Kleemann D, Stengel B
HNO-Klinik, MediClin Müritz-Klinikum GmbH, Weinbergstr. 19, 17192, Waren (Müritz).
HNO. 2010 Mar;58(3):305-12. doi: 10.1007/s00106-009-2018-9.
In the literature the potential effect of sexual steroids on the development and growth of laryngeal carcinomas, and even other tumor entities of the upper aerodigestive tract, within the context of multifactorial carcinogenesis has been the subject of controversial discussion. Experimental cell studies have provided evidence for the differentiated effects of these agents. Apart from the male preponderance in tumor formation, the high incidence at an age characterized by decreased peripheral androgenic signalling should be noted.
Two patients with chronic symptoms and abnormal hormone levels are reported who underwent a hormonal trial regimen. The course of their disease was followed up for a period of more than 10 years.
In the first case of a patient suffering from chronic hyperplastic laryngitis for 17 years, a close correlation was found between the treatment with the 5alpha-reductase inhibitor Finasteride, the drop in serum levels of dihydrotestosterone (DHT), and the appearance of an invasive squamous cell carcinoma of the vocal cord. During the postoperative 7-year follow-up without recurrence the androgen serum levels were within normal range. The laryngeal mucosa did not display any further dysplastic changes. Retrospective studies of the biopsies demonstrated a significant degree of epidermal growth factor receptor (EGFR) expression, the characteristic high degree of EGFR activity in all of the tumor tissue, and a significantly lower degree of activity in the subsequent excision biopsies. In the second patient, who had undergone previous surgery for mesopharyngeal cancer at another site before the present tumor operation, rapid recurrence was seen within 2 years. Despite radical revision surgery and subsequent irradiation the patient insisted on carrying on with his work. He complained about a general lack of stamina and libido. His androgen serum levels were at the low-end of the normal range and even below that. The daily administration of 25 mg dehydroepiandrosterone (DHEA) resulted in normal androgen serum levels and improved his wellbeing. He has been free of recurrence for 10 years.
Occasional long-term follow-up of patients supports the circumstantial evidence of previous experimental cellular studies that a dysbalanced androgen metabolism appears to act as cofactor in the genesis and development of malignant tumors of the upper aerodigestive tract.
在文献中,性类固醇在多因素致癌作用背景下对喉癌乃至上呼吸道消化道其他肿瘤实体的发生和生长的潜在影响一直是有争议的讨论主题。实验性细胞研究已为这些药物的差异化作用提供了证据。除了肿瘤形成中男性占优势外,还应注意到在周围雄激素信号降低的年龄阶段发病率较高。
报告了两名有慢性症状且激素水平异常的患者,他们接受了激素试验方案。对其疾病进程进行了超过10年的随访。
在第一例患有慢性增生性喉炎17年的患者中,发现使用5α-还原酶抑制剂非那雄胺治疗、血清双氢睾酮(DHT)水平下降与声带浸润性鳞状细胞癌的出现之间存在密切相关性。术后7年无复发随访期间,雄激素血清水平在正常范围内。喉黏膜未显示任何进一步的发育异常变化。对活检标本的回顾性研究表明,表皮生长因子受体(EGFR)表达程度显著,所有肿瘤组织中EGFR活性特征性地高,而在随后的切除活检中活性程度显著较低。在第二例患者中,在本次肿瘤手术前曾在另一部位接受过中咽癌手术,术后2年内迅速复发。尽管进行了根治性翻修手术及随后的放疗,但患者坚持继续工作。他抱怨普遍缺乏耐力和性欲。他的雄激素血清水平处于正常范围的低端甚至更低。每天服用25mg脱氢表雄酮(DHEA)使雄激素血清水平正常,并改善了他的健康状况。他已无复发10年。
对患者的偶尔长期随访支持了先前实验性细胞研究的间接证据,即雄激素代谢失衡似乎在上呼吸道消化道恶性肿瘤的发生和发展中作为辅助因素起作用。