Reduction incidence of myocardial infarction associated with a national legislative ban on smoking.

AIM: The aim of the present study was to assess change in admissions for acute myocardial infarction (AMI) in the period immediately subsequent to the coming into force of law no. 3/2003 ''Protection of the health of non-smokers''. METHODS: Four Italian regions (Piedmont, Friuli Venezia Giulia, Lazio and Campania) took part in the study. Data regarding admissions for AMI were taken from the daily discharge papers of patients aged between 40 and 64 (cod. ICD9-CM 410.), in the period 10 January-10 March 2001-2005. Repeated admissions were excluded. Admission rates standardised by age and overall total, and specifically by region, age and gender were calculated. The hypothesis of a significant reduction between 2005 and 2004 was also checked. RESULTS: The results showed a decrease in the number of cases and in the standardised rates between 2004 and 2005. The number of admissions estimated with a linear regression model for 2005 was significantly higher than that really observed (+13%). The decrease between the 2005 and 2004 rates was noteworthy for all four regions. Analysis by gender shows that the effect is observed only in male patients and in the age classes 45-49 and 50-54. CONCLUSION: This study shows that there has been an appreciable reduction in the incidence of heart attacks in the period immediately subsequent to the coming into force of the non-smoking Law in the populations surveyed, and that this reduction mainly regards men of working age. The reduction reverses a trend that has been evident for a number of years, namely that of a decidedly upward trend in the number of admissions for AMI.

Italy: the first European country to forbid smoking in closed spaces. First results.

Second-hand smoke is a well-known risk factor for several diseases, including lung cancer, chronic obstructive pulmonary disease, asthma. Evidence exists that smoke-free policies have an effect on reducing or eliminating the exposure to second-hand smoke, decreasing the prevalence of smokers, encouraging smokers to quit or preventing the initiation of smoking, and reducing cigarettes consumption among smokers. Italy has been the first European country to forbid smoking in closed places, also in working areas not open to the public, as protection to the health of the entire population. This article describes the first results obtained from the application of this new law, the positive effects and unexpected modifications in the behaviour and social habits of the Italian people, thus, revealing itself an important instrument to protect public health.

p53 nuclear accumulation and multiploidy are adverse prognostic factors in surgically resected stage II colorectal cancers independent of fluorouracil-based adjuvant therapy.

To identify the prognostically highest risk patients, DNA content and p53 nuclear or cytoplasmic accumulation, evaluated by monoclonal antibody DO7 and polyclonal antibody CM1, were determined in 94 surgically resected stage II (Dukes B2) colorectal cancers, treated or not with adjuvant 5-fluorouracil-based chemotherapy. Sixty-one (65%) of the tumors were aneuploid, 16 (17%) of which had a multiploid DNA content; 50 (53%) displayed DO7 nuclear p53 accumulation, and 44 (47%) showed cytoplasmic CM1 positivity. In multivariate analysis, only multiploidy and p53 nuclear positivity emerged as independent prognostic indicators of a poorer outcome. Positivity for p53 was associated with shorter survival in 5-fluorouracil-treated and untreated patients. Therefore, in patients with Dukes B2 colorectal cancer, a biologic profile based on the combined evaluation of DNA multiploidy and p53 status can provide valuable prognostic information, identifying patients to be enrolled in alternative, more aggressive therapeutic trials.

Independent prognostic value of peritoneal immunocytodiagnosis in endometrial carcinoma.

Among the clinical parameters that play a pivotal role in predicting the outcome of patients with endometrial carcinoma, intraperitoneal microscopic dissemination represents an important cause of recurrences. To date, peritoneal cytology has been incorporated into the current surgical staging system (International Federation of Gynecology and Obstetrics 88), although its predictive value remains a controversial issue. In this study the authors investigated the possibility of applying immunocytochemistry (ICC) to the diagnosis of peritoneal washing (PW) aimed at improving conventional cytology and verifying the prognostic value of peritoneal malignant cells. The authors analyzed 182 PWs sampled from endometrial cancer patients. The ICC analysis was performed using two monoclonal antibodies (MAbs)--AR-3 and B72.3--that in combination recognize more than 95% of endometrial carcinomas. The presence of peritoneal-free cancer cells was identified morphologically in 27 of 182 lavages (14.8%) and ICC in 50 of 182 (27.5%), with a significant improvement (p <0.0001). Five-year survival analysis, comparing results of ICC and cytodiagnosis, demonstrated a significant decrease of disease-free survival in patients with peritoneal microscopic disease. Furthermore, multivariate analysis showed that ICC diagnosis of PWs is an independent prognostic factor. Data indicate that the use of selected MAbs allows one to identify cytologically false-negative cases, providing results that are highly predictive of a worse clinical outcome.

Role of P53 and BCL-2 in high-risk breast cancer patients treated with adjuvant anthracycline-based chemotherapy.

PURPOSE: Adjuvant therapy has become an integral component of the managment of primary high-risk breast cancer patients. However, a considerable fraction of women receive no benefit from this treatment. This study investigates whether a number of biopathological factors can influence the outcome of patients submitted to adjuvant chemotherapy involving the use of high-dose epirubicin and cyclophosphamide. METHODS: One hundred and fifty-seven primary breast cancer patients, considered at high risk according to the St. Gallen Meeting Consensus Conference, were evaluated immunohistochemically for estrogen, progesterone receptors, p53, bcl-2, HER-2/neu, and Ki-67, of which the results were correlated with patient outcome. RESULTS: Results obtained demonstrated that p53 is a significant predictor of disease-free survival (DFS P < 0.0001) and overall survival (OS P = 0.0002) both in ductal and lobular carcinomas, whereas bcl-2 expression seems to be of prognostic value only in lobular carcinomas (DFS P = 0.01; OS P = 0.02). CONCLUSIONS: This data indicates that in high-risk breast cancer patients the immunohistochemical evaluation of p53 and bcl-2 may be of clinical value in distinguishing different responses to adjuvant anthracycline-based chemotherapy.

Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: independent prognostic role of p53 and bcl-2.

About 40% of patients with colorectal carcinoma will develop local or distant tumour recurrences. Integrated analyses of bio-pathological markers, predictive of tumour aggressiveness, may offer a more rational approach to planning adjuvant therapy. To this end, we analysed the correlation between p53 accumulation, Bcl-2 expression, DNA ploidy, cell proliferation and conventional clinico-pathological parameters by testing the prognostic significance of these variables in a series of 171 colorectal carcinoma patients with long-term follow-up. The relationships among the various bio-pathological parameters, analysed by multiple correspondence analysis, showed 2 different clinico-biological profiles. The first, characterised by p53 negativity, Bcl-2 positivity, diploidy, low percentage of cells in S-phase (%S-phase), a low Ki-67 score, is associated with Dukes' A-B stage, well differentiated tumours and lack of relapse. The second, defined by p53 positivity, Bcl-2 negativity, aneuploidy, high %S-phase and elevated Ki-67 score, correlates with Dukes' C-D stage, poorly differentiated tumours and presence of relapse. When these parameters were examined according to Kaplan-Meier's method, significantly shorter disease-free (DFS) and overall survival (OS) were also observed in patients bearing p53 positive and Bcl-2 negative tumours, in Dukes' B stage. In multivariate analysis, p53 accumulation and Bcl-2 expression emerged as independent predictors of a worse and better clinical outcome, respectively. Our results indicate that, in colorectal adenocarcinomas, a biological profile, based on the combined evaluation of p53 and Bcl-2, may be useful for identifying high risk patients to be enrolled in an adjuvant setting, mainly in an early stage of the disease. Int. J. Cancer (Pred. Oncol.) 84:545-552, 1999.

Diagnostic and prognostic value of peritoneal immunocytology in gastric cancer.

PURPOSE: Among the clinical factors with a pivotal role in the prediction of outcome for patients with gastric cancer, intraperitoneal (i.p.) microscopic dissemination may represent an important cause of recurrences, even in the early stages of the disease. In this context, the cytologic examination of intraoperative peritoneal washings may be essential to identify metastatic free cells, although a number of false-negative cases may be encountered. PATIENTS AND METHODS: To determine whether immunocytochemical (ICC) methods that used a panel of three monoclonal antibodies (MoAbs), B72.3, AR3, and BD5, directed to gastric cancer-associated antigens can improve peritoneal cytology by providing more accurate prognostic indications, we immunocytochemically and morphologically evaluated 144 peritoneal washings sampled from patients surgically treated for gastric cancer. RESULTS: The ICC analysis allowed the identification of metastatic free peritoneal cells in 35% of the patients, with a 14% improvement over routine cytopathology (P < .0001). Furthermore, a 54-month survival analysis by Kaplan-Meier curves showed a statistically significant decrease in overall survival (OS) in patients with stages I through III disease with peritoneal microscopic disease detected morphologically and/or by ICC at the time of the primary surgery. CONCLUSION: Our data indicate that the use of a combination of selected MoAbs may allow the identification of cytologically false-negative cases that provide valuable prognostic information. This may be useful to stratify patients on more adequate therapeutic trials.

The role of multiploidy as unfavorable prognostic variable in colorectal cancer.

OBJECTIVE: To analyze the prognostic value of DNA multiploidy in a prospective study on frozen surgical tissue samples from primary colorectal cancer. SUMMARY BACKGROUND DATA: Survival data from eleven prospective studies collectively comprising about thirteen hundred patients showed that aneuploidy correlated with a 5-year disease-free survival (DFS) significantly poorer than diploidy, and showed the limited prognostic value of results from retrospective studies employing paraffin-embedded material. METHODS: Multiple tumor samples of fresh/frozen surgical tissues from 120 colorectal cancer patients who had undergone radical surgery were taken for flow cytometric analysis of DNA content, and proliferative activity, shown as percentage of cells in S-phase (%S). The minimum follow-up of this series was 30 months. Univariate and multivariate analyses determined the independent significance of both clinical and biological variable on DFS. RESULTS: Values of %S equal to or higher than 17.3 correlated with a 5-year DFS poorer than values lower than 17.3 (44.5% vs 85.2% respectively; p = .03), even if only in patients younger than 64. The subgroup with multiploid tumors showed a significantly poorer 5-year DFS (44.5% vs. 62.6% in the non multiploid patients; p = .02). Subgrouping the Dukes'B stage alone by multiploidy, the difference in DFS was much more evident (31.2% vs. 68% respectively; p = .0004) and multivariate analysis showed multiploidy as the only significant variable. Above all, adjuvant therapy did not absolutely modify the unfavorable outcome of the multiploid Dukes'B patients. CONCLUSIONS: The prospective evaluation of ploidy allowed us to identify a very high-risk subgroup of patients with multiploid tumors. This biological characterization was easy to demonstrate and, above all in node-negative patients, reliable and very effective in terms of prognosis. The presence of multiploidy should result in a more aggressive therapeutic approach in the adjuvant setting.

The application of hyperthermia in regional chemotherapy.

To evaluate the role of hyperthermia combined with chemotherapy in the loco-regional treatment of tumors, a retrospective analysis was done with 228 limb melanoma patients treated with hyperthermic antiblastic perfusion (HAP). A series of treatment- and tumor-related prognostic factors was analyzed to establish their influence on tumor response, loco-regional control, and survival. Concerning tumor response, the logistic model showed that the number of lesions and the minimal tumor temperature (min T) maintained their individual predictive values (P < 0.000001 and P = 0.04, respectively). For loco-regional control, only the number of lesions had a significant predictive value. No direct correlation was found between the treatment-related variables and loco-regional control. However, the 5-year survival rate was significantly higher for patients who achieved a complete response (CR) (51.5%, P = 0.0033) as compared to those who did not (33.3%), providing indirect evidence of the role of the treatment. Multivariate analysis showed that both disease-free and overall survival are strongly influenced by numerous clinical variables and the min T always maintained its significance. When analyzing the subgroup of 119 patients evaluable for tumor response, the Cox model selected the tumor response as the dominant factor for both disease-free and overall survival. These data seem to demonstrate that the optimization of treatment parameters is crucial in determining the CR rate, which, in turn, positively affects the disease outcome. HAP is the treatment of choice for recurrent limb melanoma, and hyperthermia plays an important role in exploiting the efficacy of this technique.