上尿路尿路上皮癌368例根治标本的临床病理特点及预后分析

Clinicopathologic characteristics and prognosis of upper tract urothelial carcinoma： an analysis of 368 radical nephroureterectomy specimens

目的探讨上尿路尿路上皮癌（UTUC）的流行病学、临床病理特点及预后。方法收集368例于北京大学第三医院行根治术治疗并经病理证实为UTUC的病例，分析其流行病学及临床病理特点。获得随访资料214例，随访1～216个月，平均41个月。结果368例UTUC中男性128例，女性240例，男女比为1：1.9；年龄31—88岁，中位年龄68岁。肿瘤部位包括肾盂148例，输尿管155例，肾盂及输尿管均受累58例，肾盂输尿管移行处7例。14．7％（54／368）的患者有肾移植病史，更容易在65岁之前发生UTUC（P〈0．01），且肿瘤易双侧同时发生（P〈0．01）和呈多灶性分布（P=0．004）。组织学上低级别101例，低级别伴高级别成分（10％～90％）17例，高级别247例。高级别UTUC多发生于女性患者（P=0．010），且组织学变异型较多见（P〈0．01）。组织学分级与T分期（P〈0．01）、脉管内瘤栓（P=0．001）、神经侵犯（P=0．005）、伴原位癌（P=0．001）及大片坏死（P=0．020）呈正相关性。分期上T2-T4肿瘤组织学变异型较多见（P=0．010）；T分期与肿瘤大小（P〈0．01）、脉管内瘤栓（P〈0．01）、神经侵犯（P〈0．01）及淋巴结转移（P=0．001）均呈正相关性。本组病例中214例获得完整随访信息，其中存活138例，死亡76例。组织学分级（P=0．002，P=0．005）、T分期（P〈0．01，P〈0．01）、脉管内瘤栓（P=0．001，P=0．008）、神经侵犯（P〈0．01，P=0．001）及伴大片坏死（P=0．017，P=0．023）均与患者总生存期和无病生存期呈负相关性，其中T分期（P〈0．01，P〈0．01）及伴大片坏死（P=0．004，P=0．014）均为总生存期和无病生存期的独立预后因素，神经侵犯（P=0．007）及淋巴结转移（P=0．007）仅为总生存期的独立预后因素。结论UTUC女性患者多见，。肾盂与输尿管发病率基本持平，后者略为多见。有肾移植病史的患者发病年龄较轻，多以复查体检或疼痛发现占位性病变；且肿瘤易双侧和多灶。UTUC的组织学分级、T分期、脉管内瘤栓、神经侵犯及伴大片坏死均与患者总生存期和无病生存期呈负相关性，其中T分期及伴大片坏死均为总生存期和无病生存期的独立预后因素。

Objective To evaluate the epidemiology, clinicopathological features and prognosis in upper tract urothelial carcinoma （UTUC） patients. Methods All archival 368 UTUC cases that underwent radical nephroureterectomy between September 1999 and October 2014 were reviewed, and their clinicopathological features were analyzed. Follow-up time was 1 -216 months, with a mean follow-up of 41 month. Results One hundred and twenty-eight male and 240 female patients were included, with a mean age of 68 years ranging from 31 to 88 years. Tumor locations were classified in detail as follows： 148 renal pelvic tumors, 155 ureteral tumors, 58 renal pelvic and ureteral tumors, and 7 transitional tumors. Patients with history of renal transplantation （14. 7% ,54/368 ） were more likely to develop UTUC before the age of 65 （ P 〈 0. 01 ）, with bilateral tract involved （ P 〈 0. 01 ） and muhifocal distributed （ P = 0. 004 ）. Histological grade was significantly associated with T stage （P 〈 0. 01 ） , lympho-vaseular involvement （P = 0. 001 ） , neural invasion （ P = 0. 005 ） , carcinoma in situ （ P = 0. 001 ） and extensive necrosis （ P = 0. 020）, while high-grade UTUC predominantly occurred in female patients （P = 0. 010） and histological variants （P 〈 0. 01 ）. T stage was positively correlated with tumor size （ P 〈 0. 0! ）, lympho-vascular involvement （ P 〈 0. 01 ）, neural invasion （ P 〈 0. 01 ） and lymph node metastasis （ P = 0. 001 ） . Furthermore, among the 214 followed-up cases, 76 died of the disease. Histological grade （P = 0. 002, P = 0. 005）, T stage （ P 〈 0.01, P 〈 0. 01 ）, lympho-vascular involvement （ P = 0. 001, P = 0. 008）, neural invasion （P 〈 0.01, P = 0. 001 ） and extensive necrosis （ P = 0. 017, P = 0. 023 ） were significantly associated with shorter overall survival and cancer specific survival of UTUC patients, respectively. In multivariable analyses, T stale （ P 〈0.01, P 〈0.01 ） and extensive ~ecrc^sis （ P =0. 004, P =0.014） were independent predictive factors of both overall survival and cancer specific survival, while neural invasion （P = 0. 007） and lymph node metastasis （P = 0. 007 ） were independent predictors of the overall survival. Conclusions Chinese UTUC reveals its unique epidemiology. UTUC more commonly occurs in women and has a similar incidence between the renal pelvic and ureteral carcinoma. Patients with history of renal transplantation are prone to detect UTUC through physical examination rather than hematuria. Histological grade, T stage, lympho-vascular involvement, neural invasion and extensive necrosis are predictors of survival in UTUC patients, while advanced-stage and extensive necrosis are independent predictors of poor outcome.