皮肤进展期黑色素瘤的瘤体内治疗进展

瘤体内注射指向肿瘤局部病灶内注射抗肿瘤药物,在杀灭注射部位肿瘤细胞的同时,并可能引发免疫反应,产生“旁观者”效应,对非注射病灶也发挥抗肿瘤作用。2015年10月美国食品和药物管理局审批通过黑色素瘤瘤体内注射治疗的新型药物Talimogene laherparepvec上市,用于首次手术后复发的黑色素瘤患者不可切除的皮肤、皮下和淋巴结病灶的局部治疗,引发人们对该治疗手段的极大关注。本文对以往用于皮肤进展期黑色素瘤瘤体内注射治疗的药物及其相关疗效进行综述,其中包括细胞因子、质粒及溶瘤病毒等,并对该类型药物的进一步发展提出展望。     

Local and intralesional therapy of in-transit melanoma metastases

Regional relapse of melanoma may occur as satellite or in-transit metastases proximal to the primary tumor in the direction of the lymph flow. The management of in-transit metastases is challenging because the efficacy of treatment is largely dictated by the biological behavior of the patient's melanoma. This review examines local treatment modalities.     

New approaches to the systemic treatment of melanoma.

Metastatic melanoma is an incurable condition with a median survival of about 6 months. Chemotherapy can result in objective tumour responses but only in a minority of cases and remissions are short-lived, 3-6 months. DTJC is the most active single agent with response rates of 15-20% and although combination chemotherapy can result in higher response rates there is no response duration or survival advantage. Phase II studies have suggested that combining chemotherapy with biological response modifiers may result in higher response rates, in the order of 50% and the results of two large randomized trials investigating this approach are awaited. Adjuvant trials currently focus on interferon and/or vaccine strategies. Further data are required before any adjuvant treatment can be regarded as standard.     

Evaluation of immunotherapy in the treatment of melanoma

These data show that the extraordinary potency of the immune system can be harnessed to control or destroy melanoma. The proven impact has been limited for patients who have melanoma, but has been dramatic and lasting in selected groups. Recent improvements in understanding of immunology, including mechanisms regulating immune responses and methods of tumor cell escape, are already yielding improved clinical outcomes and potential avenues for extending benefits to more patients. Thus, although the full potential of this treatment modality has yet to be realized, the vanguard of the "treatment of tomorrow" has clearly arrived.     

Prospective comparison of intralesional and multipuncture BCG in recurrent intradermal melanoma.

Fifty-nine patients with metastatic melanoma predominantly localized in the skin were randomly assigned to treatment with BCG given either intralesionally (IL-BCG) or by multiple puncture vaccination at a nontumor bearing site in the skin (MPV-BCG). Half the patients with IL-BCG experienced moderate fever, chills and malaise, suggesting systemic exposure to this live organism. However, only three of these patients required systemic antituberculous chemotherapy and all responded to it. MPV-BCG treated patients experienced significantly less systemic toxicity. Among fully evaluable patients 45% objective response rate was seen in the IL-BCG group and a 9% response rate in the MPV-BCG group, a significant difference. The only complete responses were seen in the IL-BCG group. Among fully evaluable patients, median survival was 21.1 months in the IL-BCG group and 13.3 months in the MPV-BCG groups (NSD). No patients with pretreatment anergy to all skin tests utilized, experienced objective response to BCG.     

Electrochemotherapy with cisplatin: the systemic antitumour effectiveness of cisplatin can be potentiated locally by the application of electric pulses in the treatment of malignant melanoma skin metastases

The application of electric pulses to skin tumour nodules enhances the antitumour effectiveness of cisplatin. This treatment approach, known as electrochemotherapy, was employed in the treatment of skin metastases and lymph node metastases in malignant melanoma patients. Electric pulses were applied to tumour nodules in order to potentiate locally the antitumour effectiveness of systemic cisplatin-based chemoimmunotherapy. The study included nine malignant melanoma patients with skin metastases and metastases in lymph nodes not amenable to surgery, undergoing cisplatin-based chemoimmunotherapy. The antitumour effectiveness of the chemoimmunotherapy was compared with the antitumour effectiveness of electrochemotherapy, i.e. application of electric pulses to tumour nodules together with cisplatin-based chemoimmunotherapy. Application of electric pulses to the 27 skin tumour nodules potentiated locally the antitumour effectiveness of cisplatin. Four weeks after the treatment, 48% of the tumour nodules had an objective response (OR), compared with 22% of the 18 tumour nodules treated with cisplatin-based chemoimmunotherapy alone. Furthermore, the median time to progression was longer in the electrochemotherapy-treated nodules (21 weeks) than in the chemoimmunotherapy-treated nodules (4 weeks). This study shows that application of electric pulses to malignant melanoma tumour nodules can potentiate the antitumour effectiveness of cisplatin in patients undergoing systemic cisplatin-based chemoimmunotherapy. Therefore, electrochemotherapy may be used as an adjunct to systemic ongoing cisplatin treatment, predominantly in patients in whom antitumour effectiveness needs to be potentiated locally.     

Primary free dermatoplasty in surgical treatment of skin melanoma]

At the P. A. Herzen Research Institute of Oncology since 1967 to 1974 during surgical treatment of 108 patients with skin melanoma 114 plastic operations were performed, using free skin plasty with full-sickness graft perforated after the B. V. Parin technic. An analysis of the immediate results of the treatment indicated that complete healing of the graft was gained in 85 (76.4+) cases, partial necrosis being noted in 18 (15.8%), total necrosis--in 8 (7%), suppuration--in 3 (2.6%). Late results of the treatment were followed up in 105 of 108 patients. Recurrences in the graft were observed in 3 patients. Disseminated skin proximal to the transplanted graft--in 6 patients, recurrences in a scar above the graft--in 2.     

眼睑原发黑色素瘤伴全身多发转移的18F-FDG PET/CT 1例

<正>患者男性,70岁,1962年偶然发现右侧上眼睑肿物（色素痣）,呈小米粒大小,后逐渐增大并感觉不适,于2003年1月行“肿物切除术”,自述病理诊断为良性,术后未行其他治疗。2020年6月自觉右眼睑疼痛,肿物于2020年6月至7月间明显增大,2020年7月于北京大学第一医院行右眼上睑肿物诊断性切除,术后病理示：右眼上睑鳞状上皮黏膜组织,     

Evaluation of melanoma/skin cancer screening in Massachusetts. Preliminary results

Although screening for melanoma/skin cancer is theoretically of value, few data are available to evaluate its effectiveness or the value of a visual exam by a dermatologist as a cancer screening tool. From the 2560 persons screened for melanoma/skin cancer in Massachusetts in 1986 and 1987, the authors followed the positive screenees to determine their final diagnosis. The authors obtained information on 85% of these persons, and found nine malignant melanomas, 91 non-melanoma skin cancers, 39 dysplastic nevi, and three congenital nevi. The sensitivity of the visual exam by a dermatologist was 89% to 97% and the predictive value positive was 35% to 75% for skin cancer. The authors conclude that the yield of screening is equivalent to that of other major cancer screening efforts and that the sensitivity and predictive value of the visual examination by the dermatologist is appropriate for a cancer screening tool.     

Role of electrochemotherapy in the treatment of metastatic melanoma and other metastatic and primary skin tumors

Electroporation is a novel therapeutic modality that uses pulsed electrical currents to enhance the uptake of drugs, vaccines and genes into cells, and has been used for over 20 years. Electroporation therapy using cytotoxic drugs is called electrochemotherapy. Electrochemotherapy has been studied in vitro, in vivo and in clinical trials. It is potentially useful for treating patients with metastatic tumors, such as melanoma, and even select primary tumors, such as head and neck squamous cell carcinomas and basal cell carcinoma. Various chemotherapeutic agents have been tested with electroporation therapy, but bleomycin and cisplatin are the two most widely used. The biological basis of electroporation therapy is outlined in this review and basic science studies and the limited clinical studies that have involved electrochemotherapy are reviewed. Particular focus is placed on trials involving melanoma, head and neck cancers and other primary and metastatic skin cancers.     

Role of electrochemotherapy in the treatment of metastatic melanoma and other metastatic and primary skin tumors

Electroporation is a novel therapeutic modality that uses pulsed electrical currents to enhance the uptake of drugs, vaccines and genes into cells, and has been used for over 20 years. Electroporation therapy using cytotoxic drugs is called electrochemotherapy. Electrochemotherapy has been studied in vitro, in vivo and in clinical trials. It is potentially useful for treating patients with metastatic tumors, such as melanoma, and even select primary tumors, such as head and neck squamous cell carcinomas and basal cell carcinoma. Various chemotherapeutic agents have been tested with electroporation therapy, but bleomycin and cisplatin are the two most widely used. The biological basis of electroporation therapy is outlined in this review and basic science studies and the limited clinical studies that have involved electrochemotherapy are reviewed. Particular focus is placed on trials involving melanoma, head and neck cancers and other primary and metastatic skin cancers.     

Malignant lymphoma of the skin

Diagnosis and therapy of malignant lymphoma of the skin were reviewed. Cutaneous T-cell lymphoma (CTCL), which is a new name for mycosis fungoides and Sezary syndrome, is one of the peripheral T-cell malignancies. It is generally confined to the skin for a long period of time, distinct from other malignant lymphomas, and may then progress to involve the lymph nodes and internal organs with a fatal outcome. Thus, diagnosis and therapy of CTCL may be different from those of other malignant lymphomas. Diagnostic characteristics of clinical, histopathological, haematological and immunological findings of CTCL were described. Differentiation between CTCL and adult T-cell leukemia-lymphoma (ATL) were discussed. As for the therapy for CTCL, there are five therapeutic modalities; local chemotherapy, PUVA therapy, electron beam irradiation therapy, systemic chemotherapy and combined modality. However, the most appropriate therapy for each stage of CTCL has not yet been determined. The advantages and dis-advantages of each therapeutical modality were discussed.