Liver tumours in children: Current surgical management and role of Transplantation

This article reviews the current surgical management of liver tumours in children in the light of improved chemotherapy, surgical techniques and outcomes from transplantation. It is a principle of management that complete removal of a tumour must be achieved for cure. Neoadjuvant chemotherapy may downstage advanced local disease to enable safe curative tumour resection. When this is not achievable, transplant is indicated. Conventional indications for transplant are unresectable stages 3 and 4 tumours confined to the liver. With the realisation that lifelong immunosuppressive therapy has considerable adverse consequences, there has been a recent trend towards extreme and ‘acrobatic’ liver resection to avoid transplantation, but still obtain a cure. The current literature is reviewed in the light of these trends and our own experience.

From the pursuit of excellence to the quest for significance: Promotion of a Childsafe South Africa

Trauma represents a major burden of disease in South Africa. Children are disproportionately affected by trauma; rightly, childhood trauma can be referred to as ‘the neglected childhood killer disease’. Unlike the field of infectious diseases, where vaccinations and prevention are the norm, paediatric trauma is usually ignored and prevention strategies are scarce. In this article, we review paediatric trauma and its effect on our society in light of the development of more effective child safety promotion strategies

Our surgical heritage: the role of the Department of Paediatric Surgery in the development of paediatric surgery in Cape Town, in Africa, and around the world

The Department of Paediatric Surgery at the University of Cape Town has made a remarkable contribution to the academic body of knowledge of Paediatric Surgery both in South Africa and around the world. It has played a key role in the development of the specialty in South Africa and through the South African diaspora has trained many paediatric surgeons who have made their mark internationally. More recently it has become a major focus of teaching and training for African paediatric surgeons. This article traces this legacy through its origins in the early 1920s to its current prominent position in the world paediatric surgical community

Surgery for the complex Wilms tumour

The prognosis of children with Wilms tumour has greatly improved since the introduction of adjuvant radiotherapy and chemotherapy more than 70 years ago with a current overall long-term survival approaching 90%. Before this, surgery was the only option with around 20% survival, even in low-risk categories. The focus is now on management options for those patients in specific subgroups, who continue to have lower event-free survival and who suffer from the long-term effects of treatment. These include those with anaplastic histology, bilateral Wilms, biologically high-risk tumours and those that relapse (Aldrink et al. in J Pediatr Surg 54(3):390-397, 2019). The major advances that have already been made in risk assessment and tailoring the chemotherapy/radiotherapy to achieve maximum advantage with minimum toxicity and long-term morbidity have been predicated on safe and complete resection and staging of the tumour. There are, however, still surgical challenges faced with respect to resection of 'complex' tumours; thus, surgeons need to understand their role and advance their expertise in the overall treatment of children with Wilms tumour. These include very large tumours not responding to chemotherapy, ruptured tumours, tumours with intravascular invasion into the inferior vena cava (+/- 10%), heart and hepatic veins (+/- 4%) and Wilms tumours in horseshoe kidneys (< 1%) (Kieran and Ehrlich in Urol Oncol , 2015). This review describes surgical strategies and techniques used in these situations, gleaned from the authors' experience in the surgical management of over 300 children with Wilms tumours in our centres over the last 30 years

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease