Dermatofibrosarcoma protuberans treated at a single institution: a surgical disease with a high cure rate.

PURPOSE: Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade, cutaneous sarcoma with autocrine overproduction of the platelet-derived growth factor (PDGF) beta-chain from gene rearrangement as a key pathogenetic factor, now susceptible of molecular-targeted therapy. The aim of this retrospective analysis was to explore the outcome of patients with primary or recurrent DFSP. PATIENTS AND METHODS: Two hundred eighteen patients surgically treated at the Istituto Nazionale per lo studio e la cura dei Tumori (Milan, Italy) over 20 years were reviewed. Local relapse, distant metastasis, and survival were studied. RESULTS: One hundred thirty-six patients (62.4%) presented with a primary DFSP, while 82 patients (37.6%) had a recurrent disease. In the primary group, margins were microscopically positive in 11.8%, while in the recurrent group they were positive in 14.6% (P =.613). In the primary group, patients undergoing re-excision after inadequate previous surgery had residual disease in 62% of cases. Reconstructive surgery was needed in 30%, significantly more frequently in patients with a recurrence or a head and neck tumor. The crude cumulative incidence of local relapses was 4% at 10 years, and 2% at 10 years for distant metastases. No significant difference was found between primary and recurrent patients, as well as between positive and negative margins. CONCLUSION: This being one of the largest mono-institutional series of DFSP, we confirm that long-term outcome is excellent, in terms of both local and distant control, after a wide excision with negative margins. Reconstructive surgery is often needed. Novel medical therapies will be of use in a limited subgroup of patients.     

p53 Is a Master Regulator of Proteostasis in SMARCB1-Deficient Malignant Rhabdoid Tumors

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Trastuzumab in combination with metronomic cyclophosphamide and methotrexate in patients with HER-2 positive metastatic breast cancer

Background  

HER2/neu overexpression is linked to promotion of angiogenesis in breast cancer. We therefore tested the activity of the combination of Trastuzumab with metronomic, low dose chemotherapy with cyclophosphamide (CTX) and methotrexate (MTX) in metastatic breast cancer (MBC).     

Letrozole plus GnRH analogue as preoperative and adjuvant therapy in premenopausal women with ER positive locally advanced breast cancer

Patients with large ER positive tumors candidate to preoperative chemotherapy may also benefit from a concurrent endocrine intervention, but this issue has been scarcely investigated due to concerns arising from unfavorable results emerged from an adjuvant trial of concurrent tamoxifen and chemotherapy. We retrospectively investigated the activity of letrozole plus GnRH analogue (GnRH-a) administered concurrently with preoperative chemotherapy and as adjuvant treatment in premenopausal women with locally advanced ER positive breast cancer consecutively admitted at the European Institute of Oncology. Results were compared with those of a non-randomized unmatched control group of premenopausal women with locally advanced ER positive breast cancer receiving preoperative chemotherapy, followed by tamoxifen and GnRH-a after surgery. Primary endpoints were pathological complete response (pCR) rate, decrease of Ki67 and disease free survival (DFS). One-hundred and nineteen women constituted the study group, while 95 patients served as controls. The pCR rate was 5.0 vs 1.1% in the study and control group, respectively. A statistically significant greater suppression of Ki67 was observed in patients receiving chemoendocrine therapy as compared with controls (P = 0.003). At a median follow up of 59 months, 26 events occurred in the chemoendocrine group and 48 in the control group. Five-year DFS was 78 vs 41% in the study and in the control group, respectively [adjusted HR 0.46, 95% CI 0.27-0.79, P = 0.0047]. The concurrent administration of letrozole and GnRH-a with preoperative chemotherapy was highly effective in premenopausal women with large ER positive breast cancer in terms of decreased proliferation and of improved DFS. Randomized studies are warranted to establish the role of the addition of endocrine therapy to chemotherapy as standard preoperative approach for ER positive locally advanced breast cancer as well as of letrozole in combination with GnRH-a for the treatment of premenopauasal women with early breast cancer.     

Searching for cognitively optimal challenge point in physical activity for children with typical and atypical motor development

Statement of problemGrowing evidence testifies that different types of physical activity (PA) interventions promote cognitive development, but the specific impact of the cognitive demands inherent in PA still remains underconsidered. This study investigated whether (1) increasing the cognitive demands of PA positively impacts children's executive function and (2) this ‘enrichment’ also matches the ability/skill level of children with Developmental Coordination Disorder (DCD).MethodsTwo hundred and fifty children aged 5–10 years participated in different physical education interventions, lasting six months, with or without special focus on cognitively demanding PA. Before and after the intervention, children's executive function was tested with the attention and planning subscales of the Cognitive Assessment System and their motor developmental level classified as typical, borderline, or DCD according to their performance evaluated by the Movement Assessment Battery for Children.ResultsAmong indices of executive function, those of Attention showed a differential effect of PA type as a function of children's motor developmental level: typically developing children gained greatest attentional benefit from PA with additional cognitive demands, while children with coordinative problems/impairment from the PA program without cognitive enrichment. Changes from DCD to borderline or normal developmental status did not differ in frequency as a function of intervention type.ConclusionsResults showed that cognitively more or less challenging PA programs are differently efficacious for promoting attention development and highlight the need to find and continuously reset the degree of task complexity in PA to match the optimal challenge point of normal and special children populations.     

Survival of pleural malignant mesothelioma in Italy: a population-based study

A median survival time of about 9 months is generally reported among malignant pleural mesothelioma cases. Recently, better results in terms of survival and performance status have been reported in clinical trials that included highly selected patients. We describe the survival of pleural mesothelioma patients and the factors predictive of survival in an unselected, population-based setting. Pleural mesothelioma cases (4,100) registered from 1990 to 2001 by 9 Italian regional mesothelioma registries contributing to the network of the National Mesothelioma Registry were followed until December 31, 2005. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards regression) analyses of survival were carried out according to selected individual characteristics, including limited information on treatment in a subset of 578 cases. The median survival time was 9.8 months (95% confidence interval: 9.4-10.1). In multivariate analysis, younger age at diagnosis and epithelioid histotype were associated with significantly reduced hazard ratios. Positive effects of gender (women) and being diagnosed in a hospital with a thoracic surgery unit were of border-line statistical significance. No association with calendar period of diagnosis or asbestos exposure was present. Treatment was not associated with a statistically significant improvement in survival. This is the largest population-based study on survival in patients with pleural mesothelioma to date. Age and morphology were the main prognostic factors. Results regarding the effect of treatment were disappointing but may be useful to assess the future impact, at the population level, of recently introduced therapies.     

Engagement of PI-3-kinase mediated protein kinase C zeta activation in protecting Friend cells from ionizing radiation-induced apoptosis

Murine erythroleukemia cells (Friend) respond to ionizing radiation with the activation and nuclear translocation of p85alpha subunit of phosphatidylinositol-3-kinase (PI-3-kinase) which mediates the downstream activation and nuclear translocation of atypical Protein kinase C zeta (PKC zeta). This event occurs mainly upon high dose of ionizing radiation (15 Gy) and is concomitant to an increase in BrdU incorporation, which probably accounts for a predominant repair DNA synthesis. Following treatment with wortmannin, a relatively specific inhibitor of PI-3-kinase, both an increased number of apoptotic cells and the inhibition of protein kinase C zeta translocation were detected. Altogether the evidence suggests a potential role of the PI-3-kinase/PKC zeta pathway in protecting Friend cells from ionizing radiation-induced apoptosis offering PKC zeta for consideration as possible target of pharmacological treatments.     

Is axillary lymph node dissection necessary in elderly patients with breast carcinoma who have a clinically uninvolved axilla?

BACKGROUND: Axillary dissection in elderly patients with early-stage breast carcinoma who do not have palpable axillary lymph nodes is controversial because of the associated morbidity of the surgery, reduced life expectancy of the patients, and efficacy of hormone therapy in preventing recurrences and axillary events. METHODS: The authors performed a retrospective analysis of 671 consecutive patients with breast carcinoma who were age >or= 70 years and who underwent conservative breast surgery with axillary dissection (172 patients) or without axillary dissection (499 patients). Tamoxifen always was given. The effects of axillary dissection compared with no axillary dissection on breast carcinoma mortality and distant metastasis were analyzed using multiple proportional-hazards regression models. Because the assignment to axillary treatment was nonrandom, covariate adjustments were made for baseline variables that influenced the decision to perform axillary dissection and for prognostic factors. RESULTS: The crude cumulative incidence curves for breast carcinoma mortality and distant metastasis did not appear to differ significantly between the two groups (P = 0.530 and P = 0.840, respectively). The crude cumulative incidences of axillary lymph node occurrence at 5 years and 10 years were 4.4% and 5.9%, respectively (3.1% and 4.1%, respectively, for patients with pT1 tumors). CONCLUSIONS: Elderly patients with breast carcinoma who have no evidence of axillary lymph node involvement may be treated effectively with conservative surgery and tamoxifen. Immediate axillary dissection is not necessary but should be performed in the small percentage of patients who later develop overt axillary lymph node involvement.     

Evaluation of quality of care through hospital discharge reports: an example of rectal cancer surgery

This study was undertaken to evaluate the usefulness of hospital discharge data for monitoring the impact of a regional practice guideline on treatment of colorectal cancer. The aims of the study were: i) estimating process and outcome indicators; ii) exploring the relationship between patient and hospital characteristics and these indicators. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for all risk factors analysed. All 3,614 patients undergoing potentially curative resection for rectal cancer in 75 hospitals in Piedmont (Italy) between 1997 and 2000 were included. Occurrences of abdominoperineal resections (APR), postoperative complications, reinterventions and hospital mortality were 16.2%, 11.0%, 5.5% and 4.4%, respectively. APR was performed more frequently in patients with distant metastases or urgently admitted and by hospitals with a lower volume of cases (< 25 per year) compared to hospital with more than 50 cases per year (OR = 1.50, CI = 1.16-1.94). The strongest predictors for mortality and complications were: older age, distant metastases and urgency of admission. Incidence of complications and of reinterventions was also increased among males and in patients with lesions of the lower rectum. The rate of complications showed an increasing trend during the period, from 8.5% to 14.5% likely reflecting improvement in coding during time. Low hospital workload was associated to a reduced risk of complications and reinterventions, but there was evidence of underreporting of secondary diagnoses and procedures in smaller hospitals. Outcome indicator based on secondary diagnoses and procedures are of limited value in monitoring improvement of care since they reflect also differences in coding during time and among providers.