人增生性瘢痕中整合素连接激酶表达及与血管生成的关系

目的 探讨不同生长期人类瘢痕中整合素连接激酶(ILK)表达及与血管生成的关系.方法 (1)将笔者单位2009年12月-2010年12月收治的15例烧伤瘢痕患者按瘢痕生长时间分为:小于6个月组、6～12个月组、大于12个月组,每组5例.采集各组瘢痕组织,用免疫组织化学法观察ILK的表达分布,实时荧光定量RT-PCR法检测ILK mRNA的表达水平.(2)取小于6个月组瘢痕组织,分离培养瘢痕微血管内皮细胞(MEC),免疫磁珠法纯化后用花青类荧光染料Cy3标记的凝血因子Ⅷ进行鉴定,以人皮肤Fb为对照.取对数生长期MEC,按随机数字表法分为3组:对照组,仅用含微血管生长添加剂的M131培养液培养;空质粒组,用空载质粒转染;ILK互补DNA转染组,用ILK互补DNA表达质粒转染.转染24h后,实时荧光定量RT-PCR法检测各组细胞中ILK、激酶功能区受体(KD R)、fms样酪氨酸激酶1(Flt1)的mRNA表达情况.对数据进行单因素方差分析. 结果 (1)小于6个月组瘢痕组织表皮基底细胞、MEC及Fb胞质中均有ILK阳性表达,6～12个月组瘢痕组织中仅表皮基底细胞可见ILK阳性表达,大于12个月组瘢痕组织中ILK阳性表达不明显.(2)小于6个月组瘢痕组织中ILK mRNA表达水平(0.34±0.16)明显高于6～12个月组(0.17±0.06)及大于12个月组(0.07±0.13),F=37.007,P - 0.000.(3)纯化后MEC呈铺路石样密集生长,胞质中凝血因子Ⅷ呈阳性表达;人皮肤Fb中未见凝血因子Ⅷ表达.(4)ILK互补DNA转染组瘢痕MEC中ILK、KDR及Flt-1的mRNA表达水平分别为57.807±5.556、0.836±0.014、0.162±0.005,均显著高于对照组的0.018±0.003、0.028±0.020、0.023±0.004和空质粒组的0.042±0.005、0.039±0.0070.046±0.003(F值分别为87.110、11.241、18.199,P值均小于0.01).结论 ILK主要表达于小于6个月的早期瘢痕组织中,并可以通过调节瘢痕MEC中的KDR及Flt-1 mRNA表达来影响早期瘢痕的血管生成,在早期瘢痕增生过程中具有重要作用.     

Natural history of cutaneous malignant melanoma

The rising incidence of cutaneous malignant melanoma with the consequent increase in mortality from melanoma has intensified efforts to understand the factors that initiate the malignant transformation of melanocytes and to define those tumor-host interactions that play a relevant role in the clinical course of this disease. Increased exposure to solar radiation has been proposed as an explanation for the rising incidence of melanoma observed in light-skinned races. Because of the low incidence of melanoma in darkly pigmented races and its tendency in these individuals to develop in relatively nonpigmented areas, such as the sole of the foot, it is postulated that melanin, in addition to its well-known photoprotective effects, may protect against certain intrinsic carcinogenic agents. Developing cutaneous malignant melanomas progress through several cell types that have varying potentials for invasion and metastasis. This developmental process can be appreciated by examination of the various histologic types of melanomas. Early superficial spreading melanoma and lentigo maligna melanoma are characterized by cells that exhibit a prolonged intraepidermal growth phase, and most of these lesions can be diagnosed while they are still curable by simple surgical therapy. Subpopulations of more aggressive cells eventually develop, however. These cells also may characterize the initial stages of nodular melanoma in which the intraepidermal growth phase is absent and early invasion is common. Prognosis for survival depends on the depth of invasion of the primary tumor. Microstaging of the depth of invasion together with information as to mitotic index, sex, site, age, and histologic type will usually predict the natural history of the disease. With present-day management, the overall long-term, disease-free survival rate of patients with cutaneous melanoma is 60–70% and compares favorably with that of the more common cancers.

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Résumé La fréquence croissante des mélanomes malins et l'augmentation de la mortalité ont stimulé les recherches qui étudient les facteurs de transformation maligne des mélanocytes et les interactions hôtetumeur qui jouent un rôle important dans l'évolution de cette maladie. On a suggéré que l'exposition aux rayons solaires expliquait l'augmentation de fréquence du mélanome dans les races à peau claire. Comme le mélanome est rare dans les races à peau foncée et qu'il apparait, chez ces individus, de préférence dans les zones non pigmentées, telles que la plante du pied, on pense que la mélanine, outre ses effets photoprotecteurs, pourrait également protéger contre certains agents carcinogènes intrinsèques. Au cours de leur développement, les mélanomes malins cutanés passent par divers types cellulaires dont les potentialités invasives et métastatiques varient. Ce mode de développement peut être démontré par l'étude des divers types histologiques de mélanomes. Le mélanome à extension superficielle au stade précoce et le mélanome malin à aspect de lentigine sont caractérisés par des cellules qui ont une longue phase de croissance intra-épidermique: la plupart de ces lésions peuvent être diagnostiquées à un stade où elles sont encore curables par la seule chirurgie. Plus tard peuvent se développer des sous-populations de cellules plus agressives. Ces cellules peuvent être également caractéristiques des stades initiaux du mélanome nodulaire, pour lequel la phase de croissance intra-épidermique est absente et l'invasion souvent précoce. Le pronostic dépend de la profondeur de l'envahissement par la tumeur primitive. L'histoire naturelle de la maladie peut en général être prédite par la définition microscopique du degré d'envahissement et de l'index mitotique, ainsi que par le sexe, l'âge et la localisation. Avec les possibilités thérapeutiques actuelles, la survie à long terme sans récidive est de 60–70%; elle est donc comparable à celle d'autres cancers plus fréquents.

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Supported by Grant No. CA-17954 of the National Cancer Institute, the Pericles P. Stathas Memorial Fund, and the Carol Thomas Brigham Memorial Fund.     

Neck dissection for cutaneous malignant melanoma

This retrospective study examines the experience of the Sydney Melanoma Unit in the management of cervical lymph nodes among patients with cutaneous melanoma of the head and neck. From 1960 to 1990, 397 patients had neck dissections for cutaneous malignant melanoma of the head and neck. This number represents 40% of all patients treated for head and neck melanoma at the Sydney Melanoma Unit during this period. Neck dissections were therapeutic in 152 patients, elective in 234 patients and for an unknown indication in 11 patients. Lymph nodes were histologically positive in 39% of operations overall and in 7% of elective neck dissections. The incidence of recurrence in the neck after dissection was 24% overall, 28% when nodes were histologically positive and 13% when nodes were histologically negative. Patients who developed recurrent neck disease after neck dissection had a worse prognosis than those with positive nodes who did not recur, but the difference in survival was not statistically significant. Patients with histologically positive nodes had a significantly worse survival than those with negative nodes, 34% vs 67% respectively at 10 years (p < 0.001). Elective neck dissection was associated with a significant improvement in survival for patients with melanomas 1.5–3.9 mm thick, using univariate analysis. This apparent benefit was lost when multivariate analysis was carried out. Patients having elective neck dissection currently have selective modified radical dissections depending upon the anatomic site of the primary melanoma. Postoperative radiotherapy is used for multiple positive nodes or extracapsular spread.

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Resumen El presente estudio retrospectivo analiza la experiencia de la Unidad de Melanoma de Sydney con el manejo de los ganglios linfáticos cervicales en pacientes con melanoma cutáneo de la cabeza y el cuello. Entre 1960 y 1990 hubo un total de 397 pacientes sometidos a disección cervical por melanoma cutáneo de la cabeza y cuello. Estra cifra representa el 40% de la totalidad de los pacientes tratados por melanoma de la cabeza y cuello en la Unidad de Melanoma de Sydney en tal período. La disección cervical fue terapéutíca en 152 pacientes y electiva en 234 (en 11 no pudo ser determinado el tipo). Los ganglios fueron histológicamente positivos en 39% de las operaciones y en 7% de las disecciones cervicales electivas. La incidencia de recurrencia en el cuello después de disección cervical fue de 24% globalmente, de 28% cuando los ganglios eran histológicamente positivos y de 13% cuando histológicamente negativos. Los pacientes que desarrollaron enfermedad cervical recurrente después de disección cervical exhibieron un peor pronóstico que aquellos con ganglios positivos que no hicieron recurrencia, pero la diferencia en sobrevida no fue estadísticamente significativa. Los pacientes con ganglios histológicamente positivos exhibieron una supervivencia significatiemente peor que aquellos con ganglios negativos, con tasas de 34% y 67%, respectivamente, a 10 años (p < 0.001). La disección ganglionar electiva aparece asociada con una mejoría singificativa de la supervivencia de pacientes con melanomas de 1.5–3.9 mm de espesor, según el análisis univariable. Este aparente beneficio desaparece cuando se utiliza el análisis multivariable. En los pacientes sometidos a disección cervical actualmente se realizan disecciones radicales modificadas según la ubicación anatómica del melanoma primario. Se utiliza irradiación postoperatoria en casos de múltiples ganglios o de extensión extracapsular.

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Résumé Dans cette étude rétrospective, est analysée l'expérience de l'Unité des pour Mélanome de Sydney dans le traitement des adénopathies cervicales chez les patients ayant un mélanome cutané de la tête et du cou. Entre 1960 et 1990, 397 patients ont eu une lymphadénectomie du cou pour mélanome malin de la tête et du cou. Ce chiffre représente 40% de tous les patients traités pour mélanome dans cet Hôpital pendant cette période. La lymphadénectomie du cou a été thérapeutique chez 152 patients et élective chez 234 (11 indications inconnues). Les ganglions étaient histologiquement envahis dans 39% de toutes les interventions et dans 7% des curages cervicaux électifs. L'incidence de récidives localisées du cou après curage était de 24% globalement, et de 28% lorsque les ganglions étaient histologiquement indemnes. Le pronostic des patients qui ont récidivé après curage était moins bien que ceux qui, malgré l'envahissement ganglionnaire n'ont pas récidivé, mais la différence dans la survie n'était pas significative. La survie des patients dont les ganglions étaient envahis était moins bonne que ceux ayant des ganglions négatifs (34% vs 67%, respectivement à 10 ans) (p < 0.001). Le curage électif était associé à une amélioration significative du survie chez les patients ayant un mélanome épais de 1.5 à 3.9 mm en analyse monofactorielle. Cette différence disparaissait en analyse multifactorielle. Le curage cervical radical dépend du site anatomique du mélanome primitif. La radiothérapie est utile lorsque plusieurs ganglions sont envahis ou s'il existe une extension extra-capsulaire.

     

皮肤恶性黑色素瘤的外科学治疗进展

皮肤恶性黑色素瘤是起源于皮肤基底层黑色素细胞的恶性肿瘤,主要依靠组织病理学检查进行诊断,治疗策略主要包括手术治疗、化学药物治疗以及免疫疗法等全身治疗,手术仍是目前治疗的最主要方法之一。该文主要对皮肤恶性黑色素瘤的分期、外科治疗及辅助治疗等内容进行了综述。     

Metastatic breast disease from cutaneous malignant melanoma

INTRODUCTION

Malignant melanoma is one of the most rapidly increasing cancer in the world. Breast metastases from melanoma are uncommon but could reflect a widespread disease.

PRESENTATION OF CASE

We report a case of malignant widespread melanoma presenting with bilateral breast nodules in a 39 year-old pre-menopausal Caucasian woman with an history of cutaneous melanoma of the trunk. Breast clinical examination revealed the presence of a hard and mobile lump located on the left breast. Ultrasound detected two bilateral nodules corresponding to oval opacities with well-defined edges and without calcifications or architectural distortion on mammography. Fine needle aspiration cytology performed on both breast nodules confirmed that the breast lesions were metastases from primary cutaneous malignant melanoma. A total-body CT examination detected brain, lung and abdominal lymph nodes metastases.

DISCUSSION

The breast represents an uncommon site of metastatic disease from extra-mammary tumors. Imaging features of breast metastases from melanoma usually do not allow a differential diagnosis with breast primary tumors. Breast metastases may be asymptomatic or palpable as dense and well-circumscribed nodules. Breast metastases indicate a widespread disease and should lead to avoid aggressive surgical procedures because of the poor prognosis of patients affected by metastatic melanoma.

CONCLUSION

The detection of bilateral breast metastases from melanoma is highly suggestive of metastatic multi-organ disease and could be useful to address the therapeutic approach.     

The epidemiology of cutaneous malignant melanoma in Nova Scotia

BACKGROUND:

Since 1993, the annual increase in cutaneous malignant melanoma (MM) incidence has been one of the highest for all cancers registered in Canada, with the leading rate in Nova Scotia (NS). The purpose of the present study was to document the pathological and epidemiological data on MM cases found in NS.

PATIENTS AND METHODS:

All MM cases identified by the Nova Scotia Cancer Registry from January 1998 to December 2002 were evaluated. The five-year survival outlook, by major prognostic factors, was also determined. In addition, the annual incidence and mortality rates from 1972 to 2002 were computed.

RESULTS:

Between 1998 and 2002, 925 MM cases were recorded. The age-standardized incidence rate for males and females in this period was 19.2 and 16.1 per 100,000 respectively. Men 65 years of age or older had the highest age-specific rate. The most common MM had a Breslow’s depth of less than 1.0 mm (61.9%) and was Clark’s level II (34.9%). There was no significant seasonal variation noted in the time of diagnosis. Survival analyses indicated that sex, age, tumour location and thickness were significant independent predictors. Despite the increase in incidence, there have only been modest changes in the annual mortality rate.

CONCLUSION:

The incidence of MM in NS increases with age, and is nearly double for men 65 years of age or older, compared with women in the same age group. Thin melanomas on the extremities of young females have the best prognosis in NS, which is similar to other parts of the world. Incidence appears to be unrelated to season. Public health interventions are necessary to reduce the burden of this disease.     

Extensive cutaneous malignant melanoma of head and neck

Management of extensive cutaneous malignant melanomas of head and neck is usually a challenging problem especially if the tumour has nodal metastasis. A young female presented with fungating growth of right side of face extending up to the neck. Two months after surgery, she developed brain and lung metastasis. The oncological control at this advance stage is far difficult with surgical excision. In such cases, reconstruction of head and neck becomes questionable at times.     

Surgical management of cutaneous malignant melanoma. Review

Nowadays managing a cutaneous malignant melanoma can concern different kind of physicians: dermatologists, general or plastic surgeons The primary surgical procedure is a major step of the treatment. Biopsy must be total to properly determine the thickness of the tumor in case of malignancy. Wide local excision of the scar is often necessary to decrease the local and general recurrence rates. Wide local excision must be performed conforming to its own surgical rules. Managing tumor located on the face or limb extremities is a matter of plastic surgery. Sentinel node biopsy has succeeded to elective lymph node dissection. This procedure allows research of lymphatic spreading of the disease. Practice of sentinel node biopsy must be achieved in a protocolar way. Topography of the lesion can modified achievement and results of this procedure. Prognosis benefit of sentinel biopsy is now clear. Elective lymph node dissection is only performed in case of invaded sentinel node or clinically invaded lymph nodes. Local or locoregional recurrences mainly respond to surgical treatment using wide excision. However, alternative solutions are being evaluated (isolated limb perfusion).     

Management of in-transit metastases from cutaneous malignant melanoma

BACKGROUND: In-transit metastases from cutaneous malignant melanoma (cutaneous or subcutaneous deposits between the primary melanoma and regional lymph nodes) represent late-stage disease, and their treatment should be tailored accordingly. This article reviews the pathology, clinical significance and treatment options for in-transit disease from melanoma. METHODS: An initial Medline search was undertaken using the keywords 'melanoma and in-transit' and 'melanoma and non-nodal regional recurrence'. Additional original articles were obtained from citations in articles identified by the initial search. RESULTS AND CONCLUSION: In-transit metastases carry a poor prognosis. The method of treatment should be tailored to the extent of cutaneous disease. The first line of treatment remains complete excision with negative histopathological margins. There is no need for wide excision. Carbon dioxide laser therapy is valuable for multiple small cutaneous deposits. Isolated limb perfusion has a role for numerous or bulky advanced in-transit metastases in the limbs that are beyond the scope of simpler techniques. Systemic chemotherapy has response rates of about 25 per cent and is reserved for patients for whom surgery is no longer feasible.     

Late relapse from cutaneous stage I malignant melanoma

In 1,283 patients with cutaneous stage I malignant melanoma who had ten or more years of follow-up, the incidence of late recurrence (first evidence of metastases occurring ten or more years after melanoma diagnosis) was 2.7%. None of the factors of prognostic importance (anatomic site, tumor thickness, ulcerative state of primary lesion, or initial surgical treatment) proved useful in predicting those patients with late recurrence. There was no sex or age difference in either incidence of late recurrence or prognosis subsequent to recurrence. Prognosis subsequent to late recurrence depended on the site of the recurrence. Survival after distant metastases became evident was extremely short. However, in the majority (53%) of patients, late recurrence was local and survival subsequent to treatment of these metastases was often protracted, emphasizing the importance of long-term follow-up in all patients with cutaneous melanoma.