Selective lymph node dissection in patients with intermediate thickness melanoma: our experience.

The role of elective lymph node dissection (ELND) for the treatment of cutaneous melanoma has been debated for many years. Actually, the value of ELND is seriously questioned because an increasing of overall survival rates has not been demonstrated. The lymphatic mapping technique, initially performed by an intradermic injection of vital blue dye, subsequently improved by the use of radioguided surgery (RGS), proved effective for the detection of clinical occult lymph node metastasis. We performed a sentinel node biopsy on 71 patients with stage pT2/T3N0M0 melanoma. Vital blue dye mapping alone was performed on 39 patients; the remaining 32 patients had a combined lymphatic mapping with both blue dye and RGS. The sentinel node (SN) was complexively identified in 69/71 (97.2%) patients. Sixteen patients (23.2%) were found to have metastatic melanoma cells in their SN(s); all these patients underwent lymph node dissection of the affected basin. Our experience confirmed that the intraoperative detection of sentinel nodes using both blue dye and radio-guided surgery is an effective and reliable technique for selecting patients to be submitted to lymph node dissection.

Characterization of ligurian melanoma families and risk of occurrence of other neoplasia.

Germline mutations impairing the p16(INK4)-function have previously been demonstrated to be responsible for genetic predisposition in at least one half of melanoma-prone kindreds of North European origin. Familial melanoma kindreds have also been found to present an increased risk of pancreatic cancer and other cancers, but results relative to more common neoplasias incidence, in particular, are heterogeneous. We report here a clinical-epidemiological study, including the presence of additional neoplasias, in 14 apparently unrelated kindreds coming from a small geographic region of Northern Italy (Liguria), having therefore lived for generations in similar environmental conditions. We identified the common p16 missense mutation (Gly101Trp) reported in several previously studied kindreds, in 7 of 14 families, whereas the remaining 7 families had no detectable mutations in the coding region of p16 gene. Median age at diagnosis and other melanoma features were studied. When compared with the expected figures, based on regional incidence rates, a significant excess of pancreatic cancer, with 4 cases diagnosed, and of breast cancer, with 7 cases, was observed. The 7 families without apparent CDKN2A involvement were also negative for hot-spot exon 2 mutation of CDK4. Environmental factors do not appear to play a role in the excess of non-melanoma neoplasia in our families, as somewhat substantiated by the control group, composed of spouses and members of non-affected branches; they do not reveal any increased cancer incidence compared with the general population. Furthermore, given the proven significance of interaction between the melanoma susceptibility gene and the propensity to sunburns and other environmental risk factors, our results, obtained from a small but homogeneous sample, may have important implications for further risk assessment studies.

Intercellular adhesion molecule-1 (ICAM-1) and granulocyte-macrophage colony stimulating factor (GM-CSF) co-expression in cutaneous malignant melanoma lesions.

The expression of intercellular adhesion molecule-1 (ICAM-1) and granulocyte-macrophage colony stimulating factor (GM-CSF) was investigated in 25 melanoma patients by evaluating 34 fresh biopsy specimens. ICAM-1 in situ hybridization and immunochemistry for ICAM-1 and GM-CSF were performed. Most of the metastatic melanoma samples (12 out of 18) and a few of the primary melanoma lesions (three out of 16) showed ICAM-1 expression. The expression of ICAM-1 was significantly (P < 0.01) higher in metastatic lesions than in primary tumours. GM-CSF mRNA and protein were detected in 10 of the 18 metastatic samples and in two of the 15 primary lesions. A significantly high degree (P < 0.0002) of concordance between ICAM-1 and GM-CSF expression was observed: the samples that were negative or positive for ICAM-1 expression were correspondingly negative or positive for GM-CSF. Correlation with clinical and histological parameters was examined. The expression of both molecules in metastatic samples was found to be significantly (P < 0.001) associated with a shorter recurrence-free period. These findings, if confirmed by a wider number of patients, could suggest the prognostic value of the simultaneous, and probably co-ordinated, expression of ICAM-1 and GM-CSF. They also highlight the importance of preventive molecular and biochemical characterization of neoplastic cell cytokine receptors, specifically focusing on the particular cytokine to be used as anticancer therapy and/or as adjunct to chemotherapy.

Sentinel node biopsy in patients with cutaneous melanoma.

The role of elective lymph node dissection (ELND) for treatment of cutaneous melanoma is still debated. Initially, lymphatic mapping technique was performed by an intradermic injection of vital blue dye; subsequently, it was improved by the use of radioguided surgery (RGS). Preliminary experience with this technique proved effective for detection of clinical occult lymph node metastasis; it may also enable the surgeon to perform a selective lymph node dissection (SLND) to concentrate on pathologic node-positive patients for the same potential benefits that have been provided by ELND. We performed sentinel node biopsy on 48 patients with stage pT3N0M0 melanoma. Vital blue dye mapping only was carried out on 39 patients; the remaining nine patients had a combined lymphatic mapping with both blue dye and RGS. The sentinel lymph node (SLN) was identified in 46 of 48 patients (95.8%). Ten patients (20.8%) were found to have metastatic melanoma cells in their SLN(s); all these patients underwent SLND of the affected basin. Our findings confirm that the intraoperative lymphatic mapping of the SLN using both blue dye and radiodetection is an appropriate and simple technique for selecting patients who are more likely to benefit from lymph node dissection.

MEL-P, a GM-CSF-producing human melanoma cell line.

A human melanoma cell line, MEL-P, expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) and its specific receptor was newly established from a primary nodular lesion of a patient with a particularly unfavourable prognosis. Cytogenetic, immunophenotypic, cytokine and intercellular adhesion molecule (ICAM)-1 production analyses confirmed that this cell line was similar to the fresh melanoma cells from which it had been established. MEL-P constitutes a valuable model for the study of multistep tumour progression and the role of biologically active GM-CSF production in human malignant melanoma. Our results show a decreasing expression of HLA class I molecules during in vitro culture, when GM-CSF secretion attains the highest levels, and a constantly high production of ICAM-1. The inhibitory effect of GM-CSF antisense treatment on cellular growth might suggest the presence of an autocrine mechanism. On the whole, these data are consistent with the possible involvement of high GM-CSF production in the metastatic competence of melanoma cells through the autocrine mechanism of growth and/or the activation of other migration-related molecules by its local production in metastatic invasion.

[Reconstructive method for the repair of substantial loss of the head and neck area, following the excision of malignant melanoma]. / Metodiche ricostruttive per la riparazione di perdite di sostanza del distretto cervico-cefalico, conseguenti ad asportazione di melanomi maligni.

The general increase in the incidence of malignant melanoma has caused a more massive presence at the level of special sites such as the face, posing problems of the reconstruction from a cosmetic point of view. The widespread move away from large margins of exercise (3-5 cm) towards margins of approximately 1 cm surrounding the lesion, together with the improved prognosis for this pathology on the face compared to other sites, calls for greater attention to be paid to the reconstructive techniques used. Since surgery is the only solution "quoad vitam" for the patient, it is now preferable to attempt to offer the patient both a complete exeresis of the neoplasia and a satisfactory cosmetic result. In this study the authors report four cases involving the excision of malignant melanoma in the cervico-cephalic district and their consequent reconstruction using special surgical techniques.

Cytokine expression in human primary and metastatic melanoma cells: analysis in fresh bioptic specimens.

In recent years, several studies have documented that melanoma cell lines produce various cytokine/growth factors and their receptors. Since cell lines can acquire altered properties, such as changes in growth requirements, we studied constitutive cytokine gene expression in melanoma cells from 20 fresh surgical specimens: seven primary melanomas and 13 metastases (12 lymph-node metastases and one subcutaneous metastasis). After tumour cell isolation by discontinuous gradient, we tested for mRNA expression by means of reverse-transcriptase polymerase chain reaction. Most melanoma cells tested expressed growth factors: basic fibroblast growth factor (bFGF), interleukin (IL)1 alpha, IL-1 beta, IL-6 and IL-8 and, in five cases out of 20, expressed granulocyte-macrophage colony-stimulating factor (GM-CSF) (two out of five were also positive for GM-CSF receptor). Our results do not point to a direct correlation between cytokine expression and clinical stage at the time when the bioptic specimen was obtained. However, they allow us to suggest a possible metastatic tumour cell phenotype, in which autogenous GM-CSF expression could modulate immune response against the tumour cell itself or could potentiate metastatic colonization properties.

[Isolated hyperthermic antiblastic perfusion in recurrent melanoma of the extremities]. / La perfusione isolata ipertermico-antiblastica nel melanoma recidivo degli arti.

Twenty-two patients with recurrent melanoma of the limbs, underwent Hyperthermic Antiblastic Perfusion (HAP). HAP lasted 60 min, with maximal local temperature of 40.5-42 degrees C and melphalan 10 mg/L limb volume as antiblastic agent. Fourteen patients had in-transit metastases and 8 local recurrences. Regional nodes were involved in 6 patients. Systemic leakage monitored with 125I or 99Tc ranged between 5 and 30% (mean 19%). No operative mortality nor major complications occurred. Local toxicity scored Wieberdink grade I in 6 patients, grade II in 11 and III in 5. Response rate (UICC) in the 9 patients treated with unexcised lesions was 88% (55% complete responses). After a median follow-up of 27 months (1-92) 9 patients relapsed after a median time of 17 months, and 15 patients are currently disease free, 4 of them being re-excised and one reperfused. Actuarial 5 year survival is 67%, with 45% disease free to the first relapse. Our results are consistent with the literature indicating HAP as a safe procedure with a high evidence of clinical responses.

Radiotherapy and hyperthermia in the treatment of primary Merkel cell carcinoma of the skin: a case report.

We report a case of a large Merkel cell skin tumor (left cheek) in an 83 year-old woman treated by a combination of radiotherapy and hyperthermia. A complete response to the treatment was observed and without side effects. The patient has now been followed for 12 months without signs of recurrence, nodal disease, or distant metastasis.

In vitro antimicrobial effects of fresh split skin, homologous-cultured epithelium and porcine split skin grafts for wound coverage.

Various biological dressings, for example, human fresh and cadaver skin grafts, homologous cultured human epithelium and deep frozen porcine split skin (Lyocutis), have been used to treat skin loss. Each of these biological dressings has its advantages and disadvantages. The antimicrobial properties of each dressing type are important since bactericidal activity influences the lifespan of the transplanted tissue. In the present study the in vitro antimicrobial effects of human fresh skin, homologous cultured epithelium and Lyocutis were compared to in vivo bactericidal activity of these dressings and possible clinical applications are recommended.

Unilateral reduction mammaplasty: sculpturing the breast from the undersurface.

Various traditional mammaplasty techniques have been suggested for unilateral breast reduction, and an inverted-T incision is still the most popular approach. However, unilaterally performed traditional techniques can rarely provide long-lasting symmetry because the operated and the unoperated breasts react differently to aging, weight changes, and pregnancy. Considerable residual scarring, interference with clinical and mammographic evaluation, and limited versatility are all major drawbacks of traditional procedures. We have performed unilateral mammaplasties on 47 patients with various types of congenital and acquired asymmetries, reducing and sculpturing the breast from the undersurface by means of minimal incisions, always avoiding horizontal scarring in the inframammary crease. Through a vertical infra-areolar incision, the breast is completely detached from the underlying pectoralis fascia and hooked up, thus completely exposing the undersurface of the mammary cone. The breast can thereafter be reshaped according to the size and shape of the contralateral breast by means of a discoid resection and/or selective sectoral removal of excessive subcutaneous tissues; modifications of the basic discoid resection can increase anterior projection of the new breast mound and can change the inclination of the anteroposterior breast axis on the anterior chest wall both on the horizontal and vertical planes. The results show that if criteria for patient selection are carefully respected, the procedure can provide long-lasting symmetry with minimal residual scarring and fully preserve the breast anatomy, function, and vascularization.

Immediate reconstruction of the penis using an inferiorly based rectus abdominis myocutaneous flap.

A new method for reconstruction of the penis using an inferiorly based rectus abdominis myocutaneous flap is described that seems to be particularly suitable for immediate one-stage reconstruction. Function of the residual portion of rectus muscle is preserved, and the abdominal wall is not significantly weakened.

Transposition of myocutaneous flaps in breast reconstruction following radical mastectomy: latissimus dorsi vs. rectus abdominis flap.

We evaluated two homogeneous groups of patients (20 each) who had undergone radical mastectomy and who underwent breast reconstruction in our department by transposition of a latissimus dorsi or of a rectus abdominis myocutaneous flap. The results achieved were very similar (in terms of postoperative hospitalization, complication rate, thoracic symmetry). We therefore believe that both these techniques should be considered as first choice in breast reconstruction following radical mastectomy. However, from the aesthetic viewpoint, the use of the latissimus dorsi is best suited to tall, slim patients, whereas the rectus abdominis allows us to obtain better results in patients of sturdy build, with a voluminous residual breast.

Present day role of plastic surgery in management of chronic radiation wounds: our experience.

Traditional procedures to resurface soft tissues defects following excision of chronic radiation wounds involve the use of skin grafts or skin flaps. However, the poor vascularity of the recipient bed is the reason for the high failure rate of skin grafts. Local skin flaps will often fail because of radiation injury to tissues within the flap itself. Distant skin flaps allow repair with healthy tissues, but these complicated multistaged procedures require prolonged hospitalization. The main advantage of myocutaneous flaps is the possibility of resurfacing large wounds in one step only, with tissues transposed from areas far from the radiation field. The Authors' experience using myocutaneous flaps of latissimus dorsi, pectoralis major, rectus abdominis and tensor fascia lata and the results obtained so are discussed.

Long-lasting complications with the use of polyurethane-covered breast implants.

Polyurethane-covered breast implants have been recommended by some authors for aesthetic and reconstructive procedures, since with these implants the incidence of capsular contracture is insignificant and risks of implant displacement or exposure are reduced. Reports on the use of these implants focus merely on aesthetic aspects, and risks associated with disintegration and incorporation of the polyurethane-coating are often overlooked. The authors have observed several complications associated with the use of these prostheses; two cases of long-lasting complication are described, which are ascribed to difficult removal of infected fragments of the coat and to delayed foreign body reaction to polyurethane. The authors believe that the hazards associated with these implants outweigh their advantages for primary use, but suggest their use for secondary procedures in patients who have had recurrent problems with smooth implants.

Anterior transposition of the latissimus dorsi muscle through minimal incisions.

Latissimus dorsi transposition is a useful procedure for the correction of various congenital and acquired thoracic deformities. The authors describe a surgical technique which allows anterior transposition of the whole muscle through minimal incisions. The technique has been used in 33 patients with post-mastectomy or post-subcutaneous mastectomy deformities, Poland's syndrome, deep radionecrosis, quadrantectomy, or breast underdevelopment following burns. The technique has proven safe and reliable, although the control of bleeding is difficult. Results are evaluated and compared with those obtained using traditional techniques; the absence of any significant posterior deformity is pointed out. The authors also suggest the use of this technique for breast reconstruction in patients presenting skin deficiencies: a tissue expander placed under the muscular flap makes it possible to avoid the transposition of a skin island.