Objective To investigate the clinical effect of precise sequential interventional therapy in patients with unresectable hepatic metastasis after surgery for colorectal cancer. Methods The clinical data of 63 patients with unresectable hepatic metastasis after surgery for colorectal cancer,who were admitted to Air Force General Hospital,PLA from January 2005 to September 2012,were collected. According to therapeutic methods,these patients were divided into precise sequential interventional therapy group( group A,33 patients) and systemic chemotherapy group( group B,30 patients). The patients in group A underwent transcatheter arterial chemoembolization and radiofrequency ablation,and those in group B underwent systemic chemotherapy. The percentages of peripheral blood CD3+,CD4+,and CD8+T cells and CD4+/ CD8+ratio were measured before and after the initial treatment. The level of carcinoembryonic antigen( CEA) was measured and compared before the initial treatment and after the final treatment,and follow- up was conducted to observe tumor progression and survival.The t- test was applied for comparison of continuous data between groups; the chi- square test was applied for comparison of categorical data between groups; the Wilcoxon rank sum test was applied for comparison of clinical effect; the Log- Rank test was applied for comparison of survival rate. Results In group A,the percentages of CD3+,CD4+,and CD8+T cells and CD4+/ CD8+ratio changed significantly after the initial treatment( t = 4. 52,- 3. 27,2. 95,and 4. 54,all P < 0. 05); serum CEA level also changed significantly after treatment( 38. 76 ± 9. 57) μg/ml vs( 10. 53 ± 8. 62) μg/ml,t = 2. 13,P = 0. 03). The serum level of CEA after the final treatment showed a significant difference between group A and group B( 10. 53 ± 8. 62) ug / L vs( 35. 21 ± 10. 22) μg / L; t = 5. 23,P < 0. 01). Group A had a significantly higher objective response rate than group B( 66. 7% vs 43. 3%; Z =- 2. 042,P = 0. 041). Group A had a significantly longer survival time than group B,and group A had a significantly higher surrival rate than group B( 45. 5% vs 23. 3%,χ2= 3. 97,P = 0. 046).Conclusion In patients with unresectable hepatic metastasis after surgery for colorectal cancer,precise sequential interventional therapy can improve their immune function,increase clinical outcome,and prolong survival time.
按照UDCA治疗应答情况，637例患者中436例发生完全应答，201例为应答不良。性别分布中，完全应答组与应答不良组分布无统计学意义(P值均＞0.05)，基线存在肝硬化的患者UDCA应答率更高(78.9% vs 71.1%，P=0.032)，生化指标中，TBil、AST、ALP、TBA和TC在两组间存在统计学差异(P值均＜0.001)。免疫指标中，应答不良组IgA、IgM水平及抗Gp210阳性率均较高(P值均＜0.05)。预后风险评分中，应答不良组MRS、Globe评分、UK-PBC评分均高于完全应答组(P值均＜0.001)(表 2)。
表
2
UDCA治疗完全应答与应答不良患者基线指标及风险评分差异
Table
2.
Differences of baseline characteristics and risk scores between PBC with complete response and poor response to UDCA treatment
根据IgM预测UDCA应答不良的最佳临界值将患者分为IgM≥1.5×ULN及IgM＜1.5×ULN两组，性别分布、年龄、肝硬化占比在两组中比较差异均无统计学意义(P值均＞0.05)；IgM≥1.5×ULN组AST、ALP、TC显著高于IgM＜1.5×ULN组(P值均＜0.05)；IgM≥1.5×ULN组IgG水平及抗Gp210阳性率显著高于IgM＜1.5×ULN组(P值均＜0.001)。IgM≥1.5×ULN组经过UDCA治疗后发生应答不良患者显著高于IgM＜1.5×ULN组(38.3% vs 27.1%，P=0.003)(表 5)。
表
5
不同IgM水平PBC患者基线临床特征及UDCA疗效比较
Table
5.
Comparison of baseline characteristics and the outcome of UDCA treatment between PBC with different levels of IgM
UDCA是PBC治疗的一线药物，可显著改善部分PBC患者非肝移植存活率[11-12]，但仍有30%~40%的患者对UDCA治疗无应答，本研究中显示UDCA完全应答率为68.4%，对于这部分患者需要及时联合一种或两种二线药物来改善胆汁淤积以预防疾病进展[13]。UDCA治疗可能影响IgM水平，研究[14]发现UDCA能够显著降低细菌CpG诱导的总IgM和IgM-AMA的产生，但对IgG-AMA的水平却无影响。IgM与肝硬化相关症状和肝脏相关事件的发生关系密切，在UDCA联合苯扎贝特治疗过程中，不论ALP及GGT下降与否，当IgM水平持续异常时，患者的预后均较差，其生存期显著低于IgM水平正常化的患者，治疗过程中IgM水平的逐步正常化可能提示预后较好[15]。对于UDCA不完全应答的PBC患者，在给予联合利妥昔单抗治疗后，IgM水平随着肝功能指标的好转而逐步下降[16]。IgM正常化可作为长期预后的预测指标，但初始IgM正常患者IgM水平的变化情况及预测因素尚缺乏研究。在本研究中，UDCA治疗基线IgM平均水平为2.76 g/L，IgM升高的占比为56.0%，在UDCA完全应答组与应答不良组之间，基线IgM水平存在显著性差异(P=0.034)，进一步分析IgM升高与IgM正常组患者的临床特征及在UDCA治疗1年后的疗效差异，发现IgM正常组UDCA应答率高于IgM升高组(71.8% vs 65.8%)，但两组差异无统计学意义(P=0.108)，通过ROC曲线分析获得IgM预测UDCA治疗1年后应答不良风险的最佳临界值(1.5×ULN)，按最佳临界值进行分组后，结果显示IgM＜1.5×ULN组的PBC患者发生UDCA应答率显著高于IgM≥1.5×ULN组(72.9% vs 61.7%, P=0.003)，IgM≥1.5×ULN组发生UDCA应答不良风险是前者的1.416倍(95%CI: 1.129~1.776)，因此基线IgM水平可能有助于预测PBC治疗应答。
[1]LIU HZ,YANG BQ,LI YS,et al.Retrospective clinical analysis of 63 patients with liver metastasis of colorectal cancer[J/CD].Chin J Oper Proc Gen Surg:Electronic Edition,2012,6(2):41-43.(in Chinese)刘洪洲,杨丙全,李永胜,等.63例大肠癌肝转移患者的回顾性临床分析[J/CD].中华普外科手术学杂志:电子版,2012,6(2):41-43.
[2]DAI Z,ZHENG RS,ZOU XN,et al.Analysis and prediction of colorectal cancer incidence trend in China[J].Chin J Prevent Med,2012,46(7):598-603.(in Chinese)代珍,郑荣寿,邹小农,等.中国结直肠癌发病趋势分析和预测[J].中华预防医学杂志,2012,46(7):598-603.
[3]WENG HW,CAI XL.Investigation of quality of life and psychological conditions in patients with colorectal cancer[J/CD].J Dig Oncol:Electronic version,2014,6(1):23-27.(in Chinese)翁慧雯,蔡晓琳.结直肠患者生活质量及心理状况的调查研究[J/CD].消化肿瘤杂志:电子版,2014,6(1):23-27.
[4]KUMAR R,PRICE TJ,BEEKE C,et al.Colorectal cancer survival:an analysis of patients with metastatic disease synchronous and metachronous with the primary tumor[J].Clin Colorectal Cancer,2014,13(2):87-93.
[5]ABDALLA EK,JEAN-NICOLAS V,ELLIS LM,et al.Recurrence and outcomes following hepatic resection,radiofrequency ablation,and combined resection/ablation for colorectal liver metastases[J].Ann Surg,2004,239(6):818-827.
[6]GLEISNER AL,CHOTI MA,LIA A,et al.Colorectal liver metastases:recurrence and survival following hepatic resection,radiofrequency ablation,and combined resection-radiofrequency ablation[J].Arch Surg,2008,143(12):1204-1212.
[7]PULITANC,BODINGBAUER M,ALDRIGHETTI L,et al.Liver Resection for colorectal metastases in presence of extrahepatic disease:results from an international multi-institutional analysis[J].Ann Surg Oncol,2011,18(5):1380-1388.
[8]MICHAEL V,LAURA K,ROHI A,et al.Radiological-pathological analysis of WHO,RECIST,EASL,mRECIST and DWI:imaging analysis from a prospective randomized trial of Y90±sorafenib.[J].Hepatology,2013,58(5):1655-1666.
[9]DONG JH,HUANG ZQ.Precise liver resection——new concept of liver surgery in 21st century[J].Chin J Surg,2010,47(21):1601-1605.(in Chinese)董家鸿,黄志强.精准肝切除——21世纪肝脏外科新理念[J].中华外科杂志,2010,47(21):1601-1605.
[10]CABIBBO G,LATTERI F,ANTONUCCI M,et al.Multimodal approaches to the treatment of hepatocellular carcinoma[J].Nat Clin Pract Gastroenterol Hepatol,2009,6(3):159-169.
[11]ZHANG HY,FENG ZQ,ZHANG HY,et al.Efficacy of precise sequential therapy for primary liver cancer[J].Chin J Digest Surg,2012,11(1):73-78.(in Chinese)张洪义,冯志强,张宏义,等.原发性肝癌精准序贯治疗的疗效分析[J].中华消化外科杂志,2012,11(1):73-78.
[12]CANNON R,ELLIS S,HAYES D,et al.Safety and early efficacy of irreversible electroporation for hepatic tumors in proximity to vital structures[J].J Surg Oncol,2013,107(5):544-549.
[13]VOGL TJ,FARSHID P,NAGUIB NN,et al.Thermal ablation of liver metastases from colorectal cancer:radiofrequency,microwave and laser ablation therapies[J].Radiol Med,2014,7(119):451-461.
[14]WAITZ R,SOLOMON S.Can local radiofrequency ablation of tumors generate systemic immunity against metastatic disease?[J].Radiology,2009,251(1):1-2.
[15]HAEN SP,PEREIRA PL,SALIH HR,et al.More than just tumor destruction:immunomodulation by thermal ablation of cancer[J].Clin Dev Immunol,2011,2011:160250.
[16]GOLDBERG SN.Science to practice:can we expand focal interventional oncologic ablation treatments into an effective systemic therapy?[J].Radiology,2013,267(2):321-323.
[17]DROMI S,WALSH MS,TRAUGHBER B,et al.Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity[J].Radiology,2009,251(1):58-66.
[18]WISSNIOWSKI TT,HAENSLER J,SCHUPPAN D,et al.Activation of tumor specific T-lymphocytes caused by radio frequency ablation of liver tumors-a patient study[J].Gastroenterology,2003,124(4):a772.
HAN L, LIANG QS, XIE H, et al. Value of baseline IgM level in predicting the treatment response of primary biliary cholangitis[J]. J Clin Hepatol, 2022, 38(4): 815-820. DOI: 10.3969/j.issn.1001-5256.2022.04.015.
HAN L, LIANG QS, XIE H, et al. Value of baseline IgM level in predicting the treatment response of primary biliary cholangitis[J]. J Clin Hepatol, 2022, 38(4): 815-820. DOI: 10.3969/j.issn.1001-5256.2022.04.015.
下载:
DownLoad: