Survival of adults treated for medulloblastoma using paediatric protocols

We retrospectively studied 26 consecutive adults treated for medulloblastoma using paediatric protocols. Between 1987 and 2003, patients 18 years old were given adjuvant chemotherapy consisting of one of two 'paediatric' regimens (depending on the time of presentation) and craniospinal local-boost radiotherapy: regimen A (n = 12), vincristine (VCR), intrathecal and/or intravenous methotrexate and conventional radiotherapy; or regimen B (n = 11) sequencing intensive doses of multiple agents followed by hyperfractionated accelerated radiotherapy (HART). A VCR-lomustine-based maintenance followed both regimens. Three additional patients received a tailored treatment due to their impaired neurological status after surgery. The median age at diagnosis was 26 years (range 18-41 years). With a median follow-up of 46 months, 5-year disease-free and overall survival rates were 65+/-11% and 73+/-10%, respectively, for the series as a whole. All patients who received regimen B (5 of whom had metastatic Chang M2-M3 disease) are alive with no evidence of disease at 39 months. Although the number of patients is limited, our data suggest that the sandwich sequential, moderately intensive chemotherapy in combination with HART is an effective treatment for medulloblastoma in adults, and this approach seems to overcome previously-recognised risk factors.     

Adjuvant and neoadjuvant chemotherapy for osteosarcoma of the extremities: 27 year experience at Rizzoli Institute, Italy

Around 1148 patients with non-metastatic osteosarcoma of the extremity were treated in a single institution between 1972 and 1999 with 4 different protocol of adjuvant and 7 different protocols of neoadjuvant chemotherapy. The rate of limb salvage increased from 20% to 71%. The 5-year event-free survival (EFS) and overall survival (OS) were 57% and 66%, respectively. The 10-year EFS and OS were 52% and 57%, respectively, and the results significantly correlated with serum alkaline phosphatase levels; the type of chemotherapy (adjuvant vs neoadjuvant); and with histologic response to pre-operative treatment. Aggressive chemotherapy and surgery could cure about the 60% of patients with osteosarcoma of the extremity. However, since local or systemic relapses, myocardiopathies and a second malignancy are possible even 5 or more years since the beginning of treatment, a long-term follow-up is recommended.     

Converging patterns of colorectal cancer mortality in Europe

Trends in mortality rates from colorectal cancer during the second half of the 20th century were analysed for 21 European countries and grouped in three broad European regions. For each gender, age-standardised (world standard population) mortality rates were computed by the direct method, and joinpoint analysis was used to identify significant changes in rates. A favourable pattern in colorectal cancer mortality for both genders was observed in most European countries from the 1990s onwards. Colorectal cancer mortality rates were still in the upward direction in some Eastern European countries, as well as in some Mediterranean countries. Mortality rates tended to converge at around 20/100000 in men and around 11/100000 in women. This converging pattern is even clearer when colorectal mortality rates are examined in three broad European regions. Similar mortality rates over recent calendar years have been reached by countries where mortality has been decreasing in recent decades and in those countries (mainly Eastern European and Mediterranean countries) which have experienced a recent levelling-off and decrease. If recent trends are maintained, colorectal cancer mortality is likely to decline further in Europe in the current decade.     

Bovine seminal ribonuclease is cytotoxic for both malignant and normal telomerase-positive cells

Bovine seminal-ribonuclease (BS-RNase) is a member of the 'ribonucleases with special biological actions' family since it possesses specific anti-tumour, anti-spermatogenic and embryotoxic activities and exerts an immunosuppressive effect on T lymphocytes. In previous studies it was demonstrated that BS-RNase induced apoptosis in proliferating, malignant and normal cells and that telomerase activity loss also caused apoptotic death in neoplastic cells. Since an obvious relationship between cell proliferation and telomerase activity exists, the aim of this work was to study if the pro-apoptotic cytotoxic action exerted by BS-RNase on proliferating malignant cells (HT29) and proliferating normal cells (PHA-stimulated lymphocytes) could be linked to a possible BS-RNase effect on telomerase activity. In BS-RNase-treated HT29 cells (Na-butyrate-differentiated or not) and human lymphocytes (proliferating or not), we investigated cell vitality (MTT method) and morphology (SEM), BS-RNase localization (immunofluorescence), telomerase activity (TRAP-ELISA method), hTR mRNA expression (RT-PCR), and hTERT levels (western blot). While no BS-RNase effect was detectable on not proliferating cells, a clear relationship was noticed between the diminished number of vital elements of both proliferating cell populations after treatment (48 h and 72 h for HT29 and PHA-stimulated lymphocytes, respectively) with 50 microg/ml BS-RNase and the decrease of their telomerase activity. At the same time, we found that hTR levels, the RNA subunit of telomerase, in proliferation-inhibited BS-RNase-treated cells were diminished. Moreover, by immunofluorescence technique, we detected BS-RNase in the HT29 cell nucleolus after 3-h treatment. Therefore, as hTR has been recently proven to co-fractionate with nucleoli, we hypothesize that a BS-RNase direct action on the telomerase hTR subunit could be a possible mechanism of action by which BS-RNase exerts its pro-apoptotic effects only on proliferating cells.     

Brain tumors in children and adolescents: cognitive and psychological disorders at different ages

Cognitive and psychological disorders are among the most frequently observed sequelae in brain tumor survivors. The goal of this work was to verify the presence of these disorders in a group of children and adolescents diagnosed with brain tumor before age 18 years, differentiate these disorders according to age of assessment, identify correlations between the two types of impairments and define possible associations between these impairments and clinical variables.The study involved 76 patients diagnosed with brain tumor before age 18 years. Three age groups were formed, and all the patients received a standardized battery of age-matched cognitive and psychological tests.According to our findings, all three groups present with cognitive and psychological-behavioral disorders. Their frequency varies according to age of onset and is strongly associated to time since diagnosis. The performance intelligence quotient (PIQ) was more impaired than the verbal intelligence quotient (VIQ). Internalizing problems, withdrawal and social problems were the most frequent psychological disorders. Correlations were found between cognitive impairment and the onset of the main psychological and behavioral disorders.These findings are relevant as they point out the long-term outcome of brain tumor survivors. Hence, the recommendation to diversify psychological interventions and rehabilitation plans according to the patients' age.     

The predictive value of CD8, CD4, CD68, and human leukocyte antigen-D-related cells in the prognosis of cutaneous malignant melanoma with vertical growth phase

BACKGROUND: To establish the prognostic value of immune system cells that infiltrate melanoma, the authors evaluated the distribution and density of T lymphocyte subsets, macrophages, and dendritic cells in samples of primary cutaneous melanoma from 47 patients with Stage I and II melanoma according to the American Joint Committee on Cancer staging system. METHODS: Immunohistochemical demonstrations of CD8 and CD4 lymphocytes, CD68 macrophages, human leukocyte antigen-D-related (HLA-DR) cells, S-100 protein, and melanoma-associated antigens Melan A and HMB-45 were performed. The results were derived from independent histopathologic reviews by two pathologists. The low-density, moderate-density, and high-density groups of cells that infiltrated the base of the tumor during the vertical growth phase were compared with the overall survival rate using the Kaplan-Meier method and the log-rank test. Clinical variables (gender, age, tumor location, Clark level, vascular/lymphatic invasion, and thickness) also were analyzed. RESULTS: The CD8 lymphocytes exhibited independent statistically positive significance in survival (log-rank test, 8.49; P = 0.01) between patients in different lymphocyte density groups. There was a difference in 5-year survival among patients in the high-density group (78.8%), the moderate-density group (44.4%), and the low-density group (25.0%). The CD4 lymphocytes, which were less numerous than CD8 cells, had similar distribution. There also was a correlation of HLA-DR cells with overall survival (log-rank test, 5.29; P = 0.02). CD68 cell density was not found to be correlated with survival. CONCLUSIONS: The presence and number of infiltrating CD8 lymphocytes as well as the overall occurrence of HLA-DR cells may be considered independent, favorable prognostic factors in melanoma. The current results may be important for identifying other prognostic factors with which to evaluate disease progression and develop immune therapies for patients with melanoma.     

F-18-fluorodeoxyglucose positron emission tomography in differentiating malignant from benign pancreatic cysts: A prospective study

The differential diagnosis between benign and malignant pancreatic cystic lesions may be very difficult. We recently found that F-18-.uorodeoxyglucose positron emission tomography (18-FDG PET) was useful for the preoperative work-up of pancreatic cystic lesions. This study was undertaken to confirm these results. From February 2000 to July 2003, 50 patients with a pancreatic cystic lesion were prospectively investigated with 18-FDG PET in addition to helical computed tomography (CT) and, in some instances, magnetic resonance imaging (MRI). The validation of diagnosis was based on pathologic findings after surgery (n = 31), percutaneous biopsy (n = 4), and according to follow-up in 15 patients. The 18-FDG PET was analyzed visually and semiquantitatively using the standard uptake value (SUV). The accuracy of FDG PET and CT was determined for preoperative diagnosis of malignant cystic lesions. Seventeen patients had malignant cystic lesions. Sixteen (94%) showed increased 18-FDG uptake (SUV >2.5), including two patients with carcinoma in situ. Eleven patients (65%) were correctly identified as having malignancy by CT. Thirty-three patients had benign tumors: two patients showed increased 18-FDG uptake, and four patients showed CT findings of malignancy. Sensitivity, specificity, positive and negative predictive value, and accuracy of 18-FDG PET and CT in detecting malignant tumors were 94%, 94%, 89%, 97%, and 94% and 65%, 88%, 73%, 83%, and 80%, respectively. 18-FDG PET is accurate in identifying malignant pancreatic cystic lesions and should be used in combination with CT in the preoperative evaluation of patients with pancreatic cystic lesions. A negative result with 18-FDG PET may avoid unnecessary operation in asymptomatic or high-risk patients. Presented at the Forty-Fifth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004 (oral presentation). This study was supported by the Ministero Università e Ricerca Scientifica (Cofin 2001068593-001), Rome, Italy.