Biomedical subjects
Publications and source records attributed to P Pacini.
The study has been carried out on biopsies taken from four patients affected by squamous cell carcinoma and four patients affected by undifferentiated carcinoma of nasopharyngeal type (UCNT). Three healthy volunteers have served as controls. All the specimens have been studied by SEM. The neoplastic conditions cause obvious alterations both in the mucosal surface and in the morphology of the cellular apex.
The atrial natriuretic factor (ANF) plays an important role in the pathogenesis of congestive heart failure (CHF), by influencing electrolyte and water balance and by modifying peripheral vascular resistance, thus affecting left ventricular performance. Anthracycline derivatives are glycoside antibiotics, active against a wide spectrum of tumours. It is well known that acute and severe dose-related delayed cardiotoxicity constitutes the major limitation to their optimal use. A total of 26 female patients (mean age 53 years) undergoing monochemotherapy for advanced breast cancer, were studied. 4'-Epidoxorubicin (Epidx) 120 mg/m2 intravenously was administered every three weeks for a total of a mean of 6.6 therapeutic cycles (3 to 10). Left ventricular ejection fraction (LVEF) determined by radionuclide ventriculography and circulating ANF were measured periodically in all patients. Epidx administration was limited at a cumulative dose ranging between 840 and 1200 mg/m2 because of a 25% decrease in LVEF and due to a progressive rising in ANF plasma levels. Furthermore, two patients who presented clinical symptoms of CHF had also significantly increased ANF levels (56 and 49% respectively). The current evidence suggests an important pathophysiological role of ANF in anthracyclinic related CHF. Hopefully measurement of plasma ANF will provide a simple non-invasive method of assessing ventricular dysfunction related to anthracycline cardiac toxicity and might represent an additional objective indicator of the severity of haemodynamic compromise in patients with impaired cardiac function.
2740 consecutive breast cancers undergoing physical examination were reviewed. Ninety-two subclinical cancers detected at mammography were excluded from further evaluation and the study focused on palpable false benign cancers. The sensitivity of physical examination varied according to T category (TIS = 0.48, T1 = 0.70, T2 = 0.90, T3 = 0.89, T4 = 0.93), age (20-29 = 0.77, 30-39 = 0.58, 40-49 = 0.75, 50-59 = 0.84, 60-69 = 0.90, greater than 69 = 0.94) and operator (range 0.69-0.89), a significant difference being recorded in favor of more expert operators. Multivariate analysis (Cox) showed that T category, patient's age and operator experience are independent determinants of sensitivity. This study confirms that physical examination is not very sensitive, particularly for small tumors and in younger women and should always be performed by expert operators.
The rationalization of the follow-up schedule for patients treated for breast cancer appears essential due to the high incidence of this disease. The authors retrospectively analyze their series (3,596 patients, from 1971 to 1990) to assess the patterns of both early loco-regional recurrences and distant metastases. Patterns and outcome of local and regional recurrences are reported according to site. The international literature on the subject is reviewed, and the schedule currently employed in the follow-up of breast cancer patients at the Radiotherapy Unit of Florence is reported. Due to the patterns of relapse a more intensive clinical follow-up schedule is suggested during the first 5 years. Less intensive follow-up continues over the whole patients' life span, since failures can occur even after 5 years. Mammography should be repeated every year in the same period to detect eventual homolateral and/or contralateral relapses. Other diagnostic tools should be employed only when symptoms set in. On the ground of the current literature on the subject, no negative impact on survival should be expected from this follow-up schedule.
The authors report on a consecutive retrospective series of 150 male breast cancers. Clinical, diagnostic and therapeutic features are compared over time and with respect to a large consecutive series of female breast cancers. Both age at diagnosis and tumor stage were more advanced in males than in females. Poor alertness of both men and doctors for this infrequent disease may account for such a delay in diagnosis. The use of mammography increased over time and sonography or cytology were frequently and successfully employed in the last decade. Unfortunately no improvement of tumor stage at diagnosis was observed over time in the present series. A time trend was also evident for the type of surgical and postoperative treatment. Modified radical mastectomy and adjuvant chemo- or hormone therapy were increasingly adopted, although Halsted operation and postoperative radiotherapy were still common in the last decade due to the relatively high proportion of locally advanced T3-4 cancers. Both disease-free and overall survival were worse in men than in women, even after adjustment by stage at diagnosis. This study suggests that male breast cancer has a worse prognosis with respect to female breast cancer and provides no complete explanation of this finding, except for an intrinsic higher aggressivity. No evidence was found which may justify a different diagnostic or therapeutic approach with respect to female breast cancer.
The authors report on 228 cases of suspected breast cancer local recurrences studied by fine needle aspiration cytology (FNAC). The nature (malignant = 133, benign = 95) of suspected lesions was assessed on histology (no. = 46) or according to unequivocal follow-up (no. = 182). Inadequacy rate was 0.20, 0.09 or 0.35 in total, cancer or benign cases, respectively, and was particularly high (0.50) for benign chest wall lesions. Accuracy was determined on adequate smears; dubious reports were assumed as positive. Sensitivity and specificity were 0.96 and 0.97, respectively. The routine use of FNAC is recommended since it helps in the differential diagnosis of suspicious cases and may bypass surgical biopsy of positive cases not eligible for surgical treatment.
The differentiation of the gallbladder mucous membrane in chick embryos has been studied from the 11th day of incubation until hatching (stages 37-46 of Hamburger an Hamilton 1951) with scanning electron microscope. The surface of the mucous membrane, at the 11th day of incubation, appears regularly smooth. From the 12th day onwards, longitudinal folds appear on the surface of the mucous membrane, becoming more and more numerous and complicated in the following days. During the last days of incubation, branching and anastomosing folds are present. At the 11th day of incubation, the epithelial cells lining the gallbladder surface have flattened apices, with short microvilli. From the 12th day onwards, the epithelial cells show dome shaped apices, with long numerous microvilli. From the 15th day of incubation onwards, some particular secretory cells can be detected. The appearance of these cells is probably related to the water-absorbing function of the gallbladder which in the last days of incubation completes its functional development, because of precise digestive requirements of the chick embryo.
The nasopharyngeal carcinoma is a greatly interesting model of study. Its morphology has been studied in 8 patients affected by squamous cells carcinoma (4 cases) and by undifferentiated carcinoma (4 cases). By means of a fibre-optic pharyngoscope equipped with mechanical biopsy forceps, biopsies have been taken and subsequently studied by scanning electron microscopy (SEM). Squamous cells carcinoma is characterized by large, flattened elements, generally equipped with a network of microridges. Irregular microvilli or smooth apices have been observed too. Desquamating elements often accumulated in waves or vortices, as far as little cornified structures have been described. Undifferentiated carcinoma shows a great morpho-structural disorder. In a rugged surface, it is possible to observe element highly varying for size and shape. The apical plasmalemma is characterized by pleomorphic microvilli, while it must be emphasized the presence of little pseudopod-like extrusions of some cellular apices. Ciliated elements have been observed too, whose apical specializations are distorted or irregularly disposed. Necrotic zones are particularly frequent, in which bacteria or mycetes proliferate. The role of SEM in the study of this tumour is emphasized, because of the close relation between epithelial patterns and natural history of nasopharyngeal carcinoma.
The authors report on 182 cases of intrathoracic metastases (ITM = lung, pleura or mediastinum) observed as first single recurrences in the course of the follow-up of patients treated for primary breast cancer. ITM were detected on standard two-views chest X-ray (CXR) at regular follow-up visits and in absence of subjective symptoms (102 A cases) or in the interval between two consecutive planned controls because of the onset of subjective symptoms (80 S cases). The average disease-free interval since primary treatment was significantly shorter in A with respect to S cases (40.3 vs. 28.5 months, P less than 0.001) as a consequence of the early detection achieved by CXR survey. On the contrary, prognosis was not influenced by ITM early diagnosis as the 10-year survival since primary treatment did not differ significantly between A or S cases (12% vs. 10%, P = 0.68). Results were confirmed on multivariate (Cox's) analysis, adjusting for potential confounders such as age or nodal status. Periodic CXR survey looks a very questionable policy as it does not seem to have any favourable impact on prognosis. Its routine use in breast cancer patients should thus be carefully reconsidered.
Circulating osteocalcin (BGP), the major noncollagenous bone protein, is elevated in patients with certain metabolic bone disease while its behavior in cancer patients, particularly those with bone metastases, is unclear. We measured circulating BGP in 37 healthy females, in 13 female patients with benign breast disease, and in a group of 51 cancer patients (breast, lung, prostate, and bladder) with and without bone metastases, before and after 4'-epidoxorubicin (4'-Epidx) therapy (4'-Epidx 120 mg/m2 every 3 weeks). Under basal conditions, mean BGP levels of all of these subjects fell within the normal range of 2.0-5.0 ng/ml (mean +/- SD, 4.8 +/- 1.0 ng/ml). In cancer patients without bone metastases BGP levels measured before and after 4'-Epidx therapy were not significantly different (4.4 versus 4.6 ng/ml). Only in breast cancer patients with multiple bone metastases was circulating BGP higher after the onset of antiblastic treatment and through the entire course of therapy, accompanied by bone pain remission and regression of bone lesions (BGP = 6.7 +/- 1.3 ng/ml). Thus an increase in BGP concentration can be considered as a biological marker of recovered osteoblast activity during therapeutically induced stabilization or regression of skeletal metastatic lesions.
Epirubicin (EpiDx) belongs to the class of anthracycline antibiotics. It is an analog of doxorubicin (Dx) modified in the sugar moiety and in which the stereochemistry at the hydroxyl group bearing C-4' has been inverted. The purpose of this study was to evaluate in an experimental model and in a clinical trial the cardiotoxic effects of EpiDx vs Dx. Cellular oxygen uptake was measured in vitro for equal concentration of Dx and EpiDx with a Warburg manometric apparatus and ATP intracellular concentration by high-pressure liquid chromatography. Dx inhibits cellular endogenous respiration of rat heart slices by 34% vs control, while EpiDx reduces oxygen uptake by 18%. ATP intracellular concentration was significantly reduced by both anthracycline derivates. The same results were obtained after Dx administration in vivo which enabled us to correlate the biochemical parameter (QO2) with the histological cardiac damages shown by light microscopy. For the clinical trial, we studied a total of 22 patients undergoing chemotherapy for solid tumors in an advanced stage. Nine of these were treated with Dx for a total of 66 therapeutic cycles and reached a maximal cumulative dose of 540 mg/m2. Thirteen were treated with EpiDx for a total of 121 cycles (maximal dose reached 720 mg/m2). The dosage of both agents were equal, 60 mg/m2 every 3 weeks. Acute cardiotoxicity was evaluated, measuring creatine-kinase isoenzyme MB(CK-MB) serum level before and 15 h after anthracyclines administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Of the new anthracycline derivatives, epirubicin is the antibiotic whose antitumor activity is comparable to that of doxorubicin while its cardiotoxicity is reduced by half. We therefore incorporated into our continuing study on anthracycline antitumor effects and toxicity a group of 22 evaluable patients, mean age 52 years, with advanced breast cancer, all of whom had previously undergone chemotherapy, radiotherapy and/or hormonal therapy. Epirubicin was administered at a dose of 120 mg/M2 every 3 weeks, for a maximum of 10 such cycles. The left ventricular ejection fraction (LVEF), determined by radionuclide ventriculography, was measured periodically in all patients. We observed 2 complete responses and 13 partial responses (CP + PR = 69%) of 61 weeks' mean duration; in 3 cases lesions remained stationary while the disease progressed in 4 patients. No patients died of acute toxicity. The main side effects were severe alopecia in 82% of the subjects and moderate degrees of nausea without vomiting in 41%. After 6 treatment cycles, 4 patients showed mild cardiotoxicity and at an epirubicin cumulative dose of 1,200 mg/M2 2 patients developed congestive heart failure (CHF). Hematological toxicity was in no case so severe as to require a reduction in the dose but only a postponement of treatment by 3 to 5 days in 9% of cycles. Without increasing hematological or cardiac toxicity, epirubicin, at a dose of 120 mg/M2, has shown itself to be a highly effective agent against advanced breast cancer.
The authors evaluated the diffusion of conservative treatment of breast cancer in Italian radiotherapy departments during 1984-1985. T1 and small T2 (less than 3 cm in maximal diameter) cases were particularly considered. Conservative surgery and radiotherapy of breast cancer was adopted in 88.4% of the Italian radiotherapy centers. Quadrantectomy and axillary dissection was the surgical procedure routinely adopted. Large differences emerged in radiation treatment among the different departments, particularly with regard to the irradiation of regional lymph nodes. A total of 1561 T1 and 279 T2 cases were submitted to a conservative treatment in 1984, and respectively 2185 and 334 in 1985. The 1985 versus 1984 increase in cases treated was 40% for T1 and 18% for T2.
This article reports on a consecutive series of 3627 breast cancer (BC) patients undergoing preoperative staging by chest x-ray (CXR), bone x-ray (BXR) or bone scintigraphy (BS), and liver ecography (LE) or liver scintigraphy (LS). The detection rate (DR) of preclinical asymptomatic distant metastases depended on the T and N category (TNM classification system), and was very low (CXR: 0.30%, BXR: 0.64%, BS: 0.90%, LE: 0.24%, LS: 0.23%). The sensitivity, determined after a 6-month follow-up, was below 0.50% for all tests. The highest value (0.48%) was recorded for BS, which also had the lowest specificity (0.95%). The entire preoperative staging policy using the studied tests seems questionable due to poor sensitivity and an extremely low DR of distant metastases.
The authors report on 767 consecutive primary Stage I-II breast cancer cases followed-up from 3 to 8 years. The estrogen receptor (ER) content was determined in all cases and did not influence the treatment choice. A correlation was attempted between ER and menstrual or pathological nodal status (N) or the 5-year disease-free survival (DFS). ER was correlated with menopausal status ER+ cases being more frequent in postmenopausal patients, whereas no correlation was observed between ER and nodal status. In absence of nodal involvement (N-) the prognosis was not influenced by the ER status. A significantly better DFS was evident for ER+ respect to ER- patients in the N+ series but such a correlation is questionable as the adjuvant treatment (hormone or chemotherapy) given to such patients may have influenced the DFS according to the ER status. According to the present study, ER determination should not be used as a discriminant in the performance of adjuvant postoperative treatment based on a prognostic judgment.
To date only few and often disagreeing studies about human nasopharynx are available. The present research has the purpose to give a contribution to the knowledge of nasopharyngeal epithelium using S.E.M. The study was carried out on biopsies taken from 20 healthy volunteers. The surface of nasopharynx is covered by ciliated cells, microvilli provided cells and goblet cells. Areas covered with squamous epithelium and presumably transitional epithelium were observed. The possibility that ciliated cells become microvilli provided cells is discussed.
A case of hair casts in an 8-year-old girl is described. The disorder is rare, the first description dating back to 1897 with a total of only 31 cases reported in the literature since then. The results of research conducted using the optic and electron microscopes (transmission and scanning) are recorded. These studies show that the typical lesion consists of two concentric layers of keratinized cells of differing structure: one resembling the inner layer of Huxley's sheath and the outer layer resembling Henle's layer.
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