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Biomedical subjects

N Cascinelli

Publications and source records attributed to N Cascinelli.

At least 19 recordsLinked to original sources

Study of the biological and prognostic significance of the antigen CaMBr8 on breast carcinoma.

We previously reported that the expression on the primary tumour of the antigen CaMBr8 was related to a short survival, attributable either to higher tumour aggressiveness or a poor response to oophorectomy. To further verify the CaMBr8 prognostic value, we analysed retrospectively 862 breast cancer patients with a 19 year follow-up. In this series, CaMBr8 expression was found to be associated to some negative prognostic factors (premenopausal status, lymphnode invasion, a high number of mitosis and HER-2/neu oncoprotein expression), but had no influence on the patients' survival. Direct association with a poor prognosis was only evident in patients with lobular or mixed breast carcinoma, which however represent only a small fraction of the total breast cancers. Another possibility was that CaMBr8 could identify a subgroup of patients which did not respond to hormone therapy. To verify this hypothesis we evaluated on a second series of 116 patients the relationship between CaMBr8 expression and hormone-receptor levels. A negative association emerged which was also observed in vitro in the human breast cancer line MCF-7 treated with Sodium Butyrate, a differentiation inducer, which reduced hormone-receptor levels and increased CaMBr8 expression. In conclusion, the longer survival of CaMBr8 negative tumour patients observed in the initial study, was probably related to a better response to oophorectomy, due to the hormone-receptor level of their tumours.

Adult

Results obtained by using a computerized image analysis system designed as an aid to diagnosis of cutaneous melanoma.

Results obtained using a computerized image analysis system as an aid to clinical diagnosis of melanoma are reported. The system comprises a colour television camera connected through a digitizing board to a 386 personal computer. By means of original algorithms able to measure the shape, the colours and texture of a pigmented lesion of the skin, the system provides eight on/off indicators that are matched with the histological diagnosis to identify benign and malignant pigmented lesions. The chances that a given lesion is malignant increase with the increasing number of positive indicators. The training field of the system was constituted of images and data of 169 cutaneous lesions in 165 patients. Taking two positive indicators as the threshold between pigmented benign and malignant lesions, the efficiency of the system is 0.98, the positive predictive value is 0.45 and the negative predictive value is 0.95. These values were confirmed in a series of 44 pigmented lesions, 10 of which were melanoma, that constitute the present test series. The authors conclude that this computerized image analysis system should be regarded as a useful aid to diagnosis for a non-expert clinician. The system limit is transformation within a naevus.

Adult

Treatment of recurrent in transit metastases from cutaneous melanoma by isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine activated killer cells. A pilot study.

Chemoresistant melanoma cells are known to be susceptible in vitro to lymphokine activated killer (LAK) cells. To obtain a high LAK/tumour cell ratio in vivo and avoid systemic toxicity due to interleukin-2 (IL-2), we used IL-2 plus LAK cells in the treatment of in transit melanoma metastases of the limbs by isolation perfusion (IP). In vivo immunological modifications induced by this immunotherapeutic approach were also analysed. Six patients previously treated with IP in extracorporeal circulation with tumour cytotoxic drugs and presently relapsing or not responding, were submitted to locoregional adoptive therapy consisting of 5 days systemic administration of IL-2 (Proleukin, EuroCetus) (9-12 x 10(6) IU/m2/day c.i.). Autologous LAK cells were derived from leukapheresis and subsequent in vitro stimulation with IL-2; LAK cells were then given along with IL-2 (120-2400 IU/ml of perfusion priming) to the affected limb by IP. In addition, 7-16 x 10(9) LAK cells were administered by systemic infusion the day after together with IL-2 (9-12 x 10(6) IU/m2/day) by c.i. for 5 days. All patients concluded the treatment without major toxicity. The analysis of circulating lymphocytes obtained from extracorporeal circuit at different times revealed rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues. Clinical responses included four partial and one complete response; another patient had stable disease. All patients are presently alive. Follow-up after IP ranges from 8 to 22 months.

Adult

In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. II: Discriminant analysis between nevus and melanoma.

Reflectance spectrophotometry from 420 to 780 nm on 31 primary melanoma and 31 benign nevi has been performed by using an external integrating sphere coupled to a spectrophotometer. Measurements show that reflectance spectra of melanoma and nevi manifest dissimilar patterns. From these spectra four variables, whose physical and/or physiological meanings remain to be investigated, have been derived. All of them are significantly different when compared between melanoma and nevi. A discriminant function between the two groups of lesions has been determined by using a stepwise discriminant analysis, resulting in a test with a sensitivity of 90.3% and a specificity of 77.4%. This method of discrimination between melanoma and nevi seems to have a discriminating power almost equal to that of a clinical judgement from a specialized medical doctor, thus suggesting a new method for screening skin pigmented lesions.

Diagnosis, Differential

Locally recurrent breast cancer after 'radical' surgery.

Tumor recurrence at the site of radical surgery for mammary carcinoma has been studied in 101 cases. Analysis revealed the proximate causes--tumour size, axillary node metastases--and the more extensive type of surgery have a positive correlation even if the P values do not reach the significant value. The prognosis suggests that clinically this phenomenon, seen in the long term, does not differ from that of distant skin and subcutaneous metastases. A treatment strategy is proposed.

Adult

Prognostic significance of HER-2/neu expression in breast cancer and its relationship to other prognostic factors.

Archival surgical specimens from 1,210 female breast cancer patients treated between 1968 and 1971 and with a 19-year follow-up were reanalyzed with special reference to several parameters, such as size of the primary tumor, axillary nodal involvement, histologic grade, degree of inflammatory infiltrate (LPI) of the tumor and expression of the neu oncoprotein (p185) as detected by immunohistochemistry. In a multifactorial analysis the 4 former factors were found to be independent prognostic parameters. Over-expression of p185 was found to be related to tumor size and grade and to LPI but not to pathologic nodal status. Over-expression of p185 showed a negative impact upon survival in node-positive but not in node-negative patients. However, in the subset of node-negative patients without LPI, p185 over-expression showed the same correlation with a poor prognosis as in node-positive patients. In contrast, in node-negative and LPI-positive patients, p185 over-expression correlated with a good prognosis. Also, the prognosis of patients with positive nodes, presence of LPI and no p185 over-expression was similar to that of patients with negative nodes, absence of LPI and p185 over-expression.

Age Factors

Comparison of long-term survival of 1986 consecutive patients with breast cancer treated at the National Cancer Institute of Milano, Italy (1971 to 1972 and 1977 to 1978).

Long-term survival of 1986 consecutive patients with infiltrating duct carcinoma of the breast treated at the National Cancer Institute of Milano (Italy) in two periods of time (1971 to 1972 and 1977 to 1978) was comparatively evaluated to verify if the evolving concepts in the management of breast cancer had an impact on survival. The authors found that 10-year survival of our patients increased from 59.4% of the first period of time to 65% of the second (P = 0.005). Both node-negative (N-) and node-positive (N+) patients had an improvement of survival rates at 10 years of the same magnitude: 6.8% and 5.9% respectively. Taking into consideration both the maximum diameter of the primary tumor and the status of axillary nodes it was found that in (1) both N- and N+ patients with a primary tumor of no more than 2 cm in greatest diameter, the improvement of survival was not statistically significant; and (2) both N- and N+ patients with a primary greater than 2 cm in maximum diameter had a better chance of survival in the second time period.

Aged

Lack of effect of pregnancy on outcome of melanoma. For The World Health Organisation Melanoma Programme.

To determine the effect of pregnancy on prognosis in melanoma we investigated 388 women treated for stage 1 primary cutaneous disease during their childbearing years. 85 women had been treated before any pregnancy, 92 during pregnancy, 143 after they had completed all pregnancies, and 68 between pregnancies. Women who had received treatment while pregnant had primary tumours of significantly greater thickness than did those in the other three groups (p = 0.002). Other possible confounding factors (site, age, parity) did not differ between the groups. Once tumour thickness was controlled for, survival rate of women in whom melanoma was diagnosed and treated while they were pregnant did not differ from that in the other three groups. Cox regression analysis showed no differences between the three groups of women who were not pregnant at diagnosis. Women with melanoma should be advised about pregnancy on the basis of thickness and site of tumour and evidence of vascular spread, and not hormonal status.

Adult

Narrow excision (1-cm margin). A safe procedure for thin cutaneous melanoma.

We analyzed the results at 8 years of an international, randomized, prospective study carried out by the World Health Organization Melanoma Programme aimed at evaluating the efficacy of 1-cm-margin excision of primary melanomas not thicker than 2 mm. Data for 612 patients were assessable; 305 were randomized to receive 1-cm-margin excision and 307 to receive wide excision (margins of greater than or equal to 3 cm). The major prognostic criteria were similar in the two groups. Breslow thickness was 0.99 mm in the narrow excision group and 1.02 mm in the wide excision group. Disease-free and overall survival rates (mean follow-up period, 90 months) were similar in the two groups. Only four patients had a local recurrence as a first relapse. All underwent narrow excision, and each had primary melanomas thicker than 1 mm.

Adult

Histopathologic diagnosis of dysplastic nevi: concordance among pathologists convened by the World Health Organization Melanoma Programme.

Dysplastic nevi are an important indicator of risk of cutaneous malignant melanoma. The study of and, particularly, international communication regarding this group of lesions have been hindered by a lack of precision in diagnosis. In an effort to broaden understanding, a panel of pathologists agreed upon a set of criteria for the diagnosis of dysplastic melanocytic nevi. Two major and four minor criteria were defined. The major criteria are (1) basilar proliferation of atypical nevomelanocytes (extending at least three rete ridges or "pegs" beyond any dermal nevo-cellular component), and (2) organization of this proliferation in a lentiginous or epithelioid-cell pattern. Minor criteria are (1) the presence of lamellar fibrosis or concentric eosinophilic fibrosis, (2) neovascularization, (3) inflammatory response, and (4) fusion of rete ridges. Diagnosis required presence of both major criteria and at least two minor criteria. One hundred fourteen histologic specimens of benign acquired nevi, dysplastic nevi, and radial-growth-phase melanomas were examined by the members of this panel; their diagnoses were compared to determine degree of concordance. The established criteria yielded 92% mean concordance overall.

Diagnosis, Differential

Sister chromatid exchange analysis in familial groups of malignant melanoma patients.

Sister chromatid exchange (SCE) analysis was carried out on peripheral blood lymphocytes of 20 familial malignant melanoma (FMM) and 39 sporadic malignant melanoma (SMM) untreated patients, belonging to 10 and 39 families, respectively. The study was extended to 39 unaffected close relatives of FMM patients, to 187 unaffected close relatives of SMM patients, and to 20 unaffected unrelated individuals (control group), all examined under the same conditions. The mean SCE rates/cell were significantly higher in MM families than in the control group, and in melanoma patients than in their close relatives. The mean SCE levels of FMM and SMM patients, (8.4 +/- 0.8 and 8.0 +/- 0.3, respectively) were similar, and so were the distributions of individuals in classes of increasing SCE values (with a modal value at 7-8 SCEs/cell). The mean SCE levels of close relatives of FMM and SMM patients were also similar (5.4 +/- 0.2 and 5.4 +/- 0.1, respectively, with a modal value at 4-5 SCEs/cell), and slightly higher than in the control group (4.7 +/- 0.2 SCEs/cell). More than 7 SCEs/cell were observed in the majority (41 of 59) of FMM or SMM patients, in a smaller fraction (25 of 227) unaffected relatives, and in none of 20 unrelated unaffected individuals. These observations favor the hypothesis that higher SCE levels may be an expression of constitutional lesions predisposing to this neoplastic disease.

Adult

In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions--I. Reflectance measurements.

Reflectance spectrophotometry from 400 to 800 nm on different cutaneous pigmented lesions, including primary and metastatic malignant melanoma, pigmented nevi, lentigo and seborrhoeic keratosis, has been performed by using an external integrating sphere coupled to a spectrophotometer. Measurements show that reflectance spectra of the different lesions manifest dissimilar patterns, particularly in the near IR region. Comparison of reflectance of nevi with that of malignant melanomas results in a highly significant difference (P less than 10(-6)) between the two samples. Though interpretation of the spectra remains difficult as a result of the complexity of the optical processes of scattering and absorption, our results suggest that a detailed analysis of the reflectance spectrum may give clinically useful information, and could be utilized as an aid in clinical diagnosis of cutaneous pigmented lesions, especially where malignant melanoma is concerned.

Humans

Changes in fibrinolysis in patients with localized tumors.

An array of fibrinolysis tests was applied to the plasmas of 125 untreated patients with breast carcinoma and malignant melanoma, localized or spread to regional lymph nodes with no detectable distant metastases, to see whether or not there may be changes related to the type or to the stage of malignancy. Breast carcinoma (a mucin secreting tumor) and melanoma (a neuroectodermal tumor) were chosen as examples of tumors that can be accurately staged for localization or spread. Forty healthy subjects matched for age served as controls. The most marked differences between malignant tumors and controls were elevated plasma levels of tissue plasminogen activator antigen (P less than 0.005), plasminogen activator inhibitor (P less than 0.01), cross-linked fibrin degradation products (P less than 0.001), fragment B beta 15-42 (P less than 0.001) and histidine-rich glycoprotein (P less than 0.005). For no fibrinolysis test were results significantly different between patients with localized and spread tumors. Our data indicate that in these tumors fibrinolytic alterations are an early phenomenon unrelated to spreading.

Adult

Combined treatment of osteosarcoma of the limbs at an advanced stage, including hyperthermic-antiblastic perfusion.

Between August 1983 and September 1986 18 patients affected with osteosarcoma of the limbs in which the extent of the neoplasm would normally have required amputation were treated by two cycles of intra-arterial infusion of CDDP, associated with methotrexate at high doses administered i.v., followed by a hyperthermic-antiblastic perfusion confined to the affected limb with CDDP at high doses. At the end, the patients were administered two more cycles of methotrexate at high doses and CDDP intravenously. The immediate response, evaluated in radiological, clinical and histological terms, was such that in 11 patients it was possible to obtain satisfactory results with conservative treatment alone. None of the patients developed local recurrence.

Adolescent

Stage I melanoma of the limbs: assessment of prognosis by levels of invasion and maximum thickness.

The prognostic significance of 2 histological parameters, level of invasion and maximum thickness is evaluated in 248 cases of malignant melanoma of the limbs staged T1-3NoMo which were collected for Trial No. 1 of the W.H.O. Collaborating Centres for the Evaluation of Methods of Diagnosis and Treatment of Melanoma between September 1967 and December 1974. There is a linear relation of tumor thickness to mortality with a high statistical significance (P = 0.0002). Mortality also increases with progression of the level of invasion. The incidence of occult metastases to the regional lymph nodes increases with increasing thickness or level of invasion. Moreover the age and sex corrected survival curves are also dependent on both parameters. The comparison of the 2 methods revealed that maximal tumor thickness is a more powerful measure of prognosis than is the determination of the level of invasion.

Extremities