Luisa Massimo

Childhood Cancer Survivors in the Dark

In October 2002, the families of 1,360 longterm survivors of childhood leukemia or cancer were invited to a gala dinner commemorating the 30th anniversary of the Unit of Pediatric Hematology and Oncology of the Giannina Gaslini Children’s Hospital and Research Institute (Genova, Italy). The invitation was confidential and made no mention of past disease. Among the many families who answered, four long-term survivors declined, primarily because they had never known they had ever had cancer or did not remember. Confused about their health status and wanting to learn more about the disease they had endured, these four survivors asked to meet with the pediatrician-inchief who had cared for them more than 25 years ago. We report our findings on the experiences and distress of these four adults, who only recently learned they had cancer in early childhood. These cases provide telling examples of situations that might have been prevented if reflective communication had transpired among the patient, family, and caregivers during the original illness. The four individuals had learned from their parents only recently that they had a severe debilitating disease during early childhood and that they had to undergo regular follow-up for the following 5 years. None of them knew the exact diagnosis or name of the disease. Here are the details of each person’s story. A 36-year-old woman had abdominal Hodgkin’s lymphoma when she was 8 years old. She earned her college degree and is now a high school teacher. She was accompanied to the meeting by her husband. They concurred that theirs was a “perfect marriage.” They said the woman’s sterility was not a problem for either of them and that they had forgone adopting a child. The invitation to the gala aroused the woman’s suspicion about her past as a child patient and motivated her to request clarification. The account of her experience and the memory of some particulars, such as radiotherapy and intravenous chemotherapy sessions, together with her teaching background, induced a process of internalization and an awareness through which she reached the conclusion that she had indeed suffered from cancer early in her life. Her husband’s presence during the encounter was conducive to this realization, which both reached simultaneously. At the end of the meeting, they said they were glad to know about her past disease and to have discovered that her sterility was a late effect of the treatment. A 35-year-old woman had nonHodgkin’s lymphoma when she was 6 years old. She studied with no difficulties until age 19, when she married. She had two healthy children. When she received the invitation to the ceremony, her husband was astonished and then angry, convinced that she knew all about her disease but had, out of a lack of trust in him, hidden everything from him. During the couple’s meeting with us, she adamantly vowed she had known nothing about her disease. Dialogue was difficult at the outset of the conversation, due to each person’s unyielding stand. The compelling request for assistance was driven, above all, by the need to re-establish the trust that the couple seemed to have lost. The recollection of events occurring 25 years earlier proved From the Department of Pediatric Hematology and Oncology, G. Gaslini Scientific Children’s Hospital, Genova, Italy.

Young siblings of children with cancer deserve care and a personalized approach.

The youngest siblings may be both emotionally vulnerable and often neglected members of the family of a childhood cancer patient. The prompt identification of signs of distress in these subjects allows trained caregivers to intervene with personalized, age‐appropriate, attention, and care. A narrative approach, based on personalized listening, writings, and spontaneous drawings, can provide the means to elicit markers of psychological maladjustment in even the youngest of siblings. Two exemplary cases are reported to illustrate this approach. Pediatr Blood Cancer 2008;50:708–710.

Identification of novel prognostic markers in relapsing localized resectable neuroblastoma.

Patients with localized resectable neuroblastoma (NB) generally have an excellent prognosis and can be treated by surgery alone, but approximately 10% of them develop local recurrences or metastatic progression. The known predictive risk factors are important for the identification of localized resectable NB patients at risk of relapse and/or progression, who may benefit from early and aggressive treatment. These factors, however, identify only a subset of patients at risk, and the search for novel prognostic markers is warranted. This review focuses on the recent advances in the identification of new prognostic markers. Recently we addressed the search of novel genetic prognostic markers in a selected cohort of patients with stroma-poor localized resectable NB who underwent disease relapse or progression (group 1) or complete remission (group 2). High-resolution array-comparative genomic hybridization (CGH) DNA copy-number analysis technology was used. Chromosome 1p36.22p36.32 loss and 1q22qter gain, detected almost exclusively in group 1 patients, were significantly associated with poor event-free survival (EFS). Increasing evidence points to anaplastic lymphoma kinase (ALK) as a fundamental oncogene associated with NB. The immunohistochemical analysis of sporadic NB localized resectable primary tumors (stage 1-2) showed a correlation between aberrant ALK level of expression and tumor progression and clinical outcome. Moreover, other factors that might influence the clinical behavior of these tumors will be reviewed.

Long-term survivors of childhood cancer: Cure and care. The Erice Statement

ZusammenfassungIn den letzten Jahren ist die Anzahl von Patienten, die erfolgreich wegen einer Krebserkrankung im Kindesalter behandelt wurden, stetig angestiegen. Mitglieder des Früh- und Spättoxizitäts- sowie Ausbildungskomitees der internationalen Berlin-Frankfurt-Münster Studien-Gruppe (I-BFM-SG-ELTEC) haben 45 pädiatrische Krebsspezialisten (Onkologen, Psychologen, Pflegepersonal, Epidemiologen, Eltern und Überlebende) aus 13 europäischen Ländern (zusätzlich 5 Experten aus Nordamerika) vom 27.–29.10.2006 nach Erice (Sizilien) eingeladen, um die Lebenssituation der Kinder nach einer Krebserkrankung zu besprechen, eine Definition von Heilung festzulegen sowie die Notwendigkeit und die Organisation der Nachbeobachtung und Nachsorge zu diskutieren. Es war das erklärte Ziel der Konferenz, mit Hilfe der persönlichen und professionellen Erfahrung der Teilnehmer ein generelles Dokument zu erarbeiten, das die Meinung dieser Arbeitsgruppe zur Heilung und Nachsorge von Überlebenden einer Krebserkrankung im Kindesalter wiedergibt. Dies ist in den 10 Punkten des Erice-Dokuments zusammengefasst.AbstractThe number of individuals who have successfully completed treatment for a cancer diagnosed during childhood and are entering adulthood has been increasing. Members of the International Berlin–Frankfurt–Munster Early and Late Toxicity Educational Committee (ELTEC) invited 45 paediatric cancer experts – representing oncologists, psychologists, nurses, epidemiologists, parents, and survivors – from 13 European countries, with five additional experts from North America, to Erice, Sicily, on October 27–29, 2006, to discuss the circumstances in which the word “cure” should be used when speaking about children with cancer, and when and why continuing follow-up and care may be required. The objective of the gathering was to generate from the participants’ personal and professional experiences an overview statement of the group’s philosophy of cure and care of survivors of childhood cancer. The 10 points reflect what the group considers essential for the survivors’ cure and care.

Health migration and care disparities

To the Editor: Pediatricians realize that there is variability in the treatment of children with cancer, as highlighted by Bhatia in her excellent review [1]. There is widespread agreement that in the US these disparities are deep-rooted and historical [2]. For some countries, however, tackling this problem is a relatively new issue due in large part to the increase in health migration [3,4] over the past several years. Nearly 30% of the children with cancer currently treated in our Department come from Eastern Europe, North Africa, and Latin America, that is, regions where conditions and standards, especially for rare and complex cases, limit regular access to appropriate care [5,6]. However, immigration trends of foreign patients without medical assistance have been stable over the last few years, but the percentage of severely ill patients that are admitted to our department is on the rise (Fig. 1). Most of them come in order to undergo SCT for congenital hematologic diseases, immunodeficiency or second/third line cancer therapy. They arrive with support from the Italian Army, Non-Governmental Organizations (NGOs), Parents’ Associations, or are directly sent by their local hospitals. Only a few families can afford the full cost of stay and treatment. Moreover, approximately 9.7% of the pediatric population between 0 and 2 years of age in Italy is made up of children of immigrant workers [7] for whom coverage is provided by the National Health Service, as it is for Italian citizens. This flow of foreign patients has brought with it noteworthy difficulties that have forced our physicians and nurses to adopt different approaches towards patients and their families who often have different perceptions of health and health care. Cultural and language barriers may impede empathic dialogue between the healthcare team and families, sometime jeopardizing compliance with, and control of treatment. In extreme cases, the lack of mutual understanding can engender anger and mistrust. Beyond the medical issues, the migration of patients and their families entails countless other difficulties including financial, administrative, logistic, psychological, spiritual, and cultural ones. Furthermore, it involves numerous individuals, both inside and outside the hospital, including embassies, patients’ organizations, and NGOs. Nevertheless, cancer treatment outcomes among our foreign patients hardly parallel those of Italian children, and do not exceed 50%. There may be several reasons for this discrepancy, such as the fact that most children reach our Unit with advanced disease, severe infections, misunderstandings about medical explanations, and less compliance with therapy and rules of hygiene. Only by raising healthcare standards in those countries from which patients tend to leave can the above challenges be overcome [8]. In the meantime, medical teams having to care for culturally diverse patients must be adequately trained and supported in order to properly and sensitively deliver the necessary care. At our center we have made attempts to improve patient/health team communication by increasing the presence of cultural mediators, and we are currently looking into other strategies.

Challenge of migrating patients

Legido-Quigley and McKee raise some of the thornier issues faced by healthcare authorities dealing with patients seeking medical care outside their own country.1 As with countless other tertiary hospitals throughout Europe, our centre, the largest public paediatric facility in Italy, has had to come to grips with this new …

Translational research in hormone-related cancer.

Hormones are implicated in various types of cancer, however, several aspects of steroid activity on carcinogenesis remain elusive. Recent progress has made it possible for us to directly study the biological mechanisms of disease development, including hormone−cancer relationships, from numerous viewpoints, from numerous viewpoints, including genome abnormalities. One tool is comparative genomic hybridization array (aCGH). Furthermore, it is possible to identify the so‐called “cancer signature” by gene expression profiling, which provides new information about the role of steroids on carcinogenesis. DNA mutations and gene expression abnormalities may be associated with hormone‐related cancer. The recent discovery of microRNA provides new opportunities for understanding the fine regulation of gene expression in cancer cells, and the role of microRNA in the relationship between hormones and cancer. From these experimental models we should be able to rapidly develop translation‐to‐treatment protocols. The final goal should be to design specific labs on a microchip for prognosis and therapy of individual patients. While in clinical research there is renewed attention to stratification of patients, especially those at high risk.

Thymoma in children: Clinical and immunological features in three cases

Three cases of thymoma (two girls aged 8 and 12 years and one boy aged 4 years) are reported. The anterior mediastinal tumor was responsible in all three cases for a progressive compression of the surrounding tissues causing cough and dyspnea and, in the boy, for superior vena caval compression. A clinically silent immune imbalance was present in all three cases: although the frequency of infections was not increased, low mitogen responsiveness and/or dysgamma-globulinemia were observed on several occasions during follow-up in two of the three children, while in the third abnormally high percentages of T6+ and T9+ circulating lymphocytes were detected. Moreover, in all three, impairment of skin reactivity to common T-dependent antigens was demonstrated.

Needs and expectations of adolescent in-patients: the experience of Gaslini Children's Hospital.

Abstract Background: Adolescents affected by a severe disease who undergo high-risk treatment may experience stress, pain, extreme frustration, depression, and anger. In this large spectrum of emotions, several situations must be considered carefully. To improve coping and quality of services offered to adolescents in paediatric hospitals, we elaborated a semi-structured interview and a short questionnaire (Quality of life-adolescent-Istituto Giannina Gaslini, QoL-adol-IGG scale) to investigate the quality of life, the needs and expectations of adolescent in-patients. Methods: The study sample includes 117 in-patients aged between 10 and 20 years coming from several Italian regions who were admitted to the G. Gaslini Research Children’s Hospital for a period of 10 days or more, regardless of the disease. The QoL-adol-IGG scale was administered – after obtaining informed consent from the children and their parents – in one single encounter by trained psychologist. The distribution of the answers was evaluated after stratification by patient’s age, gender, area of residence, and clinical diagnosis. Continuous data were compared using the Kruskal-Wallis, while the χ2-test was used for categorical data. Results: Seventy-two percent had difficulty practicing normal daily activities during their stay in the hospital, not only because of the disease (40%), but also because of the poor organization within the hospital, the lack of proposals/activities and space for spare time, and the limited access to technologies. Adolescents ≥15 years were more frequently dissatisfied than youngsters concerning the access to Internet and other technologies, the possibility to make new friends and to take part in social activities. Conclusion: The results of this study, which evaluated the hospital’s organization, but also psychological functioning in a representative sample of patients, may contribute to optimize internal procedures of clinical departments where adolescent in-patients are present, on the basis of their requests and taking into account their age.