healthcare data and open science is also proposed. While not intending to cover all arguments in the complex conversation around the regulation of medicines for cancer (let alone, around the regulation of medicines in general), this chapter aims to give a basis for further reading.

The care of pediatric cancer patients is a vast departure from cancer care of adults. While the available treatment modalities-chemotherapy, radiation, and surgery-are the same, the diseases, care-delivery, and outcomes differ greatly. And just as 'children are not just little adults,' pediatric bioethics occupies a distinct place within the broader field of bioethics. In this chapter, we will begin with an introduction to fundamental principles and frameworks for understanding ethical issues in pediatrics, highlighting the triadic nature of medical decision-making between a physician, the child-patient, and the child's parent as the surrogate decision-maker. We will then delve into further details of how these principles and frameworks shape the care of children with cancer, examining specific ethical challenges commonly encountered by pediatric oncologists. We will traverse this landscape by examining issues involving (a) informed consent; (b) research involving children; (c) end of life; (d) genetic and genomic testing; and (e) professionalism. We also examine ethical challenges in clinical research, in children and more broadly. While not an exhaustive exploration of the myriad ethical issues one might encounter in pediatric cancer medicine and clinical trials, this chapter provides readers with a foundation for further reading.

There are undoubtedly sick people who suffer terribly, and of course this should not be. No patient with incurable cancer is to be so tortured for months or years that they want only to die and lack the means to do so. Being unable to die can be worse than death, one might say or think. But until we ourselves have crossed that frontier, we do not know this for certain. To die could be worse than not being able to die. One case is difficult to distinguish from the other. But we pretend we can distinguish them if we praise assisted suicide and euthanasia as solutions to a problem that we not only do not solve, but make worse. Do we need assisted suicide in the face of non-dying skills? The author's answer is no: we do not need euthanasia, neither in that nor in any other case. The logic of euthanasia itself decrees that it cannot be restricted to exceptional cases, based as it is on the idea that the patient's autonomy is to be valued more highly than their actual illness. But if autonomy were of absolute value, it could not be limited to cases of severe disease. The reasons which supporters of euthanasia cite for limiting assisted suicide to the most serious cases of illness, therefore, speak against euthanasia in general. Once the first step has been taken, the application can no longer be limited if, on the one hand, the 'autonomous' desire for death is superior to any counter-argument, and on the other hand, no state of illness is conceivable that could call into question the alleged autonomy.

Cancer is the second leading cause of death globally. Malignant tumours are responsible for about 9.6 million deaths in 2018 (Ritchie H (2019) How many people in the world die from cancer? https://ourworldindata.org/how-many-people-in-the-world-die-from-cancer ). Worldwide, about 1 in 6 deaths is due to cancer. This confronts researches with the question of their origin and doctors with treatment options. It is common sense that great efforts should be done in order to reduce the number of cancer-specific deaths. In recent years, in lots of countries a variety of cancer screening programs have been developed, investigated and improved. The basic idea of this approach seems to be quite simple: Tumours will be detected at a very early stage when patients do not yet feel clinical symptoms. Thus, using an appropriate therapy, progression of the disease can be prevented and, concerning a whole population, disease-specific mortality should be reduced. Actually, after the introduction of screening programs, an increasing number of new cancer cases can be observed associated with an apparent reduction of the case fatality rate (i.e. the proportion of deaths due to cancer). Partly, the increasing number of cancers may be explained by the fact that people have a higher life expectancy. Under this aspect, the decreased case fatality rate could be considered as a success which may be attributed to screening efforts. However, there is still insufficient evidence affirming benefits of screening programs for crucial outcomes, i.e. all-cause mortality. In this narrative review, the phenomenon that probabilities and risks are rather often interpreted in an inadmissible way will be described. Furthermore, conceptual issues and inconsistencies between evidence and opinion about screening will be explored.

In recommending and offering screening, health services make a health claim ('it's good for you'). This article considers ethical aspects of establishing the case for cancer screening, building a service programme, monitoring its operation, improving its quality and integrating it with medical progress. The value of (first) screening is derived as a function of key parameters: prevalence of the target lesion in the detectable pre-clinical phase, the validity of the test and the respective net utilities or values attributed to four health states-true positives, false positives, false negatives and true negatives. Decision makers as diverse as public regulatory agencies, medical associations, health insurance funds or individual screenees can legitimately come up with different values even when presented with the same evidence base. The main intended benefit of screening is the reduction of cause-specific mortality. All-cause mortality is not measurably affected. Overdiagnosis and false-positive tests with their sequelae are the main harms. Harms and benefits accrue to distinct individuals. Hence the health claim is an invitation to a lottery with benefits for few and harms to many, a violation of the non-maleficence principle. While a public decision maker may still propose a justified screening programme, respect for individual rights and values requires preference-sensitive, autonomy-enhancing educational materials-even at the expense of programme effectiveness. Opt-in recommendations and more 'consumer-oriented' qualitative research are needed.