A small “triangle” with a big impact
Behind the pancreas lies a compact, triangle‑shaped area bordered by three major blood vessels that supply the abdomen. Surgeons call it the TRIANGLE compartment. In standard pancreatic cancer surgery, this region is not systematically removed. For years, however, specialists have suspected that microscopic cancer cells may be hiding there, beyond what imaging and the naked eye can detect.
A team led by hepato‑pancreato‑biliary surgeon Vera Oliveira decided to put that suspicion to the test. In a prospective study of 131 patients operated at the Botton‑Champalimaud Pancreatic Cancer Centre between 2023 and 2024, the surgeons systematically removed the TRIANGLE tissue and asked pathologists to examine it in detail.
The results were notable, with cancer cells found in the TRIANGLE compartment in roughly one in three patients. These hidden cells were found not only in nearby lymph nodes, but also in fatty tissue, nerve tissue and small blood and lymphatic vessels. In nearly half of these patients, more than one type of tissue in the TRIANGLE was affected, underscoring how widely pancreatic cancer can infiltrate this small space.
Importantly, this was not only a problem in very advanced tumours. Even among patients whose cancer was considered “resectable” on scans, meaning suitable for standard surgery, around 21% had microscopic tumour deposits in the TRIANGLE. For clinicians, this helps explain why local recurrence near the original tumour site remains so common after apparently complete operations.
The technique used to clear this compartment, known as the TRIANGLE operation, is demanding, showing complication rates and mortality that are in line with what is expected for complex pancreatic surgery. For patients, it represents a more extensive local operation that may help reduce the risk of the cancer returning in the same area.
Finding cancer’s “fingerprints” in the blood
While one group of surgeons was looking for hidden cells in the abdomen, another team, led by surgeon‑researcher Filipe Borges, turned their attention to the bloodstream. Even after a technically perfect operation, a few cancer cells may escape into the body. Today, conventional scans and standard blood tests often miss them until they have already formed new tumours.
Circulating tumour DNA (ctDNA) offers a new way to detect this invisible threat. When cancer cells die, they release small fragments of their DNA into the blood, like tiny fingerprints. Using sensitive molecular techniques, clinicians can look for specific mutations, such as changes in the KRAS gene that are present in most pancreatic cancers.
To understand how powerful these fingerprints might be, the team conducted a systematic review and meta‑analysis that brought together data from 18 studies and 965 patients with pancreatic cancer who underwent surgery. They compared outcomes between patients who had detectable ctDNA in their blood before and after surgery and those who did not.
Across these studies, the pattern was consistent. Patients whose blood contained ctDNA before surgery had a higher risk of the cancer coming back and of a reduced overall survival compared to those without detectable ctDNA, approximately double the risk in terms of both disease‑free and overall survival. After surgery, the signal became even stronger: patients who still had ctDNA in their bloodstream faced more than a three‑fold increase in the risk, compared to those whose ctDNA was negative.
Importantly, this held true for patients who went straight to surgery and for those who first received neoadjuvant chemotherapy. In both groups, ctDNA behaved as a powerful warning sign that the disease was biologically more aggressive. In the future, a blood test like this could help clinicians decide which patients should receive chemotherapy before surgery, who might need more intensive treatment or closer monitoring after an operation, and whether changes in ctDNA over time provide an early indication that therapy is having the desired effect.
The authors emphasise that more prospective trials are needed before ctDNA can routinely guide such decisions in the clinic. But their study provides strong evidence that ctDNA is a meaningful prognostic marker in the surgical treatment of pancreatic cancer.
Two fronts, one goal: fewer recurrences, better outcomes
Taken together, these two studies reflect a coherent strategy at the Botton‑Champalimaud Pancreatic Cancer Centre: extend surgery where it matters, and personalise treatment using better biological information.
By removing the TRIANGLE compartment, surgeons aim to clear local reservoirs of cancer cells that standard operations may leave behind. By measuring ctDNA, they hope to detect residual microscopic disease throughout the body, long before it appears on scans. Both approaches share the same goal: to lower the risk that patients will experience a recurrence after already going through major surgery and systemic treatment.
Equally important, these studies arise from a multidisciplinary environment in which surgeons, oncologists, pathologists, radiologists and translational researchers work side by side in a coordinated programme. For people living with pancreatic cancer, this kind of integrated care increases the chances that new findings in the operating room, the pathology lab or the molecular laboratory can be rapidly translated into more informed, more tailored treatment decisions.
Text by Teresa Fernandes, Co-Coodinator of the Champalimaud Foundation's Communication, Events & Outreach Team
