Stupin Victor, Abramov Igor, Gahramanov Teymur, Kovalenko Alexey, Manturova Natalia, Litvitskiy Petr, Balkizov Zalim, Silina Ekaterina
Department of Hospital Surgery No.1, N.I. Pirogov Russian National Research Medical University, 117997 Moscow, Russia.
Chemical Analytical Department, Institute of Toxicology of the Federal Medical and Biological Agency of Russia, 192019 Saint Petersburg, Russia.
Antioxidants (Basel). 2022 Jun 20;11(6):1203. doi: 10.3390/antiox11061203.
To compare the results of surgical treatment and changes in biomarkers of cholestasis, endotoxicosis, cytolysis, lipid peroxidation, glycolysis disorders, and inflammation in patients with benign and malignant obstructive jaundice (OJ) in patients receiving and not receiving antioxidant pharmacotherapy (AOT).
The study included 113 patients (aged 21-90 years; 47 males and 66 females) who received surgical intervention for OJ due to non-malignant (71%) or malignant tumor (29%) etiologies. Patients were divided into two groups: Group I ( = 61) who did not receive AOT and Group II ( = 51) who received AOT (succinate-containing drug Reamberin) as part of detoxification infusion therapy. The surgical approach and scope of interventions in both groups were identical. Dynamic indicators of endotoxicosis, cholestasis, and cytolysis (total, direct, and indirect bilirubin, alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [AP] and gamma-glutamyltransferase [GGT]), kidney function (urea), lipid peroxidation (malonic dialdehyde, MDA), inflammation (leukocytosis), and glycolysis disorders (lactate dehydrogenase (LDH), glucose) were evaluated.
Tumor jaundice, unlike non-tumor jaundice, persisted and was characterized by a more severe course, a higher level of hyperbilirubinemia, and lipid peroxidation. The prognostic value of the direct (and total) bilirubin, MDA, glycemia, and leukocytosis levels on the day of hospitalization, which increased significantly in severe jaundice and, especially, in deceased patients, was established. Decompression interventions significantly reduced levels of markers of liver failure, cytolysis, cholestasis, and lipid peroxidation on day 3 after decompression by 1.5-3 times from initial levels; this is better achieved in non-tumor OJ. However, 8 days after decompression, most patients did not normalize the parameters studied in both groups. AOT favorably influenced the dynamics (on day 8 after decompression) of total and direct bilirubin, ALT, AST, MDA, and leukocytosis in non-tumor jaundice, as well as the dynamics of direct bilirubin, AST, MDA, glucose, and LDH in tumor jaundice. Clinically, in the AOT group, a two-fold reduction in the operative and non-operative complications was recorded (from 23% to 11.5%), a reduction in the duration of biliary drainage by 30%, the length of stay in intensive care units was reduced by 5 days, and even hospital mortality decreased, especially in malignancy-induced OJ.
A mechanism for the development of liver failure in OJ is oxidative stress with the appearance of enhanced lipid peroxidation and accompanied by hepatocyte necrosis. Inclusion of AOT in perioperative treatment in these patients improves treatment outcomes.
比较接受和未接受抗氧化药物治疗(AOT)的良性和恶性梗阻性黄疸(OJ)患者的手术治疗结果以及胆汁淤积、内毒素血症、细胞溶解、脂质过氧化、糖酵解紊乱和炎症生物标志物的变化。
该研究纳入了113例患者(年龄21 - 90岁;男性47例,女性66例),这些患者因非恶性(71%)或恶性肿瘤(29%)病因接受了OJ手术干预。患者分为两组:未接受AOT的I组(n = 66)和接受AOT(含琥珀酸盐的药物Reamberin)作为解毒输液治疗一部分的II组(n = 51)。两组的手术方法和干预范围相同。对内毒素血症、胆汁淤积和细胞溶解的动态指标(总胆红素、直接胆红素和间接胆红素、丙氨酸转氨酶[ALT]、天冬氨酸转氨酶[AST]、碱性磷酸酶[AP]和γ-谷氨酰转移酶[GGT])、肾功能(尿素)、脂质过氧化(丙二醛,MDA)、炎症(白细胞增多)和糖酵解紊乱(乳酸脱氢酶[LDH]、葡萄糖)进行了评估。
与非肿瘤性黄疸不同,肿瘤性黄疸持续存在,且病程更严重,高胆红素血症水平更高,脂质过氧化更明显。确定了住院当日直接(和总)胆红素、MDA、血糖和白细胞增多水平的预后价值,这些指标在重度黄疸患者尤其是死亡患者中显著升高。减压干预在减压后第3天显著降低了肝功能衰竭、细胞溶解、胆汁淤积和脂质过氧化标志物水平,较初始水平降低了1.5 - 3倍;在非肿瘤性OJ中效果更好。然而,减压8天后,两组大多数患者所研究的参数均未恢复正常。AOT对非肿瘤性黄疸患者减压后第8天的总胆红素和直接胆红素、ALT、AST、MDA及白细胞增多的动态变化产生了有利影响,对肿瘤性黄疸患者的直接胆红素、AST、MDA、葡萄糖和LDH的动态变化也有有利影响。临床上,AOT组手术和非手术并发症减少了两倍(从23%降至11.5%),胆汁引流持续时间缩短了30%,重症监护病房住院时间缩短了5天,甚至医院死亡率也降低了,尤其是在恶性肿瘤引起的OJ患者中。
OJ中肝功能衰竭的发生机制是氧化应激,伴有脂质过氧化增强并导致肝细胞坏死。在这些患者的围手术期治疗中加入AOT可改善治疗效果。