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Objectives: To assess changes in physicians' attitudes toward practice guidelines and towards the role of empirical evidence in the development of recommendations for clinical practice., Design: Comparison of findings from two surveys carried out in Italy in 1993 and 1997 on the same random sample of 300 physicians from two specialty societies dealing with cancer care., Results: As for goals, the only change was the increasing (from 26% in 1993 to 40% in 1997; p = 0.010) number of physicians indicating cost containment. More clinicians (43% in 1993 vs 58% in 1997; p < 0.01) stated that guidelines should be based primarily on empirical evidence, rather than on clinical experience, and that the Ministry of Health should have a role in issuing guidelines (from 21% in 1993 to 46% in 1997; p < 0.001). Physicians supporting the participation of representatives from outside the medical profession in developing guidelines increased from 6% in 1993 to 26% in 1997 (p < 0.001) for consumers, from 24% to 38% (p = 0.015) for patients, and from 16% to 33% (p = 0.003) for health care administrators., Conclusions: Overall, these changes indicate that an increasing number of clinicians acknowledge the role of empirical evidence and the need for a confrontation with other professional and societal components as to what should be done in clinical practice.

5-fluorouracil, an antimetabolite inhibiting timidilate synthetase, is one of the most used drugs in the treatment of many solid tumor types. In particular it is still central in the treatment of colorectal cancer. Nevertheless 5-FU efficiency is limited, this is due to the rapidity of its metabolism (T1/2 10 min). Many attempts have been done to increase its efficiency: 1) combinations with other antitumor drugs have been tested, but no one showed improved response rates with respect to 5-FU alone; 2) use of biological modifiers such as folinic acid and methotrexate. They interact with the biological actions of 5-FU improving its therapeutic effects. These combinations appear to be more effective than 5-FU alone; 3) continuous infusion increases the percentage of susceptible tumor cells, it makes possible the use of a high intensity dose which is active in patients resistant to 5-FU administered as bolus-injection. There are many schedules and methods of administration of 5-FU in the treatment of CRC, each of them showing different types of toxicities. This explains why there is the need to obtain a profile of 5-FU in clinical practice. The project called MISURA is though to give us this kind of information. It will be a collection of data regarding patients affected by colorectal cancer and treated with 5-FU. The collected information will be about diagnosis; ways of use, schedules, doses and tolerability of the drug; obtained responses. The aims of the study are: 1) to evaluate the use of 5-FU in clinical practice; 2) to collect data about the use of supportive therapy; 3) to know the effective incidence and prevalence of CRC in Italy. The study is retrospective, the sample consists of all patients from the oncological departments chosen to represent the national territory. The analysis of the data will be descriptive.

Hepatic metastases are a major cause of death in patients with colorectal carcinoma. Traditional intravenous chemotherapy produces responses in 10% to 30% of patients and surgical resection is feasible in approximately 20% of patients. Infusion of cytotoxic agents into the hepatic artery is the most promising form of therapy for unresectable hepatic metastases. The recent development of a totally implantable pump has allowed prolonged infusion of chemotherapeutic agents with a good compliance and quality of life of the patients. The rationale for hepatic arterial infusion (HAI) present an anatomical and pharmacological basis with the use of agents with high hepatic extraction resulting in minimal systemic toxicity. The results of eight randomized trial assessing the value of HAI Floxuridine shows that such regional chemotherapy increases the likelihood of hepatic response compared with systemic treatment (52% vs 15%). Survival information is difficult to evaluate because some of the studies are small, some had a crossover design and some others had bias factors. Extrahepatic disease develops in 40-70% of patients undergoing HAI; the use of systemic therapy plus HAI may produce a decrease in extrahepatic disease. Further studies of combined systemic/arterial regiment are necessary.

Two cases of 5-Fluorouracil (5FU) cardiotoxicity, chest pain with changes in ECG the former, and myocardial infarction the latter, are described. Review of literature shows the existence of 49 cases of cardiotoxicity due to 5FU (38 angina = 77.5% 8 myocardial infarction = 16.3%). This complication seems due to a "coronary toxicity" whose onset is very precocious and not dose-dependent. Since 5FU therapy could result very dangerous when cardiotoxicity occurs, it is strictly advisable to withdraw further administration of the drug. As a matter of fact 18 patients out of 21 who again were treated with 5FU, had more serious complications which resulted in 3 myocardial infarctions (2 deaths).

330 patients (126 with gastric neoplasms, 204 with large bowel carcinoma) were submitted to serial assays to evaluate the possible relations between C.E.A. levels, pathologic stage and histologictype of the neoplasm and to define the usefulness of the C.E.A. test in monitoring the followup of the patients with gastrointestinal neoplasms. From our experience it ensues that C.E.A. test positivity (C.E.A. greater than or equal to 5 ng/ml, according to the method employed) is higher in colon neoplasms in comparison with gastric neoplasms, in the adenocarcinomas compared with the anaplastic forms. Besides, the study of the relationship with the pathologic stage points out the scanty usefulness of the C.E.A. test in the early diagnosis of gastroenteric neoplasms (Dukes A-B-C1 = 29.2%; CH stage = 88.1%). The use of C.E.A. test during the follow up seemed us of fundamental importance. We observed that: a) after radical surgery, 72% of the patients showed a normalization of C.E.A. values; b) there is a significant relationship between clinical course and C.E.A. as it can predict, sometimes several months earlier, the occurrence of relapses and metastases; c) there is also a close relationship (P less than 0.001) between the modifications of the antigen under chemotherapy and the clinical response. At present, C.E.A. seems to play, above all, fundamental role in choosing a correct treatment after radical surgery or in modifying the chemotherapeutic treatment in non surgical cases or in non radically resected patients.

The role of vitamins A, E, C, D, folates and selenium in the chemical prevention of tumours and/or precancerous conditions is examined in the light of epidemiological studies and experimental observations. Particular mention is made of significant clinical studies that provide valuable indications about the use of vitamin A and its derivates in particular for the treatment of precancerous and cancerous conditions. Vitamin A and its derivates apparently play a fundamental role not only in the treatment of proliferating malignancies of the skin (carcinomas, severe aclinic keratosis) or involving the skin (fungoid mycosis, skin metastases of solid tumours) but also in the prevention of recurring bladder tumours and the treatment of several bronchial dysplasias.