NATIONAL BOGOMOLETS MEDICAL UNIVERSITY, KYIV, UKRAINE.
NATIONAL BOGOMOLETS MEDICAL UNIVERSITY, KYIV, UKRAINE; UKRAINIAN SCIENTIFIC AND PRACTICAL CENTER OF ENDOCRINE SURGERY, TRANSPLANTATION OF ENDOCRINE ORGANS AND TISSUES OF MINISTRY OF HEALTH OF UKRAINE, KYIV, UKRAINE.
Wiad Lek. 2023;76(3):560-567. doi: 10.36740/WLek202303115.
The aim: To evaluate changes in the levels of hepatocyte apoptosis markers in malignant obstructive jaundice (MOJ) depending on the performance of preoperative biliary decompression (PBD) and the severity degree of primary ascending cholangitis (PAC).
Materials and methods: 136 patients with MOJ complicated by cholangitis were included in the study: group A (n=84) - patients who underwent PBD; group B (n=52) - patients without PBD. The level of CASP3 and Bcl-2 (Human Bcl-2(B-cell Leukemia/Lymphoma 2) in blood serum and bile was assessed according to the principle of Sandwich-ELISA. Material collection for research was performed at the PBD stage and intraoperatively.
Results: Comparative analysis of CASP3 levels in patients of the study groups revealed that the level of this indicator in the blood and bile of group A patients was statistically significantly higher compared to group B, p=0,004 and p<0,001, respectively. There was no statistically significant difference between the study groups in the intraoperative levels of blood serum Bcl-2 (p=0,786) and bile Bcl-2 (p=0,439). The presence of a correlation between apoptosis markers in group A patients with I and II degree of PAC at the time of PBD and the main surgical intervention was determined: blood serum CASP3 - r=0,733, p<0,001 and r=0,753, p<0,001; bile CASP3 - r=0,716, p<0,001 and r=0,792, p<0,001; blood serum Bcl-2 - r=0,609, p<0,001 and r=0,495, p=0,002; bile Bcl-2- r=0,744, p<0,001 and r=0,497, p=0,002, respectively. Binary logistic regression analysis showed that the development of grade I and II PAC did not relate with the levels of apoptosis markers (p>0.05). Linear regression analysis revealed a correlation between the levels of Bcl-2 in bile during PBD and intraoperatively in group A patients with moderate grade OJ (R2=0,547, p<0,001) and between the levels of CASP3 in blood serum (R2=0,614, p<0,001), CASP3 in bile (R2=0,603, p<0,001), Bcl-2 in blood serum (R2=0,484, p<0,001) and Bcl-2 in bile (R2=0,485, p<0,001) in PBD and intraoperatively in patients with severe grade OJ. A statistically significant difference in the levels of Bcl-2 in blood serum (p<0,001) and Bcl-2 in bile (p=0,016) was found when comparing apoptosis markers in patients with moderate grade OJ of the study groups. Binary logistic analysis showed that the performance of PBD had a significant (reducing) effect on CASP3 levels in blood serum and bile taken intraoperatively in study groups patients with moderate grade OJ (R2= 0,292, p<0,001; R2= 0,184, p<0,001).
Conclusions: Prolonged OJ leads to the pathological apoptosis process. The performance of PBD statistically significantly reduces the level of CASP3 in blood serum and bile, which is confirmed by further determination intraoper¬atively in patients with OJ complicated by PAC, p<0,001. Staged surgical intervention with the performance of PBD according to clear indications is a necessary treatment strategy in patients with MOJ complicated by cholangitis.
评估恶性梗阻性黄疸(MOJ)患者术前胆道减压(PBD)和原发性上行性胆管炎(PAC)严重程度对肝细胞凋亡标志物水平的影响。
研究纳入了 136 例伴有胆管炎的 MOJ 患者:A 组(n=84)-接受 PBD 的患者;B 组(n=52)-未接受 PBD 的患者。根据夹心 ELISA 原则评估血清和胆汁中 CASP3 和 Bcl-2(人 Bcl-2(B 细胞白血病/淋巴瘤 2))的水平。研究材料收集在 PBD 阶段和手术期间进行。
对研究组患者 CASP3 水平的比较分析表明,A 组患者血液和胆汁中该指标的水平明显高于 B 组,p=0.004 和 p<0.001,分别。两组患者术中血清 Bcl-2(p=0.786)和胆汁 Bcl-2(p=0.439)水平无统计学差异。在 A 组患者中,I 级和 II 级 PAC 时 PBD 和主要手术干预的凋亡标志物之间存在相关性:血清 CASP3-r=0.733,p<0.001 和 r=0.753,p<0.001;胆汁 CASP3-r=0.716,p<0.001 和 r=0.792,p<0.001;血清 Bcl-2-r=0.609,p<0.001 和 r=0.495,p=0.002;胆汁 Bcl-2-r=0.744,p<0.001 和 r=0.497,p=0.002,分别。二元逻辑回归分析表明,I 级和 II 级 PAC 的发展与凋亡标志物水平无关(p>0.05)。线性回归分析显示,A 组中度 OJ 患者 PBD 和术中胆汁中 Bcl-2 水平之间存在相关性(R2=0.547,p<0.001),以及血清中 CASP3 水平(R2=0.614,p<0.001)、胆汁中 CASP3 水平(R2=0.603,p<0.001)、血清中 Bcl-2 水平(R2=0.484,p<0.001)和胆汁中 Bcl-2 水平(R2=0.485,p<0.001)之间存在相关性。在严重程度为 OJ 的患者中,PBD 和术中血清和胆汁中的 Bcl-2 水平存在统计学差异(p<0.001)。二元逻辑分析表明,在中度 OJ 研究组患者中,PBD 的实施对术中血清和胆汁中的 CASP3 水平具有显著(降低)作用(R2=0.292,p<0.001;R2=0.184,p<0.001)。
长期 OJ 导致病理性凋亡过程。PBD 的实施可显著降低伴有 PAC 的 OJ 患者术中血清和胆汁中的 CASP3 水平,这在进一步术中确定时得到证实(p<0.001)。根据明确的适应证进行分期手术干预和 PBD 是伴有胆管炎的 MOJ 患者的必要治疗策略。