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Biomedical subjects

G Sanna

Publications and source records attributed to G Sanna.

At least 19 recordsLinked to original sources
PubMed2006

Breast cancer in Hodgkin's disease and non-Hodgkin's lymphoma survivors.

BACKGROUND: Better therapeutic approaches for patients with Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL) resulted in high cure rates, at cost of serious late side effects. Second primary tumours are a major concern for long-term survivors, and breast cancer (BC) is the most common solid tumour among women treated for HD. MATERIALS AND METHODS: Fifty-three women treated for primary BC with previous history of malignant lymphoma were identified in our institution, 35 with HD (66%), 18 (34%) with NHL. A comparison group was randomly selected from our database matching for each patient with previous lymphoma, two patients with primary BC (rate 1 : 2) for age, stage (pathological tumour size [pT] status and nodal status), year of diagnosis, and estrogen and progesterone status (positive versus negative). The primary end points were disease-free survival (DFS) and overall survival (OS). RESULTS: The two groups of patients were compared for biological features: histopathological diagnosis, grading, lymphatic invasion, c-erbB2 overexpression, and Ki-67. Considering these variables, no significant differences were observed between the two groups with the exception of Ki-67, which was found higher in those with previous HD or NHL (65% versus 49%, respectively, P = 0.0526, borderline significant). Comparing the two groups for treatment approach, no differences were found for surgical and medical therapy (endocrine therapy and chemotherapy). However, regarding patients with node-positive disease (14 versus 35 patients), five patients in the lymphoma group (36%), compared with 24 (69%) in the matched group received anthracycline-based therapy (P = 0.0345). As expected, radiotherapy was used very differently in the two groups, with 36% of patients in the study group undergoing intraoperative radiotherapy with electrons versus 10% in the control group (P = 0.0001). Five-year DFS was 54.5% for the study cohort compared with 91% for controls (P < 0.0001). Five-year OS percentages were also statistically different (86.6% and 98.6%, respectively, P = 0.031). CONCLUSIONS: Previous history of malignant lymphoma is a negative prognostic factor for women diagnosed subsequently with BC. Some undertreatment of women with the latter might be hypothesised as the reason for the worse outcome. Influence of other variables, like previous exposure to cytotoxics, or some unknown biological features related to the previous disease and treatment, should still be investigated in the attempt to improve the dire outcome of these patients.

Adolescent↗
PubMed2006

Bisphosphonates and jaw osteonecrosis in patients with advanced breast cancer.

BACKGROUND: In recent years, several cases of mandibular necrosis associated with long-term use of bisphosphonates have been reported. The estimated incidence varies from 1% to 4.6%. PATIENTS AND METHODS: We conducted an observational study with the aim of determining the incidence of jaw osteonecrosis in advanced breast cancer patients with bone metastases under bisphosphonate treatment and to identify subjects at higher risk of developing this complication evaluating preclinical signs. We considered two groups of patients. All the patients complaining of odontostomatological symptoms underwent maxillary CT scan and maxillo-surgeon clinical examination. Asymptomatic patients were asked to perform a standard orthopantomography (OPT). RESULTS: From February 2005 to October 2005, we observed five patients with jaw bone necrosis (6%). Diagnosis was radiological and clinical. In two patients a confirmatory biopsy was performed. In the same time interval, OPTs were collected from 76 asymptomatic patients. Three OPTs revealed radiological features of suspicious mandibular necrosis. Maxillary CT scan confirmed the presence of an osteolityc area with signs of periosteal reaction. All the three patients were referred to maxillo-surgeon and two out of three patients underwent mandibular biopsy, but histopathological results were not conclusive. CONCLUSIONS: In our experience, the incidence of jaw bone necrosis in breast cancer patients seems to be higher than in other reports (6%). Radiological features of suspicious jaw necrosis were observed in three asymptomatic patients. We do not know how these findings should be considered. Anyway, standard OPT is a simple procedure, and may allow identification of periodontal conditions that in some way can predispose to the development of this uncommon event.

Adult↗
PubMed2005

Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects.

BACKGROUND: We previously demonstrated efficacy and impact on serum vascular endothelial growth factor (VEGF) for metronomic cyclophosphamide (C) and methotrexate (M) in patients with breast cancer. New metronomic schedules were investigated. PATIENTS AND METHODS: Patients with advanced breast cancer were randomized to receive oral C (50 mg daily) and M (2.5 mg twice daily on days 1 and 4) (arm A) or the same regimen plus thalidomide (200 mg daily) (arm B). RESULTS: The mean VEGF level decreased from 378.9 (+/-274.4) pg/ml at baseline to 305.9 (+/-203.6) pg/ml at 2 months (P<0.001), with similar change with respect to baseline in both arms. In 171 evaluable patients we observed three complete remissions (CR) in both arms A and B, 15 partial remission (PR) in arm A and seven in arm B, for an overall response of 20.9% [95% confidence interval (CI) 12.9% to 31%] in arm A and 11.8% (95% CI 5.8% to 20.6%) in arm B. The clinical benefit (CR+PR+SD>or=24 weeks) was 41.5% for both arms. Toxicity was generally mild. Higher neurological toxicity (2% versus 60%; P<0.0001) and constipation (8% versus 51%; P<0.0001) was observed in arm B. CONCLUSIONS: Metronomic low-dose CM induced a drop in VEGF, and was effective and minimally toxic. The addition of thalidomide did not improve results.

Administration, Oral↗
PubMed2005

Dose-finding and pharmacokinetic study of an all-oral combination regimen of oral vinorelbine and capecitabine for patients with metastatic breast cancer.

PURPOSE: A phase I study was performed to determine the maximal tolerated dose, recommended doses (RDs), safety and efficacy of oral vinorelbine when combined with capecitabine in an all-oral chemotherapy regimen in patients with metastatic breast cancer (MBC), with pharmacokinetic blood sampling to investigate potential drug-drug interactions. PATIENTS AND METHODS: Forty-four patients with MBC received as first- or second-line chemotherapy, oral vinorelbine at a dose of 60 or 80 mg/m2 on days 1 and 8 (and 15) with escalating doses of capecitabine from 1650 to 2500 mg/m2/day days 1-14 every 3 or 4 weeks. Three schedules were tested: day 1, day 8 and weekly regimens of oral vinorelbine with a 14-day course of capecitabine every 3 weeks; and a days 1 and 8 regimen of oral vinorelbine with a 14-day course of capecitabine every 4 weeks. RESULTS: With oral vinorelbine at 60 mg/m2, the RDs were established as oral vinorelbine 60 mg/m2 on days 1 and 8 plus capecitabine 2250 mg/m2/day days 1-14 and oral vinorelbine 60 mg/m2/week plus capecitabine 2000 mg/m2/day days 1-14. With oral vinorelbine at 80 mg/m2, the RD was oral vinorelbine 80 mg/m2 on days 1 and 8 plus capecitabine 2000 mg/m2/day days 1-14. Neutropenia was the main dose-limiting toxicity of the combination; it was reported in 40 patients (90.9%), with grade 3 in 14 patients (31.8%) and 6.2% of cycles, and grade 4 in 12 patients (27.3%) and 4.3% of cycles. Complications were rare with only three patients experiencing febrile neutropenia (one episode each). The most frequent non-haematological toxicity was gastrointestinal; however, the incidence of grade 3 was low, with no episode of grade 4. Hand-foot syndrome was reported in 14 patients (31.8%) and 22.6% of cycles, with grade 2 in two patients (4.5%) and 1.2% of cycles (two episodes each). No episode of grade 3 was observed. Objective responses were reported in 18 patients (three complete responses and 15 partial responses), yielding a response rate of 40.9% in the intention-to-treat population according to the investigator assessment. Results from the pharmacokinetic study demonstrated the absence of mutual pharmacokinetic interactions when both drugs were co-administered. CONCLUSIONS: The combination of oral vinorelbine and capecitabine is safe and easy to administer in an outpatient setting. This all-oral combination chemotherapy may offer a good alternative to the intravenous route for patients with MBC. Based on these promising results, a phase II study has started using oral vinorelbine 60 mg/m2/week with capecitabine 2000 mg/m2/day days 1-14 every 3 weeks as first-line chemotherapy in patients with MBC.

Administration, Oral↗
PubMed2005

Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Age of Onset↗
PubMed2005

Are all high-grade breast cancers with no steroid receptor hormone expression alike? The special case of the medullary phenotype.

BACKGROUND: Medullary carcinoma (MC) of the breast is associated with favorable prognosis compared with other histological types, despite high nuclear grade, fast proliferation and lack of steroid hormone receptor expression. We retrospectively evaluated the clinical relevance of selected immunohistochemical features of tumors in three cohorts of patients with typical medullary (MC), 'atypical' medullary (AMC) or ductal (DC) breast carcinoma. PATIENTS AND METHODS: Evaluation was performed on node-negative tumor specimens from 40 patients who had either MC (12 patients), AMC (nine patients) or DC (19 patients), treated in a single institution. All had no hormonal receptor, Ki-67 > or =30%, G3, expansive pattern of growth and peritumoral lymphocytic infiltration. In addition, p27, p21 and HER2/neu overexpression, p53, cyclin E and E-cadherin expression, presence of apoptotic cells, stromal tenascin (TN), and type of immune cell infiltration (CD3- and CD68-positive cells) were assessed. RESULTS: No difference in expression of HER2/neu, p21, p27, p53, number of apoptotic cells and CD68-positive cells was detected. Lower levels of stromal TN expression were found in MC compared with DC (P=0.0007), but differences between MC and AMC were not significant (P=0.27). A higher proportion of intratumoral CD3-positive cells was seen in MC than in AMC (P=0.046). No differences were seen between MC and DC (P=0.73). With a median follow-up of 67 months, three patients with DC had relapsed in distant sites, while one patient with AMC had a second primary. Two patients with MC had reappearance of DC in the breast. CONCLUSIONS: The three distinct disease types, selected by having similar high proliferation, had similar expression of cell cycle regulators. The lower expression of TN and massive infiltration of T lymphocytes might both indicate a special interaction between tumor cells and microenvironment, important features for conferring improved prognosis through negligible invasive and metastatic potential to MC. In our series, however, patients with a previous MC are not free from the risk of developing a subsequent DC. Finally, defining AMC as a distinct entity from DC is not justified.

Adult↗
PubMed2005

Antiphospholipid antibody tests: spreading the net.

OBJECTIVE: To examine the hypothesis that testing for new antiphospholipid antibody specificities may help to identify the antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE) with thrombosis who are repeatedly negative for anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA). METHODS: Three groups of patients with SLE were studied: (a) SLE/APS (n = 56): 51 female, mean (SD) age 46 (11) years, fulfilling 1999 Sapporo criteria for the APS; (b) SLE/thrombosis (n = 56): 53 female, age 42.6 (12) years, all with a history of thrombosis and persistently negative for aCL and/or LA; (c) SLE only (n = 56): 53 female, age 40 (11) years, without a history of thrombotic events. aCL and LA were retested in all samples. All patients were tested for anti-beta(2)-glycoprotein I (anti-beta(2)GPI) and antiprothrombin antibodies (aPT) by coating prothrombin on irradiated plates or using phosphatidylserine-prothrombin complex as the antigen (aPS-PT). RESULTS: Anti-beta(2)GPI were only present in patients from the SLE/APS group, all of whom were also positive for aCL. aPT and aPS-PT were also more commonly found in SLE/APS than in SLE/thrombosis or SLE only groups (54% v 5%, p<0.0001 or v 16%, p<0.0001 for aPT and 63% v 2%, p<0.0001 or v 11%, p<0.0001 for aPS-PT, respectively). No differences were found between SLE/thrombosis and SLE only groups (p = 1.5 for beta(2)GPI, p = 0.1 for aPT, and p = 0.1 for aPS-PT). CONCLUSION: Testing for aPT in patients with SLE with thrombosis, but persistently negative for aCL and LA, may be helpful in some selected cases. Anti-beta(2)GPI are not present in patients who are negative for aCL.

Adult↗
PubMed2005

Role of Chlamydophila abortus in ovine and caprine abortion in Sardinia, Italy.

Between 1999-2003, 14321 sera and 646 abortion samples (498 foetuses and 148 placentae) were analysed from 807 sheep and goat farms distributed all over the island of Sardinia. After notification of abortion in a flock, sera collected at random from adult animals were examined to detect antibodies specific to Chlamydophila (C.) abortus by ELISA, whereas foetuses and placenta were analysed by PCR assay. Specific IgG antibodies were detected in 611 (4.8%) sheep and 106 (5.8%) goats. From a total of 2050 ovine and 151 caprine fetal samples including muscle, liver, abomasum, spleen, brain and placenta, 29 (1.4%) ovine and 1 (0.6%) caprine samples were C. abortus PCR-positive. Placenta was the tissue with the highest detection rate. These results indicate that the seroprevalence of C. abortus infection in sheep and goats is very low in Sardinia, and PCR results demonstrate that C. abortus has no significant role in abortion, especially in goats.

Aborted Fetus↗
PubMed2004

Response of bilateral choroidal metastases of breast cancer to therapy with trastuzumab.

Intraocular metastases, especially those of the choroidal plexus, are not common in metastatic breast cancer patients and are typically associated with a poor prognosis and impaired quality of life. A 45-year-old woman with breast cancer overexpressing HER2 and metastasizing to choroidal plexus, lymph nodes and skin received a combination of trastuzumab and paclitaxel as first-line treatment. Subsequently, at progression, trastuzumab was reintroduced together with vinorelbine. Administration of trastuzumab with either paclitaxel or vinorelbine led to a rapid improvement of the ocular symptoms, associated with a rapid objective response of all metastatic lesions and a prompt improvement in the quality of life. Choroidal metastases from breast cancer overexpressing HER2 are responsive to trastuzumab and chemotherapy (paclitaxel or vinorelbine). The susceptibility of ocular metastases to this approach seems different to that of other sanctuary disease sites.

Antibodies, Monoclonal↗
PubMed2003

Central nervous system involvement in the antiphospholipid (Hughes) syndrome.

The antiphospholipid (Hughes) syndrome (APS) is characterized by arterial and/or venous thrombosis and pregnancy morbidity in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disorder or secondary to a connective tissue disease, most frequently systemic lupus erythematosus. Central nervous system (CNS) involvement is one of the most prominent clinical manifestations of APS, and includes arterial and venous thrombotic events, psychiatric features and a variety of other non-thrombotic neurological syndromes. In this review we focus on the common and some of the less common CNS manifestations that have been reported in association with antiphospholipid antibodies.

Antiphospholipid Syndrome↗
PubMed2003

Ehrlichiosis and rickettsiosis in a canine population of Northern Sardinia.

Ehrlichiosis and rickettsiosis are very common, widespread diseases. These diseases are present in Sardinia year round because its temperate weather permits the survival of many kinds of tick vectors. A thousand dogs were subjected to physical, hematological, biochemical examinations and serological tests. All 1,000 sera were analyzed by indirect immunofluorescence antibody test to detect antibodies against E. canis and R. rickettsii. A high seroprevalence (about 50%) was detected for both etiological agents, without differences in relation to sex, breed, or usage. A high seroprevalence, corresponding to 62.5% for ehrlichiosis and 64% for rickettsiosis, was observed in the age group of 13-60 months. The mortality was greatest in the males in the age group, which manifested the disease in the chronic phase.

Animals↗
PubMed2003

Central nervous system lupus: a clinical approach to therapy.

Management of central nervous system (CNS) involvement still remains one of the most challenging problems in systemic lupus erythematosus (SLE). The best available evidence for the treatment of CNS lupus is largely based on retrospective series, case reports and expert opinion. Current therapy is empirical and tailored to the individual patient. Symptomatic, immunosuppressive and anticoagulant therapies are the main strategies for the management of CNS lupus. The choice depends on the most probable underlying pathogenic mechanism and the severity of the presenting neuropsychiatric symptoms. Thrombotic and nonthrombotic CNS disease needs to be differentiated and requires different management strategies. However, this is often challenging since many, if not most CNS manifestations, may be due to a combination of different pathogenic mechanisms and multiple CNS events may occur in the individual patient. Patients with mild manifestations may need symptomatic treatment only, whereas more severe acute nonthrombotic CNS manifestations may require pulse intravenous cyclophosphamide. Plasmapheresis may also be added in patients with more severe illness refractory to conventional treatment. Recently, the use of intrathecal methotrexate and dexamethasone has been reported in a small series of patients, with a good outcome in patients with severe CNS manifestations. Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid syndrome (APS). This article reviews the clinical approach to therapy in patients with CNS lupus.

Adrenal Cortex Hormones↗
PubMed2003

Headache and systemic lupus erythematosus.

Headache is a common feature in patients with systemic lupus erythematosus (SLE) and represents a significant source of patient discomfort. The exact prevalence of headache in SLE is unknown. The results of different studies widely vary, most likely due to the use of different classification for headache and the lack of controls in most studies. The relationship between headache and SLE is also unclear since it is difficult to determine which degree and type of headaches can be explained on the basis of chronic illness, or as part of the disease spectrum of SLE. No pathogenic mechanism has so far been described that can fully explain headache induced by SLE. The role of circulating cytokines, vascular injury, neuronal damage or antiphospholipid antibodies (aPL) in the development of headache in SLE patients is also a matter of debate. Other concomitant causes such as infection or hypertension should be excluded before assuming that headache is a feature of SLE activity. Therapeutic approach of headache SLE-related remains empirical and based on clinical experience.

Adrenal Cortex Hormones↗
PubMed2002

Sustained normalization of cerebral blood-flow after iloprost therapy in a patient with neuropsychiatric systemic lupus erythematosus.

We report the case of a 30-year-old caucasian woman affected by SLE who developed neurological symptoms (prosopagnosia and visual-spatial agnosia) after nine years of disease. Brain MRI showed no abnormalities while a brain SPECT scan showed diffuse uptake defects and hypoperfusion areas in the right and left frontal-parietal regions. At that time the patient was on hydroxychloroquine (400 mg/day) and oral prednisolone (0.5 mg/kg/day) as maintenance therapy. One year later the patient showed worsening of Raynaud's phenomenon with digital dystrophic lesions and was therefore treated with an intravenous infusion of Iloprost (1.5 ng/kg/min per 6h/day for 10 days consecutively), while baseline treatment remained unchanged. One month later the patient showed a dramatic improvement in her cognitive function and subsequent SPECT scans showed the gradual disappearance of perfusion abnormalities. This first report of Iloprost treatment in CNS lupus suggests the potential therapeutic usefulness of this drug in patients with SLE and functional CNS involvement.

Adult↗
PubMed2002

Lessons from the "Euro-Lupus Cohort".

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Adolescent↗
PubMed2001

Multiple sclerosis epidemiology in Sardinia: evidence for a true increasing risk.

OBJECTIVES: To update prevalence and incidence rates of MS among Sardinians. MATERIALS AND METHODS: The present work is a "spider" kind of population based survey, conducted over the interval 1968-97, on patients with MS (Poser criteria) living in the province of Sassari, Northern Sardinia (454,904 population). RESULTS: A crude total prevalence rate of 144.4 per 100,000, an onset-adjusted prevalence rate of 149.7 per 100,000 and an average annual incidence rate of 8.2 for the period 1993-7 were found. CONCLUSION: Repeated epidemiological assessments of MS in Sardinia over decades have shown that the island is at high risk for MS. The present work highlights that MS incidence in Sardinia has been increasing over time. Although a substantial and widely spread improvement in MS case ascertainment can be postulated as the reason for such observations, a comparison between our data and those recently reported from a more industrialized province in Northern Italy seems to prove an at least partially real increase in MS risk among Sardinians and favours the hypothesis of a MS "Sardinian focus" as related to its latitude.

Adolescent↗