Acute and chronic excessive intracellular increase of reactive oxygen species (ROS) is involved in the development and progression of cardiovascular diseases. ROS are by-products of various oxidative physiological and biochemical processes. Sources of ROS are mitochondrial respiration, NADH/NADPH oxidase, xanthine oxidoreductase or the uncoupling of nitric oxide synthase (NOS) in vascular cells. ROS mediate various signaling pathways that underlie cardiovascular pathophysiology. The delicate equilibrium between free-radical generation and antioxidant defense is altered in favor of the former, thus leading to redox imbalance, oxidative stress, and increased cellular injury. An understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of cardiovascular diseases.
Background
Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have emphasized the need for further refinement and subclassification of this system.
Methods
Patients who underwent hepatectomy with curative intent for BCLC‐0, ‐A or ‐B hepatocellular carcinoma (HCC) between 2000 and 2017 were identified using a multi‐institutional database. The tumour burden score (TBS) was calculated, and overall survival (OS) was examined in relation to TBS and BCLC stage.
Results
Among 1053 patients, 63 (6·0 per cent) had BCLC‐0, 826 (78·4 per cent) BCLC‐A and 164 (15·6 per cent) had BCLC‐B HCC. OS worsened incrementally with higher TBS (5‐year OS 77·9, 61 and 39 per cent for low, medium and high TBS respectively; P < 0·001). No differences in OS were noted among patients with similar TBS, irrespective of BCLC stage (61·6 versus 58·9 per cent for BCLC‐A/medium TBS versus BCLC‐B/medium TBS, P = 0·930; 45 versus 13 per cent for BCLC‐A/high TBS versus BCLC‐B/high TBS, P = 0·175). Patients with BCLC‐B HCC and a medium TBS had better OS than those with BCLC‐A disease and a high TBS (58·9 versus 45 per cent; P = 0·005). On multivariable analysis, TBS remained associated with OS among patients with BCLC‐A (medium TBS: hazard ratio (HR) 2·07, 95 per cent c.i. 1·42 to 3·02, P < 0·001; high TBS: HR 4·05, 2·40 to 6·82, P < 0·001) and BCLC‐B (high TBS: HR 3·85, 2·03 to 7·30; P < 0·001) HCC. TBS could also stratify prognosis among patients in an external validation cohort (5‐year OS 79, 51·2 and 28 per cent for low, medium and high TBS respectively; P = 0·010).
Conclusion
The prognosis of patients with HCC varied according to the BCLC stage but was largely dependent on the TBS.
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