Shields C L
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, USA.
Trans Am Ophthalmol Soc. 2000;98:471-92.
To identify the risk factors of conjunctival malignant melanoma that predict local tumor recurrence, orbital exenteration, distant metastasis, and tumor-related mortality.
The study group consisted of 150 consecutive patients with a diagnosis of conjunctival melanoma. The clinical parameters of the patient, tumor, and treatment were analyzed in a nonrandomized fashion for their relation to 4 main outcome measures using Cox proportional hazards regression models.
The Kaplan-Meier estimate of local tumor recurrence was 26% at 5 years, 51% at 10 years, and 65% at 15 years. The mean number of recurrences per patient was 1 (median, 0). Ninety-eight patients (65%) had no recurrences, 28 patients (19%) had 1, 11 patients (7%) had 2, 5 patients (3%) had 3, and 8 patients (5%) had 4 or more recurrences. According to multivariate analysis, the factors that predicted local tumor recurrence were the location of the melanoma (not touching the limbus) (P = .01) and tumor-margin pathology (lateral margin involved) (P = .02). Multivariate analysis for features predictive of ultimate exenteration included initial visual acuity (20/40 or worse) (P = .0007), melanoma color (red) (P = .01), and melanoma location (not touching the limbus) (P = .02). Tumor metastasis occurred in 16% of patients at 5 years, 26% at 10 years, and 32% at 15 years. Metastasis was initially in the regional lymph nodes in 17 cases, brain in 4, liver in 3, lung in 2, and disseminated in 1 case. Risks for metastases with use of multivariate analysis included tumor-margin pathology (lateral margin involved) (P = .002) and melanoma location (not touching limbus) (P = .04). Tumor-related death occurred in 7% of patients at 5 years and 13% at 8 years. Risk factors for death with use of multivariate analysis included initial symptoms (lump) (P = .004) and pathologic findings (de novo melanoma without primary acquired melanosis) (P = .05). In a series of univariate analyses, the technique of initial surgery was shown to be an important factor in preventing eventual tumor recurrence (P = .07), metastasis (P = .03), and death (P = .006). Patients who were managed with excisional biopsy using the "no-touch technique" plus alcohol corneal epitheliectomy and supplemental cryotherapy fared far better than those treated with excisional biopsy alone. In addition, the surgical technique used before referral to us was critical. Those patients who had an incisional diagnostic biopsy prior to referral were at risk for more than 1 recurrence (P = .04), and those who had excisional biopsy alone without supplemental cryotherapy were at risk for eventual exenteration (P = .0006) and death (P = .04).
Conjunctival malignant melanoma is a potentially deadly tumor. In this study, metastasis was detected in 26% of patients and death occurs in 13% at 10 years. The surgical technique of tumor management was found to be possibly related to tumor metastases and death. Meticulous surgical planning, use of wide microsurgical excisional biopsy with the no-touch technique, and supplemental alcohol corneal epitheliectomy and conjunctival cryotherapy performed by experienced surgeons are advised. Incisional biopsy should be avoided.
确定可预测结膜恶性黑色素瘤局部肿瘤复发、眼眶内容剜除术、远处转移及肿瘤相关死亡率的危险因素。
研究组由150例连续诊断为结膜黑色素瘤的患者组成。采用Cox比例风险回归模型,以非随机方式分析患者、肿瘤及治疗的临床参数与4项主要结局指标的关系。
局部肿瘤复发的Kaplan-Meier估计值在5年时为26%,10年时为51%,15年时为65%。每位患者的复发平均次数为1次(中位数为0次)。98例患者(65%)无复发,28例患者(19%)复发1次,11例患者(7%)复发2次,5例患者(3%)复发3次,8例患者(5%)复发4次或更多次。多因素分析显示,预测局部肿瘤复发的因素为黑色素瘤的位置(未触及角膜缘)(P = 0.01)和肿瘤边缘病理(外侧边缘受累)(P = 0.02)。预测最终眼眶内容剜除术的特征的多因素分析包括初始视力(20/40或更差)(P = 0.0007)、黑色素瘤颜色(红色)(P = 0.01)和黑色素瘤位置(未触及角膜缘)(P = 0.02)。5年时16%的患者发生肿瘤转移,10年时为26%,15年时为32%。转移最初发生在区域淋巴结17例,脑4例,肝3例,肺2例,播散性1例。多因素分析显示转移的危险因素包括肿瘤边缘病理(外侧边缘受累)(P = 0.002)和黑色素瘤位置(未触及角膜缘)(P = 0.04)。5年时7%的患者发生肿瘤相关死亡,8年时为13%。多因素分析显示死亡的危险因素包括初始症状(肿块)(P = 0.004)和病理结果(原发性无色素性黑色素瘤)(P = 0.05)。在一系列单因素分析中,初始手术技术被证明是预防最终肿瘤复发(P = 0.07)、转移(P = 0.03)和死亡(P = 0.006)的重要因素。采用“不接触技术”加酒精角膜上皮切除术及辅助冷冻疗法进行切除活检的患者比仅行切除活检的患者预后好得多。此外,转诊至我们这里之前所采用手术技术至关重要。转诊前接受切开诊断性活检的患者有超过1次复发的风险(P = 0.04),而仅行切除活检未行辅助冷冻疗法的患者有最终眼眶内容剜除术(P = 0.0006)和死亡(P = 0.04)的风险。
结膜恶性黑色素瘤是一种潜在致命性肿瘤。在本研究中,26%的患者发生转移,10年时13%的患者死亡。发现肿瘤治疗的手术技术可能与肿瘤转移和死亡有关。建议进行细致的手术规划,采用广泛的显微手术切除活检及不接触技术,由经验丰富的外科医生进行辅助酒精角膜上皮切除术及结膜冷冻疗法。应避免切开活检。