Management of primary breast cancer.
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Adult↗
Biomedical subjects
R Grilli
Publications and source records attributed to R Grilli.
Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat.
We have reported Hexarelin (HEXA), an analog of growth hormone-releasing peptide 6 (GHRP-6), potently stimulates growth hormone (GH) secretion in infant and adult rats. This study was undertaken to further investigate Hexarelin's mechanisms of action. In 10-day-old pups, treatments with HEXA (80 micrograms/kg, b.i.d.) for 3-10 days significantly enhanced, in a time-related fashion, the GH response to an acute HEXA challenge. Qualitatively similar effects were elicited in pups passively immunized against growth hormone-releasing hormone (GHRH) from birth. In adult male rats, a 5-day pretreatment with HEXA (150 micrograms/kg, b.i.d.) did not enhance the effect of the acute challenge, and the same pattern was present after a 5-day pretreatment in male rats with surgical ablation of the mediobasal hypothalamus (MBH-ablated rats). In addition, in adult sham-operated rats, Hexarelin (300 micrograms/kg, i.v.) induced a GH response greater (p < 0.05) than that induced by GHRH (2 micrograms/kg, i.v.). However, in MBH-ablated rats 7 days after surgery, GHRH was significantly (p < 0.05) more effective than HEXA, and 30 days after surgery HEXA and GHRH evoked similar rises of plasma GH. Finally, the in vitro Hexarelin (10(-6) mol/l) effect was transient while GHRH (10(-8) mol/l) induced a longer lasting and greater GH release. Three different mechanisms, not mutually exclusive, are postulated for Hexarelin stimulation of GH secretion in vivo: a direct action on the pituitary, though of minor relevance; an indirect action that involves release of GHRH, of relevance only in adult rats; and an action through the release of a still unknown hypothalamic "factor", which in infant and adult rats elicits GH release acting sinergistically with GHRH.
Aging↗
Role of the neuronal histaminergic system in the regulation of somatotropic function: comparison between the neonatal and the adult rat.
To study possible age-related differences in the role of neuronal histaminergic pathways in the control of GH secretion, the effects of alpha-fluoromethylhistidine (alpha-FMH), an irreversible inhibitor of histamine (HA) synthesis, were examined on basal and opioid-induced GH release in neonatal and adult rats. The mechanisms involved in such effects were evaluated by measuring pituitary GH mRNA levels and hypothalamic levels of GH-releasing hormone (GHRH) and somatostatin (SRIF) mRNAs. Daily injection of alpha-FMH (20 mg/kg, s.c.) in pups of either sex, from birth until 10 days of age, caused a significant increase in baseline plasma GH and potentiated the GH response to the [Met5]-enkephalin analog FK 33-824 (1 mg/kg, s.c.) administered 3 h after the last alpha-FMH injection. GH and SRIF mRNA levels were significantly higher in alpha-FMH-treated pups than in controls, whereas no difference was observed in GHRH mRNA levels. In young adult male rats, acute administration of alpha-FMH (100 mg/kg, s.c., 3 h before) did not change significantly basal GH levels but potentiated FK 33-824 (0.3 mg/kg, intracarotid)-induced stimulation of GH secretion. Repeated administration of alpha-FMH (200 micrograms/rat, i.c.v., for 3 days) failed to modify basal and FK 33-824-induced GH secretion, caused a significant reduction in hypothalamic GHRH mRNA levels and left SRIF and GH mRNAs unchanged. These findings indicate that HA exerts an inhibitory effect on GH secretion in both neonatal and adult rats. The different effects of short-term HA depletion on hypothalamic and pituitary indices of somatotropic function observed at the two age periods may be ascribed to the immaturity of the HA system in early postnatal life and to a different functional role of GH-regulatory factors during ontogeny.
Aging↗
Appropriateness and variation of surgical treatment of breast cancer in Italy: when excellence in clinical research does not match with generalized good quality care. Progetto Oncologia Femminile.
To assess appropriateness of surgical care delivered to breast cancer patients in Italy and quantify the use of unnecessary radical procedures, a retrospective charts review of patients treated in 1988-1989 was conducted. A series of 1724 consecutive patients (median age 61 years; range 17-89) treated in 63 hospitals selected from within 8 regions with newly diagnosed operable breast carcinoma was evaluated. Overall, 541 (38%) patients had inappropriate surgery with more than two thirds of it being accounted for by the use of unnecessary mutilating Halsted mastectomy. Substantial geographic variation emerged in the overall rates of appropriateness (range 88-52%) which were not substantially affected by allowance for imbalances in patient- and hospital-related variables. Despite the important contribution given by Italian clinical researchers to the demonstration that less radical surgery can be as good as more radical procedures, still a substantial proportion of breast cancer patients are treated too aggressively. Besides pointing to the urgent need of interventions aimed at facilitating the process of technology transfer in order to promote more appropriate surgical care, these results suggest that efforts to increase patients' participation into treatment decision and awareness about alternative treatment options are warranted.
Adolescent↗
Variation in use of breast-conserving surgery in Lombardia, Italy.
The extent of variation in the use of breast-conserving surgery was analyzed using the 1990 and 1991 hospital discharge data of Lombardia, Italy. The proportion of patients undergoing breast-conserving surgery for unilateral breast cancer was estimated for each of the 10 geographic areas (9 provinces plus metropolitan Milano) in which the region is divided. Overall, the rate of use was 41% of 3,225 patients in 1990, and 45% of 3,736 patients in 1991. In both study years, patient age was strongly correlated with the likelihood of undergoing conservative surgery, with younger women more frequently treated with this approach. In each province, patients treated at centers located in the main city had a greater probability (OR, 1.54; 95% CI, 1.37-1.69) of having conservative surgery. This procedure was also more often used in private hospitals (OR, 1.59; 95% CI, 1.20-2.08) where care is paid at the point of consumption by patients, directly or through their private insurance. The observed variation in the use of the conservative procedure across the 10 regional areas was greater than that expected by chance alone (p < .0001), with rates ranging from 29% to 60%. This pattern persisted even after adjusting for the relevant patient and hospital characteristics. Despite the relatively large body of scientific evidence, it appears that the surgical management of breast cancer is more dependent on physicians' attitudes in each geographic area than on individual patients' characteristics.
Adolescent↗
A shared effort toward better quality of care. The Consensus Conference on Breast Cancer Follow-up. Consensus Conference Organizing Committee.
BACKGROUND: Even though several radiological and laboratory tests are currently used in clinical practice for breast cancer surveillance, the benefits of early detection of distant metastases have never been established. Two recently published randomized clinical trials assessing the effectiveness of an intensive follow-up strategy (with periodic clinical examination, mammography, bone scan, liver echography, chest-X-ray and laboratory tests) over a minimalist one (including only periodic clinical examination and mammography) failed to show a significant advantage for the more intensive policy. Intensive follow-up, however, is quite common in clinical practice. AIM OF THE CONSENSUS CONFERENCE: To contribute to the definition of the state of the art in this field and develop recommendations for follow-up in clinical practice. CONDUCT OF THE CONSENSUS CONFERENCE: A Jury, including representatives from all the relevant stakeholders, (professional societies, patients and consumer associations, epidemiologists, health economists and administrators) was convened to critically appraise and interpret available scientific evidence and the information provided by three specific working groups which had the task of examining the clinical, economic and psyco-social aspects of breast cancer follow-up, respectively. CONCLUSIONS: This conference was planned to make explicit and properly represent the viewpoints of all the stakeholders. Furthermore, special efforts were devoted to the development of final recommendations in sufficient detail so as to provide a significant aid for decision-making in clinical practice. It is argued that the Consensus Conference model, designed to elicit and represent the interpretation of scientific evidence by all the stakeholders, would be useful for the development of clinical policies more in line with societal values.
Breast Neoplasms↗
Economic evaluation of diagnostic follow-up after primary treatment for breast cancer. Results of the Working Group on Economic-Organizational Aspects of Follow-up.
BACKGROUND: This study examined costs associated with different 5-year follow-up regimens (intensive vs. minimum) in patients after primary breast cancer treatment. METHODS: Since the results of two randomised controlled trials showed a similar 5-year survival for asymptomatic patients followed with frequent diagnostic tests and patients followed with only routine clinical controls, the economic savings resulting from the systematic adoption of a minimum surveillance regimen were estimated for Italy. RESULTS: When considering only direct health care costs (i.e., excluding time and travel costs) and adopting a minimalist policy, the average per patient savings (5% yearly compound rate) were calculated at 3.7 million Italian lire for paying patients, 2.5 million Italian lire for patient reimbursement from private voluntary/integrative health insurance funds, and to range from 1.2 to 2.1 million Italian lire for payment to the National Health Service (NHS). Total follow-up savings for the patient cohort which had breast surgery in the last 5 years were estimated to range from 29 to 51 billion Italian lire for the NHS, 92 billion Italian lire for paying patients and 62 billion Italian lire for the health insurance funds. CONCLUSIONS: Alternative use of these savings were discussed with reference to breast cancer screening programs.
Blood Chemical Analysis↗
Implementing findings of medical research: the Cochrane Collaboration on Effective Professional Practice.
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Information Services↗
A proposal for Italian guidelines in pharmacoeconomics The Mario Negri Institute Centre for Health Economics.
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Clinical Trials as Topic↗
[Guidelines for clinical practice: instructions for use].
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Clinical Medicine↗
Variation in use of breast surgery and characteristics of hospitals' surgical staff.
OBJECTIVE: To assess whether and how the characteristics of hospitals' surgical staff can predict utilization of breast conserving surgery. We anticipated that the use of the procedure was more frequent in hospitals with a greater proportion of younger and female surgeons on their staff. SETTING: Sixty-two hospitals with different level of organization for the care of cancer patient from eight Italian regions were included. DESIGN: We collected information on the personal characteristics (age and sex) of all surgeons on the staff of the participating centers. A concurrent pattern of care study was undertaken, in order to assess the utilization of breast conserving procedures. RESULTS: The use of conservative surgery was 16%, 20%, 31%, in centers with 0%, < 20% and 20-50% female surgeons respectively (p = 0.003), while no associations emerged between the mean age of the surgical staff and the use of conservative surgery. This relationship also held true after adjusting for other patients' characteristics, such as stage of disease, age and presence of comorbidity. However, overall the use of patient-related and staff-related characteristics to predict the number of breast conserving surgeries performed in each area was able to explain only 16% of the observed variability in the use of breast conserving surgery. CONCLUSIONS: Even though in this study a large proportion of the observed variation in the use of breast conserving surgery was still left unexplained, this finding suggests that assessing the relationship between doctors' characteristics and the use of scientific evidence is an important topic for health service research and can be of some help in exploring variations in clinical practice styles.
Adult↗
Evaluating the message: the relationship between compliance rate and the subject of a practice guideline.
To explore the relationship between providers' compliance and some key aspects of the clinical messages in practice guidelines, studies published in the English language medical literature between 1980 and 1991 were retrieved through MEDLINE and through relevant review articles in the field. All published studies providing compliance rates with practice guidelines and endorsed by official organizations were eligible for the study. The clinical content and the reported compliance rate were gathered for each recommendation in the 23 studies selected. The medical and surgical procedures addressed by 143 recommendations were identified according to specialty area, type of procedure (diagnostic, surgical, etc.) and were independently classified by the authors as being high or low on characteristics thought to influence diffusion:complexity, trialability and observability. The mean compliance rate with the 143 clinical recommendations was 54.5% (95% CI: 50.2%-58.9%), with those in the specialty areas of cardiology and oncology showing the highest compliance (mean 63.6% and 62.2%, respectively). Recommendations concerning procedures with high complexity had lower compliance rates than those low on complexity (41.9% vs. 55.9%; P = 0.05), and those judged to be high on trialability had higher compliance rates than those low on trialability (55.6% vs 36.8%; P = 0.03). Overall, all the characteristics of the clinical recommendations considered in the practice guidelines could account for no more than 47% of the observed variability in compliance rates. The target area of practice and the complexity and trialability of the recommended procedure appear to be useful, if partial, predictors of the level of compliance with a practice guideline.
Cardiology↗
Growth hormone-releasing hexapeptide is a potent stimulator of growth hormone gene expression and release in the growth hormone-releasing hormone-deprived infant rat.
The growth hormone-releasing hexapeptide (GHRP-6) specifically stimulates growth hormone (GH) secretion in several animal species and humans. The mechanism of action of GHRP-6 is largely unknown, although experimental evidence indicates that it may modulate growth hormone-releasing hormone (GHRH) and somatostatin actions at the pituitary or hypothalamic level. To gain more insight into the mechanism(s) of action of GHRP-6, we studied the infant rat, an animal model highly responsive to GH-releasing stimuli. In 14-d-old rats GHRP-6 (32-600 micrograms/kg, s.c.) induced a marked and dose-dependent rise in plasma GH concentrations, maximal stimulation occurring with the dose of 300 micrograms/kg. Neither GHRH nor somatostatin antiserum prevented or modified the GH release elicited by GHRP-6. In pups passively immunized with GHRH antibodies, a 5-d treatment with GHRP-6 (80 micrograms/kg, s.c., twice daily) completely counteracted the inhibitory effect of GHRH deprivation on GH mRNA expression. In vitro GHRP-6 (10(-7) and 10(-6) M) induced a small and transient stimulation of GH release from cultured pituitary cells. These results indicate the following: 1) GHRP-6 is a potent stimulator of GH release in rat pups; 2) it stimulates GH gene expression in the GHRH-deprived pup; 3) during the neonatal period its action is not mediated by GHRH or somatostatin; and 4) its actions are not directed at the somatotrophs.
Animals↗
The influence of patient characteristics on the appropriateness of surgical treatment for breast cancer patients. Progetto Oncologia Femminile.
BACKGROUND: Within the framework of a multi-annual educational intervention sponsored by the Ministry of Health and regional health authorities, patterns of the care delivered to breast cancer patients in Italian general hospitals were monitored in order to identify areas of practice whose quality was in need of improvement. DESIGN: Information on the diagnostic and therapeutic procedures in 63 general hospitals in eight Italian regions performed in 1724 consecutive breast cancer patients were retrospectively gathered from medical records. Quality of care was assessed by a diagnostic and therapeutic score based on the observed degree of compliance with previously established courses of action. RESULTS: The median value of the overall diagnostic and staging score was 60%. About one-third of surgical operations (38%) were inappropriate: one-fourth (24%) of patients with stage I-II disease had unnecessarily radical surgery (i.e., Halsted mastectomy), and limited surgery in patients with small tumors (i.e., < or = 2 cm) was under utilized. Chronological age influenced physicians' behaviour: elderly patients were more likely to have a less intensive diagnostic work-up and less appropriate surgical treatment (with more frequent performance of an unnecessary radical operation and a less frequent utilization of limited surgery), independently of their overall health status. The presence of one or more co-existent diseases was associated with a failure to undergo axillary clearance and with a lower utilization of conservative surgery independently of age. CONCLUSION: In accord with others, this study confirms the existence of a clinically important effect of patient age on diagnostic and therapeutic behaviour and the use of unnecessarily radical surgery procedures. The paper discusses the implications of these findings for the next stage of the educational project, in which practice guidelines will be developed and implemented to improve the quality of care for breast cancer patients.
Adenocarcinoma↗
Chemotherapy for advanced non-small-cell lung cancer: how much benefit is enough?
PURPOSE: To estimate the impact of chemotherapy on survival of patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Randomized controlled trials (RCTs) published in the English-language medical literature between 1970 and 1991 were identified through MEDLINE and the reference lists of relevant articles. Six RCTs that accounted for 635 patients and compared first-line chemotherapy with supportive care in advanced NSCLC and reported survival up to at least 1 year were identified. Cumulative proportions of survival at 3, 6, 9, and 12 months for chemotherapy and control groups were derived from survival curves. RESULTS: Within each study, the effect of chemotherapy was estimated with a pooled relative risk (RR) across the four 3-month periods. An overall estimate of the RR of death at 1 year (RRM-H) was then calculated and a survival curve for chemotherapy-treated patients was constructed applying the pooled estimate of the RR (RRW) for each 3-month period. Overall, chemotherapy was associated with a 24% (95% confidence interval [CI], 13% to 34%) reduction in the probability of death when compared with supportive care. However, the effect of treatment appeared to decrease significantly after the first 6 months from therapy inception and the mean potential gain in survival, as compared with supportive care, was approximately 6 weeks (95% CI, 1 to 10). CONCLUSION: Chemotherapy is effective in the treatment of advanced NSCLC, but its impact on the length of survival is limited. Future RCTs should still include an untreated control group and should measure quality of life in addition to survival.
Antineoplastic Combined Chemotherapy Protocols↗
Inappropriate Halsted mastectomy and patient volume in Italian hospitals.
To study whether Halsted mastectomy was used only when properly indicated, a prospective survey was undertaken on the process of care of 985 breast cancer patients seen consecutively at 62 general hospitals in Northern and Central Italy. Overall, 79% of Halsted mastectomies were performed inappropriately. The procedure was less likely to be performed on more educated patients and, other factors considered, on those seen at hospitals with larger volume. We conclude that the measurement of utilization of a surgical procedure for which only a few appropriate indications exist may help identify important relationships between hospital characteristics and quality of surgical care.
Adult↗
Breast cancer surgery in 30 Italian general hospitals.
The utilization of limited surgery in patients with breast cancer operated between September 1986 and July 1988 was assessed using information collected within a cohort subsequently enrolled in a randomized clinical trial testing the efficacy of post-surgical follow up. Overall 30% had limited surgery, 61% had other more radical procedures and 9% are still undergoing an unnecessary Halsted mastectomy. Several factors were related to the lower likelihood of getting a conservative procedure: geographic distribution, age, level of education, quadrant and nodal state. The paper discusses the implications of these findings in view of the otherwise growing consensus that more radical surgery should be abandoned.
Breast Neoplasms↗
[The adjuvant treatment of operable breast carcinoma. The current status and outlook].
Breast cancer represents one of the most frequent neoplasm: every year, in Italy, 25,000 new cases are diagnosed with more than 9,000 deaths. In Italy--and also in other countries--has been shown a broad variability in the use of diagnostic or therapeutic procedures caused by different hospitals' characteristics, patients' conditions and physicians' opinions. Among the different therapeutic options, post-surgical therapy, that extends the disease-free interval and survival, fills an important position in the cure of breast cancer in relation to the overview published on Lancet the 4th and the 11th January 1992. According to this overview, patients who had surgery for breast cancer benefitted by an adjuvant therapy--hormonal or cytotoxic--with a reduction of mortality between 15 and 20%. That means, in Italy, a reduction of one thousand deaths per year for this neoplasm. Particularly the effectiveness of hormonal treatment in postmenopausal patients (not only in the oestrogen receptor (ER) positive but in the ER poor too), of ovarian ablation and chemotherapy in premenopausal patients was confirmed. In node negative patients the present overview recommends the adjuvant treatment for the risk reduction in recurrence and mortality. Nevertheless important research implications persist about treatment and a better definition of high risk patients; therefore more patient should be included in the randomized clinical trial.
Adult↗