11 More Highlights From Digestive Disease Week 2023: Part 2

David A. Johnson, MD


May 25, 2023

This transcript has been edited for clarity.

Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School.

Welcome back to this part 2 of my highlights from Digestive Disease Week (DDW) 2023, held this year in Chicago, Illinois.

As I did in part 1, I'd like to offer some high-level summaries of several studies, although you can certainly access and research the full abstracts provided in the reference list to get more specifics. But here, I simply wanted to give you some take-home messages to pique your interest.

Risk for Second Cancers Among Those With Early-Onset Colon Cancer

The first study I'd like to focus on looked at the diagnosis of early colon cancer using the National Cancer Institute's Surveillance, Epidemiology, and End Results database over an extended period of time.[1]

The authors looked at the development of a second cancer among younger adults (age 18-49 years) diagnosed with stage 0-III colorectal cancer. By age 70, the cumulative risk for a second cancer was 19.7% for men and 18.4% for women. The 25-year cumulative risk of developing a second cancer of the colon was 6.4% for men and 4.4% for women. This translates into 1 in 6 people diagnosed with early-onset colorectal cancer eventually having a second cancer.

More broadly, I think these results mean that we should be much more aggressive, dynamic, and persistent in oncogenetic testing. My personal opinion is that all such patients should be seen by a geneticist and receive appropriate monitoring depending on what we identify. Certainly, we find things well beyond just Lynch syndrome among those with early-onset colon cancer.

Bariatric Surgery May Lower Cancer Risk

Another study related to the risk for cancer development that caught my eye was on the topic of bariatric surgery.[2]

A team of investigators looked at the risk of developing cancer using a database of patients with obesity. They found that there was a significant reduction in the risk for cancer among those who underwent bariatric surgery, particularly for cancers related to the gastrointestinal and gynecologic axis, as well as of the breast and thyroid. The risk reduction for developing these cancers for those in bariatric surgery cohort was significant and ranged from approximately 40% to 60%.

These results offer yet another reason to look at bariatric surgery in a very favorable way.

New Guidance on Treating Crohn's Disease

There were a couple of noteworthy studies regarding treatment paradigms for ileal Crohn's disease.

The first study[3] compared ileocecal resection vs anti-tumor necrosis factor (anti-TNF) as an index treatment within 1 year of diagnosis, using nationwide Danish register data. Investigators noted that after up to 5 years of follow-up in patients undergoing ileocecal resection, 47.5% were taking an immunomodulator, 17.1% were on anti-TNF treatment, and 50.3% remained off any treatment. This may indicate that there is a primary role for earlier ileocecal resection.

A separate study[4] from investigators in Italy compared prophylactic immunosuppression with ileo-colonic resection in those with Crohn's disease isolated in that area and only one clinical risk factor. Groups were compared based on whether they began anti-TNF therapy immediately after surgery or underwent observation guided by endoscopy with induction based on mucosal aberrations seen at the time of follow-up colonoscopy beginning at 6 months. Investigators found similar rates of clinical and endoscopic recurrence at 12 and 24 months between the groups. This indicates that in such patients, a strategy of simply observing and aggressively resurveying for deep remission by macroscopic criteria may be the emerging norm.

Another study[5] assessed the use of subcutaneous infliximab as maintenance therapy for Crohn's disease.

Dr Stephen Hanauer presented results in patients with moderately to severely active Crohn's disease who were successfully in remission after initial induction. They were followed up for 54 weeks to determine the co-primary endpoints of clinical remission and endoscopic response. These co-primary endpoints were significantly better in the patients who received subcutaneous infliximab. The endoscopic response rate was 51.1% in the active subcutaneous infliximab cohort compared with only 17.9% in the placebo cohort.

Pharmacokinetic and pharmacodynamic data were not presented in this study but are available in the literature and surprisingly, demonstrated increased levels with the subcutaneous injections.

As you may know, this treatment is approved in Europe for inflammatory bowel disease, among other indications. We'll have to see what the US Food and Drug Administration does with these findings. However, they do signal a potentially new way to administer infliximab.

The Promise of Re-Cellularization Therapy in Type 2 Diabetes

The next study was very exciting and came from Dr Jacques Bergman and colleagues in the Netherlands.[6] It looked at re-cellularization via electroporation therapy, a novel endoscopic 1-hour procedure where they performed a duodenal mucosal delivery of electric fields. This creates apoptosis and allows the cells to repopulate and renew. This seems to preserve tissue structure, allowing better de novo insulin response.

They conducted a single-arm study of 14 patients with type 2 diabetes, who were then followed during a 2-week post-procedural isocaloric liquid diet. The primary endpoint at 6 months was whether the patients could be off insulin entirely and achieve an A1c ≤ 7.5%. At 6 months, there was a significant improvement, with 86% off insulin entirely, and all showing improvements in glycemic control.

We'll have to see where results with this very exciting procedure go with continued follow-up.

Better Strategies for Reducing Sarcopenia in Patients With Cirrhosis

There were two noteworthy studies relating to muscle mass and nutrition in patients with cirrhosis. Sarcopenia is very prevalent in these patients and leads to deterioration and is the number one reason that patients get delisted from transplant protocols.

The first study comes from investigators in India,[7] who looked at the dynamic interplay of using nutritional therapy with 30-35 kcal/kg/d and 1-1.5 grams of vegetable protein/kg/d, compared with no nutritional therapy. Treatment was maintained for 6 months and showed a dynamic improvement for its ability to minimize sarcopenia.

Another study[8] from investigators in Thailand did basically the same thing, but they used a branched-chain amino acid [supplement], as well as home-based strengthening exercises. This also showed remarkable reductions in sarcopenia.

Collectively, I think these results indicate that we are doing a relatively poor job overall in our patients with cirrhosis. We can be much more aggressive as far as nutritional plans and in-home strengthening exercises. Get a dietitian involved. We can do much better in the prevention of sarcopenia, or at least minimizing the progression toward it.

Direct Endoscopic Necrosectomy for Infected Necrotizing Pancreatitis

Next was a study from Dr Ji Young Bang and colleagues,[9] who conducted an evaluation of the best approach for infected necrotizing pancreatitis. Certainly, the standard in this indication has been transluminal stent placement followed by the performance of direct endoscopic necrosectomy. However, the best timing for when to perform this is not well evaluated.

In this multicenter study, 70 patients were randomized to direct endoscopic necrosectomy at the index exam after a lumen-apposing metal stent or a step-up approach where they came back and underwent necrosectomy after no clinical improvement. Lo and behold, they found that the aggressive de novo approach was substantially better as far as length of hospitalization, which decreased by 10 days, although there was no significant difference in treatment success.

This supports the notion of moving more quickly, which is an approach I think our interventional endoscopists are certainly going to embrace if it results in a reduction in risk and days in hospital.

Measuring the Impact of Time and COVID-19 on the Microbiome

There were also a pair of interesting studies related to the microbiome.

The first of these comes from investigators at the University of California, San Diego.[10] They showed tremendous variation, both in diurnal and seasonal patterns, on the microbiome. Using data from the American Gastroenterological Association's American Gut Project, they show a dramatic variation based just on day-to-day activities. Time of day makes a tremendous difference, and seasonal changes also make a dramatic difference as it relates to the microbiome.

When we start to mitigate toward certain biomic signatures, we need to remember what time of day these signatures were procured and wait and see how this transpires in a mitigation strategy.

The final study[11] comes from investigators in Hong Kong, who assessed alterations to the microbiome using a proprietary probiotic in patients with long COVID. In a double-blind, placebo-controlled trial, they found that there was a significant improvement in long COVID symptoms. Improvements were shown in gastrointestinal symptoms, as well as some of the symptoms of mental fogginess and fatigue, with an approximately 20% advantage observed over those who received placebo.

This is another situation where we'll have to wait and see where it goes, but it does tell us that the microbiome is involved in patients with long COVID. It should be noted that this was studied in patients before the emergence of certain COVID variants, so we're not sure how this applies to those.

In summary, this year's DDW featured lots of exciting information, which we'll look forward to seeing in peer-reviewed publications.

I'm Dr David Johnson. Thanks for listening.

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.

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