Breast cancer in the elderly: treatment of 1500 patients

There is a significant difference in the extent of treatment offered to the elderly with breast cancer; in the United States, while 98% of patients less than 65 years of age receive standard treatment, 81% of those older than 65 years were treated according to protocol. This study's goal was to evaluate disease-specific survival and local-regional recurrence in breast cancer patients more than 65 years of age at diagnosis. A total of 1500 patients with invasive breast carcinoma were treated consecutively from May 1971 to July 2002 at the University of Florence, Florence, Italy. All patients were more than 65 years of age. The median age was 70.6 years (range 65.1-87.3 years).The median follow-up was 8.7 years (range 1-30 years). The crude probability of survival (or relapse occurrence) was estimated using the Kaplan-Meier method and survival (or relapse occurrence) comparisons were carried out using Cox proportional hazard regression models. The Cox regression model by stepwise selection showed as independent prognostic factors for disease-specific survival (DSS), the occurrence of a local relapse (p < 0.0001), pN status (p < 0.0001), the type of surgery (p < 0.0001), and the use of radiotherapy (p < 0.0006) and chemotherapy (p = 0.01). For local disease-free survival (LDFS), the Cox regression model by stepwise selection showed that mastectomy (p < 0.0001), histotype (p < 0.0001), pN status (p < 0.0001), and pT status (p = 0.001) were the only independent prognostic factors. Age was not a prognostic factor for DSS nor LDFS. We suggest treating patients with appropriate treatment for their prognostic factors.     

Bacterial vaginosis and preterm delivery: an open question

OBJECTIVE: To evaluate the prevalence of bacterial vaginosis in a population of Italian pregnant women and to study its association with adverse pregnancy outcomes, particularly preterm delivery. STUDY DESIGN: After giving informed consent, 598 women were consecutively enrolled at their first prenatal visit (13-18 weeks of gestation). The presence of bacterial vaginosis was assessed by Gram's method at 13-18 weeks of gestation (early bacterial vaginosis) and at 28-32 weeks of gestation (late bacterial vaginosis). Univariate and multiple logistic regression models of analysis were used to assess the statistical significance of the data. RESULTS: Preterm delivery occurred in 14.7% of pregnant women positivefor bacterial vaginosis at theirfirst prenatal visit and in 6.9% of healthy women (OR 1.6, CI 1.07-2.51). In patients with bacterial vaginosis, preterm delivery occurred more often in the 36th week of gestation (78.6%). CONCLUSION: The presence of bacterial vaginosis at an early gestational age is associated with preterm delivery, although in the study population the condition did not seem to be related to great prematurity.     

Assessment of liver circulation by quantitative scintiangiography: evaluation of the relative contribution of the hepatic arterial and portal venous blood flows to liver perfusion

Quantitative hepatic scintiangiography was previously used for evaluating the relative contribution of hepatic arterial and portal venous blood flows to the hepatic circulation. The present study compares 3 different procedures (automatic and manual integration, and slope fitting methods) for analyzing the hepatic time activity curves obtained after bolus i.v. injection of 370 MBq 99mTc-diethylentriaminopentacetic acid. Twenty five subjects were studied: five controls, ten cirrhotics, and ten portal hypertensive patients previously submitted to side to side portacaval anastomosis. The correspondence between results given by the different methods was satisfactory only in shunted patients, and the reproducibility of computed parameters was quite poor for all procedures. Accordingly, none of the methods can be considered as supporting reliable quantitative pathophysiological evaluations. However, the hepatic arterial/portal venous flow ratio was found to be increased in liver cirrhosis and in shunted patients and therefore, in spite of the limitations underlined before and of the absence of data on the reproducibility of consecutive injections, hepatic scintiangiography may be of some clinical utility.     

Radical radiotherapy for early glottic cancer: Results in a series of 1087 patients from two Italian radiation oncology centers. I. The case of T1N0 disease

PURPOSE: To retrospectively evaluate local control rates, late damage incidence, functional results, and second tumor occurrence according to the different patient, tumor, and treatment features in a large bi-institutional series of T1 glottic cancer. METHODS AND MATERIALS: A total of 831 T1 glottic cancer cases treated consecutively with radical intent at the Florence University Radiation Oncology Department (FLO) and at the Radiation Oncology Department of the University of Brescia-Istituto del Radio "O. Alberti" (BS) were studied. Actuarial cumulative local control probability (LC), disease-specific (DSS), and overall survival (OS) rates have been calculated and compared in the different clinical and therapeutic subgroups with both univariate and multivariate analysis. Types of relapse and their surgical salvage have been evaluated, along with the functional results of treatment. Late damage incidence and second tumor cumulative probability (STP) have been also calculated. RESULTS: In the entire series, 3-, 5-, and 10-year OS was equal to 86%, 77%, and 57%, respectively. Corresponding values for LC were 86%, 84%, and 83% and for DSS 96%, 95%, and 93%, taking into account surgical salvage of relapsed cases. Eighty-seven percent of the patients were cured with function preserved. Main determinants of a worse LC at univariate analysis were: male gender, earlier treatment period, larger tumor extent, anterior commissure involvement, and the use of Cobalt 60. At multivariate analysis, only gender, tumor extent, anterior commissure involvement, and beam type retained statistical significance. Higher total doses and larger field sizes are significantly related (logistic regression) with a higher late damage incidence. Scatterplot analysis of various combinations of field dimensions and total dose showed that field dimensions >35 and <49 cm2, together with doses of >65 Gy, offer the best local control results together with an acceptably low late damage incidence. Twenty-year STP was equal to 23%, with second tumor deaths being more frequent than larynx cancer deaths (67 of 831 vs. 46/831). CONCLUSION: The results of this study support the opinion, suggested by some international guidelines, that radiotherapy is standard treatment for T1 glottic cancer. Better results are obtained in patients with less extended disease and with 4-6 MV photon beams. The use of doses in excess of 65 Gy and of field sizes of 36-49 cm2 is probably the best technical choice available. Late damage is infrequent, but careful follow-up is warranted to detect early not only relapses (because conservative salvage surgery is feasible), but also second malignant tumors, which constitute the main cause of death in these patients and are potentially curable.     

Budd-Chiari syndrome with fatal outcome in a patient with polycythemia vera and antiphospholipid antibody syndrome

We report the case of a 41-year-old woman, affected by Vaquez syndrome, admitted to our hospital for a severe pain in the right hypochondrium, suddenly followed by hepatomegaly and ascites. The clinical and laboratory data were suggestive of hepatic insufficiency and abdominal ultrasonography, integrated by color Doppler and computed tomography, revealed an interrupted hepatic venous outflow. In addition a spontaneous prolonged partial thromboplastin time was present and the patient was found to be positive for lupus anticoagulant. A transient clinical improvement, with a partial reperfusion of suprahepatic veins, was achieved with medical treatment by using anticoagulants, diuretics and paracentesis. However, the patient showed a subsequence of suprahepatic venous thrombosis, although two transjugular intrahepatic portosystemic shunts with stent placement and local thrombolysis were performed. The polycythemia vera is a disease mainly associated with Budd-Chiari syndrome but, in our patient, the thrombotic event occurred in spite of normal values of hematocrit and platelet count. Certainly in this case the lupus anticoagulant positivity represents an additional thrombogenic factor. Nowadays the antiphospholipid antibody syndrome is a recognized and not unusual cause of Budd-Chiari syndrome but, to our knowledge, this is the first case characterized by the presence of polycythemia vera and antiphospholipid antibody syndrome to be reported.     

Native versus primary prosthetic valve endocarditis: comparison of clinical features and long-term outcome in 353 patients

BACKGROUND AND AIM OF THE STUDY: The study aim was to compare preoperative and intraoperative features, and long-term outcome of patients operated on for native (NVE) and primary prosthetic valve endocarditis (PVE). METHODS: Between January 1978 and December 2002, 258 patients (mean age 47.5 +/- 16 years) were referred for NVE, and 95 for PVE. Demographics, clinical preoperative conditions, indications to surgery, microbiological data, surgical pathology, early postoperative course and long-term outcome were compared via hospital chart review and outpatient clinic follow up. RESULTS: Female sex prevailed in the PVE group (49.5%) versus NVE (27.1%; p < 0.0001). Mitral valve involvement was more common in PVE (46.3% versus 24.8%, p = 0.0001), and multivalvular in 16.3% of NVE patients versus 4.2% of PVE (p = 0.001). Active endocarditis (80.6% versus 58.9%, p = 0.00004) and preoperative embolism (29.5% versus 11.6%, p = 0.0002) were significantly prevalent in the NVE group. Emergency operation (21.1% versus 10.5%, p = 0.009) and preoperative NYHA class IV or V (40% versus 19.8%, p < 0.0001) were significantly more frequent in PVE. Overall hospital mortality was 11.3% (n = 40), with 6.6% among NVE patients and 24.2% among PVE (p < 0.0001). Mean follow up (94% complete) was 5.8 +/- 5.3 years (6.0 +/- 5.5 years for NVE versus 5.1 +/- 4.6 years for PVE, p = 0.191), and total follow up was 1,707.85 patient-years. Actuarial survival at 1, 5, 10 and 15 years was respectively 91, 82, 67.5 and 48.8% in NVE, and 79.7, 64.2, 33.5 and 33.5% in PVE (p = 0.0016). A significantly lower survival in PVE versus NVE was found for the mitral site subgroup (p = 0.018), but not for the aortic site (p = 0.14). Actuarial freedom from reoperation for recurrent endocarditis at 1, 5, 10 and 15 years was 97.5, 91.4, 80.5 and 49.4% in NVE versus 90.8, 84.9, 59.4 and 43.9% in PVE (p = 0.015). CONCLUSION: PVE patients were older, presented with more compromised clinical conditions, and had worse early and long-term outcomes than NVE patients. PVE had a higher incidence of recurrence and worse prognosis, especially if the mitral valve was involved.     

E-cadherin impairment increases cell survival through Notch-dependent upregulation of Bcl-2

The role of E-cadherin in tumorigenesis has been attributed to its ability to suppress invasion and metastization. However, E-cadherin impairment may have a wider impact on tumour development. We have previously shown that overexpression of mutant human E-cadherin in Drosophila produces a phenotype characteristic of downregulated Notch. Hence, we hypothesized that Notch signalling may be influenced by E-cadherin and may mediate tumour development associated with E-cadherin deficiency. De novo expression of wild-type E-cadherin in two cellular models led to a significant decrease in the activity of the Notch pathway. In contrast, the ability to inhibit Notch-1 signalling was lost in cells transfected with mutant forms of E-cadherin. Increased Notch-1 activity in E-cadherin-deficient cells correlated with increased expression of Bcl-2, and increased resistance to apoptotic stimuli. After Notch-1 inhibition, E-cadherin-deficient cells were re-sensitized to apoptosis in a similar degree to wild-type E-cadherin cells. We also show that Notch-inhibiting drugs are able to significantly inhibit the growth of E-cadherin-deficient cells xenografted into nude mice. This effect was comparable with the one observed in animals treated with the chemotherapeutic agent taxol, a chemical inducer of cell death. In conclusion, our results show that aberrant Notch-1 activation, Bcl-2 overexpression and increased cell survival are likely to play a crucial role in neoplastic transformation associated with E-cadherin impairment. These findings highlight the possibility of new targeted therapeutical strategies for the treatment of tumours associated with E-cadherin inactivation.     

Biweekly rituximab, cyclophosphamide, vincristine, non-pegylated liposome-encapsulated doxorubicin and prednisone (R-COMP-14) in elderly patients with poor-risk diffuse large B-cell lymphoma and moderate to high 'life threat' impact cardiopathy

This Phase II study assessed feasibility and efficacy of a biweekly R-COMP-14 regimen (rituximab, cyclophosphamide, non-pegylated liposome-encapsulated doxorubicin, vincristine and prednisone) in untreated elderly patients with poor-risk diffuse large B-cell lymphoma (DLBCL) and moderate to high 'life threat' impact NIA/NCI cardiac comorbidity. A total of 208 courses were delivered, with close cardiac monitoring, to 41 patients (median age: 73years, range: 62-82; 37% >75years) at a median interval of 15·6 (range, 13-29) days; 67% completed all six scheduled courses. Response rate was 73%, with 68% complete responses (CR); 4-year disease-free survival (DFS) and time to treatment failure (TTF) were 72% and 49%, respectively. Failures were due to early death (n=3), therapy discontinuations (no-response n=2; toxicity n=6), relapse (n=6) and death in CR (n=3). Incidence of cardiac grade 3-5 adverse events was 7/41 (17%; 95% confidence interval: 8-31%). Time to progression and overall survival at 4-years were 77% and 67%, respectively. The Age-adjusted Charlson Comorbidity Index (aaCCI) correlated with failures (P=0·007) with patients scoring ≤7 having a longer TTF (66% vs. 29%; P=0·009). R-COMP-14 is feasible and ensures a substantial DFS to poor-risk DLBCL patients who would have been denied anthracycline-based treatment due to cardiac morbidity. The aaCCI predicted both treatment discontinuation rate and TTF.