Etoposide, cisplatin, epirubicin chemotherapy in the treatment of pediatric liver tumors

To discuss the potential benefit of a chemotherapy regimen including etoposide (etoposide, cisplatin, epirubicin [EPE]), the authors report a single-institutional experience regarding 13 children with hepatoblastoma (HB) and 7 with hepatocellular carcinoma (HCC). Chemotherapy achieved partial response in 8/9 HB and in 4/5 HCC. Eight initially unresectable HB subsequently had liver resection. Event-free survival and overall survival at 5 years were 84 and 88% for HB (nonmetastatic cases: 91 and 100%), 29% for HCC. EPE chemotherapy seems to be effective in the treatment of childhood malignant liver tumors. Etoposide could be suggested as part of intensive multidrug regimens for HCC and high-risk HB.     

WT1 gene analysis in sporadic early-onset and bilateral wilms tumor patients without associated abnormalities

The WT1 gene is responsible for two different genetic conditions characterized by genitourinary anomalies and susceptibility to Wilms tumor (WT): the WAGR syndrome and the Denys-Drash syndrome. Although only rarely, WT1 constitutional mutations have been reported also in WT patients without congenital defects. Due to the high survival rates that characterize the disease, these individuals must be identified and counseled in relation to their risk to transmit a cancer-predisposing genetic lesion to their offspring. Recently, tumor bilaterality and early age of onset have been suggested to be risk factors for carrying germline WT1 mutations. The authors investigated 20 patients with sporadic WT, without evidence of congenital abnormalities, diagnosed before 2 years of age and/or with bilateral presentation, for the occurrence of WT1 mutations. Southern blot analyses identified homozygous whole-gene or intragenic deletions at the tumor level in three cases. However, none of the identified alterations was found to be present at the germline level. In addition, no mutation in the coding exons and flanking sequences of WT1 was detected in the remaining 17 cases. These results suggest that early age of diagnosis and bilaterality are not by themselves efficient predictors of germline WT1 alterations in WT patients without associated abnormalities.     

Bilateral preaxial polydactyly in a WAGR syndrome patient

We report on a 30-month-old baby girl with typical clinical features of WAGR syndrome. In addition, the patient showed bilateral preaxial polydactyly of the feet. Cytogenetic and fluorescent in situ hybridization (FISH) analyses identified a deletion, del(11)(p13p14.1), extending from 6.1 to 21.7 Mb in size. Although the simultaneous appearance of WAGR and polydactyly has been already described, to our knowledge this is the first case in which the characterization at the cytogenetic molecular level of a patient with these phenotypes is reported. These observations indicate that preaxial polydactyly may be another feature of the WAGR syndrome and suggest the existence of a related gene in the WAGR critical region or in its proximity.     

Use of the word “cured” for cancer patients—implications for patients and physicians: the Siracusa charter

Long-term survival for adult patients with solid tumours continues to increase. For some cancers, the possibility of recurrence after a number of years is extremely low, and the risk of death becomes similar to that of the general population of the same sex and age.During the Fifth European Conference on Survivors and Chronic Cancer Patients held in Siracusa, Italy, June 2014, oncologists, general practitioners, epidemiologists, cancer patients and survivors, and patient advocates joined to discuss the possible use of the term “cured” in reference to some adult patients with solid tumours. The specific focus was the appropriateness of using the term in communicating with cancer patients, survivors, and their families. Initial results of the discussion, in concert with a review of the published literature on the subject, were later further discussed by all participants through electronic communication. The resulting final statement aims to suggest appropriate ways to use the word “cured” in the clinical and communicative setting, to highlight the potential impact of the word on patients, and to open a critical discussion concerning this timely and delicate matter.     

Bax mutation and overexpression inversely correlate with immature phenotype and prognosis of childhood germ cell tumors

Primary childhood germ cell tumors (GCTs) represent a rare and heterogeneous group of tumors that varies in histologic differentiation, age of presentation and clinical outcome. In malignant neoplasms, apoptosis is a prognostic marker and a predictive factor of response to therapy. Therefore, the study of the expression and mutation of molecules involved in the regulation of apoptosis could be useful in order to both predict the clinical outcome and design self-tailored therapeutic approaches. We retrospectively analysed tissue samples of 54 childhood GCTs. The expression of p53 and BAX protein was assessed by immunohistochemistry (IHC). Moreover, we investigated the presence of mutations in the BAX and p53 genes SSCP-PCR and direct sequencing. IHC analysis of BAX protein expression showed that 14 out of 54 tumors (26%) had no BAX protein expression, in the remaining 40 patients (74%) the intensity of BAX was low in 20 patients (37%) and high/intermediate in 20 (37%). BAX was mutated in 6 patients. p53 was expressed in 43 patients (79.6%), was not detectable in the remaining 11 (20.4%) and mutated in only 3 patients. p53 mutational status and expression were not correlated to the overall survival (OS). On the other hand, both IHC score and mutations for BAX were correlated to sacrococcygeal primary localization. BAX mutations were inversely correlated with OS (p=0.0419) while BAX IHC intensity was directly correlated with OS (p=0.0376). The stratification for histotype showed a direct correlation between BAX IHC and OS in both immature teratoma (p=0.045) and mixed malignant GCT (p=0.010) while the correlation was lost in mature teratoma (p=0.300). These results indicate that both mutations and BAX protein levels are useful molecular biological markers for prognosis and clinical management of pediatric GCT.     

Adopting model checking techniques for clinical guidelines verification

ObjectivesClinical guidelines (GLs) are assuming a major role in the medical area, in order to grant the quality of the medical assistance and to optimize medical treatments within healthcare organizations. The verification of properties of the GL (e.g., the verification of GL correctness with respect to several criteria) is a demanding task, which may be enhanced through the adoption of advanced Artificial Intelligence techniques. In this paper, we propose a general and flexible approach to address such a task.Methods and materialsOur approach to GL verification is based on the integration of a computerized GL management system with a model-checker. We propose a general methodology, and we instantiate it by loosely coupling GLARE, our system for acquiring, representing and executing GLs, with the model-checker SPIN.ResultsWe have carried out an in-depth analysis of the types of properties that can be effectively verified using our approach, and we have completed an overview of the usefulness of the verification task at the different stages of the GL life-cycle. In particular, experimentation on a GL for ischemic stroke has shown that the automatic verification of properties in the model checking approach is able to discover inconsistencies in the GL that cannot be detected in advance by hand.ConclusionOur approach thus represents a further step in the direction of general and flexible automated GL verification, which also meets usability requirements.     

Secondary osteosarcoma: a challenge indeed

International Journal of Clinical Oncology - The risk of survivors developing a secondary bone sarcoma after being treated for pediatric cancers is well established. The aim of this study was to...     

Undifferentiated nasopharyngeal carcinoma in children and adolescents: comparison between staging systems.

BACKGROUND: New criteria for classifying nasopharyngeal carcinoma were defined in the 5th edition of the American Joint Committee on Cancer (AJCC) staging manual. We investigated the clinical implications of the new system by comparing it with the 4th edition in a cohort of pediatric undifferentiated nasopharyngeal carcinoma (UNPC). PATIENTS AND METHODS: We retrospectively restaged 54 patients younger than 17 years who had biopsy-proven UNPC, treated between 1965 and 1999 in a single institution. RESULTS: Using the 5th edition an overall downstaging of the population according to T status, N status, and stage grouping was evident along with a better correlation with likelihood of survival. The comparison between local and advanced disease according to T stage (T1+T2 vs. T3+T4) became highly significant in the new system (P = 0.0011 vs. P = 0.067 in the 4th edition). CONCLUSIONS: As far as prognostic categories are concerned, the 5th edition of the AJCC staging manual appears to be an improvement over the previous classification, even though for pediatric patients a uniform distribution among stages cannot be observed because most children present with advanced disease. The overall downstaging should be taken into consideration for the stratification of patients in future trials.