Pantanowitz Liron, Dezube Bruce J
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Curr Opin Oncol. 2004 Sep;16(5):443-9. doi: 10.1097/00001622-200409000-00006.
Kaposi sarcoma, which has reached epidemic proportions in parts of Africa and in the Western world, continues to pose a problem in patients with AIDS receiving highly active antiretroviral therapy (HAART). This article reviews the new and important information regarding the epidemiology, biology, and management of Kaposi sarcoma that was published in the last year.
Worldwide Kaposi sarcoma herpesvirus/human herpesvirus 8 (HHV8) seropositivity has been found to exceed the incidence of Kaposi sarcoma. Therefore, investigators have justifiably implicated other cofactors (eg, blood-sucking arthropods, angiotensin converting enzyme inhibitors, hemodialysis, and iron) in the development of Kaposi sarcoma. In the transplant setting, Kaposi sarcoma lesions have been shown to originate from the engraftment of donor tumor cells. The detection of HHV8 in Kaposi sarcoma lesions has provided a new diagnostic tool to help differentiate Kaposi sarcoma from its mimics. Kaposi sarcoma lesional cells, now confirmed to be of lymphatic origin, have been shown to express several chemokine receptors, some of which may help explain the predilection for skin. Regression of Kaposi sarcoma has been characterized histologically for the first time. The finding that some tumor cells can remain in an atrophic state even in completely regressed lesions suggests that they have the potential to recur. Protease inhibitor-based and nonnucleoside reverse transcriptase inhibitor-based HAART regimens have been verified to be similarly effective. Although antiretrovirals have been noted to favorably alter the clinical characteristics of Kaposi sarcoma favorably, they seem not to alter the natural history of this disease. In the HAART era, because CD4 cell count was shown no longer to provide prognostic information about AIDS-related Kaposi sarcoma, the traditional classification system for staging AIDS-related Kaposi sarcoma has been refined. Also, a new staging system for classic Kaposi sarcoma has been proposed.
Numerous advances have emerged regarding Kaposi sarcoma during the last year, many of which still need to be translated into clinically useful information. The results of new clinical trials involving antivirals purposely directed against HHV8 and antiretrovirals for HIV-uninfected people are anticipated. Finally, although investigators during this period did provide us with additional potential therapeutic targets, more novel approaches such as RNA interference and gene therapy have been also proposed as options in the future management of Kaposi sarcoma.
卡波西肉瘤在非洲部分地区和西方世界已呈流行态势,对于接受高效抗逆转录病毒治疗(HAART)的艾滋病患者而言,它仍是一个难题。本文回顾了过去一年发表的关于卡波西肉瘤流行病学、生物学及治疗方面的新的重要信息。
在全球范围内,已发现卡波西肉瘤疱疹病毒/人类疱疹病毒8(HHV8)血清阳性率超过卡波西肉瘤发病率。因此,研究人员有理由认为其他辅助因素(如吸血节肢动物、血管紧张素转换酶抑制剂、血液透析和铁)与卡波西肉瘤的发生有关。在移植环境中,已证明卡波西肉瘤病变源自供体肿瘤细胞的植入。在卡波西肉瘤病变中检测到HHV8为区分卡波西肉瘤与其相似疾病提供了一种新的诊断工具。现已证实卡波西肉瘤病变细胞起源于淋巴管,这些细胞已被证明表达多种趋化因子受体,其中一些可能有助于解释其对皮肤的偏好。首次从组织学上对卡波西肉瘤的消退进行了描述。研究发现,即使在完全消退的病变中,一些肿瘤细胞仍可处于萎缩状态,这表明它们有可能复发。基于蛋白酶抑制剂和基于非核苷类逆转录酶抑制剂的HAART方案已被证实具有相似的疗效。尽管已注意到抗逆转录病毒药物能有利地改变卡波西肉瘤的临床特征,但它们似乎并未改变该疾病的自然病程。在HAART时代,由于CD4细胞计数已不再能提供有关艾滋病相关卡波西肉瘤的预后信息,因此对艾滋病相关卡波西肉瘤分期的传统分类系统进行了完善。此外,还提出了经典卡波西肉瘤的新分期系统。
去年在卡波西肉瘤方面有诸多进展,其中许多仍需转化为临床有用信息。预计针对HHV8的抗病毒药物及针对未感染HIV人群的抗逆转录病毒药物的新临床试验结果将会出现。最后,尽管在此期间研究人员为我们提供了更多潜在治疗靶点,但也有人提出RNA干扰和基因治疗等更多新颖方法作为未来卡波西肉瘤治疗的选择。