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Research solves pancreatic cancer mystery

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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

Welsh Government ‘utterly failing’ on waiting lists

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PLAID CYMRU has called for action to tackle the NHS backlog, accusing Labour of “utterly failing” and leaving more than 620,000 people languishing on long waiting lists.

Mabon ap Gwynfor, the party’s shadow health secretary, warned waiting lists have hit record highs in every month since March, including each month of the First Minister’s time in office.

He said: “And what’s been the response of this [Welsh] Government? Firstly, to blame everybody else: blame the patients, blame health managers, blame royal colleges, blame everybody and deny responsibility.

“After 25 years of governing, they decided to go on a listening exercise and hear people telling them what they should have known years ago.

“Then, each month leading up to Christmas, a new strategy was put in place, and each month, the numbers on waiting lists were increasing.”

Plaid Cymru MS Mabon ap Gwynfor
Mabon ap Gwynfor, Plaid Cymru’s health, social care and housing spokesperson

Leading a Plaid Cymru debate, Mr ap Gwynfor pointed to his party’s five-point plan to tackle NHS waiting lists which was unveiled this week.

His colleague Sioned Williams raised the “alarming” rise of the use of private health care, warning deep-rooted inequalities are becoming increasingly stark.

Accusing Labour of eroding Aneurin Bevan’s vision for the NHS, she said statistics show a 77% rise in admissions to private hospitals in Wales over five years.

Ms Williams added: “58% of Welsh people have either accessed private health care or know friends or family who have done so, which is higher than the UK average.”

Llŷr Gruffydd, a fellow Plaid Cymru Senedd Member, said: “Now, the situation in north Wales, in my region, is frightening, if I’m honest…. There is a whole generation of children and young people with conditions such as ADHD and autism being let down.”

James Evans, the Conservatives’ shadow health secretary, warned the NHS is in crisis, with more than 23,000 people waiting at least two years for treatment.

“This isn’t just inefficiency,” he said. “It’s a symptom of a deeper problem and the chronic underfunding and neglect of our social care system.”

Mr Evans called for an independent review of NHS Wales to “fix a system that has been broken by years of Labour mismanagement”.

Conservative MS James Evans
Conservative shadow health secretary James Evans

Russell George, who chairs the Senedd’s health committee, raised concerns about Powys health board’s “ridiculous” proposals to balance its books.

The Tory said: “In Shrewsbury or Telford hospital, a Welsh patient could be sitting talking to a consultant and the consultant tells them, ‘We’ve got capacity to see you. We would see you if you were an English patient but we’re not able to because Powys is not able to pay.’”

Labour’s Buffy Williams said years of chronic underfunding from successive Conservative UK Governments has been catastrophic for the Welsh NHS.

Jeremy Miles, who was appointed health secretary in September, pointed to signs of progress on the Welsh Government’s priority of reducing the longest waiting times.

Health secretary Jeremy Miles
Health secretary Jeremy Miles

He told the Senedd the number of people waiting more than two years has reduced by two thirds since 2022, with 3% waiting at least two years compared with 10% at the peak.

Mr Miles said: “The health service is making progress despite the increasing demands upon it but there is much more to be done in order to ensure that people are treated sooner.”

Following the debate on January 15, Senedd Members voted 39-11 against the Plaid Cymru motion before the Welsh Government’s amended version was agreed, 26-24.

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Health

Senedd Members criticise ‘appalling’ cancer delays

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SENEDD Members quizzed Wales’ health secretary after a damning report revealed “alarming” shortcomings in cancer services, including a lack of leadership.

James Evans, the Conservatives’ shadow health secretary, said this week’s Audit Wales report laid bare chronic mismanagement of cancer services.

Questioning his opposite number Jeremy Miles, Mr Evans told the Senedd: “This failure has caused widespread confusion and inefficiencies in patient care.

“Despite a staggering 54% real-terms increase in spending on cancer services over the past 13 years, the NHS in Wales continues to miss the target for starting cancer treatment.

“Leadership failures have resulted in shocking delays for patients, with some waiting over 100 days to begin treatment. These delays exacerbate anxiety and lead to poorer survival rates, which are already worse in Wales than any other nation across the UK.”

Conservative MS James Evans
Conservative MS James Evans

He urged the Welsh Government to fix a leadership vacuum, dismantle bureaucratic silos and ensure patients no longer face appalling delays that cost lives.

Mr Miles welcomed the report, recognising the picture painted by the auditor general that too many people are waiting too long for treatments they should be getting faster.

The health secretary said: “It is true to say for a number of cancers in a number of parts of Wales those targets are being met and sometimes being exceeded quite significantly.

“But the overall picture, I accept, is that targets are not being met.”

Mr Evans, who represents Brecon and Radnorshire, warned of workforce planning failures, severe staff shortages, over-reliance on agencies, and recruitment and retention problems.

He said: “These staff shortages are directly delaying cancer diagnosis and treatment, worsening outcomes for patients.

“Despite repeated warnings from organisations like the Wales Cancer Alliance, the Welsh Government has failed to deliver a comprehensive workforce strategy.”

Mr Miles pointed to a 27% increase in workforce numbers, adding that Wales is not the only country to have difficulty recruiting to certain disciplines such as radiology.

The health secretary agreed about the “unsustainable” reliance on agency staff.

Mr Evans added: “There is becoming an outrage in the public about the ballooning number of managers across the NHS compared to frontline health care providers.”

He suggested overall increases in the workforce – from 72,000 to 91,000 between 2014 and 2023 – have not addressed frontline clinical shortages.

“Shockingly, administrative and estate staff have increased by 51% in that time,” he said.

Mr Evans asked: “After 26 years, how can the Labour Welsh Government justify the bloated expansion of administrative roles while patients face unacceptable delays for treatment due to a lack of frontline staff?”

Mr Miles replied: “The member makes an easy point, and a populist point, but the truth is a complex healthcare system requires people who are competent….

“There has been an increase in recruitment to the NHS across all disciplines and all important roles which enable the NHS to be effectively run.”

He added: “A world view which suggests that managers and those running the NHS simply should be taken out of the system, I think, is a very naive perspective.”

Plaid Cymru MS Mabon ap Gwynfor
Plaid Cymru MS Mabon ap Gwynfor

Mabon ap Gwynfor, Plaid Cymru’s shadow health secretary, also led on the scathing Audit Wales report during health questions on January 15.

He urged the minister to back his party’s proposed reforms of NHS governance.

Mr Miles said November’s report “echoed” a statement he gave in the Senedd and a speech he made two weeks earlier.

He told the chamber: “I was very pleased to see the kind of fresh thinking I was seeking to bring to the challenges which we face was agreed to by Plaid Cymru.

“And I see the same thing in the plan that was published … yesterday in relation to tackling waiting lists.”

Mr ap Gwynfor hit back: “That’s a disappointing response because you seem to be in complete denial about the problems in the health service.”

The Dwyfor Meirionnydd Senedd Member called for a guarantee that a target for 80% of all cancer patients to receive treatment within 62 days by March 2026 will be met.

He warned that the quality and accessibility of health data is “not up to scratch”, with Public Health Wales “fundamentally hamstrung” in its ability to project future demand for services.

He said: “The Wales cancer registry is meant to provide timely data on cancer incidence … but it hasn’t published validated cancer data since 2021, shamefully this means Wales can’t fully take part in essential national cancer audits … nor global studies.”

Mr Miles replied: “We have actually improved the publicly available data and we publish on a monthly basis about 18 pages of cancer treatment statistics, so that they can be scrutinised.

“We do want to improve transparency further.”

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Health

Wales to take part in largest ever UK wide pandemic response exercise

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Wales will take part in the largest ever UK wide pandemic response exercise this Autumn.

The commitment is part of the Welsh Government’s comprehensive response to the UK Covid-19 Inquiry’s first module published today, which examined the nation’s preparedness and resilience prior to the pandemic.

The response outlines the significant steps already taken to strengthen Wales’ emergency preparedness.

First Minister Eluned Morgan said: “Our priority is to keep the people of Wales safe. We are committed to learning lessons from the pandemic and building on the existing foundations to ensure Wales is prepared for future emergencies.

“Over the past six months, we have worked with other devolved governments and the UK Government to carefully consider and begin the progress of implementing these important recommendations from the inquiry.

“We have taken action to improve our emergency response capabilities and will continue to build on this.

“This will include Wales playing a full role in the major exercise this Autumn to test the UK’s capabilities, plans and procedures to prepare for possible future pandemics.”

A new group is being established – the Wales Coordination Group – to oversee the planning and participation of Wales in the exercise. It will have representation from all key organisations involved at the national and local level, in recognition of the broad scope of the exercise.

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