When chronic inflammation turns dangerous

The connection between gallstones, chronic inflammation, and cancers of the gallbladder and bile ducts is often misunderstood, sometimes delaying diagnosis and narrowing treatment options.

According to Loma Linda University Cancer Center, gallbladder and bile duct cancers, together known as biliary cancers, require a clearer understanding of what truly raises risk, and what does not.

“Gallstones and gallbladder cancer are completely different processes,” says Aaron Saunders, MD, chief of the Division of Surgical Oncology at Loma Linda University Health. “Just because someone has gallstones does not mean they’re destined to develop a gallbladder cancer.”

Common condition, rare cancer

Gallstones affect an estimated 6% of the population — about one in 16 people. In contrast, the lifetime risk of gallbladder cancer is closer to one in 400. Most people who undergo gallbladder removal for gallstones or inflammation never have cancer detected.

However, the relationship looks different when viewed from the cancer side.

“The majority of patients diagnosed with gallbladder cancer do have gallstones present,” Saunders says. “That association raises questions, but it’s difficult to prove cause and effect when gallstones themselves are so common.”

What matters most, he says, is chronic inflammation over time.

Why inflammation matters

Across many cancers, repeated injury and long-standing inflammation can damage DNA and increase the likelihood of cancer-causing mutations.

“Almost any chronic inflammation increases the chance that DNA becomes damaged,” Saunders says. “Not every mutation leads to cancer, but that’s typically where cancer begins.”

In the gallbladder, chronic inflammation, often caused by gallstones, may go unnoticed for years. Some patients experience repeated right-sided abdominal pain after fatty meals, while others have few or no symptoms.

“It’s not uncommon for us to remove a gallbladder and realize it’s been inflamed for a very long time, even when the patient didn’t know it,” Saunders says.

Inflammation also plays a significant role in bile duct cancers, particularly those arising within the liver. Conditions such as chronic liver disease, cirrhosis, and immune-related disorders can increase risk. While gallbladder cancer rates appear relatively stable, bile duct cancers are increasing.

A late-diagnosis challenge

Gallbladder and bile duct cancers are frequently diagnosed at later stages, largely because there are no routine screening tests.

“Most of the time, these cancers are found incidentally or once they start causing symptoms,” Saunders says. “And when symptoms appear, the disease is often already advanced.”

Symptoms may be vague, such as abdominal discomfort, digestive issues, or abnormal liver tests, and can easily be attributed to more common conditions. Jaundice or persistent pain often signals more advanced disease.

In some cases, early gallbladder cancer is discovered unexpectedly after surgery for gallstones or inflammation. While gallbladder removal alone may be curative in rare early cases, many patients require additional surgery, chemotherapy, or radiation.

Why outcomes can be sobering

Compared with other gastrointestinal cancers, biliary cancers remain difficult to treat.

“When a cure isn’t possible, survival is often measured in months rather than years,” Saunders says. “The only real opportunity for long-term survival is catching the cancer early enough to remove it completely.”

Even when surgery is an option, five-year survival rates range from roughly 10% to 40%, depending on stage and location. Surgery must completely remove the tumor while preserving enough liver function to sustain life — a balance that isn’t always achievable, though sometimes made possible with liver transplant when a resection alone is not safe.

If cancer has spread beyond the liver or bile ducts, surgery is no longer beneficial, and treatment shifts to chemotherapy, radiation, or newer localized therapies.

Understanding real risk and not panic

While these cancers are serious, Saunders emphasizes that most people with gallstones or gallbladder disease will never develop a biliary cancer.

“The goal isn’t fear, it’s awareness,” he says. “Especially for people with long-standing symptoms, chronic inflammation, or underlying liver disease.”

Maintaining a healthy weight, limiting alcohol use, exercising regularly, and eating a diet rich in fruits and vegetables can help reduce inflammation and lower overall cancer risk.

An estimated 12,000 people in the United States are diagnosed with gallbladder or bile duct cancer each year; rare, but significant enough to warrant attention.

Why specialized care matters

Treatment often requires coordination among multiple specialists, making early referral to an experienced center critical.

“These cancers aren’t managed by one doctor alone,” Saunders says. “Patients benefit from a multidisciplinary team that can evaluate every option, from surgery and chemotherapy to clinical trials and emerging therapies.”

For patients with persistent gallbladder symptoms, abnormal imaging, or chronic liver disease, Saunders encourages early evaluation and advocacy.

“Addressing gallbladder or bile duct disease early can change what’s possible if cancer is found,” he says.

If you have ongoing gallbladder symptoms, unexplained jaundice, or chronic liver disease, talk with your doctor about further evaluation. Learn more about specialized surgical oncology care at Loma Linda University Cancer Center.