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Biomedical subjects

N Cascinelli

Publications and source records attributed to N Cascinelli.

At least 91 records · Page 5Linked to original sources

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↗

Chromosome abnormalities and fragile sites in human melanoma.

Chromosome analysis in short-term lines of three primary and seven metastatic malignant melanomas showed aneuploid karyotypes with recurrent abnormalities of chromosomes 1 (five cell lines), 6 (nine cell lines), and 7 (six cell lines). The breakpoints observed on the rearranged chromosomes frequently coincided with loci of known oncogenes and fragile sites. Two of the cell lines were analyzed after xenograft into nude mice and showed the presence of the same chromosomal changes observed in the parental cell lines, indicating the stability of the karyotype. A tendency toward an increased chromosomal fragility in peripheral blood lymphocytes was observed in five melanoma patients compared to ten normal individuals. However, there was no increased level of expression of specific fragile sites corresponding to the breakpoints observed in melanoma cells.

Chromosome Aberrations↗

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↗

Cell kinetics: an independent prognostic variable in stage II melanoma of the skin.

The prognostic role of cell kinetics (expressed as 3H-thymidine labelling index, 3H-TdR LI) was assessed on 145 patients with pathologic stage II melanoma subjected only to therapeutic lymph node dissection. The 3H-TdR LI determined on metastatic nodes was related to relapse-free survival and to survival. In particular, 3-year relapse-free survival was significantly different from patients with slowly and rapidly proliferating melanomas (40% vs 22%, P = 0.007), and this finding was consistently found for overall survival (68% vs 46%, P = 0.007). Moreover, in patients with high 3H-TdR LI tumours, the risk of relapse and death within the first year from lymphadenectomy was two-fold that of patients with low 3H-TdR LI tumours. Multiple regression analysis showed that 3H-TdR LI retained its prognostic significance on relapse-free and on overall survival even when the number of involved nodes and type of nodal metastases were considered. Present findings suggest that 3H-TdR LI can contribute to select high-risk stage II melanoma patients.

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↗

The role of parotidectomy in the treatment of nodal metastases from cutaneous melanoma of the head and neck.

Forty-six patients affected by head and neck melanoma were submitted to elective or therapeutic parotidectomy associated with laterocervical dissection from 1980 to 1983 at the National Cancer Institute of Milan. The study showed that parotidectomy is indicated in the presence of clinically palpable nodes or where primaries originate in the temporo-zygomatic area. It also demonstrated that survival is not affected by type of dissection performed and that cervical lymphadenectomy must always be associated with parotidectomy because of the high incidence of occult metastases in other nodal groups in these cases.

Adult↗

Differences between in vivo and in vitro activation of cancer patient lymphocytes by recombinant interleukin 2: possible role for lymphokine-activated killer cell infusion in the in vivo-induced activation.

In this study 15 consecutive melanoma patients were treated with two courses of bolus recombinant interleukin 2 (rIL2) and rIL2 plus in vitro-generated lymphokine-activated killers (LAK), respectively. The immunological monitoring performed after 4 days of rIL2 or rIL2 plus LAK, indicate that the in vivo peripheral blood lymphocyte (PBL), activation (spontaneous proliferation, tumor cytotoxicity, number of DR+ PBL, obtained after the second cycle of rIL2 plus LAK is significantly higher than after the first cycle of rIL2 alone. During the 5-day interval between the two courses, PBL activation returns to baseline levels and no evidence for increased sensitivity of PBL to rIL2 is present. To further confirm this, two additional patients were studied, in whom rIL2 was administered by continuous i.v. infusion. In these two patients the in vitro versus in vivo PBL activation could be directly and simultaneously compared by using in vitro the same concentration of rIL2 reached and maintained in the patients' sera. The PBL activation induced in vivo by a cycle of rIL2 alone was significantly less (about 10 times) than that obtained in vitro with a comparable rIL2 concentration. Thus, the infusion of in vitro highly activated PBL could explain the increased in vivo lymphocyte activation of the second cycle of rIL2 plus LAK over the first cycle of rIL2 alone.

Cell Line↗

A phase II study of the administration of recombinant interleukin 2 (rIL-2) plus lymphokine activated killer (LAK) cells in stage IV melanoma patients.

From January 1987 to February 1988, 15 stage IV melanoma patients were treated with two courses of bolus injection of rIL-2 plus LAK cell infusions at the National Cancer Institute of Milan. The original treatment regimen included a first course of rIL-2 administration (400 micrograms/m2 bolus injection 3 times a day [TID] for 4 days) and a second course of rIL-2 administration (800 micrograms/m2 bolus injection TID for 7 days) separated by 4 consecutive daily leukaphereses. Autologous lymphokine activated killer (LAK) cells were reinfused into each patient on three occasions during the second period of rIL-2 administration. Due to the appearance of grade III-IV neurological, hepatic and cardiopulmonary toxicity, 7 patients discontinued dosing before the end of treatment, one patient desired to be withdrawn and one patient died from rapidly progressive disease, although complications of rIL-2 administration may have contributed to her death. Only 6 patients completed the schedule without evidence of major intolerance, even though the planned dose during the second course of rIL-2 was reduced to 400 micrograms/m2. The complete duration of treatment ranged from 11 to 19 days. The total dose of rIL-2 injected ranged from 12.6 to 30.4 mg. The number of infused LAK cells ranged from 15.5 x 10(9) to 60 x 10(9)/patient. Two of the 14 evaluable patients showed a minor anti-tumor response. In 5 patients new metastases in other sites were documented from 2 to 5 months after completion of dosing. No apparent association was found between progression of the disease (or the appearance of new metastases) and the total dose of rIL-2 injected, the number of LAK cells administered or the number of days of treatment. By December 1988, all patients had died of their disease in a period ranging from 3 to 14 months from the last injection of rIL-2. The lack of significant clinical responses in this study and the high toxicity of this treatment lead us to conclude that at least as far as melanoma patients are concerned, adoptive immunotherapy with rIL-2 plus LAK cells (as described here) is not a justifiable treatment option unless new evidence presents itself.

Adult↗

Long-term survival and prognostic factors for 2170 breast cancer patients treated at two cancer centers (Milan and Houston).

Data on 2170 consecutive patients with breast cancer submitted to curative surgery with or without combined radiotherapy in the period 1968-1972 at the National Cancer Institute of Milan (Italy) and at the University of Texas M.D. Anderson Cancer Center of Houston (Texas, USA) were analyzed to evaluate the prognosis of breast cancer patients after loco-regional treatment only and to verify if different prognostic factors have the same relevance. Forty-four percent of patients were alive without evidence of disease at the end of the follow-up in both centers: 14% of patients treated in Milan died without evidence of breast cancer with an intercurrent disease, whereas the death rate for intercurrent disease was 27% in Houston. Thirty-seven percent of the patients in Milan and 26% of the patients in Houston died from breast cancer. A considerable percentage of patients (23.4% in Milano, 38.2% in Houston) had one or more of the required items not specified in the clinical chart. Since the lack of information was considered a possible source of bias, the series were divided into two groups: the first collecting patients with all information available, the second gathering patients with at least one of the required items missing. The latter group was defined "unknown". Multivariate analysis of survival, carried out by means of Cox's regression model, showed that mortality of these patients for all causes was significantly affected by the following criteria: status of regional nodes (P = 2 X 10(-13)), unknown (P = 10(-9)), maximum diameter of primary tumor (P = 7 X 10(-10)), age of the patients (P = 10(-4)), site of primary (P = 0.01), and Center (P = 0.04). A significant interaction was found between center and a) age of the patients, b) menopausal status and c) unknown. The relative P values were 6 X 10(-7) for age and center, 8 X 10(-3) for menopausal and center, 3 X 10(-2) for unknown and center. Multivariate analysis of breast cancer mortality was significantly affected by: status of regional nodes (P = 10(-18)), diameter of primary (P = 5 X 10(-14)), unknown (P = 2 X 10(-13)), center (P = 2 X 10(-6)), site of primary (P = 0.002), and age of the patients (P = 0.03). The same significant interaction as for mortality from all causes was found. It is concluded that comparability of results obtained in different institutions may be dependent on the standardization and availability of patients data.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Seven years experience with hyperthermic perfusions in extracorporeal circulation for melanoma of the extremities.

One hundred forty patients affected by high risk or locally advanced melanoma of the extremities were submitted to hyperthermic perfusion in extracorporeal circulation at the National Cancer Institute of Milan, Italy. Using adequate temperature and drug dosage, we increased survival of stage IIIA patients from 8-15% to 51% and stage IIIAB patients from 7-8% to 35%, and good local control was achieved in stage IV patients. A comparison was made with 297 patients with similar disease treated in a previous period in this institute with conventional therapies such as surgery with or without chemotherapy. In stage IIIA patients we obtained 51% overall survival at 5 years in perfused cases, whereas survival in the series with conventional treatment reached 16%. Similarly, in stage IIIAB patients we observed 34% (perfused) versus 16% (conventional treatment) survival. There are still no data available for high-risk stage I, in which perfusion is employed as an adjuvant treatment.

Antineoplastic Agents↗

The significance of conversion of skin reactivity to efficacy of bacillus Calmette-Guérin (BCG) vaccinations given immediately after radical surgery in stage II melanoma patients.

A group of 668 stage II melanoma patients was entered into a randomized prospective study aimed at evaluating the efficacy of adjuvant BCG, 5-(dimethyltriazeno)imidazole-4-carboxamide (DTIC), or a combination of the two, given immediately after radical lymph node dissection. Of these, 176 patients received BCG and 164 BCG plus DTIC. These 340 patients had histologically proven metastatic nodes and 156 had a negative skin reactivity to BCG at the beginning of treatment. The distribution of known prognostic factors (sex, age, number of positive nodes, extracapsular invasion) was balanced in the groups of patients either with initially negative or with positive skin reactivity. All patients who were initially non-reactive to BCG developed skin reactivity after 6.7 +/- 9 BCG vaccinations. Disease-free and overall survival of patients receiving BCG or BCG + DTIC with an initially negative skin reactivity to BCG was significantly (P = 7 x 10(-3) better than that observed in patients with an initial positive skin reactivity. This finding was still evident after adjustment for other known prognostic criteria (P = 0.02). It seems likely that the initial BCG skin reactivity as such marks the prognosis; however, some therapeutic effect of BCG treatment in patients having initially no skin reactivity to BCG, can not be ruled out.

Adult↗