A small study conducted in 1992 of 25 patients at high risk for colorectal cancer (CRC) and 19 non-high-risk patients was the origin for the standard that 33 random biopsies were required to rule out dysplasia, David T Rubin, MD, explained at the Advances in Inflammatory Diseases (AIBD) virtual regional meeting on March 5.

Dr Rubin is the Joseph Kirsner Professor of Medicine, chief of Gastroenterology, Hepatology, and Nutrition, and director of the Digestive Diseases Center at the University of Chicago.

“It was actually 33 biopsies,” he noted. “The conclusion from this very small study was that if you had 33 biopsies that were negative for dysplasia, you had a 90% confidence that you didn’t miss any. This became the standard, as many of you may know.”

J Arnold Bargen, MD, of the Mayo Clinic, was among the first to address the risk of CRC among patients with ulcerative colitis (UC), Dr Rubin explained. In an article from 1928, Dr Bargen observed, “The sequence of events in some cases of malignant disease of the colon is chronic ulcerative colitis, multiple polyposis and malignant disease…The only hope, it seems, is preventive treatment, that is, the cure of the colitis and the removal of the polyps.”

That standard of 33 random biopsies was based on the idea that dysplasia is invisible and on the concept of a field effect for dysplasia risk, Dr Rubin said, “meaning when the organ became at risk for dysplasia, it could happen in lots of places, so if you just sample it throughout the bowel, you’ll find it in one of those samples and it will tell you what the whole organ is doing. That’s largely been disproven.”

In that past 3 decades, there has been a major “evolution of our ability to see dysplasia” with both the recognition that most dysplasia is visible and with the development of technology, such as narrow-band imaging with high-definition scopes and dye-spray chromoendoscopy, he continued. “There’s been a movement away from random biopsies and a movement away from doing surgery for everybody. When I was younger in my career, even a single biopsy with dysplasia was supposed to prompt proctocolectomy, and we now know that’s unlikely to be necessary.”

St Mark’s Hospital in London, which has the longest continuously collected database on CRC, shows significant progress in reducing CRC morbidity and mortality, Dr Rubin said. Cancer rates are dropping and when found, the CRC is in earlier stages, thanks to the impact of effective prevention strategies.

One of the most important strategies is control of histologic inflammation. “We have come to appreciate that you can actually accumulate inflammation and that can be predictive” of cancer risk. St Mark’s has developed a score that can calculate the cumulative burden of inflammation and its association with the risk of developing neoplasia. The Rubin Lab has validated this score, showing that accumulated inflammation does contribute to the risk of cancer.

“Control of disease objectively over time is essential,” he said. “The risk is not ‘set’ after one episode of severe inflammation and can be reset with subsequent control.”

Surgery may be needed in cases of unresectable neoplasia, recurrent neoplasia, or when a patient’s inability or unwillingness to follow up make the risk unacceptable. Yet even the surgical options have improved from the time when total proctocolectomy was the standards. “We’ve shown more recently segmental resection is possible,” he noted.

The American Gastroenterological Association and the American College of Gastroenterology recommend the control of inflammation associated with UC as the first measure for the management of CRC risk. In addition, Dr Rubin delineated, both organizations advise the use of high-definition scopes with narrow-band imaging; use of dye-spray chromoendoscopy with standard definition scopes or when there is a history of dysplasia; targeting all suspicious areas; and performing endoscopic resection rather than biopsies.

“The idea here is whether we can move all this back a step; what else can we do along this pathway? Can we push the detectable preclinical phase earlier with better technology? We can and we have,” Dr Rubin said. Randomized clinical trials have demonstrated that dye spray chromoendoscopy is clearly superior to standard definition white light, but not to high-definition scopes with white light. High-definition white light and high-definition narrow band are similar in their detection abilities, he said and the latter, in addition to iSCAN and autofluorescence, are equal to dye spray, according to the findings of several studies.

“Dye spray is messy and complicated,” he noted. “I still use dye spray for specific lesions, to define their margins, but for the most part I use narrow band imaging in my scopes.”

There are occasions when nontargeted biopsies may be useful, “not just for your routine surveillances,” but for assessing disease activity and the extent of disease to look for chronic changes, and to assess for neoplasia when the visualization is suboptimal due to poor preparation, inflammation, or polyposis. Dr Rubin also suggested nontargeted biopsies “when the endoscopist is less experienced at identifying dysplasia, and to clarify the presence of chronic colitis in an area of a detected lesion.”

After a colonoscopy that finds no dysplasia, when should patients with UC return for a repeat exam? The existing recommendations call for every 1 to 5 years, although Dr Rubin explained, “I don’t do 5 years very often; the longest I typically go is 3 years.”

Patients with moderate or severe inflammation; primary sclerosing cholangitis; a family history of CRC in a first-degree relative aged 50 or under; dense pseudopolyposis; and history of invisible dysplasia or higher-risk visible dysplasia less than 5 years previously should return in 1 year, he said.

Dr Rubin stressed the importance of obtaining surgical consultation whenever dysplasia is found in setting of colitis. “This doesn’t mean they are definitely going to have surgery,” he said, noting that several factors will weigh into that decision as they do in defining risk.

“You don’t always have to do a total proctocolectomy, especially with older patients,” he noted. “Experience has shown that segmental colectomy may be possible” among patients with deep remission of the distal colon and rectum, a single lesion or focus of dysplasia, those who are older and need their rectum to maintain continence, and those who can and will follow up for active surveillance. “It’s not unreasonable to think about this.”

Among all the preventive measures that can be taken for patients with UC, treating to deep remission “might be the most powerful primary prevention,” Dr Rubin stated. “Patients who achieved normalization of their biopsies have demonstrated significantly reduced subsequent risk of neoplasia.”

He concluded, "We’ve made some great progress, but we have to keep our eye on the ball. We certainly can’t do less intensive work; we just need to use our new technology smarter.”

—Rebecca Mashaw

 

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Reference:
Rubin DT. How to survey in 2002: Do we still need 32? Presented at: Advances in Inflammatory Bowel Diseases regional meeting. March 5, 2022. Virtual.