Results from the integrated surveillance system for the 2006 Winter Olympic and Paralympic Games in Italy.
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Disease Notification↗
Biomedical subjects
D Lombardi
Publications and source records attributed to D Lombardi.
Innovative schedule of oral idarubicin in elderly patients with metastatic breast cancer: comprehensive results of a phase II multi-institutional study with pharmacokinetic drug monitoring.
BACKGROUND: To determine if protracted low-dose oral idarubicin (IDA), feasible in a previous dose-finding study, would result in similar activity and a better toxicity profile in patients with metastatic breast cancer. PATIENTS AND METHODS: Elderly women (> or=65 years) with metastatic breast carcinoma were treated with 7.5 mg/day for 21 consecutive days, every 4 weeks. After the first fourteen patients, due to excessive toxicity, the protocol was amended to 5 mg/day. IDA and Idarubicinol (IDOL) plasma concentrations (C(trough)) were investigated in all patients. RESULTS: Between April 1999 and June 2004, 47 elderly patients were accrued in this two-part study (14 and 33 patients respectively). The median age was 74 and 75 years respectively. Visceral involvement was present in most patients. A partial response was noted in 7/31 patients (22%; 95% CI, 9.6-41.1%). Eleven patients had stable disease (33%). At the dose of 5 mg/day the treatment was well tolerated. Neutropenia grade 4 was present in only 6% of patients; alopecia > grade 1 and cardiotoxicity did not occur. The median time to progression was 3 months and the median overall survival was 17 months. IDA C(trough) and IDOL C(trough) levels were significantly associated with haematologic toxicity. CONCLUSION: This study shows that idarubicin at the dose of 5 mg/day for 21 consecutive days is feasible and effective in elderly breast cancer patients but do not demonstrate an improvement in efficacy. A determination of the IDA and IDOL plasma levels (C(trough)) is predictive for toxicity.
Administration, Oral↗
Dose-finding study of weekly docetaxel, anthracyclines plus fluoropyrimidines as first-line treatment in advanced breast cancer.
BACKGROUND: The efficacy and safety of prolonged fluoropyrimidines, either intravenously or orally, prompted their integration with taxanes and anthracyclines in the treatment of advanced breast cancer (ABC). We conducted three subsequent dose-finding studies on first-line chemotherapy in ABC with anthracyclines, either epirubicin (E) or doxorubicin (A), and docetaxel (T), both given on days 1 and 8 every 3 weeks, plus continuous infusion (CI) 5-fluorouracil (F) or capecitabine (X). PATIENTS AND METHODS: Sixty-two patients (37% dominant visceral disease, 48% locally advanced disease, 45% two or more sites involved), received different doses of T (60--80 mg/m(2)), A (40--50 mg/m(2)) or E (60--90 mg/m(2)) and X (1,650 and 2,000 mg/m(2)), or CI F at a fixed daily dose of 200 mg/m(2). Cardiac function was monitored at baseline and then every four cycles by echocardiography. RESULTS: The median number of cycles per patient with all regimens was four (range one to eight). Haematological and gastrointestinal toxicity defined the maximum tolerated doses, at T-80/E-90 mg/m(2) with TEF, T-70/A50/X-2,000 mg/m(2) with TAX and T-70/E-80/X-1,650 mg/m(2) with TEX. Two patients treated with TEF developed transient cardiac toxicity (dilatative cardiomyopathy and coronary subtotal stenosis requiring stenting) after cumulative E doses of 400 mg and 1,100 mg/m(2), respectively. Fifty-nine patients were evaluable for response; the overall response rates (ORR) were comparable between regimens (54% with TEF, 71% with TAX and 86% with TEX), with an 81% ORR in 31 patients with locally advanced disease. CONCLUSIONS: The addition of fluoropyrimidines to weekly, intermittent ET is well tolerated and active in ABC.
Adult↗
Treatment of older breast cancer patients with high recurrence risk.
Adjuvant treatment of elderly women affected by breast cancer who have a high risk of recurrence is one of the most questionable issues in clinical oncology. The use of tamoxifen in women with hormone receptor-positive tumors is a relatively simple therapeutic option considering the favourable toxicity profile, whereas the administration of adjuvant chemotherapy is more complicated and a variety of aspects need to be considered. The estimated life expectancy, the presence and degree of comorbid conditions, the geriatric assessment and estimated benefit from treatment should be taken into account. Due to the lack of data from clinical trials in women over the age of 70, the approach is still experimental. Clinical trials evaluating the role of adjuvant chemotherapy in high risk patients are currently being developed and hopefully in the near future, more convincing data on the best drugs, regimens and benefits for the treatment of elderly breast cancer patients will become available.
Aged↗
Protein interactions provide new insight into Nm23/nucleoside diphosphate kinase functions.
Nm23-NDPKs besides contributing to the maintenance of the cellular nucleoside triphosphate pool, exert regulatory properties in a variety of cellular events including proliferation, invasiveness, development, differentiation, and gene regulation. This review focuses on recently discovered protein-protein interactions involving the Nm23 proteins. The findings herein summarized provide new and intriguing suggestions for a more extensive understanding of the biological functions of the Nm23 proteins.
Adaptor Proteins, Signal Transducing↗
Ifosfamide in advanced/disseminated breast cancer.
Ifosfamide is an alkylating agent active in various tumor types including breast cancer. The availability of mesna (sodium 2-mercaptoethanesulfonate) has increased its safety, avoiding the main dose-limiting side effect, urotoxicity. Interesting activity as a single agent, with response rates ranging from 7 to 30%, is reported in pretreated patients; more attractive data derived from phase II studies on ifosfamide combined with drugs known to be active in advanced breast cancer show response rates always over 35%. This review has taken in consideration papers published after 1995 and available on PubMed medline: the data indicate a potential usefulness of ifosfamide in the clinical management of advanced breast cancer, even if the exact therapeutic role of the drug in this setting should be derived from randomized studies not yet available.
Antineoplastic Agents, Alkylating↗
The retinoblastoma-related Rb2/p130 gene is an effector downstream of AP-2 during neural differentiation.
Rb2/p130, a member of the Retinoblastoma family of growth and tumour suppressor genes, is extensively implicated in the control of cell cycle and differentiation. The minimal promoter region of Rb2/p130 in T98G human glioblastoma cells was identified and its analysis revealed the presence of a KER1 palindromic sequence able to bind the transcription factor AP-2, a regulatory protein that plays a crucial role in ectodermal differentiation. This KER1 site interacted in vitro with AP-2, and AP-2 overexpression increased Rb2/p130 transcription and translation. We also found that rat PC12 pheochromocytoma cells, when induced to differentiate by NGF, displayed an increase of AP-2 protein levels and of Rb2/p130 transcription and protein levels. AP-2-transfected PC12 cells displayed enhanced transcription and translation of Rb2/p130 and of the cdk inhibitor p21(WAF1/CIP1), a gene known to be under the control of AP-2, but unable by itself to elicit PC12 differentiation. Overexpression of either AP-2 or Rb2/p130 elicited per se cell differentiation in the absence of NGF, while coexpression of AP-2B, a negative regulator of AP-2 transcriptional activity, inhibited only AP-2-induced differentiation. Altogether, these results indicate that Rb2/p130 is a critical effector of AP-2 in sustaining ectodermal differentiation.
Animals↗
High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel.
BACKGROUND: Clinically overt central nervous system (CNS) involvement occurs in 10%-15% of patients with advanced breast cancer. PATIENTS AND METHODS: The International Breast Cancer Study Group (IBCSG) conducted a dose-finding phase I trial of epirubicin (E) and docetaxel (D) as first-line therapy in advanced breast cancer patients. The study was expanded into a phase II at the recommended doses of E 90 mg/m2 and D 75 mg/m2 every three weeks. From July 1996 to May 1998, a total of 92 patients (median age 50 years) entered the two studies. RESULTS: Twenty-eight out of ninety-two patients treated with the combination of E and D (30%) developed CNS metastases (95% confidence limits, 26%-35%), which were cerebral in twenty-five patients, leptomeningeal in two, and both in one. Of these 28 patients, 19 (68%) had an objective response. Median time for the development of CNS metastases from the start of chemotherapy was 15 months (range 5-42), if excluding the 6 patients presenting CNS progression within 3 months from start of treatment. It is notable that 11 patients (39%) had progression in the CNS only. Median survival from appearance of brain metastases in the whole group was only three months (range 1-22). C-erbB-2 overexpression was found in 14 out of 16 patients (87%) in whom the assay was performed (3+ in 10, 2+ in 1 and 1+ in 3 cases). CONCLUSIONS: As anthracycline- and taxane-containing regimens are increasingly used both in the metastatic and in the adjuvant setting, a careful monitoring of any neurological symptom is advisable. Our preliminary observation on the possible increase of incidence of CNS involvement in patients with advanced breast cancer receiving this effective drug combination requires further evaluation.
Adult↗
Interplay between the antimetastatic nm23 and the retinoblastoma-related Rb2/p130 genes in promoting neuronal differentiation of PC12 cells.
Increasing evidence indicates that the nm23 genes, initially documented as suppressors of metastasis progression, are involved in normal development and differentiation. We have shown previously that the murine nm23 gene enhances pheochromocytoma PC12 cells responsiveness to NGF by accelerating cell growth arrest and neurite outgrowth. The present study was aimed at elucidating the mechanisms by which nm23 controls cell proliferation and promotes neuronal differentiation. We demonstrated that nm23 modulates the expression of the Rb2/p130 gene, a negative regulator of cell cycle progression also implicated in the maintenance of the differentiated state. Furthermore, we showed that nm23-H1 mutants, defective in inhibiting the invasive phenotype, downregulate Rb2/p130 expression and inhibit NGF-induced PC12 cell differentiation. In synthesis, our results provide first evidence of interplay between the nm23 and the Rb2/p130 genes in driving PC12 cells neuronal differentiation and suggest that the antimetastatic and the differentiative nm23 functions can have similar features.
Amino Acid Substitution↗
Low prevalence of antigliadin and anti-endomysium antibodies in subclinical/silent celiac disease.
OBJECTIVE: Endomysial antibodies (EMA) are a well-known hallmark of celiac disease, but some recent studies showed that the prevalence of these antibodies in clinical practice is lower than expected. The aim of our study was to determine the prevalence of antigliadin (AGA) and EMA antibodies on a consecutive series of subclinical/silent celiac patients. METHODS: We studied 115 consecutive patients with subclinical (92 patients) or silent (23 patients) forms of celiac disease. AGA and EMA were screened in all patients. Histopathology of celiac disease was expressed according to the Marsh classification. RESULTS: The overall AGA in subclinical form were positive in 77% (14 of 18) of patients with partial villous atrophy (VA), in 84% (21 of 25) of patients with subtotal VA, and in 90% (27 of 30) of patients with total VA, whereas EMA were positive in 88.88% (16 of 18) of patients with partial VA, in 92% (23 of 25) of patients with subtotal VA, and 96.66% (29 of 30) of patients with total VA. On the other hand, AGA were positive in 0% (zero of two) of patients with Marsh I and in 30% (three of 10) of patients with Marsh II, whereas EMA were positive in 0% (zero of two) of patients with Marsh I and in 40% (four of 10) of patients with Marsh II (Marsh I-IIIa vs Marsh IIIb-c, p = < 0.005 in overall AGA-positive patients and p = < 0.0001 in EMA-positive patients). At the same time the overall AGA in silent form were positive in 60% (three of five) of patients with partial VA, in 66.66% (four of six) of patients with subtotal VA, and in 77.77% (seven of nine) of patients with total VA, whereas EMA were positive in 80% (four of five) of patients with partial VA, in 83.33% (five of six) of patients with subtotal VA, and in 88.88% (eight of nine) of patients with total VA. On the other hand, overall AGA were positive in 0% of patients with both Marsh I (zero of one) and Marsh II (zero of two), as well as EMA were positive in 0% with both Marsh I (zero of one) and Marsh II (zero of two) (Marsh I-IIIa vs Marsh IIIb-c, p = < 0.001 in overall AGA-positive patients and p = < 0.007 in EMA-positive patients). CONCLUSIONS: At this time small bowel biopsy seems to be the only correct procedure to diagnose a case of suspected celiac disease, especially in patients with mild symptoms or suspected for celiac disease, because they belong to high-risk groups.
Adolescent↗
High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer.
PURPOSE: We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized prostate cancer. MATERIALS AND METHODS: Between October 1988 and December 1998, 1,100 patients with clinical stages T1c-T3 prostate cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months. RESULTS: At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] +/- 4), 58% (95% CI +/- 6) and 38% (95% CI +/- 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI +/- 8) compared to 90% (95% CI +/- 8) for those treated with 75.6 to 86.4 Gy. (p = 0.04) [corrected]. The corresponding rates were 50% (95% CI +/- 8) versus 70% (95% CI +/- 6) in intermediate risk cases (p = 0.001), and 21% (95% CI +/- 8) versus 47% (95% CI +/- 6) in unfavorable risk cases (p = 0.008) [corrected]. Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI +/- 2) compared with 5% (95% CI +/- 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI +/- 2) compared with 14% (95% CI +/- 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity. CONCLUSIONS: Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio.
Adenocarcinoma↗
The ABCD rule of dermatoscopy does not apply to small melanocytic skin lesions.
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Diagnosis, Differential↗
[Vertigo in adolescents with hemicrania].
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5-Hydroxytryptophan↗
[Adolescentology's study in Tuscany: activity 2000-2001].
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Adolescent↗
[Counseling services for adolescents in three Tuscany areas].
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Adolescent↗
[Adolescent health care in pediatric departments of Tuscany].
BACKGROUND: Admission to Pediatric Departments for 0/18- year-old patients is an important issue for the best organization of pediatric hospital assistance. Aim of the study. To locate adolescent health care and identify the percentage of adolescent admissions to Pediatric Departments in an Italian region (Tuscany). METHODS: Adolescent health care in pediatric departments and pediatric admissions (0-18 years old) in 1999 into the reference hospital of Pisa and into 5 other regional hospitals in Tuscany are reported. The percentages of patients, subdivided by age, hospitalyzed in Pediatric Departments have been determined. RESULTS: In 1999 the admissions for subjects aged 0 to 18 years were 12573 of which 4966 adolescents (39.6 %). The percentage of adolescent admissions is not smaller than children's admissions (aged 0 to 1 year: 16.2%; aged 2 to 5 years: 26.2%; aged 6 to 9 years: 17.8%; aged 10 to 14 years: 20.4%; aged 15 to 18 years: 19.2%). Analysis by age demonstrated a continuous decrease of patient percentages admitted to Pediatric Departments with the increased age. A minority of 15/18- year-old subjects has been admitted to Pediatric Departments. CONCLUSIONS: The percentage of adolescent admissions is similar to there of children. Most adolescents are admitted to structures unsuitable for assistance to subjects aged 0 to 18 years. These data underline the necessity for a strong recovery of adolescent admissions to pediatric structures also equipping suitable nursing rooms.
Adolescent↗
Combined 3-dimensional conformal radiotherapy and transperineal Pd-103 permanent implantation for patients with intermediate and unfavorable risk prostate cancer.
PURPOSE: To evaluate the efficacy and morbidity of combined 3-dimensional conformal radiation therapy (3D-CRT) and brachytherapy for intermediate/unfavorable risk prostate cancer. MATERIALS AND METHODS: Between May 1996 and November 1997, 65 patients with intermediate/unfavorable risk prostate cancer were treated with 3D-CRT (50.4 Gy) followed by a transperineal permanent Pd-103 implant. Patients with one or two adverse prognostic features (PSA > 10 and Gleason > or = 7) were classified as intermediate risk and unfavorable risk, respectively. Forty-seven patients (71%) had intermediate risk and 18 (29%) had unfavorable disease risk. The median age of this group was 65 years (range, 42-76 years), and the median pretreatment PSA level was 8.0 ng/ml (range, 1.7-42.0 ng/ml). The clinical stage of these patients was as follows: Tlc, 36 (55%); T2a, 27 (42%); T2b/T3, 2 (3%). Fifteen patients (23%) had a Gleason < or = 6, 41 patients (63%) were classified as Gleason 7, and 9 (14%) as Gleason > or = 8. Fifty-two (80%) received neoadjuvant androgen deprivation (NAAD) for cytoreduction. The median follow-up was 36 months (range, 24-42 months). RESULTS: The PSA relapse-free survival rate at 3 years was 87%, with a median PSA value at last follow-up of 0.25 ng/ml. The relapse-free survival was 90% for those who had an initial PSA < or = 10 ng/ml and 80% for patients who had an initial PSA > 10 ng/ml (p = 0.5). No difference in outcome was observed between patients with intermediate and unfavorable risk disease. Eight patients (13%) developed late Grade 2 rectal bleeding. Twenty-three patients (42%) required medication for urinary symptoms during the first 6 months after therapy. Three patients (5 %) noted rare stress incontinence at last follow-up. Of the 44 patients who were potent prior to therapy, 17 (26%) developed erectile dysfunction (ED). CONCLUSION: Although the follow-up is short, the early biochemical outcome of combined 3D-CRT and brachytherapy for intermediate/unfavorable risk prostate cancer is promising. While rectal toxicity is minimal, urinary side effects are more common. Further follow-up is necessary to fully evaluate the efficacy of this combined therapeutic approach.
Adult↗
Long-term urinary toxicity after 3-dimensional conformal radiotherapy for prostate cancer in patients with prior history of transurethral resection.
PURPOSE: To report on the long-term urinary morbidity among prostate cancer patients with a prior history of a transurethral resection of the prostate (TURP) treated with high-dose 3-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Between 1988 and 1997, 1100 patients with clinically localized prostate cancer were treated with 3D-CRT. Of these, 120 patients (8%) were identified as having had a prior TURP and are the subjects of this analysis. The median age was 71 years (range: 49-83 years). The clinical stages of the patients were T1c: 33 (28%); T2a: 38 (32%); T2b: 15 (13%); and T3: 34 (27%). Neoadjuvant androgen ablation therapy was given to 39 (33%). The median radiation dose prescribed to the planning target volume was 75.6 Gy (range: 64.8-81 Gy). The median elapsed time from TURP to initiation of 3D-CRT was 69 months (range: 4-360 months). The median follow-up time was 51 months (range: 18-109 months). RESULTS: Five patients of the 120 with a prior history of TURP (4%) developed a urethral stricture after 3D-CRT which was corrected with dilatation. The 5-year actuarial likelihood of >/= Grade 2 late urinary toxicities was 9%. No Grade 4 urinary toxicities were observed in this group of patients. Among 110 patients who were completely continent of urine prior to 3D-CRT, 10 (9%) developed stress incontinence requiring 1 pad daily for protection or experienced occasional leakage (not requiring pad protection). The 5-year incidence of >/= Grade 1 stress incontinence was 18% in patients who developed acute >/= Grade 2 GU symptoms during the course of 3D-CRT compared to 7% for patients who experienced Grade 1 or no acute urinary symptoms (p = 0.05). The radiation dose (>/=75.6 Gy vs. <75.6 Gy), the number of prior TURP procedures, or the volume of resected tissue at the time of TURP had no significant impact on the long-term urinary morbidity outcome. A multivariate analysis demonstrated that the presence of Grade 2 acute urinary symptoms was the only predictor of >/= Grade 1 stress incontinence after 3D-CRT in this group of patients. CONCLUSIONS: Despite prior TURP, the incidence of >/= Grade 3 urinary toxicities is low. Nevertheless, especially among patients with a prior history of TURP who experience Grade 2 acute urinary symptoms during radiation treatment, a higher risk of stress incontinence is observed.
Aged↗