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中华腔镜泌尿外科杂志(电子版) ›› 2026, Vol. 20 ›› Issue (02) : 147 -153. doi: 10.3877/cma.j.issn.1674-3253.2026.02.004

临床研究

凝血酶原时间与膀胱癌患者接受内镜下冷冻消融治疗后复发的相关性分析
宋再桪, 胡锦中, 殷秋萍, 陈艺凌, 党天安, 牟泽中(), 徐晨阳(), 姜昊文()   
  1. 200040 上海,复旦大学附属华山医院泌尿外科
  • 收稿日期:2025-11-23 出版日期:2026-04-01
  • 通信作者: 牟泽中, 徐晨阳, 姜昊文
  • 基金资助:
    国家自然科学基金项目(82373222,82202970); 上海市自然科学基金青年项目(25ZR1402048); 中国博士后科学基金第77批面上资助项目(2025M772172)

Analysis of the correlation between prothrombin time and postoperative recurrence in bladder cancer patients who underwent endoscopic cryoablation therapy

Zaixun Song, Jinzhong Hu, Qiuping Yin, Yiling Chen, Tian'an Dang, Zezhong Mou(), Chenyang Xu(), Haowen Jiang()   

  1. Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China
  • Received:2025-11-23 Published:2026-04-01
  • Corresponding author: Zezhong Mou, Chenyang Xu, Haowen Jiang
引用本文:

宋再桪, 胡锦中, 殷秋萍, 陈艺凌, 党天安, 牟泽中, 徐晨阳, 姜昊文. 凝血酶原时间与膀胱癌患者接受内镜下冷冻消融治疗后复发的相关性分析[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2026, 20(02): 147-153.

Zaixun Song, Jinzhong Hu, Qiuping Yin, Yiling Chen, Tian'an Dang, Zezhong Mou, Chenyang Xu, Haowen Jiang. Analysis of the correlation between prothrombin time and postoperative recurrence in bladder cancer patients who underwent endoscopic cryoablation therapy[J/OL]. Chinese Journal of Endourology(Electronic Edition), 2026, 20(02): 147-153.

目的

冷冻消融作为一种微创治疗方式,在膀胱癌中应用广泛,但术后复发率仍较高,缺乏有效预测标志物。本研究旨在探究实验室指标与膀胱癌冷冻消融术后复发风险的相关性。

方法

本研究基于一项多中心、前瞻性、随机对照研究(ChiCTR编号:ChiCTR-INR-17013060)的膀胱癌患者队列进行事后分析。所有患者冷冻消融术后在第7天及4~6周复查实验室指标,并通过超声、膀胱镜进行3年随访,确认复发情况。采用单因素及多因素Logistic回归分析。采用最佳截断值对凝血酶原时间(PT)进行分组,并评估不同分组与临床病理特征之间的关系。

结果

共纳入72例患者,随访期间11例复发。单因素分析显示,年龄(OR=1.082,95%CI:1.008~1.173,P=0.039)、肿瘤数量(OR=2.851,95%CI:1.295~6.773,P=0.011)和术后第7天的PT (OR=0.423,95%CI:0.164~0.889,P=0.043)与复发显著相关。多因素分析证实术后第7天PT缩短为复发的独立危险因素(OR=0.222,95%CI:0.053~0.602,P=0.013)。采用PT截断值12.1 s将患者分组,低PT组患者低级别肿瘤比例更高(P=0.028),血小板水平更高(P=0.014),活化部分凝血活酶时间更短(P<0.001)。

结论

术后第7天PT缩短是膀胱癌冷冻消融术后复发的独立危险因素。

Objective

Cryoablation, as a minimally invasive treatment, is widely used in bladder cancer. However, postoperative recurrence remains relatively high, and reliable biomarkers for predicting recurrence risk are still lacking. This study aims to explore the correlation between laboratory indicators and recurrence risk after cryoablation of bladder cancer.

Methods

This study is a post-hoc analysis based on a cohort of bladder cancer patients from a multicenter, prospective, randomized controlled trial (ChiCTR registration number: ChiCTR-INR-17013060). All patients underwent laboratory testing on postoperative day 7 and at 4-6 weeks. Recurrence was assessed over a 3-year follow-up period using ultrasound and cystoscopy. Univariate and multivariate Logistic regression analyses were conducted between the recurrence and non-recurrence groups. Patients were grouped according to prothrombin time (PT) using the optimal cutoff value, and the relationship between different groups and clinicopathological characteristics was evaluated.

Results

A total of 72 patients were included, with 11 experiencing recurrence during follow-up. Univariate Logistic regression analysis showed that age (OR=1.082, 95%CI: 1.008-1.173, P=0.039), tumor number (OR=2.851, 95%CI: 1.295-6.773, P=0.011), and PT on postoperative day 7 (OR=0.423, 95%CI: 0.164-0.889, P=0.043) were significantly associated with recurrence. Multivariate analysis identified shortened PT on postoperative day 7 as an independent risk factor of recurrence (OR=0.222, 95%CI: 0.053-0.602, P=0.013). When patients were stratified by a PT cutoff value of 12.1 seconds, patients in the low PT group had a higher proportion of low-grade tumors (P=0.028), higher platelet levels (P=0.014), and shorter activated partial thromboplastin time (P<0.001).

Conclusion

Shortened PT on postoperative day 7 is an independent risk factor of recurrence after bladder cancer cryoablation.

图1 膀胱癌内镜下球囊冷冻消融关键步骤注:a示TURBt后的创面基底;b示冷冻消融导管球囊末端在膀胱镜直视下稳定定位于肿瘤床;c示球囊充盈并进行冷冻,形成冰球覆盖肿瘤床及周缘;d示完成冷冻循环并复温后创面情况
表1 冷冻消融术后7 d Logistic回归分析评估膀胱癌患者复发的危险因素
表2 冷冻消融术后4~6周单因素Logistic回归分析评估膀胱癌患者复发的危险因素
表3 不同凝血酶原时间组患者临床及病理特征比较
[1]
Fukushima H, Kobayashi M, Kawano K, et al. Effect of preoperative bacteriuria and pyuria on intravesical recurrence in patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy[J]. In Vivo, 2017, 31(6): 1215-1220. DOI: 10.21873/invivo.11193.
[2]
Roknsharifi S, Wattamwar K, Fishman MDC, et al. Image-guided microinvasive percutaneous treatment of breast lesions: where do we stand?[J]. RadioGraphics, 2021, 41(4): 945-966. DOI: 10.1148/rg.2021200156.
[3]
Mohammed A, Miller S, Douglas-Moore J, et al. Cryotherapy and its applications in the management of urologic malignancies: a review of its use in prostate and renal cancers[J]. Urol Oncol, 2014, 32(1): 39.e19-27. DOI: 10.1016/j.urolonc.2013.04.004.
[4]
Liang Z, Fei Y, Lizhi N, et al. Percutaneous cryotherapy for metastatic bladder cancer: experience with 23 patients[J]. Cryobiology, 2014, 68(1): 79-83. DOI: 10.1016/j.cryobiol.2013.12.004.
[5]
Hruby GW, Marruffo F, Ortiz J, et al. Transurethral bladder cryoablation in the porcine model[J]. Urology, 2007, 70(2): 391-395. DOI: 10.1016/j.urology.2007.03.028.
[6]
Power NE, Silberstein JL, Tarin T, et al. Endoscopic spray cryotherapy for genitourinary malignancies: safety and efficacy in a porcine model[J]. Ther Adv Urol, 2013, 5(3): 135-141. DOI: 10.1177/1756287212465457.
[7]
Zou L, Liu R, Xu C, et al. Ureteroscopic cryoablation for patients with upper tract urothelial carcinoma of a solitary kidney: a porcine model and our pilot clinical experience[J]. Ann Surg Oncol, 2021, 28(13): 9201-9208. DOI: 10.1245/s10434-021-10233-5.
[8]
Chen Y, Xu C, Mou Z, et al. Endoscopic cryoablation versus radical nephroureterectomy for upper tract urothelial carcinoma[J]. Eur Urol Oncol, 2024, 7(6): 1453-1461. DOI: 10.1016/j.euo.2024.04.012.
[9]
Czech AK, Gronostaj K, Frydrych J, et al. Identification of potential prognostic factors for absence of residual disease in the second resection of T1 bladder cancer[J]. Cent European J Urol, 2019, 72(3): 252-257. DOI: 10.5173/ceju.2019.1908.
[10]
Sylvester RJ, van der Meijden APM, Oosterlinck W, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials[J]. Eur Urol, 2006, 49(3): 466-465;discussion475-7. DOI: 10.1016/j.eururo.2005.12.031.
[11]
Thiele C, Hirschfeld G. Cutpointr: improved estimation and validation of optimal cutpoints in R[J]. J Stat Soft, 2021, 98(11): 1-27. DOI: 10.18637/jss.v098.i11.
[12]
Mou Z, Chen Y, Zhang Z, et al. Cryoablation inhibits the recurrence and progression of bladder cancer by enhancing tumour-specific immunity[J]. Clin Transl Med, 2023, 13(5): e1255. DOI: 10.1002/ctm2.1255.
[13]
Xu C, Jiang S, Zou L, et al. Endoscopic balloon cryoablation plus transurethral resection for bladder cancer: a phase 2, multicenter, randomized, controlled trial[J]. Cancer, 2023, 129(3): 415-425. DOI: 10.1002/cncr.34563.
[14]
Pandolfi F, Altamura S, Frosali S, et al. Key role of DAMP in inflammation, cancer, and tissue repair[J]. Clin Ther, 2016, 38(5): 1017-1028. DOI: 10.1016/j.clinthera.2016.02.028.
[15]
Vénéreau E, Ceriotti C, Bianchi ME. DAMPs from cell death to new life[J]. Front Immunol, 2015, 6: 422. DOI: 10.3389/fimmu.2015.00422.
[16]
黄海, 任海林. 凝血功能与泌尿系肿瘤的研究进展[J]. 临床医学进展, 2023, 13(10): 16406-16411. DOI: 10.12677/ACM.2023.13102296.
[17]
Ruf W, Yokota N, Schaffner F. Tissue factor in cancer progression and angiogenesis[J]. Thromb Res, 2010, 125 Suppl 2(02): S36-S38. DOI: 10.1016/S0049-3848(10)70010-4.
[18]
Voigtlaender M, Holstein K, Leuenroth S, et al. Clinical evidence that coagulation activation drives cancer progression - a report of 2 cases[J]. Oncol Res Treat, 2015, 38(9): 449-452. DOI: 10.1159/000433501.
[19]
Billroth T. Lectures on surgical pathology and therapeutics[M]. London, United Kingdom: The New Sydenham Society 1878.
[20]
Klepfish A, Greco MA, Karpatkin S. Thrombin stimulates melanoma tumor-cell binding to endothelial cells and subendothelial matrix[J]. Int J Cancer, 1993, 53(6): 978-982. DOI: 10.1002/ijc.2910530620.
[21]
Carney DH, Stiernberg J, Fenton JW 2nd. Initiation of proliferative events by human alpha-thrombin requires both receptor binding and enzymic activity[J]. J Cell Biochem, 1984, 26(3): 181-195. DOI: 10.1002/jcb.240260306.
[22]
Chen LB, Buchanan JM. Mitogenic activity of blood components. I. Thrombin and prothrombin[J]. Proc Natl Acad Sci USA, 1975, 72(1): 131-135. DOI: 10.1073/pnas.72.1.131.
[23]
Gasic GJ, Gasic TB, Galanti N, et al. Platelet-tumor-cell interactions in mice. The role of platelets in the spread of malignant disease[J]. Int J Cancer, 1973, 11(3): 704-718. DOI: 10.1002/ijc.2910110322.
[24]
赵汉卫, 徐良, 邵先安. 凝血酶原时间联合纤维蛋白降解产物评价多发伤预后的临床研究[J]. 血栓与止血学, 2024, 30(2): 69-73. DOI: 10.3969/j.issn.1009-6213.2024.02.005.
[25]
Thomas GM, Brill A, Mezouar S, et al. Tissue factor expressed by circulating cancer cell‐derived microparticles drastically increases the incidence of deep vein thrombosis in mice[J]. J Thromb Haemost, 2015, 13(7): 1310-1319. DOI: 10.1111/jth.13002.
[26]
Khorana AA, Kamphuisen PW, Meyer G, et al. Tissue factor as a predictor of recurrent venous thromboembolism in malignancy: biomarker analyses of the CATCH trial[J]. J Clin Oncol, 2017, 35(10): 1078-1085. DOI: 10.1200/jco.2016.67.4564.
[27]
Bernstein DE, Jeffers L, Erhardtsen E, et al. Recombinant factor VIIa corrects prothrombin time in cirrhotic patients: a preliminary study[J]. Gastroenterology, 1997, 113(6): 1930-1937. DOI: 10.1016/s0016-5085(97)70013-1.
[28]
Van Bruggen S, Martinod K. The coming of age of neutrophil extracellular traps in thrombosis: where are we now and where are we headed?[J]. Immunol Rev, 2023, 314(1): 376-398. DOI: 10.1111/imr.13179.
[29]
Thålin C, Hisada Y, Lundström S, et al. Neutrophil extracellular traps: villains and targets in arterial, venous, and cancer-associated thrombosis. arterioscler thromb vasc biol[J]. 2019, 39(9):1724-1738. DOI: 10.1161/ATVBAHA.119.312463.
[30]
Geddings JE, Hisada Y, Boulaftali Y, et al. Tissue factor-positive tumor microvesicles activate platelets and enhance thrombosis in mice[J]. J Thromb Haemost, 2016, 14(1): 153-166. DOI: 10.1111/jth.13181.
[31]
Heuberger DM, Schuepbach RA. Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases[J]. Thromb J, 2019, 17(1): 4. DOI: 10.1186/s12959-019-0194-8.
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