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N Cascinelli

Publications and source records attributed to N Cascinelli.

At least 55 records · Page 3Linked to original sources
PubMed1996

Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma.

BACKGROUND: Primary cutaneous melanoma is often infiltrated lymphocytes that provide the opportunity to study what may be the local immunologic reaction to the tumor and to correlate the presence of these lymphocytes with overall survival. In an attempt to delineate the histologic diagnostic criteria, to classify different categories of lymphocytic infiltrates, previously described by Elder et al. at brisk, nonbrisk, and absent, and to verify their prognostic significance, we reviewed 285 consecutive cases of primary cutaneous melanomas (American Joint Committee on Cancer Stage I and II). METHODS: In addition to clinical variables (age, sex, and location of tumor) and the presence of tumor infiltrating lymphocytes in the vertical growth phase, the histopathologic attributes reviewed included mitotic rate, thickness, and regression. The results were derived from independent histopathologic review by two pathologists (C.G.C., M.C.M., Jr.) on separate occasions. A multivariate analysis of survival was performed with the Cox's regression model. RESULTS: The 5- and 10-year rates for melanoma with a vertical growth phase and a brisk infiltrate were 77% and 55%, respectively. For tumors with a nonbrisk infiltrate, the 5- and 10-year survival rates were 53% and 45%, respectively, and for tumors with absent tumor infiltrating lymphocytes, the 5- and 10-year survival rates were 37% and 27%, respectively. Mitotic index, thickness, and tumor infiltrating lymphocytes were statistically (univariate analysis) significant prognostic factors (P = 0.003, 0.000001, 0.0003, respectively), whereas the presence or absence of regression is not. In the univariate statistical analysis, the sex of patients and site of melanoma also were statistically significant (P = 0.00001 and 0.002 respectively), whereas age (P = 0.98) was not statistically significant. The multivariate analysis of thickness, mitotic rate, and tumor infiltrating lymphocytes showed that thickness and presence tumor infiltrating lymphocytes were significant and independent histologic prognostic factors. With regard to the clinical factors, sex retained its independent prognostic significance. The histologic characteristics of melanoma with vertical growth phase (brisk, nonbrisk, and absent) are exemplified. CONCLUSIONS: We demonstrated that when categories of tumor infiltrating lymphocytes are strictly defined, they indeed have very strong predictive value for primary cutaneous melanomas with a vertical growth phase. This work confirms the work of Clark et al. and fully illustrates the brisk, nonbrisk, and absent categories of infiltration. Finally, a multivariate analysis comparing thickness, mitotic rate and presence of tumor infiltrating lymphocytes showed that only thickness and presence of tumor infiltrating lymphocytes are significant and independent positive histologic prognostic factors.

Adult↗
PubMed1996

Clinical diagnosis and therapy of cutaneous melanoma in situ.

BACKGROUND: The frequency of in situ melanoma is increasing, and it is often diagnosed fortuitously by histology. METHODS: We retrospectively reviewed 121 melanomas in situ in 113 patients with the aim of identifying the clinical features of, and optimal surgical treatment for this cutaneous malignancy. Treatment was limited surgery with 3 mm margins of excision in 69 cases (57%) and wider margins of excision (more than 3 mm) in 52 cases (43%). The lesions had a median diameter of 1 cm (range, 2-35 mm) and were generally macular (92% of cases) asymmetric (87%), with an irregular border (88%) and nonuniform pigmentation (98%), usually in shades of brown (41%) and black (48%). These features had permitted a clinical diagnosis of melanoma or suspected melanoma in 62% of cases and of doubtful nevus in an additional 18% of cases. RESULTS: At a median follow-up of 4 years, there were six local recurrences (three treated by limited surgery and three by wider excision), all in situ melanomas. CONCLUSIONS: The typical clinical features of melanoma in situ, which are similar to those of early invasive melanoma, are usually sufficiently distinctive to suggest the clinical diagnosis of melanoma or suspected melanoma. Except for large size and superficially extended lesions (larger than 2 cm), adequate treatment is excision with 3 mm margins, although larger lesions (larger then 2 cm) may have an appreciable incidence of local recurrence.

Aged↗
PubMed1996

The invisible colours of melanoma. A telespectrophotometric diagnostic approach on pigmented skin lesions.

Reflectance images of 43 pigmented lesions of the skin (18 melanomas, 17 common melanocytic naevi and eight dysplastic naevi) were acquired by a telespectrophotometric system and were analysed in the spectral range from 420 to 1040 nm, to discriminate melanoma from benign melanocytic entities. Different evaluations were carried out considering the whole spectrum, the visible and the near infra-red. A total of 33 (76.7%) lesions were correctly diagnosed by the telespectrophotometric system, compared with 35 (81.4%) correct clinical diagnoses. Reflectance in the infra-red band appears diagnostically relevant. A larger study is needed to prove the validity of this diagnostic method.

Diagnosis, Differential↗
PubMed1996

Biological activity and clinical efficacy of intravenous high-dose thymopentin in metastatic melanoma patients.

Eight patients with cutaneous metastatic melanoma were submitted to high-dose intravenous thymopentin (TP5) treatment for 5 weeks: three patients received 1 g three times a week, three received 1 g daily and two received 2 g daily. Four out of eight patients presented a partial response of cutaneous lesions lasting for 1-7 months, and six remain alive with evidence of disease after a follow-up of 2-7 months. A remarkable histologic observation is the presence of tumour necrosis, which was seen as both single cells and large confluent areas. The majority of lymphoid cells present in the tumour are CD45RO+ and CD4+. The CD4+ cells might play an important role in the anti-tumour immune local response by secreting cytokines and inducing apoptotic and necrotic cell death. This hypothesis seems to be confirmed by the presence of a high number of CD4+ cells around intratumoral vessels, while the presence of endovascular micro-thrombosis provides indirect evidence of cytokine activity. Cellular lysis may be produced by the activity of both CD8+ and CD4+ lymphoid cells. The role of TP5 may be an activation of CD4+ and CD8+ lymphoid cells. Clinical and pathological data indicate that TP5 is able to produce consistent clinical and immunological effects in melanoma patients with cutaneous metastases.

Adjuvants, Immunologic↗
PubMed1996

Tumor infiltrating lymphocytes in lymph node melanoma metastases: a histopathologic prognostic indicator and an expression of local immune response.

In lymph node melanoma metastases, the expansive proliferation of tumor cells may be compared, structurally and cytologically, to the vertical growth phase (VGP) observed in primary melanoma. Both in VGP and in nodal metastases, tumor infiltrating lymphocytes (TILs) may be present with different patterns. In the evaluation of the primary tumor, these patterns have been defined as brisk, non-brisk, and absent. The histologic slides of regional lymph node metastases, the site of first recurrence in 99 consecutive melanoma patients, were reviewed. Disease-free survival of these cases and whether or not they were treated with rIFN alpha-2A was recorded to identify any relationship among different patterns of TILs, therapy, and prognosis. Of 99 cases, 16 were classified as brisk, 37 as non-brisk, and 46 as absent. At 30 months of follow-up the disease-free survival was 81.3% for brisk cases, 46.8% for non-brisk cases, and 29.3% for absent groups (p = .007). Multivariate analysis confirmed the prognostic value of TILs in predicting disease-free survival in patients with regional node metastases. The difference according to the presence or absence of relapse is particularly evident when comparison is made between treated and untreated patients. In conclusion the evaluation of first-recurrence regional node melanoma metastases for TILs, using the same histopathologic criteria as in VGP of primary melanoma, subdivides the cases in brisk, non-brisk, and absent groups. Also, the presence of these patterns in metastatic node melanoma deposits is correlatable to disease-free survival. Our results further stress the difference of prognosis patients treated with rIFN alpha-2A compared to the untreated group. The TILs evaluation may prove useful in selecting those melanoma stage II patients who will best respond to therapy with biologic response modifiers, because the TILs may be the local immune effector cell targets of rIFN alpha-2A or of other biologic agents.

Humans↗
PubMed1996

Cytokine-based gene therapy of human tumors. An overview.

This review first summarizes the different strategies of gene therapy of cancer and then focuses on the immunological approach. Several studies in animal models with cytokine gene-transduced tumor cells indicate that local cytokine release usually results in tumor growth inhibition. Moreover, in a number of cases vaccination with such cells can reduce growth of established tumors or even cure the tumor-bearing animals. Translation of such a principle in human clinical setting is reported. We have transduced human melanoma cells with genes coding for interleukin (IL)-2, IL-4 or B7-1 and characterized such lines. The phenotype did not change after gene insertion but the functional, immunostimulatory activity of IL-2 or B7-1 gene-transduced melanoma cells was significantly increased compared to that of parental lines. These-lines were then used to vaccinate melanoma patients. Preliminary results of trials with IL-2 gene-transduced cells are presented which indicate a weak clinical response and the activation of a melanoma-specific cytotoxic T lymphocyte response in a low percentage of patients.

Animals↗
PubMed1995

Excision of primary melanoma should allow primary closure of the wound.

There is no doubt about the fact that surgery is mandatory for primary melanoma. The problem in the recent past has been how wide and deep the excision of primary melanoma has to be. Results published from the World Health Organization (WHO) Melanoma Program have clearly demonstrated that a procedure involving up to 2-mm thickness and 1-cm margins is safe. Further trials dealing with melanoma thicker than 2 mm are being carried out, and preliminary results confirm that even in this case narrow excision is the correct procedure. At present we may assume that for stage I melanoma the excision of the primary tumor should in the majority of cases allow primary closure of the wound.

Humans↗
PubMed1995

Prognostic significance of laminin production in relation with its receptor expression in human breast carcinomas.

Laminin is a basement membrane glycoprotein whose expression has been widely related to cancer progression. Laminin production by primary breast carcinomas was investigated using immunohistochemistry on archival specimens from a retrospective series with long term follow-up. Laminin production was found to be independent of the clinical and pathological variables analyzed, whereas a statistically significant direct association with the expression of the laminin receptor and a negative association with the differentiation-related antigen Ca-MBr8 were observed. Survival analysis indicated that laminin positivity by itself has no prognostic significance. However, when analyzed together with the laminin receptor expression, laminin was associated with a good prognosis in receptor-negative tumors and with the worst prognosis in receptor-positive tumors.

Breast Neoplasms↗
PubMed1995

Isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine-activated killer cells in the treatment of in-transit metastases from limb cutaneous melanoma.

BACKGROUND: Therapies of advanced melanoma patients with interleukin-2 (IL-2) and cytotoxic lymphocytes have produced interesting results, but a larger diffusion of these treatments is limited by the severe side effects due to IL-2 systemic infusion. A strictly regional administration of IL-2 and cells by an isolation perfusion (IP) in extracorporeal circulation (ECC) for the treatment of regional melanoma metastases could improve tolerability and efficacy of this specific modality of immunotherapy. METHODS: Ten patients were submitted to adoptive immunotherapy with IL-2 and lymphokine-activated killer (LAK) cells by IP in ECC. The schedule of treatment included the first course of a 5-day systemic administration of IL-2 (Proleukin, EuroCetus 9-12 x 10(6) IU/m2/day continuous infusion); autologous LAK cells were obtained via leukapheresis and after in vitro activation were given (range 8-28 x 10(9)) along with IL-2 (120-2,400 IU/ml of perfusion priming) to the affected limb by IP; IL-2 (9-12 x 10(6) IU/m2/day) was also administered by systemic continuous infusion for 5 days starting on the day after IP. RESULTS: All patients concluded the treatment without any major local or systemic toxicities. Clinical responses included one complete and six partial remissions; three patients had stable disease. All patients are alive. Follow-up after IP ranged from 12 to 35 months (median: 22). The analysis of circulating lymphocytes revealed the rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues. CONCLUSIONS: IP with IL-2 and LAK cells is a new approach for the treatment of in-transit metastases due to cutaneous melanoma. The treatment appears to be feasible and reliable. Further biological and immunological studies should permit amelioration of the present modality of treatment.

Adult↗
PubMed1995

In vivo spectrophotometric evaluation of neoplastic and non-neoplastic skin pigmented lesions. III. CCD camera-based reflectance imaging.

Reflectance spectroscopy, which allows an objective evaluation of the color of surfaces, has recently been proposed as a useful tool to discriminate cutaneous melanoma from other pigmented cutaneous lesions. A novel spectrophotometric system based on the use of a charge coupled device camera provided with a set of interference filters has been developed to acquire images of cutaneous pigmented lesions at selected wavelengths ranging from 420 to 1040 nm. For each filter, an image was captured, digitized by a frame grabber and stored in a personal computer to perform off-line data handling. Reflectance images were acquired of 22 cutaneous pigmented lesions including melanoma and dysplastic, compound and junctional nevus. From each spectral image, three parameters, i.e. mean reflectance, variegation index and lesion area; were derived at the corresponding wavelength. The wavelength dependence of the three parameters was significantly different when melanoma was compared to the other investigated lesions. Although preliminary, our results suggest that telespectrophotometry gives useful information and could be utilized as an aid in the clinical diagnosis of cutaneous pigmented lesions.

Humans↗
PubMed1994

Treatment of primary or relapsing limb cancer by isolation perfusion with high-dose alpha-tumor necrosis factor, gamma-interferon, and melphalan.

BACKGROUND: Utilization of alpha-tumor necrosis factor (alpha-TNF) in clinical practice is limited by severe general side effects. Very promising results with low toxicity were reported with administration of alpha-TNF by isolation perfusion in extracorporeal circulation. METHODS: From December 1991 to November 1992, 14 patients underwent perfusion with alpha-TNF (2-4 mg, total dose), gamma-interferon (1.5 x 10(6) IU), and melphalan (10 mg/l/perfused limb). Twelve patients presented in-transit metastases of the limbs, one patient, a clear cell sarcoma of the hand, and one patient, a wide spindle cell carcinoma of the thigh. Perfusion lasted 90 minutes and was conducted in mild hyperthermia (38-40.5 degrees C, muscle temperature). RESULTS: Nine complete regressions and four stable diseases were recorded. In one case, a reliable evaluation of response was not possible for diffused tissue necrosis. Five patients relapsed or progressed locally from 3 to 4 months after surgery, five presented distant localizations from 2 to 7 months after surgery, and one died of disease 6 months after perfusion. Twelve patients are alive, seven without evidence of disease. A septic-like shock syndrome was observed in all patients and required administration of dopamine, dobutamine, or noradrenaline. One patient died 30 days after perfusion from a multiorgan-failure syndrome, likely due to alpha-TNF. The follow-up time ranges from 4 to 15 months (median, 6). CONCLUSIONS: The preliminary, impressive results reported in other series were not completely confirmed in this study adopting the same treatment scheme. Further clinical experience and biologic data are needed to state the real efficacy of the approach and to reduce the severe general toxicity consistently associated with this type of treatment.

Adult↗
PubMed1994

Inconsistent expression of HLA-B antigens on peripheral blood lymphocytes of stage I melanoma patients: an indicator of poor prognosis.

The survival of stage I melanoma patients was evaluated and compared with the detectable expression of HLA antigens. Of 904 patients who were surgically treated, 219 were HLA typed on peripheral blood lymphocytes. Four consecutive HLA typings were considered necessary. Median follow-up was 8 years. Two main groups of patients were considered: (a) patients with consistent detectable expression of antigens; and (b) patients with inconsistent detectable expression of antigens. Patients with consistent HLA antigens detection had an 8-year survival rate of 87.7% compared with 49.2% of patients with an inconsistent rate (P10(-7). Multivariate analysis of survival of the 182 HLA-typed patients who survived at least 24 months from surgery showed that two of the criteria had an independent impact on survival: tumour thickness (P 0.02) and HLA typing (P 2 x 10(-5). Inconsistent detection of HLA antigens on peripheral blood lymphocytes during the first 24 months after surgery is an indicator of poor prognosis in stage I melanoma patients.

Female↗