Abstract:

Objective　To explore the clinical significance of carbohydrate antigen 19-9 (CA19-9) and neutrophil to lymphocyte ratio (NLR) in the prognosis of patients with gallbladder cancer after radical surgery. Methods　Seventy-two patients with gallbladder cancer who underwent radical resection in Linyi Central Hospital from January 2015 to December 2021 and completed one-year follow-up were selected as a gallbladder cancer group, including 39 cases and 33 cases who were (63.19±3.85) years old. According to the 1:1 matching principle, another 72 patients with gallbladder polyps during the same period were selected as a control group, including 37 males and 35 females who were (62.54±3.52) years old. The serum levels of CA19-9 and NLR's were compared between the two groups at admission. The levels of CA19-9 and NLR's were compared between the patients with different outcomes at admission and 1 week after the surgery and between the patients with different pathological parameters. Spearman analysis was used to investigate the correlations of CA19-9 and NLR with pathological parameters and disease outcomes at admission. The receiver operating characteristic curve (ROC) was used to investigate the predictive values of the combined detection at admission and 1 week after surgery for poor outcomes in the patients with gallbladder cancer. Results　The serum level of CA19-9 and NLR at admission in the gallbladder cancer group were higher than those in the control group [(237.14±38.41) U/ml vs. (31.87±6.43) U/ml and (4.02±1.25) vs. (1.84±0.43); both P<0.05]. The serum levels of CA19-9 and NLR's at admission and 1 week after the surgery in the patients with poor prognosis were higher than those in the patients with good prognosis [(261.71±25.33) U/ml vs. (218.56±24.52) U/ml, (4.73±1.02) vs. (3.48±0.75), (181.64±28.58) U/ml vs. (85.43±12.19) U/ml, and (3.37±0.48) vs. (2.24±0.53); all P<0.05]. Comparison of serum level of CA19-9 and NLR between the patients with different pathological parameters: those in the moderately and highly differentiated patients were lower than those in the poorly differentiated patients [(208.41±22.83) U/ml vs. (294.60±23.18) U/ml and (3.14±0.47) vs. (5.78±0.69)]; those in the stage Ⅰ-Ⅱ patients were lower than those in the stage Ⅲ-Ⅳpatients [(188.43±25.63) U/ml vs. (276.11±23.08) U/ml and (2.95±0.57) vs. (4.88±0.64)]; those in the patients with no lymph node metastasis were lower than those in the patients with lymph node metastasis [(206.93±24.25) U/ml vs. (287.49±16.64) U/ml and (3.38±0.49) vs. (5.09±0.73)]; both indicators were negatively correlated with tissue differentiation (r=-0.698 and -0.533), and positively correlated with clinical stage (r=0.742 and 0.659), lymph node metastasis (r=0.701 and 0.634), and disease outcome (r=0.588 and 0.719) (all P<0.05). The areas under the curves (AUC) of serum CA19-9 and NLR for predicting poor prognosis in the patients at admission and 1 week after the surgery were 0.776 (95%CI 0.718-0.839) and 0.834 (95%CI 0.768-0.906), respectively. The optimal predictive sensitivities were 87.10% and 93.55%, respectively; the optimal predictive specificities were 68.29% and 73.17%, respectively. Conclusion　CA19-9 and NLR are upregulated in the serum of patients with poor prognosis after radical cholecystectomy for gallbladder cancer. These two indicators are correlated with clinical pathological parameters and disease outcomes. The combined detection has certain predictive value for prognosis and can be used as auxiliary indicators for clinical prediction of the patients' postoperative prognosis.

Key words:

Gallbladder cancer, Carbohydrate antigen 19-9, Neutrophil to lymphocyte ratio, Radical surgery, Disease outcomes, Predictive value

摘要：

目的　探讨糖类抗原19-9（carbohydrate antigen 19-9，CA19-9）、中性粒细胞/淋巴细胞比值（neutrophil to lymphocyte ratio，NLR）在胆囊癌根治手术后患者疾病转归中的临床意义。方法　选取2015年1月至2021年12月于临沂市中心医院行胆囊癌根治术且均完成1年随访的72例胆囊癌患者为胆囊癌组，其中，男39例，女33例，年龄（63.19±3.85）岁。根据1∶1配对原则，另选取同期72例胆囊息肉患者为对照组，其中，男37例，女35例，年龄（62.54±3.52）岁。比较两组入院时血清CA19-9水平、NLR，比较入院时、术后1周不同疾病转归胆囊癌患者血清CA19-9水平、NLR，比较不同病理学参数胆囊癌患者血清CA19-9水平、NLR。Spearman分析入院时血清CA19-9水平、NLR与病理学参数及疾病转归的相关性。采用受试者操作特征曲线（receiver operating characteristic curve，ROC）分析入院时、术后1周血清CA19-9水平、NLR联合检测对胆囊癌患者转归不良的预测价值。结果　入院时，胆囊癌组血清CA19-9水平、NLR均高于对照组［（237.14±38.41）U/ml比（31.87±6.43）U/ml、（4.02±1.25）比（1.84±0.43）；均P<0.05］。转归不良患者入院时、术后1周血清CA19-9水平、NLR均高于转归良好患者［（261.71±25.33）U/ml比（218.56±24.52）U/ml、（4.73±1.02）比（3.48±0.75），（181.64±28.58）U/ml比（85.43±12.19）U/ml、（3.37±0.48）比（2.24±0.53）；均P<0.05］。不同病理参数胆囊癌患者血清CA19-9水平、NLR比较：中高分化患者低于低分化患者［（208.41±22.83）U/ml比（294.60±23.18）U/ml、（3.14±0.47）比（5.78±0.69）］，Ⅰ～Ⅱ期患者低于Ⅲ～Ⅳ期患者［（188.43±25.63）U/ml比（276.11±23.08）U/ml、（2.95±0.57）比（4.88±0.64）］，无淋巴结转移的患者低于有淋巴结转移的患者［（206.93±24.25）U/ml比（287.49±16.64）U/ml、（3.38±0.49）比（5.09±0.73）］，且两指标水平与组织分化程度（r=-0.698、-0.533）呈负相关，与临床分期（r=0.742、0.659）、淋巴结转移（r=0.701、0.634）、疾病转归（r=0.588、0.719）均呈正相关（均P<0.05）。入院时、术后1周血清CA19-9水平、NLR联合预测胆囊癌患者转归不良的曲线下面积（area under the curve，AUC）分别为0.776（95%CI 0.718～0.839）、0.834（95%CI 0.768～0.906），最佳预测灵敏度分别为87.10%、93.55%，最佳预测特异度分别为68.29%、73.17%。结论　CA19-9、NLR在胆囊癌根治术后转归不良患者血清中表达上调，两指标与临床病理参数及疾病转归均有一定相关性。两者联合检测对转归情况具有一定预测价值，可作为临床预测根治术后患者转归情况的辅助指标。

关键词:

胆囊癌, CA19-9, NLR, 根治手术, 疾病转归, 预测价值