TALK LIKE A NEONATAL AND PAEDIATRIC SURGEON

Antibody — protein molecules found in the blood that aid the recognition of pathogens and other harmful substances

Biomedicine — the branch of medicine that involves applying biological and biochemical research to medical research and practice

Cancer — a disease in which certain cells in the body grow uncontrollably and spread to other parts of the body

Fluorescence — the emission of light by a substance that has absorbed light or other electromagnetic radiation

In vitro — a process that takes place outside of a living organism (e.g., in a tissue culture dish)

Neonatal — relating to newborn children

Neuroblastoma — a type of cancer that forms from certain immature nerve cells

Paediatric — the branch of medicine relating to children and the diseases that affect them

Tissue — any of the materials that make up the body (e.g., specialised cells and their products)

Tumour — a mass of tissue formed when cells grow uncontrollably and which can be benign or malignant

Cancers come in a wide array of shapes and sizes and can affect different parts of the body in different ways. High-risk neuroblastoma is a type of cancer that occurs principally in babies and young children. It affects around 100 children every year in the UK and in its more aggressive form has a low survival rate. Neuroblastoma occurs when specialised nerve cells, called neuroblasts, are left behind from the child’s time in the womb and become cancerous. “High-risk neuroblastoma is an aggressive cancer, which has often spread to multiple organs by the time of diagnosis,” says Dr Stefano Giuliani. Stefano is a surgeon at UCL Great Ormond Street Institute of Child Health (ICH) in London. He is working on a pioneering research study that could dramatically improve survival rates for children with this cancer.

Challenges of surgery

Treatment for neuroblastoma involves surgically removing the entire tumour, but this is a challenging task even for the most experienced surgeons. “The neuroblastoma grows around the largest and most critical vessels, nerves and organs in the body,” explains Stefano. “This raises the risk of damaging these tissues during surgery, which can lead to dangerous situations such as severe bleeding.”

Currently, it is not easy to tell the difference between cancerous tissue and normal healthy tissues during surgery, which is why this procedure is so challenging. “There is a need to develop a tumour-specific detection strategy to help surgeons easily see tumour cells versus normal anatomical structures,” says Stefano. This need forms the foundation of his research project. 

Fluorescence-guided surgery

Fluorescence-guided surgery (FGS) could provide the solution to solving this issue. “FGS is possibly one of the greatest innovations in surgery,” says Stefano. “We are developing specific fluorescence probes which can clearly highlight cancer cells.” Fluorescent molecules are those that ‘light up’, emitting a certain wavelength of light when exposed to either visible light or other wavelengths such as ultraviolet or infrared.

These fluorescence probes are formed using a clever biochemical technique. The main way the body’s immune system naturally detects pathogens or cancers is via the use of antibodies – molecules whose shape matches other molecules only found on the surface of specific harmful cells. Biomedical scientists have found the antibody specific to neuroblastoma and can modify this in the lab to attach a fluorescent particle to it.

When these modified antibodies are introduced to the body, they attach to the neuroblastoma cells and nowhere else. This means that when the tumour is exposed during surgery, it is literally ‘lit up’ against surrounding tissue by all the fluorescent molecules attached to it. For surgeons, this makes it much easier to distinguish cancerous cells from healthy cells and remove the tumour accurately. High-resolution scanners can be used to detect any leftover cancer cells not visible to the naked eye, making surgery as comprehensive as possible.

Progress and next steps

“We have obtained good data in vitro and in animal models for this technique,” says Stefano. “We are about to submit an important paper to publish these results.” ‘In vitro’ refers to experiments not performed on living organisms, using cancer cells grown in the lab. Typically, this is the first step of testing new medical techniques, which precedes testing on animals, which precedes testing on humans. Once in vitro experiments had been completed, the team moved on to using FGS to remove neuroblastoma in mice. “Animal models are essential to obtain meaningful data before using the same technologies in humans,” says Stefano. “Now, the next step will be to translate our findings to humans in a clinical trial.”

The team hopes this new technology will be saving children’s lives within five years. “Surgery will be more precise, leaving less cancer behind and bringing benefits to rates of survival and recovery from surgery,” explains Stefano. “Patients will receive less extensive and more targeted surgery, with less risk of complications.” By removing the smallest parts of the tumours, it is expected that recurrence will be much reduced. In time, this technique could be extended to treat many different types of cancer, potentially saving many lives worldwide.

DR STEFANO GIULIANI
Consultant Neonatal and Paediatric Surgeon at Great Ormond Street Hospital, Associate Professor at UCL Great Ormond

Street Institute of Child Health, Co-Investigator at the Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS), London, UK

Fields of research: Neonatal and Paediatric Surgery, Cancer Research

Research project: Using fluorescent antibodies to clearly distinguish tumours, allowing safer and more precise surgery for treatment of neuroblastoma in children

Funders: Medical Research Council (grant reference MR/T005491/1), Wellcome Trust-Innovator Award (grant reference 222111/Z/20/Z)

Wellcome/EPSRC Centre for Interventional and Surgical Sciences at University College London (WEISS, grant number 203145Z/16/Z), GOSHCC cancer infrastructure award

ABOUT NEONATAL AND PAEDIATRIC SURGERY

Neonatal and paediatric surgery involves surgery specific to babies and children. Often, the conditions they face, and the appropriate treatments, differ to those for adults, which has led to the development of these specialised fields. Like many medical professionals, the work of neonatal and paediatric surgeons like Stefano is typically split between treating patients and performing research.

“A particularly skilled professor of surgery inspired me when I was a medical student in Italy. His surgical skills, humanity and determination made me willing to pursue a career in academic surgery,” says Stefano. “I love my job, and I believe passion and dedication are essential to succeed in any career.”

The Great Ormond Street ICH is world-famous for leading the way in paediatric care, and Stefano’s work is contributing to this reputation. “One of my proudest achievements is having developed an independent research group on image-guided surgery,” he says. “This has been my dream for many years, and I obtained it with the support of ICH and my academic mentors, Professor Anderson and Professor De Coppi.”

Though there have been many advances in the field, both in terms of knowledge and technologies, Stefano believes there is a lot more progress to be made, presenting exciting opportunities for the next generation. “Paediatric and neonatal surgery is one of the most fascinating fields in medicine,” he says. “There is a lot to discover in complex fields such as foetal development, congenital anomalies, rare diseases and cancers.”