成人肾上腺皮质癌预后的影响因素分析
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摘要
【目的】探讨影响成人肾上腺皮质癌(ACC)预后的潜在因素。【方法】回顾性收集2011年12月至2017年3月在中山大学孙逸仙纪念医院就诊并经病理确诊的成人ACC患者,主要收集患者的临床资料及术前实验室检查结果。采用Kaplan-Meier法绘制生存曲线及计算中位生存时间和平均生存时间,采用Log-rank检验比较各组间生存率差异,采用单因素及多因素Cox回归模型计算风险比(HR)及95%置信区间(95%CI)。【结果】纳入成人ACC患者20例。中位随访时间13个月(6～73个月),平均生存时间49.2个月(6～73个月),1年总生存率为70.0%。Cox多因素分析结果提示合并皮质醇高分泌(HR=14.53,95%CI:1.11-190.80,P=0.042)、低钾血症(HR=23.60,95%CI:2.49-223.79,P=0.006)的ACC患者预后不良。此外,在18例行根治性切除术的患者中,多因素分析结果提示合并低钾血症(HR=6.45,95%CI:1.41-29.54,P=0.016)的患者肿瘤复发风险增加。【结论】合并皮质醇高分泌、低钾血症是影响成人ACC预后的独立危险因素。
【Objective】To analyze the prognostic determinants of adrenocortical carcinoma(ACC)in adults.【Meth?ods】All adult patients who were admitted to Sun Yat-sen Memorial Hospital,Sun Yat-sen University from December2011 to March 2017 and pathologically diagnosed ACC were included in this study. The clinical data and preoperative lab?oratory examinations of those patients were analyzed retrospectively. Overall survival or disease-free survival was calculat?ed and survival curves were plotted by Kaplan-Meier and compared by log-rank test. Harzard ratios(HRs)with their95% confidence intervals(CIs)were calculated by univariate and multivariate Cox regression model.【Results】The study included 20 adult patients with ACC,with a median follow-up of 13 months(6～73 months). The mean survival time of those patients was 49.2 months(6～73 months),with a 1-year survival rate of 70.0%. The results of multivariate Cox re?gression analysis revealed that the presense of cortisol hypersecretion(HR=23.60,95% CI:2.49-223.79,P=0.006)and hypokalemia(HR=23.60,95% CI:2.49-223.79,P=0.006)were predictors of poor prognosis of ACC.Moreover,in 18 patients with completely resected ACC,the presense of hypokalemia resulted in a worse disease-free survival.【Conclu?sion】The presense of cortisol hypersecretion and hypokalemia are independent risk factors associated with poor prognosis of ACC in adults.
【Objective】To analyze the prognostic determinants of adrenocortical carcinoma(ACC)in adults.【Meth?ods】All adult patients who were admitted to Sun Yat-sen Memorial Hospital,Sun Yat-sen University from December2011 to March 2017 and pathologically diagnosed ACC were included in this study. The clinical data and preoperative lab?oratory examinations of those patients were analyzed retrospectively. Overall survival or disease-free survival was calculat?ed and survival curves were plotted by Kaplan-Meier and compared by log-rank test. Harzard ratios(HRs)with their95% confidence intervals(CIs)were calculated by univariate and multivariate Cox regression model.【Results】The study included 20 adult patients with ACC,with a median follow-up of 13 months(6～73 months). The mean survival time of those patients was 49.2 months(6～73 months),with a 1-year survival rate of 70.0%. The results of multivariate Cox re?gression analysis revealed that the presense of cortisol hypersecretion(HR=23.60,95% CI:2.49-223.79,P=0.006)and hypokalemia(HR=23.60,95% CI:2.49-223.79,P=0.006)were predictors of poor prognosis of ACC.Moreover,in 18 patients with completely resected ACC,the presense of hypokalemia resulted in a worse disease-free survival.【Conclu?sion】The presense of cortisol hypersecretion and hypokalemia are independent risk factors associated with poor prognosis of ACC in adults.
引文
[1] Hoff AO, Berruti A. 5th International ACCSymposium:Future and Current Therapeutic Trialsin Adrenocortical Carcinoma[J]. Horm Cancer,2016,7(1):29-35.
[2] Creemers SG,Hofland LJ,Korpershoek E,et al.Future directions in the diagnosis and medicaltreatment of adrenocortical carcinoma[J]. EndocrRelat Cancer,2016,23(1):R43-R69.
[3]中华医学会内分泌学分会.库欣综合征专家共识(2011年)[J].中华内分泌代谢杂志,2012,28(2):96-102.Chinese Society of Endocrinology. Expert consensuson Cushing′s syndrome(2011)[J]. Chin JEndocrinol Metab,2012,28(2):96-102.
[4] Berruti A,Baudin E,Gelderblom H,et al. Adrenalcancer:ESMO Clinical Practice Guidelines fordiagnosis,treatment and follow-up[J]. Ann Oncol,2012,23 Suppl 7:i131-i138.
[5] Berruti A,Fassnacht M,Haak H,et al. Prognosticrole of overt hypercortisolism in completely operatedpatients with adrenocortical cancer[J]. Eur Urol,2014,65(4):832-838.
[6] Szyszka P,Grossman AB,Diaz-Cano S,et al.Molecular pathways of human adrenocorticalcarcinoma-translating cell signalling knowledgeinto diagnostic and treatment options[J].Endokrynol Pol,2016,67(4):427-450.
[7] Else T,Kim AC,Sabolch A,et al. Adrenocorticalcarcinoma[J]. Endocr Rev,2014,35(2):282-326.
[8] Rao S N, Habra M A. 5th International ACCSymposium:Old Syndromes with New Biomarkersand New Therapies with Old Medications[J]. HormCancer,2016,7(1):17-23.
[9]刘洋,王椿,丁振宇,等.肾上腺皮质癌的临床预后分析[J].四川大学学报(医学版),2012,43(2):293-296.Liu Y,Wang C,Ding ZY,et al. Prognosis of Patientswith Adrenocortical Carcinoma[J]. J Sichuan Univ(Med Sci),2012,43(2):293-296.
[10]张明峰,王椿,黄慧,等.成人肾上腺皮质癌预后因素的分析[J].四川大学学报(医学版),2015,46(2):248-252.Zhang MF,Wang C,Huang H,et al. PrognosticDeterminants of Adrenocortical Carcinoma in Adults[J]. J Sichuan Univ(Med Sci),2015,46(2):248-252.
[11]Tella S H, Kommalapati A, Yaturu S, et al.Predictors of survival in Adrenocortical Carcinoma:An analysis from the National Cancer Database(NCDB)[J]. J Clin Endocrinol Metab,2018,103(9):3566-3573.
[12]张发明,林浩,潘金成,等.肾上腺皮质癌中血管拟态和VEGFR-2的表达及临床意义[J].中山大学学报(医学科学版),2015,36(2):215-220.ZHANG FM,LIN H,PAN JC,et al. ClinicalSignificances of Vasculogenic Mimicry and VEGFR-2 in Adrenocortical Carcinoma[J]. Sun Yat-senUniv(Med Sci),2015,36(2):215-220.
[13]廉建坡,祝宇.肾上腺皮质癌的治疗进展[J].现代泌尿外科杂志,2015,20(4):275-280.Lian JP, Zhu Y. Advances in treatment ofAdrenocortical Carcinoma[J]. J Modern Urology,2015,20(4):275-280.
[14]Livhits M,Li N,Yeh M W,et al. Surgery isassociated with improved survival for adrenocorticalcancer,even in metastatic disease[J]. Surgery,2014,156(6):1531-1540,1540-1541.
[15]Kim Y,Margonis G A,Prescott J D,et al. CurativeSurgical Resection of Adrenocortical Carcinoma:Determining Long-term Outcome Based onConditional Disease-free Probability[J]. Ann Surg,2017,265(1):197-204.
[16]Erdogan I,Deutschbein T,Jurowich C,et al. Therole of surgery in the management of recurrentadrenocortical carcinoma[J]. J Clin EndocrinolMetab,2013,98(1):181-191.
[17]Fassnacht M, Kroiss M, Allolio B. Update inadrenocortical carcinoma[J]. J Clin EndocrinolMetab,2013,98(12):4551-4564.
[18]Machado NO,Al QH,Al WK,et al. LaparoscopicAdrenalectomy for Large Adrenocortical Carcinoma[J]. JSLS,2015,19(3).
[19]Dworakowska D,Drabarek A,Wenzel I,et al.Adrenocortical cancer(ACC)-literature overviewand own experience[J]. Endokrynol Pol,2014,65(6):492-502.
[20]Margonis GA,Kim Y,Tran TB,et al. Outcomesafter resection of cortisol-secreting adrenocorticalcarcinoma[J]. Am J Surg,2016,211(6):1106-1113.
[21]冯莉霞,王华庆.恶性肿瘤患者合并低钾血症治疗的研究现状[J].医学综述,2013,19(18):3310-3312.Feng LX, Wang HQ. Research Progress ofTreatment in Hypokalemia among Cancer Patients[J]. Medical Recapitulate,2013,19(18):3310-3312.
[22]Eliacik E,Yildirim T,Sahin U,et al. Potassiumabnormalities in current clinical practice:frequency,causes,severity and management[J].Med Princ Pract,2015,24(3):271-275.
[2] Creemers SG,Hofland LJ,Korpershoek E,et al.Future directions in the diagnosis and medicaltreatment of adrenocortical carcinoma[J]. EndocrRelat Cancer,2016,23(1):R43-R69.
[3]中华医学会内分泌学分会.库欣综合征专家共识(2011年)[J].中华内分泌代谢杂志,2012,28(2):96-102.Chinese Society of Endocrinology. Expert consensuson Cushing′s syndrome(2011)[J]. Chin JEndocrinol Metab,2012,28(2):96-102.
[4] Berruti A,Baudin E,Gelderblom H,et al. Adrenalcancer:ESMO Clinical Practice Guidelines fordiagnosis,treatment and follow-up[J]. Ann Oncol,2012,23 Suppl 7:i131-i138.
[5] Berruti A,Fassnacht M,Haak H,et al. Prognosticrole of overt hypercortisolism in completely operatedpatients with adrenocortical cancer[J]. Eur Urol,2014,65(4):832-838.
[6] Szyszka P,Grossman AB,Diaz-Cano S,et al.Molecular pathways of human adrenocorticalcarcinoma-translating cell signalling knowledgeinto diagnostic and treatment options[J].Endokrynol Pol,2016,67(4):427-450.
[7] Else T,Kim AC,Sabolch A,et al. Adrenocorticalcarcinoma[J]. Endocr Rev,2014,35(2):282-326.
[8] Rao S N, Habra M A. 5th International ACCSymposium:Old Syndromes with New Biomarkersand New Therapies with Old Medications[J]. HormCancer,2016,7(1):17-23.
[9]刘洋,王椿,丁振宇,等.肾上腺皮质癌的临床预后分析[J].四川大学学报(医学版),2012,43(2):293-296.Liu Y,Wang C,Ding ZY,et al. Prognosis of Patientswith Adrenocortical Carcinoma[J]. J Sichuan Univ(Med Sci),2012,43(2):293-296.
[10]张明峰,王椿,黄慧,等.成人肾上腺皮质癌预后因素的分析[J].四川大学学报(医学版),2015,46(2):248-252.Zhang MF,Wang C,Huang H,et al. PrognosticDeterminants of Adrenocortical Carcinoma in Adults[J]. J Sichuan Univ(Med Sci),2015,46(2):248-252.
[11]Tella S H, Kommalapati A, Yaturu S, et al.Predictors of survival in Adrenocortical Carcinoma:An analysis from the National Cancer Database(NCDB)[J]. J Clin Endocrinol Metab,2018,103(9):3566-3573.
[12]张发明,林浩,潘金成,等.肾上腺皮质癌中血管拟态和VEGFR-2的表达及临床意义[J].中山大学学报(医学科学版),2015,36(2):215-220.ZHANG FM,LIN H,PAN JC,et al. ClinicalSignificances of Vasculogenic Mimicry and VEGFR-2 in Adrenocortical Carcinoma[J]. Sun Yat-senUniv(Med Sci),2015,36(2):215-220.
[13]廉建坡,祝宇.肾上腺皮质癌的治疗进展[J].现代泌尿外科杂志,2015,20(4):275-280.Lian JP, Zhu Y. Advances in treatment ofAdrenocortical Carcinoma[J]. J Modern Urology,2015,20(4):275-280.
[14]Livhits M,Li N,Yeh M W,et al. Surgery isassociated with improved survival for adrenocorticalcancer,even in metastatic disease[J]. Surgery,2014,156(6):1531-1540,1540-1541.
[15]Kim Y,Margonis G A,Prescott J D,et al. CurativeSurgical Resection of Adrenocortical Carcinoma:Determining Long-term Outcome Based onConditional Disease-free Probability[J]. Ann Surg,2017,265(1):197-204.
[16]Erdogan I,Deutschbein T,Jurowich C,et al. Therole of surgery in the management of recurrentadrenocortical carcinoma[J]. J Clin EndocrinolMetab,2013,98(1):181-191.
[17]Fassnacht M, Kroiss M, Allolio B. Update inadrenocortical carcinoma[J]. J Clin EndocrinolMetab,2013,98(12):4551-4564.
[18]Machado NO,Al QH,Al WK,et al. LaparoscopicAdrenalectomy for Large Adrenocortical Carcinoma[J]. JSLS,2015,19(3).
[19]Dworakowska D,Drabarek A,Wenzel I,et al.Adrenocortical cancer(ACC)-literature overviewand own experience[J]. Endokrynol Pol,2014,65(6):492-502.
[20]Margonis GA,Kim Y,Tran TB,et al. Outcomesafter resection of cortisol-secreting adrenocorticalcarcinoma[J]. Am J Surg,2016,211(6):1106-1113.
[21]冯莉霞,王华庆.恶性肿瘤患者合并低钾血症治疗的研究现状[J].医学综述,2013,19(18):3310-3312.Feng LX, Wang HQ. Research Progress ofTreatment in Hypokalemia among Cancer Patients[J]. Medical Recapitulate,2013,19(18):3310-3312.
[22]Eliacik E,Yildirim T,Sahin U,et al. Potassiumabnormalities in current clinical practice:frequency,causes,severity and management[J].Med Princ Pract,2015,24(3):271-275.