RESUMO
BACKGROUND: Hepatic complications are increasingly recognized after the Fontan operation. The development of hepatocellular carcinoma (HCC) is associated with high mortality when diagnosed, but its incidence and risk factors are poorly understood. We conducted a systematic review and meta-analysis of the cumulative incidence of HCC after Fontan and associated risk factors. METHODS: We searched PubMed, CINAHL, and MEDLINE databases for articles reporting the cumulative incidence of HCC after Fontan operation on March 21, 2023. A single-arm random effects meta-analysis was conducted to assess cumulative incidence at 10, 20, and 30 years after Fontan. Meta-analysis of the difference of the medians was used to assess the influence of risk factors on the development of HCC. RESULTS: Four studies including a total of 1320 patients reported cumulative incidence. The cumulative incidence of HCC at 10, 20, and 30 years after Fontan was 0% (95% CI 0.00-0.01), 2% (0.01-0.06), and 7% (0.03-0.17) respectively. Seven studies including 6,250 patients reported overall incidence of HCC and associated risk factors. At a median 18.4 (IQR 11.9-24.9) years of follow-up, incidence of HCC was 2% (0.01-0.04). Only use of anticoagulation was associated with a lower risk of HCC (RR 0.3, 95% CI 0.1-0.88). DISCUSSION: By 30 years after Fontan, cumulative incidence of HCC is high (7%). Risk of HCC development prior to 10 years post-Fontan is low (0%), though the decision to defer HCC surveillance in this period may require future investigation based on larger studies. Screening with ultrasound every 6 months starting 20 years post-Fontan is reasonable, however, further research regarding timing, cost-effectiveness, additional risk factors associated with HCC risk, and different screening modalities is required.
RESUMO
Infantile haemangioma is the most common tumour of infancy, yet the origin of these lesions remains controversial and the predictable life cycle is poorly understood. Much new information on infantile haemangiomas has emerged over the past decade, but experts continue to debate fundamental features, including cell of origin, nonrandom distribution, and mechanisms regulating the sometimes explosive growth and slow involution. The development of useful laboratory models has been difficult, in turn restricting the development of treatment options available to the clinician. Despite this, new research and creative thinking has spawned several hypotheses on the origin of these tumours and their interesting clinical behaviour, including suggestions of an intrinsic defect in local endothelial cells, a contribution of circulating endothelial progenitors or haemangioblasts, embolisation of shed placental cells and developmental field defects. While no single hypothesis seems to describe all features of infantile haemangioma, continued research seeks to integrate these ideas, create a better understanding of these important tumours and bring new treatments to the clinic.