Let's stop worrying about pigmented skin lesions in children.
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Adolescent↗
Biomedical subjects
N Cascinelli
Publications and source records attributed to N Cascinelli.
Prognosis based on primary breast carcinoma instead of pathological nodal status.
In breast cancer patients, prognostic information required to plan post-surgical therapy is obtained mainly through axillary dissection. This study was designed to establish a new prognostic score based solely on parameters of the primary tumour as an alternative to axillary surgery in assessing prognosis. Eight different prognostic factors, including menopausal status, tumour size, grading, lymphatic invasion, desmoplasia, necrosis, c-erbB-2 and laminin receptor expression, were evaluated retrospectively on a large series of primary breast carcinoma patients. From multivariate analysis, four independent parameters were selected and examined, alone and in combination, for their prognostic potential. These parameters were used to generate a prognostic score that was analysed retrospectively in 467 N0-N1a patients to determine its predictive value for survival. The score, which includes variables such as tumour size, grading, laminin receptor and c-erbB-2 overexpression, was established based on the number of negative prognostic factors: score 1 refers to cases in which all four parameters reflect a good prognosis, scores 2 and 3 refer to tumours in which, respectively, one or two of the four parameters reflect a poor prognosis, whereas score 4 refers to tumours with three or four poor prognosis factors. Analysis of the overall survival of the four score groups shows that patients with score 1 tumours (22% of the total) had the best prognosis with a 15 year survival of 82%, patients with score 2 and 3 had an intermediate prognosis, whereas score 4 patients had the poorest prognosis with a 15 year survival of only 38%. Moreover, survival in the N+ score 1 cases was found to be longer than that in the total N- patients. Our data suggest that the primary tumour score provides more reliable prognostic information than pathological nodal status, and that axillary dissection can be avoided in a large number of patients.
Breast Neoplasms↗
Active immunization of metastatic melanoma patients with interleukin-4 transduced, allogeneic melanoma cells. A phase I-II study.
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Animals↗
Interleukin-2 gene-transduced human melanoma cells efficiently stimulate MHC-unrestricted and MHC-restricted autologous lymphocytes.
Two human melanoma lines were transduced by a retroviral vector with the gene of the human interleukin-2 (IL-2) and characterized for their immunological properties in comparison with the parental lines. Transduction resulted in the production of biologically active IL-2 in the average amounts of 2,282 and 2,336 pg/ml per 10(5) cells per 24 hr over 3 and 2 months by the Me14932/IL-2 and the Me1B6/IL-2 lines, respectively. Melanoma-transduced cells lost their tumorigenicity in nude mice. No major changes in the phenotype were observed in IL-2 gene-transduced lines. In fact, more than 90% of cells expressed class I and II(DR) HLA, adhesion molecules, integrins, and melanoma-associated antigens. Irradiation with 100-400 Gy, while inhibiting tumor cell growth in vitro, allowed the release of IL-2 by the transduced cells for at least 5 weeks. The two melanoma lines also maintained susceptibility to lysis by lymphokine-activated killer (LAK) cells and by a HLA-A2-restricted melanoma-specific cytotoxic T lymphocyte (CTL) clone recognizing the melanoma antigen (Melan-A). In a limiting dilution assay, transduced, but not parental melanoma lines unless added with an amount of IL-2 comparable to that released by the transduced cells, were able to expand both nonspecific and melanoma-specific CTL precursors from autologous peripheral blood lymphocytes (PBL). In mixed lymphocytes-tumor cultures, IL-2 gene-transduced melanoma cells stimulated the expansion of major histocompatibility complex (MHC)-unrestricted effectors from autologous PBL, and of CD3+ CD8+ MHC-restricted CTL from tumor-invaded lymph nodes. These results indicate that IL-2 gene transduction does not alter significantly the expression of the immunologically relevant molecules of human melanoma lines while increasing their ability to stimulate both specific and nonspecific lymphocyte responses. These lines will be of value in the vaccination of melanoma patients.
Animals↗
Childhood cutaneous melanoma.
Seventeen consecutive patients no older than 14 years with cutaneous melanoma were observed from 1975 to 1991 at the Istituto Nazionale Tumori, Milan; this series represented 0.8% of all cutaneous melanomas observed at the Institute during this period. Ten were males and seven females. Nine lesions arose on limbs, seven on the trunk, and one on the head and neck area. Reexamination of the clinical records suggests that childhood melanoma may present with unusual characteristics such as unusual appearance of the primary lesion and lack or scarcity of pigmentation. At first observation ten patients had stage I disease nine underwent surgery alone while in one surgery was performed in combination with regional lymph node dissection and chemotherapy. All the stage II patients underwent excision of the primary lesion and lymph node dissection. One of the 2 stage III patients received lymph node dissection only, and the other no treatment. Analysis of this series of 17 cases does not indicate that cutaneous melanoma in children is more aggressive than in adults. It is stressed that, although rare, the physician should be aware that cutaneous melanoma may occur in prepuberty.
Adolescent↗
Acral lentiginous melanoma. A histological type without prognostic significance.
BACKGROUND: Acral lentiginous melanoma (ALM) is reported to have a poorer prognosis than melanomas of other histotypes. OBJECTIVE: The purpose of this paper is to verify if ALMs, per se, have a more aggressive behavior or if the poorer prognosis of these patients is due to a later diagnosis. METHODS: Clinical charts of 165 patients with acrally located melanoma were reviewed as well as all histological slides. In all patients, histotype, Clark's level, Breslow thickness, pigmentation, presence of ulceration, and regression were reported. Mitotic index, vascular invasion, and microscopic satellitosis were also determined. Survival of the 64 patients with ALM was compared with survival observed in the remaining 101 acral (nonlentiginous) melanomas. RESULTS: Melanoma localized at acral sites constitute 8.9% of the 1845 patients with melanoma treated at our Institute from 1975 to 1990. All were Caucasian, 57 were males, and 108 females. Out of the 165 patients with this localization, 64 (38.8%) were classified as ALM. Disease-free and overall survival of the 64 ALM patients were not different at a statistically significant level compared with the areas observed in the other acral nonlentiginous melanoma. CONCLUSION: The survival difference between ALM and other histological types is due to a later diagnosis and not to a more aggressive behavior of ALM.
Disease-Free Survival↗
Scintigraphic detection of melanoma metastases with a radiolabeled benzamide ([iodine-123]-(S)-IBZM).
UNLABELLED: Iodine-123-(S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl] benzamide ([123I]-(S)-IBZM) is a radiolabeled benzamide usually employed to study neuropsychiatric disorders, such as schizophrenia and Parkinson's disease. The ectodermic origin of melanocytes and the presence of melanin in the substantia nigra are the theoretic basis of the experimental use of this class of tracers for melanoma imaging. METHODS: Eleven patients with proven metastatic melanoma entered the study. Whole-body and planar scintigrams were performed 2, 4 and 24 hr after intravenous injection of a mean tracer activity of 205 MBq. The dosimetric evaluation was performed by the Medical Internal Radiation Dose Committee method. RESULTS: The [123I]-(S)-IBZM scans allowed the detection of all six cutaneous lesions, five of six superficial pathologic lymph nodes, four of five pulmonary and one of two hepatic metastases. The maximum tumor-to-background ratio was 2.6 in planar images. The hepatobiliary excretion of the tracer may limit detection of intra-abdominal lesions. Dosimetry is similar to data for nononcologic patients. CONCLUSION: Although it is unclear if the mechanism of radiopharmaceutical uptake in melanoma is due to binding to membrane receptors or due to interactions with intracellular structures, radiolabeled benzamide is a promising tracer to detect melanoma.
Adult↗
European School of Oncology advisory report. Sun exposure, UVA lamps and risk of skin cancer.
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Humans↗
Prognostic significance of the 67-kilodalton laminin receptor expression in human breast carcinomas.
BACKGROUND: The 67-kd laminin receptor is a cell-surface protein that binds laminin with high affinity. In vitro studies suggest that this protein is involved in the progression of human tumors to invasive cancers (metastasis), but there have been few in vivo studies. Identification of such proteins would allow development of therapies aimed at interfering with their mechanisms of action. PURPOSE: This large retrospective study was designed to investigate the association of expression of this laminin receptor molecule with established prognostic factors and overall survival in breast carcinoma patients. METHODS: We immunohistochemically stained archival paraffin-embedded sections of 1160 primary breast carcinomas, using an immunoperoxidase technique and the MLuC5 monoclonal antibody, which is specific for the 67-kd laminin receptor. Specimens were obtained from consecutive surgeries performed from January 1968 through December 1971. Patients with negative lymph nodes or involved regional nodes had been treated with surgery alone; those with positive axillary nodes had received surgery and radiotherapy. No chemotherapy had been administered until disease recurrence. The statistical analysis was carried out using the logrank method for the survival curves and the actuarial life table to calculate survival rates according to the different prognostic variables. RESULTS: We found statistically significant associations between laminin receptor expression and young age (P < .001), premenopausal status (P = .001), positive axillary lymph nodes (P = .01), peritumoral lymphatic invasion (P = .02), and the diameter of the tumor (P = .05). Moreover, the association of expression of the receptor protein with poor prognosis, as indicated by survival curves, was statistically significant (P < .01). For patients with receptor-negative tumors, the survival rate was 50% at 20 years; for those with receptor-positive tumors, the survival rate was 50% at 13 years. Multivariate analysis showed the laminin receptor to be an independent prognostic factor (P = .005), indicating its predictive value in relation to overall survival. CONCLUSIONS: Our data suggest that the 67-kd laminin receptor is associated with the metastatic process. IMPLICATIONS: These preliminary findings also suggest that hormones may have a regulatory role in the in vivo expression of the 67-kd laminin receptor, which supports the hypothesis that hormone therapy might inhibit expression of the receptor. Studies of expression of this receptor in tumors of patients with extremely different sex hormone levels (e.g., men and pregnant women) are in progress.
Antibodies, Monoclonal↗
Neuropsychological and neurophysiological assessment of the central effects of interleukin-2 administration.
Neuropsychiatric disturbances may occur following interleukin-2 (IL2) administration. We studied the effects of IL2 infusion on cerebral functions in 7 patients with neuropsychological tests and event-related evoked potentials (P300). We observed a failure in the cognitive performances, an increase in latency, and a decrease in amplitude of P300. These effects followed IL2 administration and were reversible.
Adult↗
Perinodular injection of thymopentin (TP5) in cutaneous and subcutaneous metastases of melanoma.
The potential therapeutic efficacy of TP5 in patients with cutaneous and subcutaneous metastases of melanoma was tested in a double-blind study comparing the drug and placebo injected perinodularly. Of the 47 nodules present in the 16 patients treated with TP5, 24 showed a measurable response, whereas only one out of 15 nodules in patients treated with a placebo showed a minor response (P = 0.02). In two patients treated with TP5 a response of two nodules not perinodularly injected was also observed. Sclerosis, CD45RO+ cells and MIB 1- cells were more frequently observed in nodules treated with TP5 than with placebo. (P = 8 x 10(-4); 0.03 and 0.01, respectively). Evaluating the trends of these findings in nodules treated with placebo; with TP5-treated, non-responding nodules; or with TP5-treated, responding, a positive trend was observed for sclerosis and CD45RO+ cells (P = 5 x 10(-4) and 2 x 10(-3), respectively) and a negative one for MIB 1 cells (P = 2 x 10(-3)). These preliminary data suggest that lymphoid cells associated with nodules regression are activated large lymphocytes (CD45RO+ and CD3-). Sclerosis might be interpreted as the final morphologic event, and reduction of proliferative activity (MIB 1- cells) as the consequence of cytolytic action.
CD3 Complex↗
The case for minimal margins and delayed regional node dissection for high-risk cutaneous melanoma.
Some aspects of the surgical treatment of cutaneous melanoma are still currently debated. There is presently a general agreement in favor of a less wide excision of primary lesions. Specifically, data coming from a randomized study of the World Health Organization (WHO) Melanoma Programme indicates that the width of resection has no impact on either disease-free and overall survival of 612 stage I entered patients. Opportunity of an elective (ELND) or delayed (DLND) lymph node dissection remains much more controversial. Complications, including lymphedema, associated with this type of surgery, and no evidence of regional lymph node disease in at least 70% of clinical stage I patients submitted to node dissection, argue for avoiding ELND. Some studies show a positive value for ELND, but they are flawed by biased entry of patients into the ELND group, and conclusions are not derived from randomized studies. Two prospective trials show that ELND does not improve the prognosis of patients with stage I cutaneous melanoma. The results of the WHO study of 553 cases will be evaluable at 20 years. So far, on the basis of many biologic, clinical, and statistical findings, there is no evidence, in our opinion, of a substantial benefit related to ELND.
Disease-Free Survival↗
Mucosal malignant melanoma of head and neck: forty-eight cases treated at Istituto Nazionale Tumori of Milan.
A series of 48 cases of malignant mucosal melanomas treated at the Milan Cancer Institute from 1975 to 1990 is retrospectively reviewed. There were 34 males and 14 females, and their ages ranged from 21 to 79 years (mean, 58). The site of origin of the tumor was the nasal cavity in 26 cases, the oral cavity in 15, larynx in two, lip mucosa in two, pharynx in two and upper esophagus in one. At presentation, the neoplasm was limited to the primary site in 60.4% of the patients. Most patients (34) were treated with surgery alone. Nine were treated with surgery combined with chemo- and/or radiotherapy and five with radiotherapy combined with chemotherapy and/or immunotherapy. Only when surgery was part of the treatment (42 of 48 cases) the patients were rendered disease free, but no further relapse of disease was documented in only five of these patients. The observed 2- and 5-year survival rate of the entire group was 45% and 21%, respectively. The 4-year disease-free survival rate was 7%. The median interval between therapy and the first relapse was 8.5 months (range, 1-66). In 44% of the patients the first recurrence of the tumor was at the primary site.
Adult↗
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↗