Experience of vaccination against invasive bacterial diseases in Veneto region (north east Italy).

The goal of this study was to describe and comment the experience of the Veneto Region in the bacterial invasive disease. Vaccination coverage was 93% against pneumococcus and 95% against haemophilus influenzae type B. Regard to meningococcus C the coverage rate was 90.1% In children, 81% at 6 years of age and 78.2% at 15 years. The preliminary data of an active surveillance of invasive bacterial diseases show that the Streptoccoccus pneumoniae was the main agent involved and that its consequences were particularly serious in elderly subjects. With regard to Neisseria meningitidis, we observed a substantial reduction in the number of cases due to serogroup C and a concomitant rise in the percentage of cases due to serogroup B. The suspension of mandatory vaccination should be maintained, the monitoring of vaccination coverage and the active surveillance proved to be a very good assessment tools.

[Increasing childhood immunization coverage by establishing structured relationships with pediatricians and family practitioners]. / Aumentare le coperture vaccinali in età pediatrica creando rapporti strutturali con la pediatria di famiglia.

An immunization strategy can take advantage of various tools, among which the pediatrician and family practitioner These figures, have been assigned the role of accompanying the child and his/her family throughout development. One of the objectives of this role is also to take a major part in the support of immunization coverage of infants, especially in light of the sospension of required immunizations in the Veneto Region. For this reason it is necessary to open dialogue on immunizations together with pediatricians and family physicians. In addition, training of these professional figures, together with healtcare operators who work in the immunization clinics, has allowed the formation and standardization of the network, as the persons who attend the immunization clinics are no longer passive users but persons who require information exchange in order to make an informed choice about immunizations for their children. Surveillance of vaccination coverage is a useful tool for evaluating the trend in vaccination refusals, and in particular it takes into consideration the motivation behind the refusal to adhere to the polio vaccine recommendations even if for now the coverage is maintained above 95%. Concluding, another strong point for the immunization program is "Genitori Più" which finds its continuity with the Regional Prevention Plan.

Regulation of longevity and stress resistance by Sch9 in yeast.

The protein kinase Akt/protein kinase B (PKB) is implicated in insulin signaling in mammals and functions in a pathway that regulates longevity and stress resistance in Caenorhabditis elegans. We screened for long-lived mutants in nondividing yeast Saccharomyces cerevisiae and identified mutations in adenylate cyclase and SCH9, which is homologous to Akt/PKB, that increase resistance to oxidants and extend life-span by up to threefold. Stress-resistance transcription factors Msn2/Msn4 and protein kinase Rim15 were required for this life-span extension. These results indicate that longevity is associated with increased investment in maintenance and show that highly conserved genes play similar roles in life-span regulation in S. cerevisiae and higher eukaryotes.

Evaluating the potential usefulness of new prognostic and predictive indicators in node-negative breast cancer patients.

The incidence of breast cancer is increasing in all Western countries. Due both to a more widespread public education and to early diagnosis by mammography screening programs, the percentage of patients with node-negative breast cancer has gone up to 70%. Thus, node-negative breast cancer is a major public health problem and, consequently, clinical research in this setting is an expanding field. A recent overview analysis confirmed the results of five prospective randomized clinical trials suggesting that systemic adjuvant therapy can benefit node-negative breast cancer patients. Because of the heterogeneity of node-negative breast cancer, it is reasonable to attempt to avoid excessive treatment morbidity and costs by using selective prognostic markers to identify patients at high risk for disease recurrence who are eligible for postsurgical systemic adjuvant therapy. It is also desirable to use predictive markers in selecting the therapy to which each patient is more likely to respond. The need for additional prognostic and predictive factors has led to identification of a plethora of potentially useful markers. As a result, the selection of patients at different risks of developing node-negative breast cancer and the choice for appropriate therapy remain difficult and confusing for the clinician. Moreover, the majority of studies have examined new markers individually rather than by multivariate analysis and retrospectively rather than prospectively. Thus, there are also important methodologic biases in such studies. This analysis consists of (a) defining the clinical "problem," (b) defining the terms of prognostic and predictive factors, (c) suggesting more appropriate laboratory and clinical approaches to properly evaluate a new indicator, (d) identifying the subsets of patients in whom the use of new prognosticators is warranted and of particular importance, and (e) providing some direction for future research on this topic. Our ultimate goals are to facilitate the understanding of node-negative breast cancer prognostic markers among clinicians, to help them select the most appropriate indicator for specific situations, and to recommend methodology for future research.

Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma.

BACKGROUND: Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. PURPOSE: This study was designed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. METHODS: In a prospective, blinded study of 165 consecutive patients, the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted microvessels per 200x field in the most active areas of neovascularization and graded microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). RESULTS: There was a highly significant (P < or = .001) association of microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer microvessels per 200x field. Moreover, microvessel density was the only statistically significant predictor of overall survival among node-negative women (P < .001). Only microvessel density (P < .001) and histologic grade (P = .04) showed statistically significant correlations with relapse-free survival in the node-negative subset. CONCLUSIONS: Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). IMPLICATIONS: Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvant therapy.

Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma.

PURPOSE: To determine the absolute and relative value of microvessel density (MVD), p53 and c-erbB-2 protein expression, peritumoral lymphatic vessel invasion (PLVI), and conventional prognosticators in predicting relapse-free (RFS) and overall survival (OS) rates in patients with node-negative breast carcinoma (NNBC). PATIENTS AND METHODS: We monitored 254 consecutive patients with NNBC for a median of 62 months. Intratumoral MVD was measured after microvessels were immunostained using anti-CD31 antibody. p53 and c-erbB-2 protein and hormone receptors were also determined immunocytochemically. Results were analyzed by both univariate and multivariate statistical analysis. RESULTS: Univariate analysis showed that MVD was significantly predictive of both RFS (odds ratio [OR], 8.30; P = .0001) and OS (OR, 4.50; P = .012) when tested as a continuous or dichotomous variable. Likewise, tumor size (OR, 3.16; P = .0012), PLVI (OR, 4.36; P = .0009), estrogen receptor (ER) status (OR, 2.35; P = .016), progesterone receptor (PR) status (OR, 2.00; P = .017), and expression of p53 protein (OR, 2.82; P = .004) were significantly associated with RFS. Tumor size (OR, 3.80; P = .0038) and expression of p53 protein (OR, 2.58; P = .024) were significantly associated with OS by univariate analysis. Multivariate analysis showed that MVD (P = .0004), p53 protein expression (P = .0063), tumor size (P = .0144), and PLVI (P = .0033) were all significant and independent prognostic factors for RFS. However, only tumor size (P = .004) and MVD (P = .047) were independent predictors for OS. c-erbB2 expression was not associated with outcome by either univariate or multivariate analysis. CONCLUSION: MVD, p53 expression, PLVI, and tumor size are independent prognostic indicators of recurrence, which are useful in selection of high-risk NNBC patients who may be eligible to receive adjuvant therapies.

Human breast cancer: prognostic significance of the c-erbB-2 oncoprotein compared with epidermal growth factor receptor, DNA ploidy, and conventional pathologic features.

PURPOSE: A study was undertaken to define the prognostic value of the expression of the c-erbB-2 oncoprotein in a series of breast cancer patients when compared by multivariate analysis with expression of the epidermal growth factor receptor (EGFR), DNA ploidy, and conventional clinicopathologic features. PATIENTS AND METHODS: Prognostic indicators were analyzed in 165 primary breast cancers. The c-erbB-2 oncoprotein was recognized by the polyclonal antibody 21N using an immunocytochemical method. Expression of the EGFR was stated immunocytochemically using the monoclonal antibody EGFR1. DNA ploidy was assessed in paraffin-embedded sections using a standard flow-cytometric method. RESULTS: Overall, 27% of carcinomas had membrane 21N-staining and were classified as c-erbB-2-positive. Overexpression of the c-erbB-2 oncoprotein was poorly associated with EGFR expression and the conventional pathologic features, and it was weakly associated with DNA ploidy and nodal status. Univariate analysis showed that c-erbB-2 expression, nodal status, DNA ploidy, and EGFR provided significant prognostic information concerning 4-year relapse-free survival (RFS) with the odds ratios (ORs) of not relapsing of 2.94, 2.83, 2.34, and 2.20, respectively. Regarding overall survival (OS) at 4 years, only nodal status and DNA ploidy had prognostic significance, with the ORs of not dying of 2.68 and 2.80, respectively. Applying multivariate analysis to RFS, 21N when adjusted for nodal status, EGFR, and DNA ploidy (full model) failed to retain prognostic value (P = .202), whereas nodal status was the most significant indicator of relapse (P = .027) followed by DNA ploidy (P = .056) and EGFR (P = .093). CONCLUSIONS: This study suggests that overexpression of the c-erbB-2 oncoprotein appears to be an important indicator of relapse in stage I-II breast cancer when singly evaluated. Multivariate analysis shows that the determination both of nodal status and DNA ploidy improves our ability to identify subsets of patients with different prognoses, and allows for a better selection of patients for systemic adjuvant treatments.

c-erbB-3 and c-erbB-2 protein expression in node-negative breast carcinoma--an immunocytochemical study.

The type I growth factor receptor family has been found to play an important role in the control of normal growth and differentiation. Moreover, the epidermal growth factor receptor and the c-erbB-2 oncogene seem to be implicated in the pathogenesis and behaviour of several cancers, including breast cancer. c-erbB-3 is a new member of the type I receptor family for which there is currently little information available on its expression in neoplastic tissues, and on its possible prognostic significance. This study was undertaken to define the prognostic value of c-erbB-3 expression in a series of node-negative breast cancer (NNBC) patients when compared, by multivariate analysis, with expression of the c-erbB-2 protein and conventional clinicopathological features. cerbB-3 was recognised by the novel monoclonal antibody RTJ1, whereas c-erbB-2 was detected by the polyclonal antibody 21N, using immunocytochemical methods. We found that overexpression of c-erbB-3 occurs frequently in NNBC. Overall, 138 of 212 carcinomas (65%) had some degree of membrane RTJ1 staining, and 28 (13%) showed strong and generalised positivity ( ). Twenty-four per cent of carcinomas had membrane 21N staining, and 12% presented strong and generalised positivity ( ). c-erbB-3 protein expression was significantly associated only with that of c-erbB-2 (P = 0.05), whereas 21N positivity was significantly associated with small tumour size (P = 0.02) and ductal histotype (P = 0.04). No significant correlation between expression of either receptor proteins or relapse-free survival was observed after a median follow-up of 63 months. Applying multivariate analysis, only tumour size approached significance. Our results indicate that analysis of expression of c-erbB-3 and c-erbB-2 alone do not seem to be useful in identifying patients with NNBC at different risk of relapse or death.

From radiotherapy to stereotactic radiosurgery: physical and dosimetrical considerations.

The aim of this presentation is to analyse the mechanical and dosimetrical parameters of the linear accelerator used in stereotactic radiosurgery. The use of the thimble and Markus chambers, TL and film in small field dosimetry are investigated. To determine the optimal irradiation technique and dose distribution, the dose volume to healthy tissue is considered.

Dosimetric considerations on multiple arc stereotaxic radiotherapy.

The aim of this paper is to present the physical and dosimetrical features of the stereotaxic radiosurgical method already published by the authors. This method concentrates the dose into the stereotaxic target volume, placed at the isocenter of a 4 MV X-ray beam. Computer calculations showed that: 9-17 arcs provide almost spherical dose distributions; the optimal photon beam quality is about 4-6 MV. The angle between adjacent rotation planes is 20-40 degrees and the arcs are 100-160 degrees wide. In this way the dose to healthy tissue is minimized. The dose distribution was experimentally verified both by ionometric and photodensitometric methods. The procedure for dose calculation at isocenter of fields as small as required by the radiotherapist, has been investigated.

Analysis of dosimetric measurements in linac radiosurgery calibration.

The aim of this paper is to analyse the dosimetric parameters of a linear accelerator used in radiosurgery treatments. The influence of these parameters on the resulting dose distribution are basic for delivering the predefined dose to the vascular or oncological target volume. Several dosimetric methods have been used to define the output factors for small fields. The thimble and the Markus chambers, TLD and film dosimetry are investigated; all these dosimetric systems give reliable and almost similar results if used in the correct way. In the determination of tissue maximum ratio (TMR) the response curves obtained by ionometric and film dosimetry were investigated. For TMR determination the use of the Markus chamber and the correction factors to be applied as a result of the small dimension of the field were also investigated.

Treatment of locally advanced squamous-cell carcinoma of the head and neck with concurrent radiochemotherapy - randomized comparison of Cisplatin versus Carboplatin.

Several phase II studies have shown that concurrent chemotherapy and radiotherapy (RT) improves the response rates and locoregional control in patients with advanced, unresectable squamous-cell carcinoma of the head and neck (H&N). However, it is still unclear which is the drug of choice to be given with RT. We therefore conducted a randomized comparison of cisplatin (CDDP)-RT versus carboplatin (CRP)-RT in such patients. The two platinum compounds were given at equitoxic doses. The primary objective of the study was to compare the side effects and the response rates of the two regimens. Radiotherapy was given at conventional dosages, 2 Gy for 5 days every week for a total dose of 64 Gy with CDDP 80 mg/m2 or CRP 375 mg/m2 for three cycles on days 1, 21 and 42. At present 53 patients are entered in the study: 27 in the CDDP arm and 26 in the CRP. The two arms were balanced for all the pre-treatment characteristics. Both the schedules were well tolerated. However, incidence of nausea and vomiting (p=0.0045); anemia (p=0.032) and peripheral neuropathy (p=0.032) was significantly greater with CDDP-RT as compared to CRP-RT. On the other hand, CRP-RT gives a significantly higher incidence of stomatitis (p=0.0067) and a marginally worse thrombocytopenia (p=0.09). The complete response (CR) rates were similar in the two arms (55.5% in the CDDP-RT versus 61.5% in that CRP-RT, respectively) as well as the overall response rates (92.5% versus 84.5%, respectively; p=0.36). The estimated 1 -and 2 year overall and disease-free survival rates were not significantly different in the two arms. In both the groups logistic-regression models showed that those patients with a CR (p=0.017); stage III (p=0.011); smaller primary (p=0.025) and limited node-involvement (p<0.001) had a significant better survival. We conclude that concurrent chemo-radiotherapy is an effective and safe treatment for patients with locally advanced H&N cancer. The combination CRP-RT possess a similar activity but a different, and perhaps a more favorable, spectrum of toxicity when compared to the CDDP-RT therapy. Survival results need to be assessed in a larger series and followed for a more prolonged time.

Locally advanced breast-carcinoma - results of a multimodal therapy including alternating neoadjuvant chemotherapy, surgery and radiotherapy.

Thirty women with locally advanced breast cancer (LABC), but no evidence of distant metastases, were prospectively treated with four fixed cycles of neoadjuvant chemotherapy (CT). This regimen consisted of epidoxorubicin (Epi) alternated every 21 days with cyclophosphamide, methotrexate and 5-fluorouracil (CMF). After this induction CT, subsequent therapy was planned according to the response obtained as follows: (a) modified mastectomy with axillary dissection was performed in patients who had major objective response (complete or partial), followed by four doses of adjuvant CT and radiotherapy (RT); (b) debulking rescue surgery followed by RT and 2nd line CT with mitomycin C were given in patients with stable disease or minor response. The response rate to induction CT was 63% (19 of 30 patients) (95% confidence limits 46-80%). Overall, 43% of patients had no persistance of tumor at the end of the planned therapy. After a median follow-up time of 36 months, disease-free survival (DFS) and overall survival (OS) were 35% and 47%, respectively. The median duration of DFS was 16 + months (4-52+ months). A significantly better OS was observed in complete responders compared to the others (77% versus 23.5%; p=0.01). Compliance to treatment was high, gastrointestinal and hematological toxicities were the most common side-effects. Thus, this multimodal approach is effective in reducing primary tumor size with acceptable morbidity. Five of the 11 (45%) patients non responsive to induction CT obtained a transient local control of disease after debulking surgery, RT and mitomycin C. To assess the role of alternating non cross resistant regimens as induction therapy in LABC vs conventional schedules, phase III comparative studies are warrented.

Multivariate-analysis of prognostic factors in 232 patients with clinical stage-I endometrial adenocarcinoma using the new figo surgical staging system.

A retrospective analysis is reported in 232 patients with clinical Stage I endometrial adenocarcinoma diagnosed between 1980 and 1988, treated with combined surgery and adjuvant irradiation. Tumors were restaged according to the FIGO (1988) surgical staging system (SSS) in order to assess the prognostic value of this revised classification and of the conventional clinico-pathological features (age, performance status, grade and depth of myometrial invasion). The 5-year relapse-free survival (RFS) and overall survival (OS) of the series was 85% and 90.8%, respectively. Both 5-year RFS and OS were not significantly different adopting the FIGO (1971) clinical Stage (Stage IA 93% and 88% vs Stage IB 88.5 and 82%. respectively) whereas they were significant by FIGO SSS (Stage IA 96% and 93% vs Stage IB 94% and 88.5% vs Stage IC 74% and 63%, respectively) (p=0.001 and p=0.0005, respectively). Other factors that significantly affected 5-year RFS or OS at univariate analysis were age (p=0.01 and p<0.0001, respectively), performance status (p=0.035 and p=0.001, respectively), grade (p=0.015 and p<0.0001, respectively) and myometrial invasion (p=0.0017 and p=0.0003, respectively). A multivariate analysis of these prognostic variables showed that FIGO SSS was the only significant and independent (p=0.01) indicator for recurrence. However, when therapy was added to the model, FIGO SSS failed to retain significance (p=0.11). Concerning OS age (p<0.0001), performance status (p=0.04) and FIGO SSS (p=0.05) were significant and independent prognosticators, also when therapy was included in the analysis. In conclusion, this study shows that the new FIGO SSS is a useful prognosticator as well as is age and performance status, in early Stage endometrial adenocarcinoma.

Pathobiological characteristics of the 1st primary and risk of metachronous contralateral invasive breast-carcinoma - clinical implications.

The study was undertaken to determine the clinico-pathobiological characteristics in a series of 49 patients who developed metachronous breast carcinoma. Possible differences between the two tumours of conventional clinico-pathological features and of some biological markers such as DNA ploidy, c-erbB-2 oncoprotein overexpression and tumour angiogenesis were evaluated. The McNemar's test for independence showed that all the characteristics analyzed between the two tumours, in the same case, were not significantly different. After a median follow-up time of 69 months the overall survival of the series was 87.5% and the only significant prognostic factor for clinical outcome was peritumoural lymphatic vessel invasion (PLVI). The median second tumour-free interval was of 32 months ( 13 to 160 months) and none of the variables analyzed on the first primary was predictive of the timing of appearance of the second tumour. To assess the association between the characteristics of the first tumour and the odds of developing a metachronous carcinoma a case-control analysis was conducted. For each woman of the present series who developed bilateral cancer (case) a woman who had unilateral breast cancer (control) was matched for the length of the follow-up. A log-logistic regression model for matched sets was also performed to assess the risk of developing the second tumour. Applying multivariate analysis we found that progesterone receptor (PgR) status was the most important prognostic factor for the odds of bilateral tumour (odds ratio 0.22, p=0.013) followed by histological grade (odds ratio 0.20, p=0.063) and presence of PLVI (odds ratio 3.13, p=0.067). These findings suggest that the knowledge on the initial primary of PgR, grading and PLVI could be important to assess the individual risk of developing metachronous breast cancer. The determination of these factors could improve our ability to identify subsets of patients operated for breast cancer with different risks for bilateral tumour, allowing for a better selection of those patients who need intensive surveillance of their contralateral breast, and eligible for chemoprevention.

Prognostic value of p53 expression in early-stage breast-carcinoma compared with tumor angiogenesis, epidermal growth-factor receptor, C-erbb-2, cathepsin-d, DNA-ploidy, parameters of cell-kinetics and conventional features.

p53 expression detected by immunocytochemistry is emerging as a novel potentially useful prognostic indicator in breast carcinoma. However, additional research is warranted because a consensus has not yet been achieved on: i) methodology and quality control issues; ii) its association with other new biological prognostic indicators; iii) its prognostic value in multivariate analysis including conventional and new pathobiological features and; iv) its clinical usefulness either as a prognostic and predictive factor. This study was undertaken in a series of 165 early-stage breast cancer patients (median follow-up of 5 years) to compare the prognostic role of p53 expression with that of several other markers that have been found to be of value, using a multivariate statistical analysis. These factors are: tumour angiogenesis, epidermal growth factor receptor (EGFR), c-erbB-2 expression, cathepsin D, growth fraction by Ki-67 antibody, DNA ploidy and S-phase fraction. The main results observed were: i) 47 of 165 (28.5%) carcinomas had pAb 1801 staining and were considered as p53-positive; ii) p53 expression was weakly associated with S-phase fraction by flow cytometry (OR=1.86; p=0.085); iii) p53 expression was significantly associated with recurrence (p53 negative [-] versus weak positive [+] tumours: p=0.07 and odds ratio of 2.21; p53 negative [-] versus high positive [++] tumours: p=0.01 and odds ratio of 2.86) and death (p53-versus +: p=0.53 and odds ratio of 1.35; p53- versus ++: p=0.05 and odds ratio of 2.53); iv) the determination of p53 is able to identify a subset of high risk patients in c-erbB-2 negative tumours, this group being generally considered at good prognosis; v) In multivariate analysis on relapse-free survival including all the above markers only tumour angiogenesis, cathepsin D, EGFR and S-phase fraction and nodal status retained significance, and for overall survival only tumour angiogenesis was significant and independent. This new information on p53 expression could be useful to the clinician for a more rationale approach in defining prognosis of breast cancer patients. The prognostic value of p53 depends on which other markers are additionally analyzed and previous studies have not always assayed tumour angiogenesis, which is the most important factor in this series. p53 still need to be assessed as a potential predictor of response to chemo or radiotherapy, because of its role in monitoring DNA damage.

Progesterone receptor determined by immunocytochemical and biochemical methods in human breast cancer.

Immunocytochemical assay (ICA) of the progesterone receptor (PgR) was performed on 152 patients with stage I-II breast cancer. We employed the rat monoclonal antibody KD-68 and a peroxidase/antiperoxidase displaying system. The results obtained by ICA (Pg(RICA)) were compared with those by the biochemical dextran-coated charcoal assay (PgRDCC). Comparing the two methods we found an overall agreement (accuracy) of 77.5%, a PgR(ICA) sensitivity of 83.5% and a specificity of 73%. Both methods were significantly associated with oestrogen receptor expression, detected by DCC (P less than 0.001 for PgRDCC and P = 0.0014 for PgR(ICA)). No significant association was found between PgR(ICA) or PgRDCC and the other clinicopathological features analysed. After a median follow-up of 36 months, the overall survival probability was 91% in PgRDCC-positive versus 81.5% in PgRDCC-negative patients (log-rank test, chi 2 = 0.91) compared to 87.5% in PgR(ICA)-positive versus 82% in PgR(ICA)-negative ones (log-rank test, chi 2 = 0.93). Disease-free survival probability was 74.5% in both PgRDCC-positive and PgRDCC-negative patients (log-rank test, chi 2 = 0.02) compared to 78% in PgR(ICA)-positive versus 71.5% in PgR(ICA)-negative cases (log-rank test, chi 2 = 0.37). The present study demonstrates that ICA is a reliable method to detect PgR, correlating well with the DCC assay. Moreover, the ICA assay seems to provide clinical information complementary to the biochemical method. The definition of its prognostic value in operable breast cancer needs additional studies, particularly in node-negative patients.

Linear accelerator radiosurgery of cerebral arteriovenous malformations.

A technique for linear accelerator radiosurgery has been used in clinical practice since 1982. The technique is based on multiple intersecting arc irradiations focused on a stereotactic target. From November 1984 to October 1988, 97 patients with cerebral arteriovenous malformations have been treated. Seventy-nine patients suffered one or more than one hemorrhage. Four patients had progressive neurological symptoms. In 14 patients, epilepsy was the principal complaint. Stereotactic localization was performed by stereotactic angiography. Lesion dimensions varied from 4 to 40 mm in diameter. Doses from 18.7 to 40 Gy were delivered in one or two sessions. Mean follow-up is 17.1 months (from 1 to 49). Four instances of minor rebleeding were observed after treatment; 3 patients complained of transient neurological deterioration. Of 56 patients who were followed longer than 1 year, 50 underwent 12-month follow-up angiography. In 26 patients complete obliteration of the malformation was demonstrated (52%), in 12 patients subtotal obliteration was obtained (24%), in 11 patients the obliteration was evident but not significant (22%), and in 1 patient the AVM was unchanged. Other angiographic features in incompletely obliterated cases were a significant reduction of flow velocity through the malformation together with a reduction in diameter of both feeding arteries and draining veins.

Linear accelerator radiosurgery of cerebral arteriovenous malformations: an update.

One hundred eighty patients affected by cerebral arteriovenous malformations (AVMs) underwent radiosurgical treatment in our department. One hundred fifty-three patients have been treated with complete irradiation of the entire AVM nidus. In 27 patients (with large and/or three-dimensional irregular target volumes), only part of the nidus was covered with a dose adequate for obliteration. Follow-up ranged from 88 to 1 months (mean, 43.1 mo). Angiographic control was performed at 12, 24, and 36 months until complete obliteration was attained. The complete obliteration rate was 46% at 1 year and 80% at 2 years. We observed 15 hemorrhages after treatment, and five patients died from them. No bleeding took place after complete angiographic obliteration. The aim of this study is to evaluate the effect of irradiation on bleeding risk after radiosurgery and before complete obliteration. Inclusive parameters of patients considered at risk were as follows: 1) all patients in the time lapse between irradiation and demonstrated complete angiographic obliteration; 2) all patients in the time lapse between irradiation and definitive treatment either by surgery or embolization; and 3) all patients in the time lapse between irradiation and death. These groups include all irradiated patients who still had incompletely obliterated AVMs. They were stratified starting from 0 time (the date of radiosurgery), and the hemorrhages were evaluated every 6 months. In totally irradiated cases, the bleeding risk decreased from 4.8% in the first 6 months after radiosurgery to 0% starting from the 12th month of the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

External stereotactic irradiation by linear accelerator.

Stereotactic radiotherapy has two advantages: (a) the possibility of giving high radiation doses to small but spatially well-defined target volumes and (b) the presence of a stepped dose gradient between the target volume and the surrounding healthy tissues. To utilize these advantages, the authors built a new stereotactic head frame by which the intracranial target is fixed to the rotational isocenter of a 4-MV linear accelerator. The collimator openings are selected according to the volume and the three-dimensional configuration of the target, and the radiation dose is based on the radiosensitivity of the lesion. After the patient is fixed to the frame, the radiation source and the patient are rotated so that the target is irradiated through infinite portals distributed over the convexity of the skull. It is thereby possible to obtain very high radiation doses centered into the target with a stepped dose gradient. The preliminary radiodosimetric tests and the operative technique are described. The advantages of this technique compared to interstitial radiotherapy and Leksell's radiosurgery are emphasized. This noninvasive procedure has been used to treat a series of intracranial tumors.