Premalignant Conditions of the Esophagus: When to Follow Up?

David A. Johnson, MD

Disclosures

February 11, 2013

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New Guidelines for Surveillance and Screening of Premalignant Conditions of the Esophagus

Hello. I am Dr. David Johnson, Professor of Medicine and Chief of Gastroenterology at Eastern Virginia Medical School. Welcome back to another installment of GI Common Concerns -- Computer Consult. In this session, I will pose a clinical question and describe the evidence base to answer that question.

This question came from a patient I saw today who had been referred for screening for Barrett esophagus. He was a 54-year-old white man with a lifetime history of reflux disease, but he had never had any type of endoscopic evaluation. I performed an endoscopy and, lo and behold, found evidence of Barrett esophagus. His biopsies showed no evidence of dysplasia, but he is understandably concerned. What should I tell this patient? When do I bring him back for surveillance?

It is perfect timing for this topic because in the December 2012 issue of Gastrointestinal Endoscopy, the American Society of Gastrointestinal Endoscopy (ASGE) Standards of Practice Committee published new guidelines[1] on the appropriate surveillance and screening for premalignant conditions of the esophagus.

Barrett Esophagus

Let's talk first about Barrett esophagus. The guidelines for screening for Barrett esophagus have received a bit of a wake-up call from a recommendation from the American College of Physicians, also published in December 2012 in Annals of Internal Medicine.[2]

This recommendation specifies that screening for Barrett esophagus should be performed only in men with symptoms of chronic reflux but who are otherwise asymptomatic. However, in women, no evidence exists to support benefit from screening. In fact, the value of screening women for Barrett esophagus is equivalent to the value of screening men for breast cancer.[2] Think about that and put it into perspective. When is the last time you screened a man for breast cancer?

As primary care providers, we need to take a "time-out" on evaluating women for Barrett esophagus in the absence of alarm features or signs and symptoms that suggest the need for endoscopy for other reasons. In men, reasonable judgment in the fifth decade of life for patients who have long-term symptoms of reflux disease should be used. Those patients should be referred appropriately with the caveat that if they do not have histologic evidence of Barrett esophagus on endoscopy, they do not need follow-up.

The ASGE guideline was quite succinct on this point. In the absence of histologic evidence of Barrett esophagus and specialized columnar metaplasia, you do not need a follow-up endoscopy. Patients often ask when they need to return for follow-up. Primary care providers and gastroenterologists alike need to "turn off that spigot," and reassure patients that they don't need to return.

Metaplasia

How about patients with metaplasia who have, like my patient, Barrett esophagus and precancerous risk? What is their relative risk? Epidemiologic studies, 2 of which have been published in the last year, suggest that the risk for progression to adenocarcinoma in nondysplastic Barrett esophagus is 0.1%-0.3% per year[3,4] -- much lower than what we thought previously. Previous guidelines stated that patients with nondysplastic Barrett esophagus should return in 1 year and then be followed every 3 years. The current ASGE guidelines, with which I entirely agree, have changed this recommendation to state that these patients should be followed in 3-5 years. The minimum surveillance interval after that would be the same, provided that you have performed adequate biopsies. According to the Seattle protocol, this means 4-quadrant jumbo biopsies at 1- to 2-cm intervals, but we have good evidence now to suggest that the standard large-particle biopsies, rather than jumbo biopsies, in all quadrants are adequate and you don't necessarily have to rush out and buy jumbo biopsy instruments for your routine biopsies.

Low-Grade Dysplasia

What if the patient has low-grade dysplasia? Low-grade dysplasia is a bit of a game-changer.

The incidence of progression to esophageal adenocarcinoma is approximately 0.7% per year -- higher than for nondysplastic Barrett esophagus but still relatively low. The ASGE recommendations differ somewhat from other current society guidelines in that you would see the patient with low-grade dysplasia (confirmed by an expert pathologist, recognizing the intrapathology variability of interpretation) in 6 months. If the biopsy results are unchanged at 6 months, the patient can then be followed yearly. All visible lesions must be biopsied separately. Low-grade dysplasia needs to be watched, but it is also an opportunity to discuss with the patient whether he or she should be referred for ablation. At this point, ablation is not my personal recommendation for low-grade dysplasia, but it is a viable option for individualized management depending on your referral center and your personal expertise.

High-Grade Dysplasia

High-grade dysplasia is different.

Previous society guidelines suggested consideration of surgical resection. In my practice, that is not an option for high-grade dysplasia. These patients are candidates, and should be referred, for endoscopic ablation. We have excellent evidence from the endoscopic ablation studies that these patients can be treated without progression to cancer, and that should be the standard of care for high-grade dysplasia. High-grade dysplasia likewise must be confirmed by an expert pathologist. All visible lesions must be resected and staged appropriately, so if there is an ulceration or nodularity, the patient should be referred for an endoscopic mucosal resection. The ASGE guidelines state that endoscopic ultrasound should be performed before the patient undergoes endoscopic mucosal resection. I typically take a "time-out" with this recommendation, too. My bias, which is weighted on the evidence and my understanding of the literature, is that these patients do not need endoscopic ultrasound for high-grade dysplasia. They need endoscopic mucosal resection of visible lesions. Endoscopic ultrasound is overused in this circumstance. It doesn't change anything. The staging is histologic, accomplished through endoscopic mucosal resection for high-grade dysplasia and intramucosal carcinoma. At this point, endoscopic ultrasound is unnecessary.

When should patients who have undergone resection or ablation return for follow-up? The experts suggest (and ASGE endorses this) that these patients should be brought back at 3 months, followed at 3-month intervals for the first year, and then at 6-month intervals for the subsequent year. After another year, follow-up should be annual; these patients are entered into a lifelong surveillance strategy, which is not discontinued. Two recently published reports support this. One was a case series published in Gastroenterology[5] describing 3 patients from centers of excellence who had ablation and subsequently developed incident cancers. Two more case reports (which are not yet published but will be in Endoscopy) emphasize that these patients can have incident cancers even after ablation therapy. This is not inconsequential; we need to follow these patients. It's not cost-effective to perform endoscopic ablation and then fail to follow them afterward.

Other Premalignant Conditions

How about other conditions?

Achalasia

Achalasia is known to be associated with esophageal adenocarcinoma -- in particular, esophageal squamous cell carcinoma.

The relative risk for squamous cell carcinoma is increased 16- to 33-fold. We do not have good evidence that surveillance is beneficial in these patients, as suggested by the current ASGE guidelines. Anecdotally, I had a patient with achalasia a couple months ago, with a 2-mm divot in the proximal esophagus. His biopsy showed squamous cell carcinoma. So, if there is an indication for endoscopic evaluation, make it scrutinizing. These patients frequently have food and liquid debris and foaminess in the proximal esophagus and must be very carefully lavaged, taking special care in the proximal esophagus. They have a high "back-flow" of the liquid, so use low volumes of fluid during lavage. Narrow-band imaging and high-resolution endoscopic evaluation may be helpful, but routine surveillance is not recommended by the ASGE.

Tylosis

Tylosis is a different story.

Tylosis is an incredibly rare condition, commonly associated with esophageal cancer. In fact, tylosis is associated with hyperkeratosis of the palms and soles and is a genetic aberration. Two pedigrees are described: an American type and a British type. The lifetime risk for esophageal cancer in the American type is 40%, and in the British type, 90%. The recommendation is to begin endoscopic surveillance of these patients at age 30 years and follow them every 1-3 years. You may not be currently following these patients, so be aware that there is a lifetime risk and they need to be followed carefully.

Caustic Ingestions

How about caustic ingestions?

Caustic ingestions account for 1%-4% of cancers of the esophagus. The most common substance involved is lye, typically in a patient who ingested lye in some type of misadventure as a child. The risk for cancer occurs at 10-70 years after the caustic ingestion and warrants surveillance and screening in these patients. The recommendation is to begin surveillance at 10-20 years after the initial event and then follow the patient at 2- to 3-year intervals. These patients should be followed relatively cautiously throughout life because cancer can occur at any time.

Summary of ASGE Recommendations

The current ASGE recommendations for Barrett esophagus can be summarized as follows:

When doing a one-time screening for Barrett esophagus in men, no follow-up endoscopy is indicated unless the patient develops signs and symptoms. If the index exam shows nondysplasia, follow-up is recommended at 3-5 years. Surveillance in some patients, based on other risks, can be discontinued.

Consider ablation for patients with low-grade dysplasia on biopsy. Follow these patients at 6-month intervals for a year and then annually with expert pathology consultation.

Patients with high-grade dysplasia should be referred for endoscopic ablation. If you choose instead to monitor these patients, they must be followed very closely with expert pathology.

Endoscopic ultrasound has no role in these patients. Patients with visible lesions should have endoscopic mucosal resection.

Follow-up of high-grade dysplasia should be at 3-month intervals for the first year, 6-month intervals for the second year, and then annually.

Other ASGE recommendations include:

No screening or surveillance recommendations were made for achalasia.

Patients with tylosis should be monitored beginning at age 30 years and then every 1-3 years. The lifetime risk for cancer is 40%-90% depending on pedigree.

The range for surveillance of patients who have experienced a caustic ingestion is broad because cancer can occur from 10 to 70 years after ingestion. These patients should be followed beginning 10-20 years after the ingestion and then every 2-3 years after they have entered a surveillance strategy.

I hope this gives you some guidance for the next time you sit down and have a conversation with a patient about relative risk for cancer and the need for follow-up, or, if you are a primary care provider, when you should refer these patients to a specialist, and when it is appropriate for gastroenterologists to follow these patients.

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