Epidoxorubicin plus ifosfamide in advanced and/or metastatic soft-tissue sarcomas.

We undertook this phase II study to evaluate the efficacy and toxicity of epidoxorubicin and ifosfamide in the treatment of locally advanced and/or metastatic soft-tissue sarcomas. We used escalating doses of epidoxorubicin (from 60 to 75 mg/m2) on day 1 and 1.2 g/m2 ifosfamide on days 1-5. Chemotherapy courses were repeated every 3-4 weeks. A total of 16 patients--13 who had not previously been treated and 3 who had undergone prior therapy with anthracyclines--entered the study. In all, 15 patients were evaluable for response and 16, for toxicity. At least two courses of chemotherapy were given. A complete remission (CR) was seen in 1 patient, a partial remission (PR) in 5, and a minor response (MR) in 1, for an objective response rate (CR + PR) of 40% (6/15); this value reached 50% in non-pretreated patients (6/12). Stable disease (SD) was observed in 40% (6/15) of patients. The relative dose intensity of epidoxorubicin ranged from 10 to 23.3 mg/m2 (median, 16.6 mg/m2). The time to objective response ranged from 4 to 12 weeks (median, 8.5 weeks). The duration of response was 4 months for the single CR, and that for the five PRs was 6+ months (range, 4-18 months). Toxicity was evaluated according to WHO criteria in 16 patients; it was mild and consisted mainly of alopecia, nausea and vomiting, and leucopenia. In only three patients did we observe grade 3 leucopenia. In one case an ifosfamide-associated encephalopathy occurred, but it regressed after 24 h. Neither chronic nor acute cardiac toxicity was reported. In this preliminary analysis, the response rate obtained with the combination of epidoxorubicin and ifosfamide was encouraging and the toxicity was acceptable.

Association between breast and colorectal cancer in a sample of surgical patients.

The frequency of adenomatous polyps and adenocarcinomas of the large bowel in 95 patients mastectomized for breast cancer, and the prevalence of breast cancer in 77 women previously operated on for colorectal cancer were evaluated by means of a case-control study. The mastectomized patients as well as the control group, underwent a left-sided colonoscopy. The latter had been selected among women spontaneously referring to our gastroenterological out-patients clinic. The choice of this self selected control group could produce a under-estimation of the relative for colon cancer in mastectomized patients. Among mastectomized patients the frequency of adenomatous polyps and colorectal cancer was 10.5% and 5.3% respectively; while the control group showed 8.5% frequency for adenomatous polyps and 3.9% frequency for cancer. These figures are not statistically different. Patients operated on for colorectal cancer and the control group underwent clinical and mammographic examination. The prevalence of breast cancer among colorectal cancer patients and the control group women was 5.2% and 0.3% respectively (10 times higher): the difference was statistically significant (P less than 0.006). In spite of the relatively small number of studied cases, our finding are consistent with the hypothesis of a correlation between breast cancer and colorectal cancer.

Chemotherapy-induced amenorrhea and other clinical and pathological parameters in the prognosis of breast cancer patients.

147 stage II pre- and perimenopausal breast cancer patients were treated with cyclophosphamide-methotrexate-5-fluorouracil (CMF)- based adjuvant regimens. 103 (72%) patients became amenorrheic during or immediately after the end of the chemotherapy program. Univariate analyses for age, menstrual status, nodal involvement, grading, estrogen and progesterone receptor status indicated no correlation between induction of amenorrhea and a significant prolongation of overall and disease-free survival. Multivariate analyses confirmed that young age at diagnosis, increasing number of infiltrated nodes, negative progesterone receptor status and grade 3 tumors are associated with a worse prognosis. Our results suggest that no benefit is expected in women with drug induced amenorrhea after CMF adjuvant treatment.

Value of multiple forceps biopsies in assessing the malignant potential of colonic polyps.

Fifty-nine colo-rectal polyps were detected at endoscopy and repeatedly biopsied before removal by endoscopic snare polypectomy. The aim of the present paper was to evaluate the reliability of multiple forceps biopsies in assessing both the malignant potential and the presence or absence of invasive cancer (IC) in colo-rectal adenomas (CRA). In order to achieve the first objective, the histologic types and the degree of dysplasia have been defined. The data obtained by means of multiple biopsies examination, compared with those of polyp in toto study, show that fractional biopsies were of value in the histologic classification of only the smallest 41 polyps (agreement 88.09%), whilst no reliability of biopsies was demonstrated in the 18 largest polyps (agreement 27.68%). In the field of dysplasia grading, the agreement was 55% and 61% for the smallest and the largest CRA respectively. These last figures are hardly acceptable. Biopsies examination gave also under- and overestimation of the histologic severity and of dysplasia as well as a significant incidence of false negative results in IC detection. It is concluded that polypectomy is the only method which provides adequate material for precise diagnosis, no matter how large a polyp. Therefore it should be performed whenever possible. Finally the authors discuss the management of small sessile adenomas.

[Biological aspects and perspectives applicable to the chemoprevention of cancer of the upper respiratory-digestive tract]. / Aspetti biologici e prospettive applicative della chemioprevenzione nel cancro delle vie aero-digestive superiori.

After defining chemoprevention a description is given of the phases of differentiation in normal epithelial cells and the features of proliferation in neoplasias developing in this epithelium. The latest studies on carcinogenesis indicate various types of prevention with which one can alter this transformation process. Epidemiological studies have shown that subjects with low serum levels of Vit-A or Beta carotenoids are at high risk of developing epithelial cancer. Three main categories of agents inducing cell transformation are described: a) physiological induction agents; b) non physiological induction agents; c) cytotoxic drugs. In regard to clinical use, some studies have focussed on the importance of Vit-A in chemoprevention of risk conditions (pre-cancerous lesions) and in prevention of cancer recurrence. The authors point out the increasing interest in the use of retinoids in the chemoprevention of head and neck cancer and report some personal clinical experience.

Left-sided stenosing lesions in colonoscopy.

Of 2625 consecutive colonoscopic examinations, 122 stenotic lesions interfered with endoscopy. The sigmoid was the most frequent site of stenosis (64%). Of the two types of endoscopic patterns, type A, in which there is an intraluminal protruding mass, is the most frequent, and type B, in which a segment of colon gradually narrows, has intact mucosa. Adenocarcinoma was the most frequent cause of type A (83%), and complications related to diverticular disease (32%) and adenocarcinoma (27%) were most often associated with type B. Colonoscopy, guided multiple biopsies, and brushing cytology gave high diagnostic accuracy for type A lesions. In type B cases, brushings were usually negative.

Occult blood testing in asymptomatic patients previously resected for colorectal cancer.

Hemoccult testing was carried out in 100 patients who had previously undergone surgical resection for colorectal cancer. Of the 15 Hemoccult-positive patients detected, endoscopic examination revealed polypoid formations in six (one with invasive carcinoma) and local recurrent tumors in three. Eighteen polypoid lesions were endoscopically detected in 10 Hemoccult-negative patients. Patient acceptance was good (above 90%) for Hemoccult testing especially when compared to the significantly lower compliance to endoscopic examination (66% in Hemoccult-negative patients). The results suggest that a significant number of lesions may be missed if the Hemoccult test is heavily relied upon exclusively for follow-up of patients previously resected for colorectal cancer.

Primary signet-ring carcinoma of the large bowel. Report of nine cases.

Nine cases of signet-ring carcinoma have been observed from among 800 consecutive histologic cases diagnosed as adenocarcinoma of the colon during a period of 10 years (0.9%). This group of nine patients (Group A) has been matched for sex, age, and stage with a group of 45 patients affected by ordinary carcinoma of the colon (Group B). Clinical and histologic parameters, including symptoms, primary tumor site, free interval from primary surgery, histochemical investigation of intracytoplasmic mucins, and survival, were evaluated. The results of this investigation showed no clinical differences between signet-ring carcinoma and ordinary carcinoma, and no statistically significant results were observed regarding the frequency of local recurrence and actuarial survival.

Selenium therapy in patients with precancerous and malignant oral cavity lesions: preliminary results.

Baseline selenium (Se) levels in serum samples were collected from 22 patients with precancerous and 19 with malignant oral cavity lesions as well as from 13 healthy controls of the same geographic areas. Mean serum Se levels were 105, 101, and 77.03 ng/ml in the precancerous, controls, and malignancy groups, respectively. A statistically significant difference (p less than 0.005) was found between the neoplastic and both the precancerous and control groups. After careful clinical evaluation, precancerous patients received three 4-week cycles of Se, in either inorganic or organic form. Of the 22 precancerous patients entering the study, 18 were available for evaluation of clinical response. The analysis of serum Se variations revealed that serum Se levels tended to increase after the first and second cycles and then gradually returned to baseline values. At the end of the therapy, there were two complete responses (CR), five partial responses (PR), six minor responses (MR), and five stable diseases (SD) with an objective response (CR + PR) of 38.8%. Progression after suspension of therapy occurred in 7 of 18 patients; this may indicate the need of a longer treatment period with this essential trace element.

[Clinical study of a prepared reducing diet: adequacy of the vitamin-mineral contribution in comparison to the nutritional and immunity status]. / Studio clinico di un preparato dietetico dimagrante: adeguatezza dell'apporto vitaminico-minerale nei confronti dello stato di nutrizione ed immunitario.

The Authors studied the effectiveness and safety of a commercial hypocaloric diet on 11 obese postmenopausal women. During the experimental period 1 meal/day has been replaced with a chemically defined low calories product. Different parameters have been evaluated to assess the nutritional status 1), anthropometric: weight, skinfold thickness, arm muscle circumference; 2) biochemical total plasma proteins, transferrin, vitamins A, E, C, B12, folic acid; plasma iron, hemoglobin, MCV, RBC; 3) immune status (T lymphocytes and immunoglobulins). Moreover blood sugar, cholesterol and triglyceride levels, as well as blood pressure have been taken into account. All the possible side effects and the diet acceptance for all the patients have been scored. After 1 month all the abnormal conditions (weight, cholesterol, blood pressure) improved, while the nutritional status and immune response remained at an optimal level.

Hospital malnutrition: incidence and prospective evaluation of general medical patients during hospitalization.

The incidence of malnutrition and the effect of hospitalization was evaluated in 100 consecutive admissions to the Clinical Pathology R Department of the University of Genoa. Nutritional deficiencies were evaluated at the time of admission and discharge from the Hospital, among patients hospitalized 2 weeks or longer, using the following nutrition-related parameters: body fat, muscle proteins, weigh, rate of weight loss plasma proteins level, vitamin B12 and folic acid plasma level, plasma iron and ferritin. We also considered the nutritional alterations in malnourished patients with relation to appetite decrease and to pathological status. At the admission to the hospital, the findings showed a high incidence (79%) of alterations in some nutritional parameters. In patients with nutritional impairments we observed a worsening of most of the nutritional parameters during hospitalization, especially in patients with severe appetite decrease and those affected by sepsis, neoplastic, gastric and renal diseases.