A genetic signature of 27 microorganisms in stool defines the high-risk population for pancreatic ductal adenocarcinoma, the most common pancreatic cancer, and could be used for early detection of the disease.

Núria Malats

Pancreatic cancer is not one of the most frequently diagnosed cancers, but it is one of the most lethal due to its early local extension and metastatic behaviour. Some of the reasons for this high fatality rate are late diagnosis of the disease, especially since symptoms are unspecific and appear rather late, and limited therapeutic options.

Using patient samples provided by a number of clinical collaborators, researchers from the Spanish National Cancer Research Centre (CNIO), led by Núria Malats, and the European Molecular Biology Laboratory (EMBL) in Heidelberg, led by Peer Bork, have found a molecular signature of 27 microorganisms in stool samples that could predict whether  patients are at high risk of pancreatic ductal adenocarcinoma, the most common pancreatic cancer, and even diagnose patients with earlier stages of the disease.

A patent has been applied for to develop a pancreatic cancer diagnostic kit that detects these microbial genomes in stool samples in a rapid, non-invasive, and affordable way. The study was published in the journal Gut [1].

Detecting pancreatic cancer early

The symptoms of pancreatic cancer are silent and often appear in the late stages of the disease, when tumours usually cannot be removed through surgery. Therefore, there is an urgent need for non-invasive, specific, and affordable tests that are able to detect the disease early and improve patient survival.

“In many cases, once pancreatic cancer is detected, it is too late. We need to diagnose the disease at a much earlier stage, before symptoms appear. To do this, we need to identify and define the population at risk and have good screening tests to detect the cancer when it is still curable,” the researchers pointed out.

Recent data suggest that the microorganisms that coexist with cells in the human body – the  microbiome – may play a role in the origin and development of pancreatic ductal adenocarcinoma.

To study this possible relationship in depth, the researchers conducted a unique case-control study with 136 individuals (57 newly diagnosed patients, 50 controls, and 27 patients with chronic pancreatitis) who were deeply characterized at epidemiological and clinical levels and from whom samples of saliva, faeces and pancreatic tissue were taken to analyse their microbiome. The subjects were recruited from two Spanish hospitals in Madrid (Ramon y Cajal Hospital) and Barcelona (Vall Hebron Hospital).

Most comprehensive study of the microbiome in pancreatic cancer

Contrary to common belief, the oral microbiome was not found to be associated with pancreatic cancer but faecal microbes were. “Sophisticated biostatistical and bioinformatics analyses have allowed us to construct a signature of 27 stool-derived microbes, mostly bacteria, that discriminates very well between cases with pancreatic cancer and controls, both in their most advanced and earliest stages,” said Malats and Bork. This gene signature was validated in an independent study carried out in two German centres, Frankfurt (Goethe University Hospital) and Erlangen (University Clinic Erlangen), and in 5792 faecal metagenomes from 25 studies in 18 countries. It is currently being studied in a Japanese population.

However, pancreatic cancer is a disease with a very complex aetiology and multiple risk factors such as age, obesity, diabetes, chronic pancreatitis, smoking, high alcohol consumption, blood type, and family history of cancer. To avoid biases and to ensure that the microbes identified are associated with pancreatic cancer and not with obesity, diabetes, or other risk factors, the authors controlled for these clinical and demographic variables in the analysis.

“This level of analysis is unprecedented in pancreatic cancer metagenome studies,” the investigators said.

As the researchers write in the pages of Gut, the high predictive value of this stool gene signature could serve as a biomarker to define the population at risk and, if validated in clinical trials, it could be used for early diagnosis of pancreatic cancer. “Currently, screening programmes are targeted to families with pancreatic cancer aggregation, which represent only 10% of the burden of the disease. The inclusion in these screening programmes of a stool analysis to identify the identified microbial signature could help to detect the rest of the population at risk,” they added.

The study

This research has been carried out in collaboration with the CNIO Epithelial Carcinogenesis Group led by Paco Real, the CNIO Molecular Cytogenetics Unit led by Sandra Rodríguez, the Ramón y Cajal University Hospital Oncological Department led by Alfredo Carrato, the Vall d’ Hebron University Hospital Digestive Disease Department with Xavier Molero, the Translational Hepatology Section in Goethe University Hospital led by Jonel Trebicka, and the group of Stephan Kersting in University Clinic Erlangen.

This study has been funded by the World Cancer Research, the European Research Council, the European Regional Development Fund, Spanish Ministry of Science and Innovation, the Carlos III Institute of Health, AESPANC-ACANPAN (Carmen Delgado and Miguel Pérez-Mateo grant) and the European Union (#018771-MOLDIAG-PACA, #259737-CANCERALIA).

Reference:
[1] Kartal E, Schmidt TSB, Molina-Montes E, et. al. A faecal microbiota signature with high specificity for pancreatic cancer. Gut. 8 March 2022.
https://doi.org/10.1136/gutjnl-2021-324755

In the United Kingdom there have been growing calls recently for increased access to publicly available bleed control kits. Easily accessible bleed control kits housed in public areas can provide a lifesaving tool and minimise the risks of critical injuries that can escalate into life-threatening catastrophic blood loss.

Increasingly, medical equipment and consumables are being developed for scenarios that could empower members of the public to take urgent action when responding to a range of common injuries and accidents, as well as criminal assaults.

The conversation around public access to bleed control kits is starting to gain traction globally, particularly for use in high population areas, such as shopping malls, arenas, and nightclubs.

Why public access to Bleed Control Kits is needed

Early medical intervention with a bleed control kit by a member of the public  can make all the difference in saving a life if the injury is severe and there is the risk of significant blood loss.

In the UK, public access to Automated External Defibrillators (AEDs) is relatively commonplace, but access to lifesaving medical devices such as bleed control kits is only just starting to gain attention, with the first publicly accessible bleed control kit installed in Birmingham in November 2020. 

Anthony Marsh, Chief Executive of West Midlands Ambulance Service, speaking to Birmingham Live, explained: “The average time it takes an ambulance crew to get to the scene is seven minutes. Catastrophic bleeding from a trauma injury such as a stabbing, shooting or road traffic collision can prove fatal in three to five minutes.”

“The bleed control kits can provide a few vital minutes until the ambulance arrives. If someone has access to one of these kits before a crew are able to arrive, they could potentially save a life.”

Bleed control kits can be housed with AEDs in public areas, in cabinets that alert emergency services when opened.

Bars, nightclubs and pubs are also becoming more aware of the need to provide emergency care in situations where alcohol becomes an aggravating factor.

What’s in a bleed control kit?

Bleed control kits contain lifesaving supplies, such as tourniquets, trauma wound dressing, examination gloves to prevent infection, scissors to remove clothing as well as chest seals and foil blankets. The kits also include essential information on how to use the kit. As with AEDs, some kits contain spoken instructions, while others contain visual instructions.

According to Reuters, research suggests that bleed control kit supplies should be stocked to support around 20 cases, which will cover minor injuries and more severe accidents that involve multiple people.

Why bleed control matters now 

Small injuries involving cuts, scrapes and grazes will not require urgent treatment for bleeding, but bleed control becomes extremely important when an injury is severe.

In the UK, between September 2020 and September 2021 there were 46,239 knife or sharp instrument related offences recorded by police. While the aim is to reduce the number of stabbings, the reality is that venues need to be prepared for the worst case scenario.

The easy availability of life-saving resources, such as bleed control kits, are essential to provide medical assistance and treatment, particularly in the event of injuries that could result in catastrophic bleeding.

Bleed Control Kits in the public domain

According to a report in The Guardian, bleed control kits have been critical in helping the public respond to injuries as a result of assaults in the UK, including knife attacks. This has led to calls for the kits to be installed “in every village, town and city”.

In London, the City of London Police have helped to install over 320 bleed control kits in late night venues, and in other cities in the UK, police forces are providing the same kits to venues seen at risk.

For private companies, Aero Healthcare provides bleed control kits starting from £63.

Training is provided for free through various charity initiatives, including Control the Bleed.

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The field of radiation cancer treatment needs to be brought into the precision medicine era, with patient-specific genomic data driving therapeutic decision-making rather than a one-size-fits-all approach, according to an expert from Cleveland Clinic, and his team of collaborators.