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A Botturi

Publications and source records attributed to A Botturi.

11 recordsLinked to original sources

Methotrexate based chemotherapy and deferred radiotherapy for primary central nervous system lymphoma (PCNSL): single institution experience.

In the following study, we present our experience in the treatment of PCNSL patients using a multi-step schedule combining chemotherapy and deferred radiotherapy. Patients were treated with two modified M-BACOD cycles and then differently according to radiological response For PR, SD and PD patients, chemotherapy was interrupted and radiotherapy initiated immediately (45 Gy Whole-brain RT). With CR patients, chemotherapy was continued with a combination of HMTX, VCZ, PCB and HD Ara-C up to a total of nine cycles. In 36 patients suitable for evaluation (2 patients had undergone tumour resection): 69.4% (25 of 36) had a complete response (CR), 19.4% (7 of 36) had a partial response(PR), 8.3% (3 of 36) had stable disease(SD), and 2.7% (one of 36) had progressive disease (PD). The PR, SD and PD patients were immediately treated by radiotherapy. In this cohort of patients, we observed 6 CR, 4 PR and 2 PD, respectively, following radiotherapy. At first relapse, a total of 16 CR patients were treated by radiotherapy for a total dose of 45 Gy. The OS was 42.1 months for the entire group of patients. In CR patients treated at the moment of recurrence by salvage radiotherapy, the TTP (time lasting from histological diagnosis until recurrence of disease before RT) was 28.3 months, with a 43.4% of disease free patients observed at 2 years. The median disease-free time observed after complete response to radiotherapy was 10.5 months. In 16 patients (34%), further progression of disease was observed following radiotherapy. Two patients developed extra-CNS disease in the breast and testis. When taking into account the patients with radiotherapy delayed at recurrence, the OS was 48 months and the survival rates were 70% and 60% at 2 years and 5 years, respectively.

Adolescent↗

Local drug delivery in recurrent malignant gliomas.

In recurrent malignant gliomas, we scheduled a protocol by adding to systemic temozolomide a local treatment delivered through a reservoire positioned in the surgically created cavity, consisting of either mitoxantrone, liposome-loaded doxorubicine or nimustine (ACNU). The progression-free survival (PFS) and survival time (ST) of the whole group of 112 patients were 8.3 and 11 months, respectively, in GBM patients, and 14 and 18 months in AA patients. To limit the selection bias in recruitment we matched locally treated patients with the whole group of patients treated for 3 years and having undergone the same protocol with the exception of local drug delivery. Variables such as age, histology and local chemotherapy delivery were proved to be statistically significant independent factors on adjunctive PFS and ST. Another group of 12 recurrent malignant gliomas with further progression was locally managed according to convection-enhanced delivery (CED) of mitoxantrone; the preliminary results show good tolerability of the schedule.

Adolescent↗

The role of the neurologist.

The contribution of the neurologist should focus on timely diagnosis with accurate differential diagnosis, indications for surgery and post-surgical treatment (in the setting of a multidisciplinary team), and follow-up of disease course/treatment-related complications.

Brain Neoplasms↗

Systemic temozolomide combined with loco-regional mitoxantrone in treating recurrent glioblastoma.

Twenty-two recurrent GBM patients were enrolled for second tumor debulking with local positioning of a Rickam reservoir, in order to locally deliver chemotherapy with the aim of controlling local tumor recurrence. We designed a protocol using systemic temozolomide (150 mg/sqm days 1-5 every 28) in association with mitoxantrone, delivered through the reservoir (4 mg/day 1-5 every 28) positioned into the area of tumor exeresis. After re-operation a residual tumor mass no larger than 2 cm was identified in 18/22 patients. The patients were treated with monthly cycles of chemotherapy until evolution of the tumor, but in no case for more than 10 cycles. Responses were evaluated by MRI scans performed every 2 months and images assessed according to MacDonald's criteria. Response rate: no complete responses (CR), 5 partial responses (PR), 13 stable disease (SD) and 4 progressive disease (PD) occurred. The median progression-free survival (PFS) and survival time (ST) of the whole group of treated patients was 7 and 11 months, respectively and more than a quarter of the patients survived over 18 months. During the study, the patients' compliance was complete and no dropouts occurred. Hematological toxicity was mild and after repeated local injections only minor neurological side-effects occurred. Despite some bias in patients' selection not excluded in this pilot study, results are interesting: the PFS was as long as the survival of recurrent GBM reported in the literature.

Adult↗

Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression.

The p38 mitogen-activated protein kinase (p38MAPK) is activated via phosphorylation in neurones and glial cells by a variety of stimuli including oxidative stress, excitotoxicity, and inflammatory cytokines. Activated p38MAPK can in turn induce phosphorylation of cytoskeletal proteins and activation of cytokines and nitric oxide, thus contributing to neurodegeneration. We investigated the expression and distribution of p38MAPK in the spinal cord of transgenic mice expressing a superoxide dismutase 1 mutation (SOD1G93A), a model of familial amyotrophic lateral sclerosis (ALS). Accumulation of p38MAPK was found by immunoblotting in the spinal cord of G93A mice during the progression of disease, but no changes were detected in its mRNA levels. Immunostaining for phosphorylated p38MAPK in lumbar spinal cord sections of SOD1G93A mice at the presymptomatic and early stages of disease showed an increased labeling in motor neurones that colocalized with phosphorylated neurofilaments in vacuolized perikarya and neurites, as detected by confocal microscopy. As the disease progressed, activated p38MAPK also accumulated in hypertrophic astrocytes and reactive microglia, as demonstrated by colocalization with GFAP and CD11b immunostaining, respectively. These data suggest that activation of p38MAPK in motor neurons and then in reactive glial cells may contribute, respectively, to the development and progression of motor neuron pathology in SOD1G93A mice.

Amyotrophic Lateral Sclerosis↗

New approach in delivering chemotherapy: locoregional treatment for recurrent glioblastoma (rGBM).

The treatment of GBM tumor recurrence is generally a hopeless challenge, since recurred tumor is resistant to the most common therapeutic efforts. Some partial results can be achieved by targeting local disease control, in view of the fact that 95% of recurrences occur locally. We present results concerning three pilot studies, all performed in recurrent GBM patients who underwent second surgery and have been treated systemically with temozolomide and locally through an Ommaya reservoire according to the following schedules: a) in 20 rGBM, 4 mg novantrone was delivered day 1,5 every 30 days; in 26 rGBM, 4 mg novantrone was delivered every 20 days in association with locoregional radioimmunotherapy (RIT); in 12 rGBM pegylated liposomal doxorubicin 4 mg was delivered day 1,5,10,15,20 with 20 days interval. Results seem very promising since there is an extension of disease free and survival, both of more than 50 % if results are evaluated in relation with the most frequent data of the literature.

Antineoplastic Agents↗

Adult brain low-grade astrocytomas: survival after surgery and radiotherapy.

In order to identify prognostic factors of survival, twelve elements of disease and treatment have been evaluated for a population of 49 patients with diffuse low-grade astrocytoma treated with surgical resection and radiotherapy. The survival values were inversely correlated with age and major residual portion. On the other hand, KPS, lobar site, grade II Daumas-Duport lesions, protoplasmatic variant, early epilepsy, hyperfractionated radiotherapy and extent of exeresis were prognostic factors correlated with survival. Tumor extent and radiation total dose were not correlated in a meaningful way. Only KPS was statistically significant when compared to all the prognostic factors. We believe that patient selection according to age, lesion site and histological features are not sufficient to generate a homogeneous tumoral population. The most appropriate therapy for treating low-grade astrocytomas is still an open subject. However, recent studies have shown that the prognostic value of a group of factors is useful to plan controlled studies that compare differentiated treatment protocols.

Adult↗

Human developing motor neurons as a tool to study ALS.

Defining the basis of the selective cell vulnerability of human motor neurons (hMNs) represents a crucial step in revealing the pathogenesis of amyotrophic lateral sclerosis (ALS). Tissue culture models offer an ideal system for identification of the hMN-specific features at the single cell level. Purified hMNs and astrocytes can today be isolated from the anterior horn of the human embryonic spinal cord. Cultures can be studied at the single cell level using cDNA/mRNA amplification techniques. The effects of molecules affecting hMN survival, neurite extension, and metabolism can be tested in vitro and the expression of selective genes assayed using DNA microarray technology. Crucial information of immediate clinical application for the treatment of patients affected by ALS can be derived after testing the efficacy of candidate pharmaceutical molecules using in vitro cell models. Adult nervous tissue or progenitor cells derived from different regions of the nervous system may be used as an alternative source of human neuronal cells. HMNs in culture, combined with the application of adequate technology, can contribute greatly to identifying the primitive critical events responsible for the cell degeneration observed in ALS, bypassing the intrinsic limitations of the non-human models of the disease.

Amyotrophic Lateral Sclerosis↗

[T1G3 bladder neoplasms: treatment and results].

The high risk of progression found in T1G3 bladder cancer influence the treatment and follow-up of this kind of patients. From January 1983 to December 1992, 803 patients with superficial bladder cancer (first presentation) had observed in the Urology Department at the Spedali Civili in Brescia. In this group, 96 patients were classified as T1G3 and our retrospective study is a critical analysis about their treatment: 13 patients underwent cystectomy as primary treatment and 83 had been cured with a transurethral resection. Of this last group, 26 patients are still without of disease (mean follow-up: 4.2 years), 30 had a recurrence which, in stage and grade, was identical or lower to the initial disease and 27 patients had a progression. Alltogether 36 patients underwent cystectomy: 15 are tumor-free and 21 died. The results of this retrospective study, led us to believe that T1G3 bladder cancer therapy is endoscopic at the beginning. Adjuvant topic chemotherapy treatments improve the recurrence rate tangibily; an early-operated cystectomy permits a good rate of recovery.

Carcinoma, Transitional Cell↗

[Morbidity of transperineal echo-guided prostatic biopsy, our experience].

We present a review of 1245 patients undergone to ultrasound guided transperineal prostatic biopsy. We examined the complications' incidence of this technique to confirm or exclude presence of prostate cancer. Indications to a prostatic biopsy include an abnormal digital rectal examination, TRUS or PSA values increased. Single biopsy or systematic mapping of prostate were performed. For prostate biopsy a "Biopsy Gun" with 18 G. needle was used. Of 1245 patients, only 31 (2.48%) showed complications. Our experience demonstrates that ultrasound guided transperineal prostatic biopsy is a safe and easy technique and it is well accepted by the patient.

Aged↗