Comments on Management of cutaneous melanoma M0: state of the art and trends, Rossi et al., Eur J Cancer 1997, 33, 2302-2312.
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Publications and source records attributed to A Bono.
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BACKGROUND: Basal cell carcinoma (BCC), the most common malignancy of the eyelid margins, poses therapeutic problems. Surgery, radiation therapy, and cryotherapy are the currently accepted methods for the treatment of this affliction. To verify the technical and clinical effectiveness of the surgical laser method, a specific approach was developed by performing laser-combined procedures under microscopic control. METHODS: A series of 26 patients underwent carbon dioxide (CO2) laser microsurgical excision of 27 primary superficial BCCs of the eyelid margins. Eighteen tumors were T1 and 9 were T2. The lesions were located at the lid margins in 18 and at the canthus in 9 cases. The eyelash line was involved in all cases, whereas intermarginal space was involved in 17 cases, without extension to the conjunctival border. Six lesions were in the lacrimal region. Median linear extent of the lesion was 5 mm (range, 4-10 mm). Treatment was performed with the patient under local anesthesia in a Day Hospital regimen. The authors used the microscope-mounted CO2 laser as a scalpel to excise the tumor mass, thus obtaining the specimen for histologic evaluation. The authors treated the deep and lateral resection margins with laser vaporization and left the wound bed to heal by secondary intention. RESULTS: No significant complications were observed. As full-thickness eyelid resections were avoided, the authors noted conservation of lid function and cosmetic aspect in all patients. With a median follow-up of 73 months (range, 18-118), only one patient had tumor recurrence after 22 months. This tumor, located at the outer canthus, had a second microsurgical laser excision, and the patient is disease free 51 months after the last treatment. CONCLUSIONS: Laser microsurgery appears to be a safe and effective treatment method for primary superficial T1 and T2 BCC of the eyelid margins without conjunctival extension.
Although narrow surgical excision may be sufficient for thin melanoma, questions remain concerning how narrow the excision should be and how it should be related to tumour thickness. To address these issues, a group of 168 consecutive patients with primary invasive melanoma up to 2 mm thick underwent ambulatory surgery with excision margins of 1 cm. 40 (24%) of these patients had lesions thicker than 1 mm. In a median follow-up of 5 years, 11 patients relapsed and 3 developed second malignancies. The crude cumulative incidence of regional and distant metastases were, respectively, 5.6% and 1.5%. No local isolated recurrence was observed, indicating that ambulatory narrow excision is justified for melanoma up to 2 mm thick.
Eighteen patients with facial actinic keratoses were treated with the retinoid fenretinide (4-HPR), applied topically twice-daily for 3 months. After 3 months of treatment, complete regression was observed in 56% and partial regression in 44% of cases. Eight patients relapsed within 3 months after drug discontinuation. Six months later, only two patients (11%) showed a treatment response (complete regression). Blood samples showed that 4-HPR was not absorbed and no local or distant adverse effects were observed. Baseline plasma retinol levels were lower than in healthy subjects, thus suggesting that reduced retinol levels might be involved in this pathology. These encouraging preliminary results suggest the need for further studies to evaluate the best dosage schedules and duration of 4-HPR topical application in actinic keratoses.
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.
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.
Biological data support the development of clinical trials designed to evaluate the activity of somatostatin (SMS) analogues in advanced breast cancer (ABC). Although previous clinical trials have failed to show antitumor activity, various factors may have biased their results. In an attempt to improve our understanding of the role of SMS analogues in ABC, 10 patients with favourable prognostic factors and who had not been heavily pretreated for advanced disease were treated with lanreotide 30 mg i.m. fortnightly (depot formulation). Blood samples were periodically taken to evaluate the effect of the drug on growth hormone (GH) and insulin-like growth factor 1 (IGF-1) and to determine drug serum levels. Although the drug was well tolerated, no clinical activity was observed. Serum GH and IGF-1 levels were not properly suppressed over time and drug serum concentrations fluctuated widely. In conclusion, SMS analogues cannot be recommended even as palliative treatment of ABC. Further studies should be undertaken to investigate the effect of higher drug doses, given subcutaneously or by means of continuous infusion, in suppressing GH and IGF-1 serum levels.
Formestane, a new selective aromatase inhibitor devoid of severe side-effects, has been shown to be active in patients with advanced breast cancer. To investigate the clinical activity and endocrinological effects of formestane as a first-line treatment, 52 patients were administered two different doses: 24 received 250 mg formestane and 28 received 500 mg formestane i.m. fortnightly. All of the patients had a performance status of 2 or less (ECOG scale), 34 (65%) had a disease-free interval of at least 2 years and 21 (40%) were both oestrogen-receptor- and progesterone-receptor-positive; 20 patients received hormone and 13, received chemotherapeutical adjuvant treatment. Objective responses were obtained in 8 patients in the 250-mg group (33%; 95% CI: 14%-52%) and in 13 patients in the 500-mg group (46%; 95% CI: 28%-64%). The median response duration in the two groups was respectively 11 and 12 months. E2 serum levels of oestradiol had significantly (P < 0.001) decreased to more than 40% below the baseline value in both groups after 15 days of treatment, and remained unchanged thereafter. Local and systemic tolerability was satisfactory. We conclude that formestane is an effective and well-tolerated agent in previously untreated patients, and that these results should be confirmed by further studies.
In a consecutive series of 165 plantar naevi, a group of 36 benign naevi with sufficiently distinctive histopathological features to justify their classification as a special entity, here designated acral-lentiginous naevus, was identified. The main morphological features distinguishing the acral-lentiginous naevi from other acral non-lentiginous naevi are: elongation of rete ridges, continuous proliferation of melanocytes at the dermo-epidermal junction, presence of single scattered melanocytes, or less commonly small clusters, within the upper epidermis, poor or absent lateral circumscription, melanocytes with abundant pale cytoplasm and round to oval, sometimes hyperchromatic, nuclei and prominent nucleoli present at the dermo-epidermal junction. Some histological features of acral-lentiginous naevi are similar to those of dysplastic naevi: however, anastomosing rete ridges, cytological atypia and well-formed lamellar fibroplasia are absent. The histopathological criteria to distinguish these naevi from melanoma are: the lack of pagetoid lateral spread, the absence of mitotic activity in the deep dermal component and the evidence of dermal naevocytic differentiation. The identification of this benign acral naevus, that we have identified as the benign counterpart of acral lentiginous melanoma, is important in order to avoid misdiagnoses and consequent under- or over-treatment of doubtful pigmented lesions of acral skin.
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.
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The European Organization for Research and Treatment of Cancer genitourinary group has completed 2 parallel prospective randomized studies, one with 30 mg. mitomycin C and the other with 50 mg. doxorubicin as adjuvant intravesical treatment after transurethral resection of superficial transitional cell bladder carcinoma. These studies were designed to compare early (the day of resection) versus delayed (between 7 and 15 days after resection) instillations and short-term (6 months) versus long-term (12 months) treatment. The results indicate that in regard to recurrence rate patients having a delayed and short-term treatment do worse than those having early instillations (for 6 or 12 months) or those having prolonged treatment (either immediate or delayed). With an average followup of 4 years survival, progression beyond T1 disease, development of distant metastases and appearance of a second primary were not influenced by the therapeutic regimen. A multivariate analysis of prognostic factors is presented, which indicates that after adjustment for these factors, patients in the delay, no maintenance arm have a significantly higher recurrence rate than the other patients.
INTRODUCTION: The therapeutic potential of R75251, a ketoconazole derivative which has shown marked antitumor activity in animals and in men, was investigated in 16 patients with advanced prostatic cancer progressing after one or more lines of hormone therapy. PATIENTS AND METHODS: Patients were given the drug at 150 mg/b.i.d. for one month. After the first month of treatment, the dose was increased to 300 mg/b.i.d. In all patients, treatment was continued until disease progression or the development of sever toxicity. Clinical and biochemical assessments were performed on days 0, 14 and 28 and then repeated on a monthly basis. RESULTS: Of the 13 evaluable patients, 12 showed stable disease by strictly employing US-NPCP criteria. However, in 3 patients a clear effect was observed on the volume of their measurable lesions. In addition, 2 of them showed a more than 50% decrease of prostate-specific antigens (PSA). Overall, 50% of patients showed some decrease in PSA baseline levels. Overall tolerance to treatment was good. CONCLUSIONS: Our results, although achieved in a small number of patients, suggest that R75251 has a moderate but definite activity in patients with hormone-refractory prostate cancer and that the value of this drug as second-line treatment in these patients should be further investigated.
Changes in the steady state level of retinols, retinaldehydes and retinyl esters in the trans and 11-cis forms and trans retinoic acid were measured in whole chicken eye during development from day 6 in ovo to day 3 post-hatch. These retinoids, quantified by different HPLC systems, were detected in this time sequence: trans-retinol and trans-retinyl esters in the first week in ovo, 11-cis-retinol in the second week. The highest level of 11-cis-retinaldehyde and 11-cis-retinyl esters was reached at the end of development in ovo; however, their levels increased further after hatching. The retinoic acid level decreased at the end of the first week, rising again at the end of the second week. The enzyme activities involved in the metabolism of these retinoids-acyl-CoA: retinol acyltransferase, trans-retinol dehydrogenase, 11-cis-retinol dehydrogenase, trans-retinyl ester hydrolase and trans: 11-cis-retinol isomerase were also estimated and they were detectable already in the first week of development in ovo. At day 6 of the biosynthesis of retinoic acid by the retinaldehyde dehydrogenase activity from retina cytosol was also shown.
AIMS AND BACKGROUND: Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue that induces the suppression of gonadal steroidogenesis, and it could therefore be a medical alternative to irreversible surgical castration. We report the clinical and endocrine results from 40 goserelin-treated premenopausal patients with advanced breast cancer. METHODS: A depot formulation of the drug (3.6 mg s.c.) was administered fortnightly for the first 4 doses, and monthly thereafter. Gonadotrophins and estradiol (E2) levels were measured before and at specific times during the treatment. RESULTS: Objective responses were observed in 17 of the 38 evaluable patients (45%), six of whom achieved complete remission. The best responses were observed on soft tissues (65%). Castration E2 levels were achieved in all of the patients. CONCLUSIONS: Our results confirm that goserelin is as effective as surgical oophorectomy in premenopausal advanced breast cancer.
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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.