Could Gallstone Disease Predict Pancreatic Cancer?

Gallstone disease may be a red flag for pancreatic ductal adenocarcinoma (PDAC), a researcher reported.

PDAC patients were diagnosed nearly three times more often with gallstone disease compared to people without cancer in the general population (4.5% vs 1.8%, respectively) and had undergone more cholecystectomies (1.8% vs 0.4%) in the year preceding their PDAC diagnosis, according to surgical oncologist Teviah Sachs, MD, MPH, of Boston Medical Center.

After multivariable adjustment for demographics and the Elixhauser score, gallstone disease was a predictor of early-stage disease (OR 1.36, 95% CI 1.16-1.60) and requirement for surgical intervention (OR 1.51, 95% CI 1.24-1.83), he said in presenting his group’s 29,000-person study at press briefing ahead of the Digestive Disease Week meeting.

“It is a bit of a chicken and the egg phenomenon,” Sachs said at the briefing. “We can’t be certain at this time to tease out whether or not gallstone disease that we’re seeing is the precursor or end result of pancreatic cancer, but we do know is that there’s an association.”

“What I would say is that if you have a patient who presents with gallstone disease and they have any other symptoms, you shouldn’t necessarily count them out to just their gallstone disease,” Sachs said. “Just taking it as part of a larger picture, making sure it’s on a differential for a patient who may present with other symptoms that might not correlate with typical gallstone disease, those are the patients that providers should focus on.”

Incidence of gallstone disease has been previously found to be greater among those with PDAC.

PDAC is a highly common form of pancreatic cancer, comprising 90% of all cases. Since this type of cancer is often only detected and diagnosed at late stages, PDAC comes with a poor prognosis that makes it the third leading cause of cancer-related mortality. Early symptoms may even be similar to those of cholelithiasis or cholecystitis, which are risk factors for pancreatic cancer.

“Screening for pancreatic cancer is not as easy as for other screenable cancers like lung, colorectal, or breast,” Sachs said. “There’s not a good imaging study that will detect it early, and there’s not good laboratory values either.”

“Our findings suggest that gallstone disease may be a way to better diagnose this type of cancer – meaning we could save more lives,” said co-investigator Marianna Papageorge, MD, a general surgery resident at Boston Medical Center, in a press release.

“Gallstone disease does not cause pancreatic cancer but understanding its association with PDAC can help combat the high mortality rate with pancreatic cancer by providing the opportunity for earlier diagnosis and treatment,” she explained.

For their study, Sachs and colleagues examined the Surveillance, Epidemiology, and End Results (SEER)-Medicare database on 14,643 patients with PDAC from 2008 to 2015 and compared them to a non-cancer cohort of an additional 14,605 patients.

A gallstone disease diagnosis was defined by cholelithiasis, cholecystitis, or cholecystectomy within 13 months before receiving a PDAC diagnosis. For the cancer cohort, researchers employed a washout period of 1 month before their diagnosis, which was excluded from those 13 months.

Over half of the PDAC patients were women, and mean age was 76 years. Nearly all were white.

Stage IV cancer was observed in 52%. Patients who had gallstone disease tended to be diagnosed earlier compared to PDAC patients who did not have gallstone disease (stage I or II PDAC: 46% vs 38%) and were more likely to undergo pancreaticoduodenectomy (18% vs 13%, P<0.0001 for both).

Median Elixhauser scores were significantly greater in PDAC patients with a gallstone disease diagnosis (5 vs 3, P<0.0001).

“[PDAC] is such a terrible disease, and survival is so low,” Papageorge said. “People present at such advanced stages, so anything we can do to try to diagnose people earlier and make sure that they’re getting curative treatment is crucial.”