Achalasia and Risk of Esophageal Cancers

Posted on November 2, 2026 by gutsandgrowth

W Leijonmarck et al. Gastroenterology 2026; 171: 481-488. Open Access! Achalasia and Risk of Esophageal Squamous Cell Carcinoma and Adenocarcinoma in a Multinational Study

Methods: “A population-based case–control study was conducted in 5 Nordic countries from 1987 to 2023. Esophageal cancer cases (n = 35,604) were matched to 10 times as many background population controls by age, sex, calendar year, and country (n = 355,869). Conditional logistic regression provided odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for smoking and alcohol, and additionally for GERD in a mechanistic model. All variables came from national health data registries.” The registries used prospectively collected data.

Key findings:

Absolute numbers of esophageal cancer: “Achalasia was present in 137 cases (96 squamous cell carcinomas and 41 adenocarcinomas) and 230 controls (99 squamous cell carcinomas and 131 adenocarcinomas)”
“Achalasia was associated with a strongly increased risk of esophageal squamous cell carcinoma (OR, 9.46)”
A moderate association was found for esophageal adenocarcinoma (OR, 3.05). This association “became attenuated and nonsignificant after adjustment for GERD and even weaker in patients treated with myotomy or pneumatic dilation.” The discussion notes the following: “possible pathway to adenocarcinoma is iatrogenic reflux caused by myotomy or pneumatic dilation that destroys the antireflux function of the lower esophageal sphincter.⁶ Alternatively, low esophageal pH that leads to adenocarcinoma in the achalasia esophagus may result from impaired esophageal clearance, allowing refluxed acid to linger, or from lactic acid production due to the fermentation of stagnant food.⁵^,²⁶^,²⁷“

My take: An increased risk is another ‘tough pill to swallow’ when diagnosed with achalasia. However, the authors note that “despite the strong association, routine cancer surveillance endoscopy may still not be recommended due to the low proportion (<1%) of achalasia in esophageal cancer.” In those with worsening dysphagia, this infrequent complication needs to be considered.

Related blog posts:

Hallgrímskirkja, the largest church in Iceland, and the Statue of Leif Erikson standing directly in front of it in downtown **Reykjavík**. The concrete facade was inspired by the basalt lava rock columns found in Iceland.

Hospitals Closing Across U.S. and This Year’s Pumpkin

Posted on November 1, 2026 by gutsandgrowth

Halloween 2026:

Daniel Wu. Washington Post 10/8/26. Hospitals are closing across America, and it’s only getting worse

An excerpt:

Closure rates were almost the same between urban and rural hospitals… according to a new study by the Harvard T.H. Chan School of Public Health.

More than 400 hospitals closed across the country from 2010 to 2025, according to the study, which analyzed data from the American Hospital Association’s annual survey. Year over year, the rate of hospital closures has increased by 4 percent, and the rate of openings has decreased by 3 percent.

Between hospital openings and closures, there was a net loss of 216 hospitals and more than 24,000 beds. The hospitals that closed were more likely to be smaller, for-profit and safety-net hospitals, which generally treat more vulnerable communities and uninsured patients…

Hospitals could face further strain due to Medicaid coverage losses and payment cuts from President Donald Trump’s One Big Beautiful Bill.

My take: Fewer hospitals will likely mean longer distances for care and increased costs due to consolidation. For many patients, longer distances could result in worse outcomes, not just an inconvenience.

Related blog posts:

Diamond Beach (Iceland) is named for the sparkling chunks of glacial ice that
wash ashore and glitter against the dark volcanic sand like scattered diamonds

Long-Term PPI Use Not Linked to Gastric Cancer in Nordic Study

Posted on October 30, 2026 by gutsandgrowth

O Duru et al. BMJ 2026; 392: e086384. Open Access! Long term use of proton pump inhibitors and risk of stomach cancer: population based case-control study in five Nordic countries

Background: “A recent systematic review on the topic concluded that although the literature suggests a positive association between proton pump inhibitor use and gastric cancer, the studies are hampered by major methodological limitations, such as low statistical power, short and incomplete follow-up, inclusion of proton pump inhibitor exposure shortly before the gastric cancer was diagnosed (protopathic bias), differences in classification of cases (methodological heterogeneity), and inability to adjust for Helicobacter pylori infection and other relevant confounders.11″

Methods: Population based case-control study using prospectively collected data from multiple complete nationwide registries in five Nordic nations. The study included 17,232 cases of gastric (non-cardia) adenocarcinoma and 172,297 controls. Long term proton pump inhibitor use occurred in 1766 (10.2%) cases and 16 312 (9.5%) controls.

Key findings:

No association was found between long term proton pump inhibitor use and gastric adenocarcinoma (adjusted odds 1.01); the risk was similar for histamine-2-receptor antagonist use (adjusted odds ratio 1.03
Multiple sources of error that led to a false positive association were identified—inclusion of proton pump inhibitor use shortly before the gastric adenocarcinoma diagnosis, short term use of proton pump inhibitors, cardia adenocarcinoma, and lack of adjustment for Helicobacter pylori related variables

My take: This study indicates that long-term PPI use is not associated with higher incidences of gastric adenocarcinoma.

Related blog posts:

Automated AI-Based Colonoscopy Assessment for Ulcerative Colitis

Posted on October 29, 2026 by gutsandgrowth

K Hammouda et al. Journal of Crohn’s and Colitis, Volume 20, Issue 8, August 2026, jjag122. Open Access! Automated AI-based Mayo Endoscopic Scoring for ulcerative colitis across adult and pediatric cohorts from diverse populations

Background: “Endoscopic evaluation remains the gold standard for assessing UC disease activity…The Mayo Endoscopic Score (MES), ranging from 0 to 3, is a widely used index to grade mucosal disease severity in trials and clinical practice, with scores of 0-1 indicating remission and 2-3 reflecting active disease.⁶ However, the clinical utility of MES is limited by substantial inter- and intra-observer variability⁷…By leveraging large, annotated datasets, DL models can automate MES grading, potentially reducing subjectivity and enhancing diagnostic consistency.¹¹“

Methods: “Using three multi-institutional datasets, we trained and validated convolutional neural network models to predict MES. The primary dataset (LIMUC; 564 adults, 11 276 images, Turkey) supported model development, with external validation on TMC (308 adults, 7978 images, China) and the Emory Pediatric dataset (EPC; 80 children, 113 images, USA).”

Key findings:

UC-Re for binary remission classification (MES 0-1 vs 2-3): “Achieved AUCs of 0.98, 0.95, and 0.98 across LIMUC, TMC, and EPC”
UC-MES for four-class grading (MES 0-3): “Demonstrated strong ordinal consistency (QWK = 0.81-0.85), comparable to inter-expert agreement (QWK = 0.88)”

(A) ROC curves for the binary UC-Re task (active vs inactive disease) in the
Emory, LIMUC, and TMC test sets (AUC 0.974, 0.980, and 0.949; average 0.97)

D) UC-MES four-class model (MES 0-3) compared with two board-certified gastroenterologists on the Emory cohort, measured by accuracy, F1-score, and quadratic weighted κ (QWK). UC-MES, Mayo Endoscopic Subscore grading; QWK, quadratic weighted kappa.

My take: This study while narrowly focusing on assessment of UC activity shows the potential of an AI-based framework to improve/standardize the interpretation of colonoscopy/endoscopy interpretation. This could help as a decision support tool and could facilitate comparison to prior evaluations. Presumably with adequate training and proof with prospective trials, these findings could be extended to a broad range of GI disorders that utilize endoscopic monitoring.

Related blog posts:

Infliximab Biosimilars As Effective as Remicade In Children With Inflammatory Bowel Disease

Posted on October 28, 2026 by gutsandgrowth

RM Maltz, J Adler. J Pediatr Gastroenterol Nutr. 2026; 83: 710-716. ImproveCareNow Pediatric IBD Learning Health System. Infliximab originator and biosimilars have similar efficacy in children with inflammatory bowel disease.

Background: “Biosimilars are nearly identical to the originator biologic with only minor differences, usually in the inactive components such as buffers or stabilizers, which have no effect on efficacy as shown in adult studies and limited pediatric studies^13–22…The introduction of biosimilars has significantly contributed to competition, which has driven down the price of the infliximab originator along with infliximab biosimilars.²³ The price of the infliximab originator dropped by more than 50% between 2018 and 2021.²³“

Methods: This was a retrospective cohort study evaluating prospectively collected data from the ImproveCareNow (ICN) Network registry. 428 children were studied using propensity score matching.

Key findings:

Efficacy at 12 months was similar as assessed by steroid-free clinical remission (p = 0.25), height-z-score (p = 0.68), hematocrit (p = 0.37), albumin (p = 0.40), and erythrocyte sedimentation rate (p = 0.06).
Time to infliximab discontinuation (p = 0.21), time to surgery (p = 0.79), and time to hospitalization (p = 0.66) were comparable between infliximab originator and biosimilar users
In subset of patients with available results (fewer than one in three patients had calprotectin results available), fecal calprotectin values were statistically higher (p = 0.032) at 12 months in patients in the biosimilar cohort. At baseline, fecal calprotectin values were >250 in 11 (60%) of biosimilar cohort compared to 22 (38%) of the originator cohort. At 12 months, 36 (54%) in the biosimilar cohort and 28 (49%) in the originator cohort had fecal calprotectin values >250.

Outcomes comparing the inﬂiximab originator (blue dashed line) to inﬂiximab biosimilar (red solid line). Time to discontinuation of originator or biosimilar infliximab with 95% conﬁdence intervals

Outcomes comparing the inﬂiximab originator (blue dashed line) to inﬂiximab biosimilar (red solid line). Proportion needing intestinal surgery with 95% conﬁdence intervals

Outcomes comparing the inﬂiximab originator (blue dashed line) to inﬂiximab biosimilar (red solid line). Proportion needing hospitalization with 95% conﬁdence intervals

My take (borrowed in part from the authors): “This study adds to the growing literature that children with IBD, regardless of initiating infliximab originator or a biosimilar, have similar clinical outcomes at 1 year.^{16–19, 21}” Despite this, many families still request/prefer Remicade.

Related blog posts:

Pre-Crohn’s Disease Stool Promotes Colitis in Germ-Free Mice Plus One

Posted on October 27, 2026 by gutsandgrowth

C Dang et al. Gastroenterology, 2026; 171, 489-503. Pre-Crohn’s Disease Stool From Discordant Siblings Promotes the Development of Colitis in Germ-Free Mice

Methods: This study was conducted as part of The GEM Project, a prospective cohort study of healthy first-degree relatives of CD patients. Germ-free mice were colonized with fecal samples from 12 pairs of discordant siblings, where one sibling later developed CD (pre-CD), and the other remained a healthy matched control (HMC). The microbiome collected wa ~2.6 years before CD diagnosis.

Key findings:

Mice receiving pre-CD stool exhibited increased weight loss, fecal lipocalin-2, and intestinal histologic damage compared with mice receiving HMC stool. Thus, mice colonized with stool from individuals who later developed Crohn’s disease showed significantly faster and more severe intestinal inflammation compared with mice colonized with stool from the siblings who remained healthy.
Fecal metabolomic analysis revealed differences in 40 metabolites between pre-CD and HMC colonized mice.

My take:

Silly take: It’s a good idea not to eat someone else’s poop — it might make you sick!
Serious take (borrowed in part from the authors): “The stool microbiome of individuals susceptible to CD is altered years before diagnosis, exhibiting greater inflammatory potential when transferred to susceptible mice.” These studies about the microbiome are remniscent of studies 15-20 years ago indicating that manipulation of the microbiome may play a role in the developement of obesity and Kwashiokor. (Related posts: Could antibiotics make you fat? gutsandgrowth, Microbiome and the risk of Kwashiokor | gutsandgrowth, Microbial transfer for metabolic syndrome? | gutsandgrowth)

Related article: M Xue, C McShane, J Kim et al. Gastroenterol 2026; 171: 641-655. Open access! β-Glucan and Inulin Estimated Intake Are Associated With Reduced Risk of Crohn’s Disease, Improved Gut Barrier and Systemic Inflammation Markers, and Multi-Omic Signatures in a High-Risk Cohort

Methods: The Genetic, Environmental, Microbial (GEM) Project prospectively followed asymptomatic first-degree relatives of individuals with CD. Habitual intake of total fiber and select fiber subtypes was estimated from baseline food frequency questionnaires and biologic samples were collected.

Key findings:

During a median follow-up of 8.5 years of 3314 first-degree relatives, 94 developed CD. Higher β-glucan (HR, 0.70) and inulin (HR, 0.68 intake were associated with lower CD risk.
Higher β-glucan and inulin intake were associated with lower lactulose–mannitol ratio, lower abundance of pathobionts (Ruminococcus torques and Lachnoclostridium), and lower concentrations of inflammation- and barrier-related proteins.
Increased β-glucan found in oats, barley and grains. Increased inulin found in garlic, onions, leeks and asparagus

Related blog posts:

NASPGHAN Paper: Dietary Management in Pediatric Aerodigestive and GI Dysmotility

Posted on October 26, 2026 by gutsandgrowth

K El-Chammas et al. J Pediatr Gastroenterol Nutr. 2026; 83: 748-760. Dietary management and feeding considerations of pediatric aerodigestive and upper gastrointestinal motility disorders.

Oropharyngeal dysphagia (OPD):

“Untreated OPD (either penetration and/or aspiration) is associated with persistent symptoms, recurrent respiratory infections, elevations in pulmonary inﬂammatory markers, and even bronchiectasis”
“Because >80% of pediatric aspiration is silent, the presence of symptoms at the time of an aspiration event should not be the determining factor when considering thickening”
“Most infants with OPD and aspiration experience improvements in swallow function over time, and thickeners/delivery vehicles can be weaned or changed as swallow function, palate, and caloric needs change. Antegrade aspiration is unlikely to be seen in neurodevelopmentally normal children older than 2 years of age exhibiting persistent lower respiratory tract infections”
Table 2 lists common thickeners and key differences. In infants, cereals and gelmix (if >37 weeks gestational age) are recommended. In older age groups, xanthan gum (SimplyThick®), Corn starch (Thick-It®), Tapioca starch, and Tara gum (PuraThick®) are options.
“Thickening gastrostomy tube feeds either with commercial thickeners or food improves GI and pulmonary outcomes and reduces the number of gastroesophageal reflux events without prolonging gastric emptying”
Table 3 provides specific recommendations including the following: ‘The recommended thickener for formula-fed infants younger than 1 year of age is cereal or purées. Commercial thickeners may be an option for some expressed breast milk- or formula-fed infants under the age of 1 year without comorbidities, depending on institutional practices.”

Esophageal Dysmotility

This section reviews several disorders including achalasia, gastroesophageal reflux, and esophageal atresia.

Reflux: In infants with reflux, “thickening of feeds can reduce overt symptoms such as vomiting but does not decrease reflux events.” Also, in this population, “a trial of maternal cows’ milk elimination, extensively hydrolyzed or amino-acid based formulas (in more severe cases with intractable symptoms) may be appropriate”
Achalasia: “There are no clear guidelines on the management of feedings in pediatric or adult patients with achalasia…Patients should be encouraged to eat in an upright position and to minimize eating for several hours before bedtime. A liquid or purée may be required with the guidance of a dietitian to ensure adequate nutritional intake while waiting for the diagnosis and definitive management of achalasia”
Esophageal atresia: “Only 28% of children with EA are consuming age‐appropriate food textures within the ﬁrst 2 years of life, with that improving to 70% of children over 5 years of age…Many infants with EA require gastrostomy tube placement because they cannot safely tolerate oral feeding or meet caloric requirements”
Table 4 summarizes recommendations for esophageal dysmotility, including “children with esophageal dysmotility should avoid foods with a high risk for esophageal obstruction/irritation, eat in an upright position, and avoid eating several hours before bedtime”

Gastric Dysmotility

“Most pediatric cases are idiopathic or post-viral, with less common causes being drug-induced or post-surgical”
“While dietary modification is often considered first-line therapy in patients with mild gastroparesis, it often results in suboptimal improvement in symptoms in clinical practice. Small, frequent meals and maintaining a post-prandial upright position may be better tolerated.^{74, 75} Liquids typically empty from the stomach faster than solids⁷⁶; therefore, increasing liquid calories and switching from solid to liquid calories later in the day may help patients with their symptoms.”
“Fatty, acidic, spicy, and high-fiber foods can exacerbate symptoms in patients with gastroparesis as they delay gastric emptying, exacerbate pain, and promote release of cholecystokinin”
“Small-particle diets, consisting of puréed, blended, or finely ground foods, facilitate gastric emptying by reducing mechanical workload on the stomach”
“Caution is advised when initiating enteral or parenteral nutrition in patients with gastroparesis given the significant overlap with functional dyspepsia and increased prevalence of feeding intolerance in adolescents with disorders of gut–brain interaction”
“In aerodigestive patients with upper gut dysmotility and feeding intolerance, gastrostomy and/or post-pyloric tube placement may provide access to decompress as well as provide nutrition when oral feeding is inadequate to sustain appropriate growth and symptom control”
“Blenderized tube feeds may be considered over commercial formulas to help with symptoms, decrease healthcare utilization, and improve quality of life…The American Society for Parenteral and Enteral Nutrition recently published detailed practice recommendations (L Epp et al. Nutr Clin Pract. 2023; 38(6): 1190-1219) providing guidance to medical providers and family pertaining to the use of BTFs regardless of their indication”

My take: This is a useful article regarding potential dietary interventions across a wide range of pediatric GI disorders. Just like medications, dietary interventions can result in complications. As such, the involvement of experienced dietitians and careful follow-up are needed.

Related blog posts:

Dysphagia:

Esophageal dysmotility:

Blenderized Diets:

Gastroparesis:

Ethan Mollick on AI’s Exponential Rise and an Otter on a Plane

Posted on October 25, 2026 by gutsandgrowth

One of the substack authors that I follow is Ethan Mollick. He is a professor at the Wharton School of Business (University of Pennsylvania) and a leading researcher on the practical impacts of artificial intelligence. Link to substack: One Useful Thing

A recent newsletter, 30 Months on the Exponential (in Charts) on 10/20/26, summarized the exponential progress of AI over the last three years, though noting the progress is uneven across many fields. In addition, the newsletter promotes his new book, Co-Existence.

One particularly fascinating tool for the past few years is an AI prompt to create an image of an ‘otter on a plane using wifi.’ It is worth reading this recent newsletter and if you are in a hurry scroll down to the ~2 minute video which is the latest iteration of an otter on a plane.

Congratulations!

Posted on October 23, 2026 by gutsandgrowth

Outcomes in Pediatric “Potential” Celiac Disease Plus One

Posted on October 23, 2026 by gutsandgrowth

B Laxer et al. J Pediatr Gastroenterol Nutr. 2026; 83: 717-722. Open Access! Heterogeneous outcomes in pediatric potential celiac disease: a multicenter longitudinal study.

Background: Potential celiac disease (PCD) is defined by positive celiac serology without villous atrophy.

Methods: This was a multicenter retrospective study with 88 children with mean follow-up of 3.3 years (with a range up to 6 years). Indications for repeat endoscopic evaluation while on a GCD included—a rise in tTG titers to >10× ULN, persistent tTG elevation >10× ULN for over 24 months and the emergence of clinical symptoms necessitating reassessment. During follow-up, only 23 patients (26.1%) underwent a repeat upper endoscopy, as per the clinician’s decision, after a median period of 29 (IQR 11.5–36.5) months from the initial PCD diagnosis.

Key findings:

17/88 (19.3%) patients progressed to Celiac Disease (CeD).
33/88 (37.5%) had normalization of anti-tissue transglutaminase antibodies (tTG), while continuing a diet containing gluten
38/88 (43.2%) continue to have PCD
Among 16 patients with high tTG levels (>×10 upper limit of normal) at PCD diagnosis, the results were similar: three (18.8%) progressed to CeD and six (37.5%) normalized tTG
Asymptomatic patients were significantly more likely to achieve serological normalization compared to their symptomatic counterparts (61.9% vs. 35.8%, p = 0.011)

Discussion Points:

“A recent meta-analysis⁹ of 1010 patients reported a progression rate of approximately 33% to CeD, while another third achieved serological normalization.”

Limitations:

Follow-up period of up to 6 years may not capture late-onset progression.
Only a small subset had a follow-up endoscopy; if all patients had had a repeat endoscopy, there would have been a higher rate of CeD diagnosis

My take: This study found about one-fifth of patients progressed from potential celiac disease to celiac disease during a mean follow-up of 3.3 years. However, 70% of patients did not undergo repeat endoscopy.

Related blog posts:

Also, in same issue:

MC Pacheco et al. J Pediatr Gastroenterol Nutr. 2026; 83: 723-727. Does diagnosis by biopsy versus serology-only affect follow-up in celiac disease? In this retrospective study wiht 54 children, there was no significant difference in frequency of clinical follow-up or decrease in TTG IgA levels between patients who were diagnosed with biopsy versus serology alone.