A NEW technique to study tissue samples in 3D has revealed that pancreatic cancers can start and grow in two distinct ways, solving a decades-old mystery of how tumours form.
The new method could help researchers to get more information from tissue biopsies and may lead to improved treatments for pancreatic cancers. The technique was developed by scientists at the Francis Crick Institute, and their results are published in Nature. The work was supported by the European Research Council and core funding from the MRC (one of the Crick’s founding partners).
The pancreas is a crucial organ that sits behind our stomach and plays a key role in digestion. It relies on a network of ducts linking it to other digestive organs, and the most common pancreatic cancers are found in the ducts. However, until now it has only been possible to see 2D slices of these ductal cancers, which contained an unexplained variety of abnormal shapes.
“To investigate the origins of pancreatic cancer, we spent six years developing a new method to analyse cancer biopsies in three dimensions,” explains Dr Hendrik Messal from the Francis Crick Institute, co-lead author of the research paper. “This technique revealed that cancers develop in the duct walls and either grow inwards or outwards depending on the size of the duct. This explains the mysterious shape differences that we’ve been seeing in 2D slices for decades.”
By analysing developing cancers in 3D, the team defined two distinct types of cancer formation: ‘endophytic’ tumours which grow inwards and ‘exophytic’ tumours which grow outwards. To find out what makes cancer cells grow in a particular way, they analysed detailed 3D images and worked with biophysicists at the Crick who created sophisticated computer models.
“We made a simulation of the ducts, describing individual cell geometry to understand tissue shape,” explains biophysicist Dr Silvanus Alt, co-lead author of the paper. “The model and experimental results both confirmed that cancer grew outwards when the diameter of the duct was less than approximately 20 micrometres, around a fiftieth of a millimetre.”
The work was made possible by an interdisciplinary collaboration between two research groups at the Crick, led by Dr Axel Behrens and Dr Guillaume Salbreux. Axel’s group works on stem cells and pancreatic cancer, while Guillaume focuses on using physics to understand biological processes.
“I think we first started discussing this when we bumped into each other in the bike shed,” says Axel. “It’s amazing what can come out of a chance encounter, we now have a patented technique to see the three-dimensional shapes of cancers and a biophysical understanding of the emergence of tumours. Now that we know pancreatic cancer can develop in these two different ways, we can start looking at whether one is likely to be more aggressive or spread in a different way. Many years from now, this could lead to improved diagnostic or treatment options.”
The team also applied the technique to other organs and found that cancers in the airways of the lungs and ducts in the liver behave in the same way. This shows that the mechanism the teams discovered is not specific to the pancreas and also applies to other cancers.
“Both the data and our models indicate that the two different mechanisms of tumour growth are purely down to the innate physics of the system,” explains Dr Guillaume Salbreux. “Like most cancers, ductal pancreatic cancer starts with a single defective cell that starts dividing. We found that very quickly, when there are only a few cells, the tumour has already started to grow either inwards or outwards depending on duct diameter. Defining this fundamental process will help us to better understand how cancer grows in many places across the body.”
Dr Mariana Delfino-Machin, Programme Manager for Cancer at the MRC, said: “Pancreatic cancer remains a very difficult disease to treat but understanding that it can grow in different ways will inform the development of more accurate treatments in the future.
“These findings came about thanks to researchers working in very different fields coming together to successfully tackle the same problem.”
Health inspectors praise for local field hospitals
TWO of the field hospitals across Hywel Dda University Health Board have been highly praised by Health Inspectorate Wales in a recently published report.
The two extra capacity sites – Ysbyty Enfys Carreg Las at the Bluestone resort near Canaston Bridge in Pembrokeshire, and Ysbyty Enfys Selwyn Samuel in Llanelli – were visited by a team in late October and was the first time HIW has inspected such settings.
The inspection examined how the risks to patients’ health, safety and well-being are being managed in these temporary sites. Inspectors found appropriate processes were in place to provide safe and effective care to patients.
The report’s summary stated: ‘We found evidence of extensive planning by the service in preparation for the provision of safe and effective care to patients within unique environments. The transformation of both sites into clinical wards was well considered. We saw evidence of good leadership and staff who were engaged and passionate in their roles.’
Dr Meinir Jones, Hywel Dda UHB’s Associate Medical Director & Clinical Lead for the field Hospitals, said: “This is excellent news and more importantly, a testament to the incredible work of our team. I’m very proud of what has been achieved at both sites, which are receiving patients to help relieve pressure on the acute hospitals. The field hospitals give us the flexibility to move patients out of hospitals after they have been assessed as no longer needing medical input, but still require some care before being discharged home or to a community care facility.”
HIW’s Interim Chief Executive, Alun Jones said: “During the COVID-19 pandemic we have adapted our approach to inspection and assurance in recognition of the pressure that healthcare settings have working under and the administrative burden that inspection can place on a settings that is being inspected. I’m pleased that we have been able to safely inspect two field hospitals ahead of the winter period and quickly provide reflections on what we found to those managing these settings.”
The inspection report for the two field hospitals is available here: www.hiw.org.uk/hywel-dda-university-health-board
Schools to remain open for now as Wales moves to ‘delay’ phase
SCHOOLS will remain open as Wales moves into the “delay” phase in containing the coronavirus, the Welsh Government has announced.
The advice will change from today (Mar 13), with people who become unwell being asked to self-isolate for seven days.
Chief medical officer Dr Frank Atherton said the trajectory of the virus was now “quite clear” and the challenge remained preparing for a significant number of cases in Wales.
Dr Atherton said: “Wales was now really in the delay phase of the virus and it would lead to some inconvenience for people not going to work or school.
“We need to reduce the demand on the health and social care system so it can prepare for peak which may be May or June.”
SCHOOLS OPEN FOR NOW
Health Minister Vaughan Gething said closing schools was not an appropriate option for now.
He told a press conference at 3.30pm Thursday (Mar 112): “Ministers have had clear advice that closing schools now is not an appropriate step to take. For now, the advice and guidance is very clear. Schools should stay open.
“To be effective measure schools would have to be closed for a significant amount of time.
“If we close schools, what impact does that have on parents? Parents could be nurses, doctors or the police. We need to keep key workers in work.
“Another point is, if parents can’t look after them then it’s likely that older members of the family or grandparents will be. Older people are the people we want to protect now and in the future.
“Furthermore, in the Easter break, lots of children will be with each other anyway. The value in closing schools is low.
“Ministers are making choices guided by the best possible evidence and scientific advice.
“Members of governments around the UK need to take a responsible approach and take steps where there is no medical advice to do so within the four nations of the UK.”
Six new cases of coronavirus have been identified in Wales, bringing the total to 25 at the time of going to press. (7pm, March 12)
785 people in Wales have been tested for Novel Coronavirus (COVID-19). 760 results were negative, and 25 results were positive.
Milford Haven School postponed the concert due to take place yesterday (Mar 12). The school stated on social media: “We have regrettably made the decision to cancel the scheduled Milford Haven Cluster Welsh Concert here at Milford Haven School tonight.
“The decision is owing to us taking a proactive approach to prioritising the health and safety of not only our own pupils, but also their families and the wider community. Please note, this is not due to any specific health concern within the school. We will announce rescheduling of this event in due course.”
ROBUST MEASURES IN PLACE
Dr Robin Howe, Incident Director for the Novel Coronavirus (COVID-19) outbreak response at Public Health Wales told The Herald that he was certain that “robust infection control measures in place.”
“The public can be assured that Wales and the whole of the UK is prepared for these types of incidents. Working with our partners in Wales and the UK, we have implemented our planned response, with robust infection control measures in place to protect the health of the public.
“We would encourage people to check the advice for returning travellers, which includes guidance for those returning from Italy, China, Thailand, Japan, South Korea, Hong Kong, Taiwan, Singapore, Malaysia, Macau, Vietnam, Cambodia, Laos, Myanmar, and Iran.
“Members of the public can help protect themselves and others by always carrying tissues, and using them to catch coughs or sneezes. They should bin the tissue, and to kill the germs, wash their hands with soap and water, or use a sanitiser gel. This is the best way to slow the spread of most germs, including Novel Coronavirus (COVID-19).
“Public Health Wales’ trained scientists are now conducting the Novel Coronavirus (COVID-19) diagnostic test in Wales. Over 90 per cent of the individuals who have been tested in Wales have been offered testing in their own home, making it as convenient as possible for them, as well as protecting our ambulance and hospital resources for those who need it most. We are not able to comment on individual cases for reasons of patient confidentiality.”
Official updates on the virus in Wales will now be given at 11:00 daily.
There are now 596 confirmed cases in the UK, up from 456 on Wednesday, and two more deaths, of people with underlying health conditions in London and Essex, taking the total to 10.
Wales confirms second positive case of Coronavirus (COVID-19)
THE CHIEF Medical Officer, Dr Frank Atherton, has confirmed that a second patient in Wales has tested positive for Coronavirus (COVID-19).
The patient is a resident in the Cardiff local authority area and has recently returned from Northern Italy, where the virus was contracted. The patient is being treated in a clinically appropriate setting.
Dr Atherton said: “I can confirm that a second patient in Wales has tested positive for coronavirus (COVID-19).
“All appropriate measures to provide care for the individual and to reduce the risk of transmission to others are being taken.
“I can also confirm that like the first case in Wales, this patient had travelled back to Wales from Northern Italy, where the virus was contracted.
“I’d like to take this opportunity to assure the public that Wales and the whole of the UK is well prepared for these types of incidents. Working with our partners in Wales and the UK, we have implemented our planned response, with robust infection control measures in place to protect the health of the public.”
To protect patient confidentiality, no further details regarding the individual will be released.
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