Demographic, behavioural and physician-related determinants of early melanoma detection in a low-incidence population.

BACKGROUND: Knowledge of the factors that influence early detection of melanoma is important in developing strategies to reduce associated mortality. OBJECTIVES: To identify sociodemographic, behavioural and medical care-related factors associated with melanoma thickness in a low-incidence population but with a high case fatality. PATIENTS AND METHODS: In a multicentre, retrospective, survey-based study of 202 patients with a recent diagnosis of invasive melanoma (< 1 year), we collected data on demographic and behavioural factors, attitudes towards prevention, access to medical care, frequency of skin self-examination (SSE) and physician skin examination (PSE) in relation to melanoma thickness. RESULTS: Thinner tumours (≤ 1 mm, 80 melanomas) were associated with female sex (P ≤ 0.049), nonnodular (superficial spreading melanoma, lentigo maligna melanoma, acral lentiginous melanoma) histological subtypes (P < 0.001), absence of ulceration (P ≤ 0.001), and location other than lower extremity or trunk location (P ≤ 0.004). Patients married at the time of diagnosis or who performed SSE during the year prior to diagnosis were more likely to have thinner tumours than those who did not [odds ratio (OR) 3.45, 95% confidence interval (CI) 1.48-8.04 and OR 2.43, 95% CI 1.10-5.34, respectively]. Full-body skin examination by a physician was not significantly associated with thinner melanoma (OR 1.99, 95% CI 0.66-6.07). CONCLUSIONS: SSE was shown to be an important factor in the detection of thin melanoma, in contrast to partial or full-body PSE, which did not show any statistically significant effect on tumour thickness.

Glottic and supraglottic laryngeal cancer: epidemiology, treatment patterns and survival in 164 patients.

PURPOSE: To evaluate the effectiveness of different therapeutic managements in relation to clinical disease stage, the location of the lesion and to register the rate of disease recurrence of patients with glottic and supraglottic laryngeal cancer, and to also study some specific epidemiologic characteristics. METHODS: A series of 164 patients with laryngeal glottic and supraglottic squamous cell cancer (SCC) treated surgically, with radiation therapy (RT), chemotherapy or combination of these was analysed. After treatment, all patients were followed up for an average of 58 months. All data concerning the primary lesion, therapeutic management, recurrence, staging, 5-year overall survival and epidemiological characteristics such as smoking and alcohol abuse were recorded and analysed in combination with the follow up data. RESULTS: The therapeutic approach most commonly used was RT for stage I tumors and surgery for stages II, III and IV. Stage I and II patients treated with RT had high recurrence rate (60%). Patients with recurrence had 45.3% 5-year overall survival rate and average survival time 80 months, whereas patients with no recurrence had 77.4% 5-year overall survival rate and average survival time 173 months (p=0.0001). There was significant difference in survival between stage I and III (p=0.035), stage I and IV (p=0.0038) and stage II and IV (0.0156). The average overall survival time for non smokers was 195 months (median 1707rpar;, while for smokers it was 99 months (median 100; p=0.0047). The average overall survival time for alcohol abusers was 79 months (median 54), while for those who did not use alcohol it was 153 months (median 150; p=0.016). CONCLUSION: The 5-year overall survival rate was 61.3%. RT alone in stages I and II proved inferior in decreasing re-currences compared with surgery. Smokers had significantly shorter overall survival.

[Eyelid melanoma: our experience a propos of 23 cases]. / Le mélanome palpébral : notre expérience à propos de 23 cas.

INTRODUCTION: Eyelid melanoma is a rare condition corresponding to less than 1% of all eyelid malignancy. The aim of the current study is to present the experience of our department. PATIENTS AND METHODS: From 1986 to 2009, 972 patients with a melanoma have been studied retrospectively. Each patient was evaluated in relation with age, sex, location of the tumor, histology (Breslow and Clark included), surgical treatment, recurrence, and finally with follow up. RESULTS: Twenty-three patients with eyelid melanoma and a strong female incidence (69.5%) were identified. Median age was 68.3 years. In most cases (71.4%), tumor was located on the right inferior eyelid in continuity with the malar region. LMM had the higher incidence (60.8%), followed by the nodular melanoma (21, 7%) and the SSM. The median Breslow was 0.77 while the median Clark 1.68. Surgery was the treatment of choice including direct closure, the use of full thickness skin graft and local or regional flaps. Three patients had local recurrence associated to nodular metastases in one of them. CONCLUSION: Surgical treatment of eyelid melanoma is a challenge for every reconstructive surgeon. Early detection remains the "gold standard" for every reconstructive option respecting the esthetic and function of this precious anatomic location.

Improvement of skin-graft survival after autologous transplantation of adipose-derived stem cells in rats.

BACKGROUND: Skin grafts are frequently used for a variety of indications in plastic and reconstructive surgery. Their necrosis is a common complication, while different therapies have been proposed. Currently, adipose-derived stem cells (ASCs) hold great promise for their angiogenic potential and role during tissue repair. In this study, autologous transplantation of ASCs was used in skin grafts in rats to determine if it increases angiogenesis, skin-graft survival and wound healing. METHODS: ASCs were isolated, cultured, labelled with fluorescent dye and injected under full-thickness skin grafts in 10 rats (group 1), while 10 others served as controls (group 2). Skin grafts were analysed after 1 week. Collagen's framework was assessed with Masson's trichrome stain and angiogenesis with von Willebrand factor (vWF) immunohistochemistry. In addition, immunohistochemical staining intensity of vascular endothelial growth factor (VEGF) and transforming growth factor b3 (TGFb3) was assessed in all grafts. RESULTS: Mean area of graft necrosis was significantly less in group 1 than in group 2 (6.12% vs. 32.62%, p<0.01). Statistically significant increase of microvessel density, collagen density, VEGF and TGFb3 expression was noted in group 1 compared with group 2 (all: p<0.01). CONCLUSIONS: These findings suggest that autologous ASCs transplantation increases full-thickness skin-graft survival and shows promise for use in skin-graft surgery. This might be both due to in situ differentiation of ASCs into endothelial cells and increased secretion by ASCs of growth factors, such as VEGF and TGFb3 that enhance angiogenesis and wound healing.

Disclosing the truth to terminal cancer patients: a discussion of ethical and cultural issues.

One of the most difficult ethical dilemmas facing health care professionals working in oncology is whether, when, how and how much to tell terminal cancer patients about their diagnosis and prognosis. The aim of this article is to review the trends in this issue worldwide. While a majority of physicians in both developed and developing countries tell the truth more often today than in the past, the assumption that truth-telling is always beneficial to patients can be questioned. The issue of truth-telling is still approached differently in different countries and cultures and there is a need for an increased awareness of cultural differences to truth-telling among patients from ethnic minorities.

Giant tumour of the heel: acquired fibrokeratoma.

Fibrokeratoma is a rare benign invasive tumour usually located on the digits. We report a 35-year-old patient with a giant acquired fibrokeratoma of the heel. Despite its large size and unusual location, the tumour was microscopically benign and was successfully excised.

Reconstruction of the chest wall.

Chest wall reconstructions can be a complex and challenging procedure and may require a multidisciplinary approach. The most common indications for chest wall reconstruction are repair of defects due to tumor resection, infection, radiation necrosis, congenital deformities or trauma. The repair of complex chest wall defects presents a challenging problem for the reconstructive surgeon. Although the majority of such defects can be repaired with the use of local and regional musculocutaneous flaps, more complicated cases require increasingly sophisticated reconstructive techniques. As defects increase in size, microsurgical techniques are necessary to augment blood flow to pedicled flaps or to provide free flap coverage from distant sites. A better understanding of the respiratory mechanics and local anatomy is crucial in managing these complex defects.

One-stage reconstruction of the antihelix and concha using postauricular island flap.

Tissue defects in the antihelix and the concha due to oncological resection and trauma can be successfully repaired with a subcutaneously based postauricular island flap. Alternative methods of regional reconstruction usually need two stages or may require grafts in some patients. We present the one-stage technique, as described by Masson, without grafts, to provide adequate reconstruction and aesthetic restoration of the area, illustrated by 62 patients. In all patients there has been a follow-up period of 12 months. This report provides evidence for the aesthetic superiority of this method. An excellent aesthetic outcome was achieved in 46 patients, an adequate outcome in 15 patients, and a poor result in only 1 patient. No flap necrosis was observed. The method has considerable advantages for the repair of anterior conchal and antihelical defects.

Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the penis.

BACKGROUND: Cyclin D1 plays an important role in regulating the progression of cells through the G1-phase of the cell cycle. The aim of the study was to investigate the expression of cyclin D1 and Ki-67 in squamous cell carcinomas (SCC) and in some premalignant lesions of the penis and to correlate it with clinicopathological parameters and patient survival. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissues from 21 SCC, 7 lichen sclerosus, 5 condyloma acuminatum and 2 erythoplasia of Queyrat were stained by immunohistochemistry for cyclin D1 and Ki-67. RESULTS: Cyclin D1-positive nuclear staining was overexpressed in 13/21 SCC (61.9%) and in one case of erythoplasia of Queyrat. Strong reactivity for Ki-67 was found in 16 (76.2%) SCC, in 3 condyloma acuminatum and in one case of erythoplasia of Queyrat. A tendency for an association between cyclin D1 expression and tumour differentiation (p = 0.07) but not the level of tumour invasion (p = 0.50) was found. The Ki-67 expression was notably increased with the advance of tumour grade, but the difference did not reach a statistically significant level (p = 0.46). A slight tendency towards a relationship between Ki-67 and cyclin D1 protein expression was observed (p = 0.32). Two patients relapsed and one died from the disease over a median follow-up period of 4.6 years (range 0.1-10.3 years). CONCLUSION: Ki-67 antibody and cyclin D1 overexpression seem to parallel each other, supporting the concept that cyclin D1 serves as a cell cycle activator. Cyclin D1 overexpression may be used as a prognostic factor of poor outcome in penile carcinoma.

The role of ThinPrep cytology in the investigation of SLN status in patients with cutaneous melanoma.

INTRODUCTION: The sentinel lymph node (SLN) biopsy in melanoma assesses reliably the status of the regional lymph node basins, provides valuable prognostic information, facilitates early therapeutic lymphadenectomy and identifies patients who are candidates for different adjuvant treatments. The current study was designed to evaluate the feasibility of cytological specimens being placed in PreservCyt as a practical collection methodology for performing evaluation of the SLN status in patients with melanomas. PATIENTS AND METHODS: From January 2004 to December 2006, 70 patients with histologically confirmed cutaneous melanoma underwent intraoperative FNA biopsy of the SLN. After identification of the SLN(s), FNA biopsy of the SLN was performed with a 0.6 mm (23 gauge) diameter needle. All the SLNs specimens were examined (using light microscopy 40 x and 200 x) by the same pathologist and cytopathologist, neither of had any knowledge of the medical history of the patient. The histological result of the excised SLN was considered as the final diagnosis. RESULTS: The unsatisfactory rate for TP cytology was 2.17%. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy (OA) for the TP technique were 92.31%, 100%, 100%, 97.06%, and 97.83%, respectively. Using TP cytology, there was greater intensity and distribution of the staining in comparison with immunohistochemistry. DISCUSSION: The accuracy of TP technique in the evaluation of the SLN status is comparable to those of the histological evaluation, and could be of paramount importance for the preoperative planning of treatment.

Island vertical trapezius myocutaneous flap procedure under the tumescent technique.

We describe the application of local anesthesia with intravenous sedation for covering a large defect of the upper back with the use of the island vertical trapezius myocutaneous flap to an 85-year-old male. According to the anesthesiologist, the patient was graded as ASA IV. A 200-ml solution which consisted of 0.75 mg xylocaine, 2 mg adrenaline (1/2,000,000) and 10 mmol/l sodium bicarbonate in a physiologic saline solution was used. The total operating time was about 90 min. During the first postoperative 24 h, the flap pedicle was checked every hour by Doppler. The postoperative course of the patient was uneventful. We believe that in selected cases, when microsurgery is not indicated due to the general medical condition of the patient, the combination of the tumescent technique with sedation and the vertical trapezius myocutaneous flap can be considered a reliable and low-risk procedure.

p53 codon 72 Pro homozygosity increases the risk of cutaneous melanoma in individuals with dark skin complexion and among noncarriers of melanocortin 1 receptor red hair variants.

BACKGROUND: p53 has a common polymorphism at amino acid 72, encoding either arginine or proline. p53Arg and p53Pro exhibit differences in various biological activities, such as cell-cycle arrest and induction of apoptosis. Numerous epidemiological studies have examined the role of this polymorphism in several human malignancies, including cutaneous cancers, with contradictory results. OBJECTIVES: To investigate the germline frequency of p53 codon 72 polymorphism in malignant melanoma in a Mediterranean population, and to examine possible associations with various clinicopathological factors. METHODS: In this hospital-based case-control study we used allele-specific polymerase chain reaction for p53 codon 72 genotyping in blood specimens from 107 Greek patients with sporadic cutaneous melanoma and 145 healthy controls. RESULTS: After adjustment for age, sex and phototype the Pro/Pro genotype was associated with increased risk for cutaneous melanoma compared with the Arg/Arg genotype (adjusted odds ratio, OR 3.17, 95% confidence interval, CI 1.03-9.78). This correlation was more pronounced in subjects with phototypes III or IV (adjusted OR 9.56, 95% CI 1.56-58.46), dark skin (adjusted OR 10.96, 95% CI 1.64-73.28), dark eyes (adjusted OR 8.86, 95% CI 1.69-46.52) and dark hair (adjusted OR 3.17, 95% CI 1.01-9.95), and among noncarriers of melanocortin 1 receptor gene (MC1R) red hair polymorphisms (adjusted OR 2.99, 95% CI 1.02-8.78). CONCLUSIONS: p53 codon 72 Pro/Pro genotype could be a risk factor for the development of melanoma in the Greek population, especially in subgroups with darker skin pigmentation, as well as among noncarriers of the MC1R red hair polymorphic variants.

Lip defects due to tumor excision: apropos of 899 cases.

Reconstructive surgery of the lips after resection of tumors requires a complete understanding of the anatomy of this region. Most lip cancers remain localized and grow slowly, with a propensity for superficial rather than vertical spread. From January 1983 to December of 2005, 899 patients underwent reconstructive surgery for skin tumors involving the lips. SCCs were the most frequent skin tumors on male patients whereas BCCs were most common on the female patients. The lower lip was the anatomic zone most frequently involved in our series. Preoperative evaluation of the patients was performed in all cases. In the last five-years, we have performed preoperative fine needle aspiration (FNA) biopsy of the tumor. The FNA sample was then examined by ThinPrep technique (Cytolyt; Cytyc, Co, Boxborough, MA, USA). In our series, from the 550 patients who had a five-year follow-up we observed 62 recurrences of the primary tumor. The five-year recurrence rate was 11.28%. The aim of this retrospective study is to report our experience in the treatment of lips tumors with selective combination of treatment modalities.

Temozolomide in combination with celecoxib in patients with advanced melanoma. A phase II study of the Hellenic Cooperative Oncology Group.

BACKGROUND: There is now increasing evidence that a constitutive expression of cyclooxygenase (COX)-2 plays a role in the development and progression of malignant epithelial tumors. Expression of COX-2 is seen in 93% of melanomas, as determined by immunohistochemistry. Temozolomide (TMZ) has demonstrated activity against melanoma and has been investigated as single agent or in combination. We designed a phase II study to assess the efficacy and toxicity of the combination of TMZ and celecoxib (a COX-2 inhibitor) in patients with advanced melanoma. PATIENTS AND METHODS: From January 2003 to July 2004, 52 patients were enrolled in the study. Nineteen patients were M1a, six M1b and 27 M1c. Patients received TMZ 200 mg/m(2) per day p.o. for 5 consecutive days every 4 weeks and celecoxib 400 mg b.i.d. p.o. for a maximum of six cycles. Celecoxib was continued until progression. RESULTS: The median age was 63 years. There were 29 males and 23 females. Among 50 assessable patients, there were 11 (21.5%) objective responses including five complete responses and six partial responses. Twenty patients (38.5%) had stabilization of their disease, and 19 (36.5%) progressed. The median time to progression was 4.6 months and the median survival 9.5 months. Twenty-two patients (41.5%) completed all cycles of treatment. Median relative dose intensity of TMZ was 0.99 (range 0.6-1.2). Most commonly seen toxic effects included anemia (27.5%), neutropenia (17.5%), thrombocytopenia (33%), nausea/vomiting (75%), gastrointestinal (52%) and fatigue (46.5%). One patient discontinued due to severe toxicity. COX-2 was determined by immunohistochemistry and was expressed in all cases. CONCLUSION: The combination of TMZ and celecoxib is safe and potentially effective in the treatment of metastatic melanoma. Randomized studies are needed to explore the role of celecoxib in combination with chemotherapy or as maintenance treatment in these patients.

Genetic variability of encephalomyocarditis virus (EMCV) isolates.

In order to evaluate the variability of encephalomyocarditis virus (EMCV), field isolates originating from different European regions and inducing different clinical pictures in pigs have been molecularly characterised. The regions targeted were the poly(C) tract, a part of the 5'-UTR (360 nucleotides), the Leader gene (201 nucleotides), the complete capsid coding region (2502 nucleotides), the 2A gene (403 nucleotides), the end of the 3D polymerase gene (305 nucleotides) and the 3'-UTR (123 nucleotides). Analyses have also been performed on a virulent field isolate, which had been subjected to serial passages in vivo and in vitro resulting, in the case of the in vitro passaged virus, in attenuation, as demonstrated by animal experiments. The present study shows that different clinical pictures, such as acute fatal myocarditis or reproductive failure, may not only be caused by EMCV isolates which are genetically diverse but also by the same isolate. Thus no correlation could be demonstrated between genotype and clinical disease. However, the European isolate which showed the highest genetic divergence also gave rise to a more complex clinical picture. Despite EMCV having been isolated from cases of acute fatal myocarditis in pigs in certain areas of the world for many years, clinical disease, including a variety of clinical pictures and pathogenicity, has only been recognised in Europe since 1986 and thus it can be considered an emerging disease in this region. These findings, associated with the reported phenotype changes of the virus under environmental changes (passages), along with its wide distribution among vertebrate species (including higher primates), shows the validity of considering EMCV as a potential pathogen for recipients in xenotransplantation.

The role of ThinPrep cytology in the evaluation of estrogen and progesterone receptor content of breast tumors.

INTRODUCTION: The objective of the current study was to analyze the potential value of immunocytochemical analysis on ThinPrep (TP)-processed smears, from fine needle aspiration (FNA) biopsies, of breast tumors for the determination of ER and PR content as compared with the immunohistochemical analysis performed on paraffin-embedded breast tumor specimens. PATIENTS AND METHODS: Percutaneous FNA biopsy of focal breast lesions in 119 female adult patients during a 31-month period was performed. Subsequently, these patients underwent surgical resection of the tumors. ER and PR status of the tumors was determined by immunocytochemical analysis on TP-processed smears and by immunohistochemical studies in paraffin-embedded sections. RESULTS: With the use of TP technique adequate material was observed in all cases. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy (OA) of the TP technique for the ER were 98.95%, 100%, 100%, 95.84% and 99.15% respectively. In addition, sensitivity, specificity, PPV, NPV and OA of the TP technique for the PR were 100%, 87.5%, 95.60%, 100% and 96.64%, respectively. CONCLUSIONS: ER and PR status can be evaluated in FNA material from breast carcinomas by using the TP technique. Sample collection and storage is simple and permits the assortment of the FNA sample for both morphologic diagnosis and ancillary studies. The accuracy of TP technique in the detection of ER and PR content is comparable to those of the histological evaluation, and could be of paramount importance for the preoperative planning of treatment.

Immunophenotypic analysis of the p53 gene in non-melanoma skin cancer and correlation with apoptosis and cell proliferation.

BACKGROUND: Sunlight precipitates a series of genetic events that lead to the development of skin cancers such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The p53 tumour suppressor gene, which plays a pivotal role in cell division and apoptosis, is frequently found mutated in sunlight-induced skin tumours. OBJECTIVE: To investigate the immunoreactivity of the p53 gene in non-melanoma skin cancers and to correlate its expression with apoptotic and cell proliferation markers. METHODS: We analysed 35 non-melanoma tumours including 19 BCCs and 16 SCCs from sun-exposed skin areas. p53 protein expression was studied immunohistochemically using the DO7 monoclonal antibody against wild-type and mutant p53 forms. The percentage of p53-immunopositive nuclei was measured by image analysis. Cell proliferation and apoptosis were also assessed by image analysis following Ki-67 immunostaining and application of the TUNEL method on paraffin sections, respectively. RESULTS: The percentage of p53-expressing cells varied from 3.5 to 90 in BCCs (median value 54.4%) and from 3.7 to 94 in SCCs (median value 40.3%). The mean value of Ki-67-positive cells was comparable in both groups of tumours with a mean value of 40.6% in BCCs and 34.6% in SCCs. Conversely, the TUNEL assay showed sporadic staining of apoptotic cells within the tumours with a mean value of 1.12% in BCCs and 1.8% in SCCs. p53 protein expression was correlated positively with cell proliferation (r = 0.75, P = 0.000001) and negatively with apoptosis (r = -0.23, P = 0.05). CONCLUSION: p53 immunoreactivity was high in the majority of the skin carcinomas examined and correlated positively with cell proliferation and negatively with apoptosis. The p53 protein overexpression appears to be related to an inactivated protein resulting from mutations of the p53 gene or other unclear molecular mechanisms.

Reconstructive surgery for kidney transplant recipients.

Many decades have passed since the first kidney transplantation, which is now the most common organ transplant performed worldwide. Despite the impressive advances, some patients may develop posttransplant complications that require proper management and treatment. The plastic and reconstructive surgeon, among others, may be called on to help resolve a number of reconstructive problems present in the immunosuppressed kidney recipients. This study presents our experience with 41 kidney recipients who needed plastic surgical treatment. Patients were placed into one of three study groups according to the type of posttransplant surgical condition. Group 1 included 17 patients with posttraumatic wound healing problems; group 2, 17 patients with skin tumors; and group 3, 7 patients with other posttransplant surgical complications. Only two of these patients had early posttransplant wound dehiscence; the remaining patients suffered late complications. In conclusion, the kidney recipient can successfully undergo minor or major reconstructive procedures. The possibility of surgical problems arising during the early posttransplant period presents increased complication rates, possibly due to high immunosuppressive drug levels.