Dear colleagues,

While large phase 3 studies typically garner the most attention, the results of smaller studies can also be very informative for routine practice. Celiac disease is often associated with severe complications, including refractory disease and several forms of cancer. However, until recently no biomarkers were known that reliably predict complications of the disease. A large cohort study now shows that persistent villous atrophy in patients maintaining a gluten-free diet is associated with the development of long-term complications, which can be predicted using a simple clinical score (Schiepatti et al.). This tool may prove helpful for identifying at-risk patients, who would be candidates for closer follow-up. Gastrointestinal bleeding due to small intestinal angiodysplasia (SIA) represents a major therapeutic challenge, since the source of bleeding is often difficult to detect by endoscopy. A small, randomized trial has shown that administering thalidomide can significantly lower the incidence of recurrent bleeding due to SIA compared with placebo (Chen et al.). Several years ago, the LIR!C trial compared laparoscopic ileocecal resection versus infliximab therapy in patients with ileocecal Crohn’s disease and luminal inflammation, reporting comparable short-term outcomes from the two approaches, and more favorable long-term outcomes following surgery. These findings have now been confirmed by a registry-based cohort study in Denmark. The new study concludes that ileocecal resection of Crohn’s disease represents a good first-line alternative to anti-TNF therapy that may potentially be more effective over the long term (Agrawal et al.). Based on these conclusions, all patients should be evaluated for surgery at an early time point – not only patients with complications or refractory disease. [...]

Most practitioners are hesitant to prescribe amitriptyline for irritable bowel syndrome and may avoid the drug altogether due to fears of its side effects. The largest randomized trial to date on the use of tricyclic antidepressants for irritable bowel syndrome (ATLANTIS) now reports that second-line low-dose amitriptyline therapy (10 mg/day) followed by titration to 30 mg was significantly more effective at improving symptoms than placebo. Treatment was safe and relatively well tolerated (Ford et al.). It is recommended that small polyps less than 10 mm in size be resected by cold snare polypectomy. Many practitioners have wondered whether prior submucosal injection might improve polyp ensnarement and reliably improve the rate of complete resection. However, a recent pragmatic study refutes this hypothesis: Submucosal injection of small polyps prior to cold snare polypectomy had no effect on the R0 resection rate or surgical complications, but did significantly prolong the procedure time (Mou et al.). While budesonide remains the standard of care for microscopic colitis, it does not consistently alleviate patients’ symptoms. A retrospective analysis of a large cohort of microscopic colitis patients at the Mayo Clinic now shows that bile acid sequestrant therapy can lead to complete or partial response, as measured by improvement in diarrhea, in nearly two-thirds of patients treated (Tome et al.). More research is now needed to elucidate the etiologic role of bile acid sequestrants and/or bile acid malabsorption in microscopic colitis.

Although fluid therapy has become a mainstay in the early management of acute pancreatitis, the impact of the composition of the fluids administered remains incompletely studied. In a prospective, multicenter cohort study with 999 patients, Lee et al. report that the use of Ringer’s lactate in the first 24 hours of hospitalization is associated with better outcomes of acute pancreatitis than normal saline.

Non-alcoholic fatty liver disease (NAFLD) is linked to a number of comorbidities and risks. A recent cohort study shows that patients with NAFLD are also at a significantly greater risk of severe infections. This elevated risk was observed across all stages of NAFLD and increased with worsening disease severity (Ebrahimi et al.). Although liver diseases are a major cause of morbidity and mortality among the general population, there are no tools for timely identification of at-risk individuals apart from recently established hepatitis B and C screening. The newly developed LiverRisk score is based on age, sex, and six standard laboratory variables, and facilitates very precise prediction of future liver-related outcomes in the general population, allowing stratification of individuals by risk to guide preventive care (Serra-Burriel et al.). While effective etiological treatment, i.e. treating the etiological cause of a liver disease, is recommended even for patients with advanced cirrhosis, the evidence for this approach has been thin. A new study confirms that treating the etiological cause of liver disease considerably improves cirrhosis patients’ prognosis, even for those with ascites as the first decompensating event. Hence, proper diagnosis and treatment of the underlying liver disease are crucial even for patients with advanced cirrhosis (Tonon et al.).

Together with the Falk Foundation team, we hope you find the literature selection in this issue of the Falk Gastro Review Journal engaging and enjoyable. Stay healthy and hopeful!

Happy reading,

Christoph Neumann-Haefelin and Peter Hasselblatt
Department of Internal Medicine II, Medical University Clinic of Freiburg (Germany)

Christoph Neumann-Haefelin

Peter Hasselblatt

Current literature articles in this edition

Sintilimab plus chemotherapy for unresectable gastric or gastroesophageal junction cancer: The ORIENT-16 randomized clinical trial

JAMA. 2023;330(21):2064–74

Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): A multicenter, randomized, double-blind, phase 3 trial

Lancet Oncol. 2023;24(11):1181–95

Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastroesophageal junction adenocarcinoma: Interim analyses from the phase 3 KEYNOTE-811 randomized placebo-controlled trial

Lancet. 2023;402(10418):2197–208

Magnitude and time-trends of post-endoscopy esophageal adenocarcinoma and post-endoscopy esophageal neoplasia in a population-based cohort study: The Nordic Barrett’s Esophagus Study

Gastroenterology. 2023;165(4):909–19.e13

Association between changes in carbohydrate intake and long-term weight changes: Prospective cohort study

BMJ. 2023;382:e073939

Daily oral GLP-1 receptor agonist orforglipron for adults with obesity

N Engl J Med. 2023;389(10):877–88

Thalidomide for recurrent bleeding due to small intestinal angiodysplasia

N Engl J Med. 2023;389(18):1649–59

Post-endoscopy care for patients presenting with esophageal food bolus impaction: A population-based multicenter cohort study

Am J Gastroenterol. 2023;118(10):1787–96

Endoscopic vacuum therapy for upper gastrointestinal leaks and perforations: Analysis from a multicenter Spanish registry

Am J Gastroenterol. 2023;118(10):1797–806