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M Casanova

Publications and source records attributed to M Casanova.

At least 19 recordsLinked to original sources
PubMed2025

Relapsed rhabdomyosarcoma: treatment recommendations from the European pediatric soft tissue sarcoma study group (EpSSG).

At least one-third of patients with localized rhabdomyosarcoma (RMS) and 60-70% of patients with metastatic RMS experience progressive disease or relapse. Following relapse, outcomes generally remain poor with limited treatment options and a high risk of subsequent recurrence. Optimal treatment requires a multidisciplinary approach incorporating chemotherapy with local control. Given the complexity of managing relapsed RMS and the challenges in developing effective treatment strategies, we aim to present clear and practical recommendations on the management of these patients across Europe. These recommendations were developed collaboratively by a group of pediatric and adolescent sarcoma experts from the European paediatric Soft Tissue Sarcoma Study Group. A careful review of the literature was performed to ensure that wherever possible recommendations are supported by the results of clinical trials or substantive retrospective reports. Such recommendations provide a standardized approach to managing relapsed cases, improving patient outcomes and offering a framework for clinicians to make informed decisions.

Humans↗
PubMed2006

Laser-beam smoothing induced by stimulated brillouin scattering in an inhomogeneous plasma.

We present results of two-dimensional simulations of the stimulated Brillouin scattering (SBS) of an optically smoothed laser beam propagating in an expanding plasma. In the weak damping limit, both backscattered and transmitted light waves exhibit an additional spatiotemporal incoherence, which is shown to be induced by SBS taking place in an inhomogeneous plasma. This mechanism is not related to laser-beam self-focusing and is thus complementary to plasma-induced smoothing [A. J. Schmitt and B. B. Afeyan, Phys. Plasmas 5, 503 (1998)]. The incoherence induced by SBS in the entrance part of the plasma could reduce the growth of parametric instabilities developing further inside the plasma and is able to significantly enlarge the spreading angle of the transmitted light. The angular width of the backscattered light is also found to be significantly larger than the aperture angle of the incident beam.

Journal Article↗
PubMed2006

Transient development of backward stimulated Raman and Brillouin scattering on a picosecond time scale measured by subpicosecond thomson diagnostic.

The excitation and the relaxation of the plasma waves and ion acoustic waves (IAW), respectively, driven by stimulated Raman (SRS) and Brillouin (SBS) backscatterings have been experimentally investigated with short-pulse lasers. The spectra have been obtained with a 0.3 ps time resolution. It is shown that SRS develops before SBS and suddenly decays around the peak of the pump, as the IAW reaches saturation. On this short time scale, electron kinetic effects play a major role for SRS saturation, contrary to ion dynamics. These results are supported by particle-in-cell simulations.

Journal Article↗
PubMed2006

A case of relapsing glioblastoma multiforme responding to vinorelbine.

Childhood malignant gliomas are rare and their clinical behavior is almost as aggressive as in adults: they resist treatment, progress rapidly and often spread. Therapeutic strategies at relapse deserve an experimental approach, since none of the conventional-dose treatments have demonstrated a clear superiority over the others and no randomized trials have proved that high-dose chemotherapy is better than conventional treatment. Vinorelbine is a semi-synthetic vinca alkaloid with an in vitro and in vivo experimentally proven broad spectrum of activity, including against malignant brain glioma. We report our experience with a 19-year-old girl with glioblastoma multiforme (GBM) of the deep temporal region recurring 6 months after completing an intensive treatment that included preradiation chemotherapy (chemotherapy as a preradiation "sandwich" phase) with a myeloablative course of thiotepa, tumor bed radiotherapy and postradiation maintenance chemotherapy. The GBM proved fully responsive to intravenous vinorelbine, with a subsequent progression-free interval lasting more than 24 months. This case report suggests that vinorelbine is effective against high-grade pediatric glioma and, since this evidence has only one precedent in the literature (and given the generally poor prognosis for this tumor), even this single success seems worth reporting.

Adult↗
PubMed2006

Muscarinic cholinoceptor activation modulates DNA synthesis and CD40 expression in fibroblast cells.

1 The aim of the present work was to examine the role of muscarinic acetylcholine receptors (mAChR) on DNA synthesis and CD40 expression in human fibroblast cells. Neonatal human skin fibroblast cultures were stimulated with carbachol in presence or absence of specific antagonists and the following parameters were measured: identification of mAChR subtypes, DNA synthesis, inositol phosphates (InsP) production and CD40 expression. 2 Human fibroblasts express mAChR with Kd 0.47 +/- 0.11 nm and Bmax 236 +/- 22 fmol mg protein(-1). Carbachol stimulates DNA synthesis, InsP and the expression of CD40. All these effects were inhibited by atropine, mustard hydrochloride (4-DAMP) and pirenzepine but not by AF-DX 116 and tropicamide, indicating that M3 and M1 mAChR are implicated in carbachol action. The relative Ki of the antagonists obtained by competition binding assay was in parallel to the relative potency for blocking both carbachol-stimulated InsP accumulation and DNA synthesis. 3 The intracellular pathway leading to carbachol-induced biological effects involved phospholipase C and calcium/calmodulin, as U-73122 and trifluoroperazine blocked carbachol effects, respectively. Calphostin C, a protein kinase C inhibitor, had no effect, indicating that this enzyme does not participate in the system. 4 These results may contribute to a better understanding of the modulatory role of the parasympathetic muscarinic system on normal human fibroblast function.

Atropine↗
PubMed2005

Stage 4 neuroblastoma: sequential hemi-body irradiation or high-dose chemotherapy plus autologous haemopoietic stem cell transplantation to consolidate primary treatment.

The aim of the present study was to evaluate the effectiveness of two consecutive nonrandomised treatment programs applied between 1989 and 1999 at the Istituto Nazionale Tumori of Milan in an unselected cohort of 59 children over the age of one with stage 4 neuroblastoma. Both treatment programs consisted of two phases, the induction of the remission phase and the consolidation phase. The induction of the remission phase consisted of intensive chemotherapy, and remained the same throughout the study period. The consolidation phase consisted of sequential hemi-body irradiation (HBI) (10 Gy per session, 6 weeks apart) in the first period (1988-June 1994) and sequential high-dose cyclophosphamide, etoposide, mitoxantrone+L-PAM and autologous haemopoietic stem cell transplantation in the second (July 1994-1999). Intention-to-treat analysis revealed a significantly better outcome for patients treated with the second program, the 5-year event-free survival probability being 0.12 for program 1 and 0.31 for program 2 (P=0.03). This finding led us to conclude that sequential HBI is useless as consolidation treatment. The high-dose chemotherapy adopted in the second program enabled a proportion of patients to obtain long-term survival but, since the clinical results remain unsatisfactory, new treatment strategies are warranted.

Adolescent↗
PubMed2004

Is alveolar histotype a prognostic factor in paratesticular rhabdomyosarcoma? The experience of Italian and German Soft Tissue Sarcoma Cooperative Group.

PURPOSE: To ascertain whether alveolar histology retains its adverse prognostic role in the subset of paratesticular rhabdomyosarcoma (RMS) patients, generally characterized by a very good outcome. PATIENTS AND METHODS: Twenty pediatric patients were treated over a 25-year period using the protocols of the Italian and German Soft Tissue Sarcoma Cooperative Groups. Clinical characteristics at presentation were much the same as in non-alveolar patients. RESULTS: The proportion of patients with alveolar histotype (8%) in paratesticular site was lower than in the general RMS population (20-30%). With a median follow-up of 122 months, 5-year EFS and OS were 78 and 89%, respectively. CONCLUSION: Our data suggest a distinctly better clinical behavior of paratesticular alveolar RMS than when the disease occurs at other sites. These patients were more intensively treated than the embryonal cases, however, so-although a treatment intensity reduction may be desiderable-the idea of eliminating the alkylating agents (as in low-risk embryonal paratesticular RMS) must be considered with great caution.

Adolescent↗
PubMed2004

Chronic clonal proliferative disease of gamma-delta (gammadelta) T-cells in a patient with rheumatoid arthritis and neutropenia: lack of the morphology and the immunophenotype of large granular lymphocytes.

Normal gammadelta T-lymphocytes have the morphology of large granular lymphocytes (LGL) and, as the LGL of alphabeta T-cells, they express pan-T antigens, NK-associated antigens and the cytotoxic molecules, perforin and granzime B. In this report we describe an unusual patient with rheumatoid arthritis and neutropenia who has a chronic gammadelta T-cell proliferation with a chronic, indolent clinical course and atypical lymphocytes, lacking the classical LGL morphology, not expressing NK-associated antigens, and not expressing perforin or granzyme B. In spite of the atypical morphological features of the clonal cells, which were suggestive of a more malignant process, the patient has been followed for 4 years without aggressive therapy. It is important to recognize this entity and to distinguish it from other gammadelta T proliferations such as the hepatosplenic gammadelta T-cell lymphoma.

Adult↗
PubMed2002

Paratesticular rhabdomyosarcoma: report from the Italian and German Cooperative Group.

PURPOSE: We report the experience of the German-Italian Cooperative Group with 216 pediatric patients with paratesticular rhabdomyosarcoma treated over 20 years. PATIENTS AND METHODS: At diagnosis, 198 patients had localized disease and 18 had distant metastases. Among the nonmetastatic patients, complete tumor resection was performed in 83% of cases. Evaluation of the retroperitoneal lymph nodes changed over the years from routine surgical staging to radiologic assessment. All patients received chemotherapy, which was reduced in intensity and duration for patients with low-risk features in subsequent protocols. Radiotherapy was administered to 10% of patients. RESULTS: Among 72 patients with a negative retroperitoneal computed tomography (CT) scan, surgical assessment detected nodal involvement in only one case. Among 23 patients with enlarged nodes on CT scans, surgery confirmed nodal spread in 65% of patients. No differences in the rate of nodal involvement were observed over the years. With a median follow-up of 110 months, 5-year survival was 85.5% for the series as a whole, 94.6% for patients with localized disease, and 22.2% for metastatic cases. Retroperitoneal nodal recurrence was the major cause of treatment failure. Univariate analysis revealed the prognostic value of tumor invasiveness, size, and resectability, as well as of nodal involvement and age, in patients with localized tumor. CONCLUSION: The outcome for patients with localized paratesticular rhabdomyosarcoma is excellent, despite the reduction in chemotherapy over the years: an alkylating agent-free and anthracycline-free regimen is adequate treatment for low-risk patients. Surgical assessment of the retroperitoneum must be reserved for patients with enlarged nodes on CT scans. Children over 10 years old carry a higher risk of nodal involvement and relapse.

Adolescent↗
PubMed2002

Quantitative comparison of radial cell columns in children with Down's syndrome and controls.

No one has examined the configuration of the minicolumns in Down's syndrome (DS) brains even though these are a basic functional unit of the cortex. In the present study, the authors used computerized imaging to examine minicolumns in the posterior superior temporal gyrus in both the brains of patients with DS and normal controls. They compared the brains of children aged 4 and 6 years with those of adults for both people with DS and the normal population. Columns in the brains of two DS children aged 4 and 6 years were almost the same size as those of the adults with DS. The neuropil space in the periphery of the columns was also considerably wider. In contrast, minicolumns in aged-matched control children were smaller, both relatively and absolutely, when compared to the mean size of adult columns. The size of the minicolumns in the normal children apparently corresponded to the overall brain size, whereas the large columns in children with DS appeared to be independent of brain size, at least in area Tpt. This seems to reflect a rapid ageing process that is striking when compared to normal controls. Columns in adults with DS were large and less cell dense, while brain volumes were significantly smaller than in controls. This combination suggests reduced neuronal complexity based on a decrease in processing units, which supports previous findings of decreased cell numbers and synaptic diminution in DS brains.

Adolescent↗
PubMed2001

Hemangiopericytoma in pediatric ages: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group.

BACKGROUND: Hemangiopericytoma (HPC) is very uncommon in childhood and comprises two different clinical entities, the adult type and the infantile type, occurring in the first year of age. We report on a series of 27 pediatric patients treated from 1978 to 1999 by the Italian and German Soft Tissue Sarcoma Cooperative Group. METHODS: Seven patients had infantile HPC; complete resection was achieved in the tumors of five patients and chemotherapy was given to four patients. Twenty children had adult type HPC; nine received complete tumor resection (four patients at diagnosis and five at delayed surgery). Post-operative radiotherapy was administered to 15 patients, chemotherapy to 19. RESULTS: Six of seven patients with infantile HPC were alive in first remission; one patient died of disease. Chemotherapy achieved an objective response in four of four patients. Among the adult type HPC cases, 5-year event free survival was 64% (median follow-up 125 months); 12 patients were alive in first remission, eight patients relapsed and died of disease. Seven of 10 evaluable patients showed good response to chemotherapy. Statistically significant differences in outcome were observed in relation to Intergroup Rhabdomyosarcoma Study grouping, size, local invasiveness, and gender. CONCLUSIONS: Infantile HPC is a unique entity probably related to infantile myofibroblastic lesions and characterized by a high response to chemotherapy, which is required in case of unresectable, life-threatening tumors. In children over 1 year of age, HPC behaves like its adult counterpart; complete surgical resection remains the mainstay of treatment, but chemotherapy and radiotherapy seem effective and are recommended in all patients with incomplete tumor resection and/or locally invasive, large tumors.

Adolescent↗
PubMed2001

Childhood malignant ovarian germ cell tumors: a monoinstitutional experience.

OBJECTIVES: We reviewed our 23-year monoinstitutional exprience with childhood malignant ovarian germ cell tumors (MOGCT), with respect to survival and iatrogenic sequelae. METHODS: Twenty-nine patients (median age 12 years) with newly diagnosed MOGCT were treated: all girls but 2 underwent surgery as initial treatment. There were 9 pure dysgerminomas and 20 nondysgerminoma tumors (5 immature teratomas, 4 yolk sac tumors, and 11 mixed histology tumors). According to the FIGO classification, 9 girls were classified as stage I, 4 as II, 11 as III, and 3 as IV, and 2 were not evaluable because they were submitted to primary chemotherapy. Twenty-four received chemotherapy with VAC, PVB, or PEB regimens, according to the ongoing protocols through the years. Three stage I girls did not receive adjuvant chemotherapy because of their histology (2 dysgerminomas, 1 immature teratoma) and stage. In the early years, postoperative radiotherapy was given alone in advanced dysgerminoma stages. RESULTS: Five patients died of their disease: 2 dysgerminomas (stage IIIc and IV) and 3 nondysgerminomas (2 stage II and 1 stage IIIc). OS and EFS rates at a median of 112 months were 81.8%. Among 24 survivors, 4 experienced iatrogenic amenorrhea because of radiotherapy and/or bilateral oophorectomy. CONCLUSIONS: MOGCT are highly chemosensitive and curable, with preservation of reproductive function. The management of recurrent disease remains an open issue.

Adolescent↗
PubMed2001

Ultrastructural study of the FVB/N mouse thymus: presence of an immature epithelial cell in the medulla and premature involution.

FVB/N inbred mice have been widely used to generate a variety of transgenic lines, but their physiology and especially their immunological characteristics are poorly documented. We therefore studied the ultrastructure of the thymus and the distribution of thymocyte subpopulations in FVB/N mice at several ages. In young FVB/N mice the stromal microenvironment exhibits the three types of epithelial cells and the two types of bone-marrow derived cells (macrophages and interdigitated cells) previously described in other strains of mice. Moreover, in the thymic medulla of young FVB/N mice, a fourth cell type with the morphological characteristics of an immature epithelial cell was present in relatively high number. Furthermore, thymocyte subpopulations distribution shows an earlier thymocyte maturation than in other strains. Finally, changes associated with thymic involution were observed about 5 months earlier than in many other mouse strains. Our results demonstrated that the FVB/N strain has a specific immunological status.

Animals↗
PubMed2001

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.

Adolescent↗
PubMed2001

Childhood leiomyosarcoma: a report from the soft tissue sarcoma Italian Cooperative Group.

BACKGROUND: Only a few reports on the clinical features and management of childhood leiomyosarcoma are available. To contribute additional information on the management of this rare tumor, we report on a series of 16 pediatric patients treated from 1982 to 1998 by the Soft Tissue Sarcoma Italian Cooperative Group. PATIENTS AND METHODS: Primary surgery was conservative in all but two patients, and consisted of biopsy--three cases, non-radical excision--four, and radical resection--nine (involving a primary re-excision in 4 of 9). In two cases secondary radical surgery was performed after primary chemotherapy. Chemotherapy was administered to 9 of 16 patients, radiotherapy to three. RESULTS: After a median follow-up of seven years (range 3-18), the five-year event-free survival (EFS) and overall survival were 56.3% and 72.9%, respectively; 12 of 16 patients were alive (nine of them in continuos complete remission). Univariate analysis was performed to compare EFS according to different subgroups: size represented the most significant prognostic factor. CONCLUSIONS: Complete surgical resection is the mainstay of treatment for leiomyosarcoma. The role of both adjuvant chemotherapy and radiotherapy has yet to be established, and awaits cooperative multicentric studies.

Adolescent↗
PubMed2001

Effects of recombinant human granulocyte-macrophage colony-stimulating factor in an intensive treatment program for children with Ewing's sarcoma.

BACKGROUND AND OBJECTIVES: A treatment program including polychemotherapy at progressively escalating doses and sequential hemi-body irradiation (HBI) was adopted between 1987-1994 at our Pediatric Unit for high risk Ewing's sarcoma. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was added to the treatment program in a phase II study fashion to evaluate, in a pediatric setting, its tolerability, as well as its impact on drug dose escalation and on the need for supportive care. DESIGN AND METHODS: The study was open-label and sequential; GM-CSF administration (5 microg/Kg s.c./d x10) was planned after each chemotherapy cycle and after each HBI session in 18 consecutive patients (group A). Thirty-eight additional patients (group B) were treated by the same therapeutic program, without GM-CSF. In 12 patients (6 in each group) long-term bone marrow cultures (LTBMC) were performed to evaluate the myeloproliferative potential throughout the chemotherapeutic program. RESULTS: Seven of 18 (39%) patients experienced side effects from GM-CSF; 3/7 discontinued GM-CSF due to anaphylactic symptoms. The degree of neutropenia, as well as the frequency of infectious episodes and the need for supportive care were significantly lower in group A than in group B. Iatrogenic thrombocytopenia, and the possibility of performing drug-dose escalation were similar in the two groups. The 5-year event-free survival probabilities for group A and B were similar. LTBMC showed that the chemotherapy-related depletion of myeloid precursors could be more pronounced in patients receiving GM-CSF cyclically. INTERPRETATION AND CONCLUSIONS: In this series, GM-CSF was shown to be effective on iatrogenic neutropenia and related complications, with no impact on thrombopoiesis, drug dose escalation and outcome.

Adolescent↗