51例恶性黑色素瘤的治疗和预后分析

我院自1972年1月至1988年12月间收治的51例皮肤及粘膜原发性黑色素瘤(后称恶黑),全部经病理确诊,根据随访资料(其中含失访5例,作死亡论者),对其治疗情况和预后关系加以分析。临床资料1.性别,年龄:男性27例,女性24例,     

74例皮肤黑色素瘤的预后及影响因素分析

目的 探讨皮肤恶性黑色素瘤的临床病理特征及预后相关因素。方法 回顾性分析南京鼓楼医院2010年1月至2016年6月收治的74例皮肤黑色素瘤患者的临床病理资料。所有入组患者均接受手术治疗,术后辅助治疗分为联合免疫治疗和未联合免疫治疗,免疫治疗方法包括细胞因子治疗和过继性免疫细胞回输疗法,未联合免疫治疗者包括术后未治疗的以及术后仅行辅助放疗或辅助化疗的患者。根据随访资料分析预后情况,并采用Cox比例风险回归模型分析影响预后的因素。结果 全组患者的中位生存期（OS）和无病生存期（DFS）分别为 32.0个月（95％CI： 20.2～43.8个月）和23.0个月（95％CI： 16.4～29.6个月）。Ⅲ期患者术后联合免疫治疗较未联合免疫治疗中位OS延长（38.0个月 vs. 10.0个月,P=0.002）。多因素分析显示,年龄、分期、淋巴结转移、原发灶溃疡和肿瘤Breslow厚度是影响皮肤黑色素瘤OS的独立因子,分期、淋巴结转移、原发灶溃疡和肿瘤Breslow厚度是影响DFS的独立因子。结论 年龄、分期、淋巴结转移、肿瘤Breslow厚度和原发灶溃疡均与皮肤恶性黑色素瘤患者的预后密切相关。Ⅲ期患者术后联合免疫治疗可延长OS。     

93例转移性恶性黑色素瘤预后分析

目的：探讨转移性恶性黑色素瘤的预后因素。方法：回顾性分析93例经病理证实的转移性恶性黑色素瘤患者的临床资料及实验室、影像学检查结果。结果：93例转移性恶性黑色素瘤患者2年生存率为10．8％(10／93)。性别、体质状况、有无肝脏转移、转移部位数目、血清LDH水平、白蛋白水平以及转移灶是否切除对患者的2年生存率有显著影响：而不同年龄患者的2年生存率无统计学差异。结论：女性、体质状况较好、无肝脏转移、单一部位转移、LDH或白蛋白水平正常以及孤立转移病灶的手术切除是预后好的指标。     

93例转移性恶性黑色素瘤预后分析

目的:探讨转移性恶性黑色素瘤的预后因素。方法:回顾性分析93例经病理证实的转移性恶性黑色素瘤患者的临床资料及实验室、影像学检查结果。结果:93例转移性恶性黑色素瘤患者2年生存率为10.8%(10/93)。性别、体质状况、有无肝脏转移、转移部位数目、血清LDH水平、白蛋白水平以及转移灶是否切除对患者的2年生存率有显著影响;而不同年龄患者的2年生存率无统计学差异。结论:女性、体质状况较好、无肝脏转移、单一部位转移、LDH或白蛋白水平正常以及孤立转移病灶的手术切除是预后好的指标。     

333例恶性黑色素瘤患者的预后相关因素分析

目的：探讨恶性黑色素瘤的预后相关因素。方法：回顾性分析2007年1月至2011年12月收治的333例恶性黑色素瘤术前患者的临床和病理资料,并对其生存情况进行随访。利用SPSS190统计软件进行分析,Kaplan—Meier法绘制生存曲线,生存率的比较采用log—rank检验,Cox回归对生存情况进行多因素分析。结果：333例恶性黑色素瘤患者男性166例,女性167例,中位年龄55岁,1年、2年生存率分别为44.4％、18.0％。皮肤型及黏膜型为主要的发病类型。多因素分析结果显示：原发部位（P〈0.001）、就诊时有无淋巴结转移（P〈0.001）、LDH水平是否正常（P〈0.001）及是否接受含DTIC方案化疗（P=0.015）对患者的生存期产生影响。而患者的年龄和性别与预后无关。结论：恶性黑色素瘤发病率低,恶性程度高,2年生存率不足20％,不同的原发部位、就诊时有无淋巴结转移、LDH水平是否正常、是否接受含DTIC方案化疗是影响患者预后的因素。早期判断患者的预后,有助于选取适当的治疗方案以进一步延长生存期。     

皮肤多发性转移性恶性黑色素瘤1例

1　临床病理资料患者男 ,6 0岁 ,因发现全身皮下多发性结节 2月余入院。始初结节较小 ,且局限于四肢屈侧 ,后见结节逐日增多、增大 ,压之微痛而来我院就诊。半年前曾因右中腹壁皮肤黑痣作激光治疗。 5年前在外院曾作左臂部肿物切除术 ,当时未作病理检验。入院查体见头面部、左腋窝、颌下、躯干及四肢散在大小不等结节 ,结节直径 0 5cm～ 3cm ,部份结节突出皮肤 ,表面红肿 ,紫兰色 ,质硬 ,轻压痛 ,与皮肤粘连 ;部份结节位于皮下 ,表面皮肤正常 ,质硬 ,活动度差。B超提示肝多发实质性占位 (转移瘤 ?) ,X线胸片双肺无异常。临床诊断为多发性…     

口腔粘膜原发性恶性黑色素瘤预后因素探讨

 目的　探讨影响口腔粘膜原发性恶性黑色素瘤预后的因素。方法　回顾分析 35例患者的临床及病理资料。结果　全组总的 5年生存率 2 8.6%。其中临床 ～ 期与 ～ 期分别为45%、6.7% (P<0 .0 1 )。雀斑样型、浅表扩散型与结节型分别为 38.9%、1 4.3% (P<0 .0 1 ) ,病变局限于上皮层者与侵及粘膜下层者分别为 50 %、1 9.1 % (P<0 .0 1 )。手术加化疗组 5年生存率 35.7% ,单纯化疗组均于 5年内死亡。结论　口腔粘膜原发性恶性黑色素瘤的预后与临床分期、病理类型、病变侵袭深度及治疗方式有关。     

227例恶性黑色素瘤预后因素的回顾性分析

目的：分析恶性黑色素瘤（MM）患者的预后影响因素,为进一步提高我国MM诊治水平提供参考。方法回顾性分析227例病历、随访资料完整的MM患者,选择性别、年龄、溃疡、卫星病灶、病理类型、发病时有无淋巴结转移、转移淋巴结数量、病理分期、肿瘤厚度、干涉史、手术切除范围、放疗史和综合治疗13个可能对患者预后产生影响的因素,采用寿命表法进行生存时间和生存率分析。Kaplan-Meier法Log-rank检验进行单因素分析,对单因素有统计学意义的再进行Cox回归模型多因素分析。结果截至2012年5月共死亡110例,其1、3、5、7年总生存率（OS）分别是81.4%、60.3%、46%、37.9%,中位生存期（MST）为57个月。单因素分析显示：溃疡、病理类型、肿瘤厚度、发病时有无淋巴结转移、转移淋巴结数量、病理分期、手术切除范围和综合治疗8个因素对MM患者的预后影响有统计学意义（P﹤0.05）。Cox回归模型多因素分析显示：肿瘤厚度、病理分期、综合治疗和手术切除范围是影响MM患者长期生存的独立预后因素（P﹤0.05）,其中肿瘤厚度、病理分期是危险因素,综合治疗、手术切除范围是保护因素。结论肿瘤厚度、病理分期、手术切除范围和综合治疗是影响MM患者生存的独立预后因素。     

79例食管恶性黑色素瘤的免疫治疗疗效及预后影响因素

目的：探讨食管恶性黑色素瘤（MEM）患者的临床特征,分析以PD-1单抗为基础的免疫治疗疗效及预后的影响因素。方法：收集2011年5月至2022 年6月在北京大学肿瘤医院黑色素瘤暨肉瘤内科收治的手术不可切除或者转移性MEM患者的临床资料,包括基本信息、病理资料、实验室指标、治疗方案和生存情况等。采用实体瘤疗效评价标准1.1进行疗效评估,用Kaplan-Meier 曲线进行生存分析,用单因素和多因素COX回归进行预后分析。结果：共收集到有完整资料的MEM患者79例,中位年龄59.0岁。大部分患者发病时伴有进食哽噎和吞咽困难等症状,以食管下段发病最为常见,NRAS和KIT 基因突变的比例较高,乳酸脱氢酶（LDH）水平升高占21.5%;其中,17 例患者接受化疗为主的治疗方案,62 例患者接受PD-1单抗为主的免疫治疗方案,客观有效率分别为5.9%和28.8%,疾病控制率分别为35.3%和72.9%,总生存期（OS）分别为7个月[95%CI（0,16.7）个月]和13.2个月[95%CI（9.5,16.9）个月]（P<0.05）。多因素分析显示,就诊时LDH水平、ECOG评分、是否有临床症状、是否接受PD-1单抗治疗与OS显著相关（P<0.05）。结论：MEM患者对PD-1单抗为主的免疫治疗应答较好,LDH升高、ECOG评分≥2分、就诊时有临床症状可能是预后的不良因素。     

85例皮肤恶性黑色素瘤手术治疗分析

目的：评价皮肤恶黑手术治疗结果并结合文献进行探讨．方法：85例皮肤恶黑，原发灶切除30例，瘤床广泛切除16例，截肢21例．其他17例。淋巴结清扫32例，其中预防性清扫7例。结果：81例获随访，1例复发，5例卫星灶．12例途中转移，15例淋巴结转移，38例血行转移．37例无瘤生存，1例带瘤生存，总生存率46．9％。结论：卫星灶、途中转移、淋巴结转移发生提示预后不良。手术切缘应根据肿瘤厚度确定。     

Prognostic factors and disease‐specific survival among immigrants diagnosed with cutaneous malignant melanoma in Sweden

Little is known about cutaneous malignant melanoma (CMM) among immigrants in Europe. We aimed to investigate clinical characteristics and disease‐specific survival among first‐ and second‐generation immigrants in Sweden. This nationwide population‐based study included 27,235 patients from the Swedish Melanoma Register diagnosed with primary invasive CMM, 1990–2007. Data were linked to nationwide, population‐based registers followed up through 2013. Logistic regression and Cox regression models were used to determine the association between immigrant status, stage and CMM prognosis, respectively. After adjustments for confounders, first generation immigrants from Southern Europe were associated with significantly more advanced stages of disease compared to Swedish‐born patients [Stage II vs. I: Odds ratio (OR) = 2.37, 95% CI = 1.61–3.50. Stage III–IV vs I: OR = 2.40, 95% CI = 1.08–5.37]. The ORs of stage II–IV versus stage I disease were increased among men (OR = 1.9; 95% CI = 1.1–3.3; p = 0.020), and women (OR = 4.8; 95% CI = 2.6–9.1; p < 0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish‐born patients. The CMM‐specific survival was significantly decreased among women from former Yugoslavia versus Swedish‐born women [hazard ratio (HR)=2.2; 95% CI = 1.1–4.2; p = 0.043]. After additional adjustments including stage, the survival difference was no longer significant. No survival difference between the second generation immigrant group and Swedish‐born patients were observed. In conclusion, a worse CMM‐specific survival in women from former Yugoslavia was associated with more advanced stages of CMM at diagnosis. Secondary prevention efforts focusing on specific groups may be needed to further improve the CMM prognosis.     

Late recurrence of stage I malignant melanoma

Although the introduction of well-established risk factors has made the clinical course and prognosis of malignant melanoma disease much more predictable, in a considerable number of patients the disease's course is still not as expected. One group to which this applies are stage I melanoma patients who develop metastatic disease after 10 years or more of a disease-free interval. In our series of 94 such patients, 6 developed late relapse of their disease. The subsequent survival of these patients did not relate to any of the primary tumors' characteristics, but to the pattern of the late recurrence. Four patients with visceral metastases were dead within 1 to 5 years following relapse, one patient with lymph node involvement is alive with metastases, and another patient with skin metastases has no signs of disease following surgery and immunotherapy. Our conclusion is that malignant melanoma patients should be placed under close follow-up for the rest of their lives.     

Molecular detection of circulating tumor cells is an independent prognostic factor in patients with high-risk cutaneous melanoma

Detection of circulating tumor cells (CTCs) might improve current staging procedures by identifying a subgroup of patients with minimal residual disease and thus a higher risk of disease recurrence. Forty patients with > or =2-mm-thick cutaneous melanoma with or without lymph node metastasis were enrolled. After standard radical surgery and adjuvant therapy in case of lymph node metastasis, patients were followed up with routine physical and radiologic assessments as well as serial PCR-based analysis of CTCs using 2 melanoma markers (tyrosinase and Melan-A/Mart-1). After a median follow-up of 30 months, 18 patients had disease recurrence and 28 were PCR-positive before the disease became clinically evident. The sensitivity of the molecular test was 83%. Median time to PCR positivity and median PCR-to-relapse time were 12 and 8 months, respectively. At multivariate analysis, PCR positivity was an independent predictor of disease recurrence (hazard ratio=2.06, 95% CI 1.07-3.35; p=0.03). Among high-risk melanoma patients, serial PCR-based analysis of CTCs can identify a subgroup at higher risk of disease recurrence, with clinically significant advance. Therefore, CTC detection might be employed for the selection of patients for adjuvant treatment and during follow-up for early indication of therapeutic failure.     

CDCA5在皮肤恶性黑色素瘤中的表达及其与预后相关性的生物信息学分析

目的:探讨CDCA5在皮肤恶性黑色素瘤(cutaneous malignant melanoma,CMM)中的表达、相关信号通路及其与患者预后之间的关系.方法:应用Oncomine和GEPIA数据库研究CDCA5基因在不同肿瘤组织中的表达情况以及与患者预后关系.此外,还收集了我院41例黑色素瘤患者及41例正常皮肤病例进...     

Radioguided sentinel lymph node biopsy in patients with malignant cutaneous melanoma: the nuclear medicine contribution

As for other solid tumors, malignant cutaneous melanoma drains in a logical way through the lymphatic system, from the first to subsequent levels. Therefore, the first lymph node encountered (the sentinel node) will most likely be the first to be affected by metastasis, and a negative sentinel node makes it highly unlikely that other nodes in the same lymphatic basin are affected. Sentinel lymph node biopsy distinguishes patients without nodal metastases, who can avoid nodal basin dissection with its associated risk of lymphedema, and those with metastatic involvement who might benefit from additional therapy. This procedure represents a significant advantage as a minimally invasive procedure, considering that only an average 20% of melanoma patients with Breslow thickness between 1.5 and 4 mm harbour metastasis in their sentinel node(s) and are therefore candidates to elective lymph node dissection procedures. The cells that originate cutaneous melanomas are located between dermis and epidermis, a zone that drains to the inner lymphatic network in the reticular dermis, in turn to larger collecting lymphatics in subcutis. Therefore, the optimal modality of interstitial administration of radiocolloids for lymphoscintigraphy and subsequent radioguided sentinel lymph node biopsy is through intradermal/subdermal injection. (99m)Tc-labeled colloids in various size ranges are equally adequate for radioguided sentinel lymph node biopsy in patients with cutaneous melanoma, depending on local experience and availability. For melanomas located in the midline area of the head, neck, and trunk, particular consideration should be given to ambiguous lymphatic drainage, which frequently requires interstitial administration virtually all around the tumor or surgical scar from prior excision of the melanoma. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy because images are used to direct the surgeon to the sites of the node(s). The sentinel lymph node should have a significantly higher count than that of background (at least 10:1 intraoperatively). After removal of the sentinel node, the surgical bed must be reexamined to ensure that all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in melanoma patients is about 98% in institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. The procedure is becoming the standard of care for patients with cutaneous melanoma because of its high prognostic value that has led to include the procedure in the most recent version of the TNM staging system.     

无色素性恶性黑色素瘤28例诊断及治疗分析

目的分析无色素性恶性黑色素瘤的诊断及治疗的结果.方法1986年3月至2000年10月,我们收治了28例无色素性恶性黑色素瘤患者,全部经免疫组化确定.结果1年生存率71%,2年生存率39%,3年生存率25%,5年生存率7%,最长生存6年.结论无色素性恶性黑色素瘤,很容易误诊为其它恶性肿瘤,需做免疫组化才能确诊,合理的将手术、化疗、单次大剂量放疗及免疫治疗结合起来,是目前治疗恶性黑色素瘤的主要方法.     

Two new trifunctional antibodies for the therapy of human malignant melanoma

Trifunctional antibodies are able to redirect T cells and Fcgamma receptor(+) accessory immune cells to tumor targets. The simultaneous activation of these different classes of effector cells results in efficient killing of the tumor cells by different mechanisms such as phagocytosis and perforin-mediated cytotoxicity. Here, we introduce 2 new trifunctional antibodies specific for human melanoma. These trifunctional antibodies recognize with one binding arm CD3 on human T cells. The other binding arm is directed against melanoma-associated proteoglycans or melanoma-associated gangliosides (GD2 as well as GD3). They mediate specific lysis of various melanoma cell lines in correlation with the level of antigen expression in short-term cytotoxicity experiments. A combination of the 2 trifunctional antibodies was equally or even more efficient. Moreover, they induced a strong Th1 cytokine pattern with high amounts of IFN-gamma and low or no IL-4. Accordingly, CD4(+) and especially CD8(+) T cells expanded, whereas B cells, NK cells and monocytes decreased. The cytokine response was up to 16-fold higher when tumor cells were present. IFN-gamma reached cytotoxic concentrations for SK-MEL-23 melanoma cells. The induction of a T-cell-activatory and melanoma cell-inhibitory cytokine milieu together with the redirection of T-cell- and accessory cell-mediated cytotoxicity are interesting features of these trifunctional antibodies. They may be a new option for the therapy of human malignant melanoma.     

Systemic therapy of malignant melanoma

The present status of medical treatment of malignant melanoma is briefly reviewed, both with regard to adjuvant therapy for individuals with high-risk melanoma and a high probability of harbouring subclinical rnicrometastases, as well as to therapy for establised disseminated (macrometastatic) disease. At present, disseminated, macrometastatic melanoma is incurable in the majority of cases. Single agent chemotherapy has modest effects and results in disease remission in a minority of patients, usually of short duration, Combination chemotherapy, or the combination of chemotherapeutic drugs and cytokines, results in increased response rates and occasionally remissions of prolonged duration. So far, no regimen has demonstrated improved survival compared to single agent therapy in disseminated melanoma. New insights into the mechanisms of resistance to chemotherapeutic drugs may lead to development of predictive tests that can identify individuals with tumors sensitive to a specific agent, as well as to the development of strategies to circumvent drug resistance. It has recently been shown that adjuvant therapy of high-risk melanoma with large doses of interferon-α2b significantly prolongs relapse-free and overall survival, at the price of considerable toxicity. Ongoing studies aim to define the optimum dose and duration of adjuvant interferon therapy. Recent advances in molecular biology and immunology may lead to the development of new treatment modalities, such as improved vaccines and other biologic therapies, which may benefit patients with malignant melanoma.