Introduction

A substantial portion of individuals diagnosed with lactose malabsorption fail to experience significant relief from a lactose-free dietary regimen (1). The ‘adult Carbohydrate Perception Questionnaire’ (aCPQ) is a simple, test-specific questionnaire for the assessment of gastrointestinal symptoms following a carbohydrate challenge (2). The aCPQ has undergone rigorous validation, it has excellent psychometric properties, and its use has been recommended to replace missing or unvalidated symptom assessments in carbohydrate breath testing (3).

Aims & Methods

Our aim was to assess symptom burden after lactose ingestion by means of the aCPQ with respect to the presence or absence of malabsorption. 753 patients with functional gastrointestinal disorders received a lactose (50 g) intolerance/H₂-breath test (180 min duration), utilizing the aCPQ for test specific, validated symptom assessment and an electrochemical hydrogen detector for quantification of end-expiratory breath hydrogen. Malabsorption (M+) was defined as an increase in end-expiratory H₂ by >20 ppm over baseline (as opposed to M-). The presence of relevant symptoms after lactose ingestion (S+) was defined as an increase of symptom scores by >20 cm in one of the five VAS scales over baseline (as opposed to S-). The maximal rise of symptom severity over baseline was determined (maximal possible rise: 100 for each symptom) and considered the individual symptom burden; the sum of individual symptom burdens was considered the total symptom burden (maximum possible sum of 500).

Results

308 patients tested M+, 445 M-, and 417 tested S+ vs. 336 S-. 80 patients (26.0%) testing M+ had no clinically relevant symptoms (S-) following the lactose challenge; in contrast, 189 patients (45.3%) testing M- had relevant symptoms after the lactose challenge. Table 1 shows the individual and total symptom burden based on the diagnosis of lactose intolerance/H2 breath test: patients with malabsorption who had no clinically relevant lactose-induced symptoms (S-/M+) reported slightly higher intensities of flatulence and diarrhea as compared to S-/M-. Malabsorbers with symptoms had higher symptom burdens as compared to absorbers except for nausea, which was not statistically different between S+/M+ and S+/M-.
Table: Symptom burden after lactose ingestion

Conclusion

Malabsorption may be just one of the factors that lead to the onset of symptoms following lactose consumption. This is crucial regarding both the diagnosis and therapy of lactose intolerance. The aCPQ is the only reliable and valid, test specific instrument to evaluate symptoms triggered by the consumption of carbohydrates. It can be used in conjunction with a breath test, which is necessary if lactose malabsorption is to be detected.

References

1. Hammer J et al. Carbohydrate induced gastrointestinal symptoms: development and validation of a test-specific symptom questionnaire for an adult population, the adult Carbohydrate Perception Questionnaire aCPQ. Eur J Gastroenterol Hepatol 2021;32:171-177
2. Hammer HF et al. European Guideline on indications, performance and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: EAGEN, ESNM and ESPGHAN consensus. United European Gastroenterol J 2022;10:15-40
3. Levitt M et al, Clinical implication of lactose malabsorption versus lactose intolerance. J Clin Gastroenterol 2013;47:471-480

Introduction

Gastric cancer ranks as the fifth most common cancer and the second leading cause of cancer-related deaths. Multifocal atrophic gastritis and gastric intestinal metaplasia (GIM) often coexist and are both associated with the risk of developing gastric cancer, with GIM being the first irreversible mucosal transformation to cancer. Endoscopic surveillance was associated with earlier cancer detection and improved survival. This study aims to evaluate the prevalence, epidemiological characteristics, and clinical features of patients with GIM.

Aims & Methods

This is a single-center, retrospective study from January 1, 2022 to December 31, 2023. Including patients aged ≥18 years who underwent esophagogastroduodenoscopy (EGD) with gastric biopsies confirming GIM, All identified cases of GIM were reviewed by gastrointestinal pathologists to confirm the diagnosis. Th primary outcome was to assess the prevalence, epidemiological characteristic, and clinical features of GIM. The secondary outcome was to evaluate adherence to recommended surveillance protocols for GIM.

Results

Among 3,663 patients who underwent EGD, GIM was identified in (4.17%, n=153). The mean age of patients with GIM was 60 years, Males represented more than half of patients (54.2%), the majority were classified as overweight (Body mass index (BMI) 25–29.9; 64%, n=97) or obese (BMI ≥30; 24.3%, n=37).Smoking was reported in (17.6%, n=27), while (5.2%, n=8) reported alcohol consumption. Moreover, (7.2%, n=11) had a history of prior gastric surgeries. Dyspepsia (33.3%) was the most common indication for EGD. Gastritis was the predominant endoscopic finding and the primary reason for performing gastric biopsies (73%, n=112 ).The most common GIM subtype was complete (52%), followed by incomplete (37%) and mixed (11%). In terms of GIM location, extensive GIM was observed in (28.7%), localized GIM in (17.6%), while the location remained unknown in (53.6%) due to the lack of a follow-up EGD for mapping. Coexisting autoimmune atrophic gastritis was observed in (12.4%, n=19), Helicobacter pylori infection was detected in (16.3%, n=25). Furthermore, Dysplasia was identified in (2.6%, n=4), with low-grade dysplasia and high-grade dysplasia each accounting for (1.3%, n=2) (Table 1). Three patients developed.gastric cancer (2%) , while (4.6%, n=7) were found to have neuroendocrine tumors (NET). First degree family history of gastric cancer was reported in (12.4%, n=19).

Conclusion

This study highlights a 4.17% prevalence of GIM among patients who underwent EGD. High BMI and male sex were observed in more than half of the patients. Dysplasia was detected in 2.6%, gastric cancer in 2%, and NET in 4.6% of cases. Many patients lacked follow-up EGD surveillance, limiting effective monitoring. Larger studies with extended follow-up are required to further investigate these associations and their clinical implications.

Clinical Case Summary

Seronegative enteropathies pose a complex diagnostic challenge, as their histology mimics celiac disease (CeD) (1). We report a 51-year-old patient with hypertension and osteoporosis, referred for abdominal pain, weight loss, and constipation. Blood tests showed no anemia; anti-transglutaminase and anti-endomysium antibodies were negative, but HLA typing was compatible with CeD. Ileocolonoscopy excluded IBD and microscopic colitis, while OEGD revealed villous atrophy (MARSH 3c). Negative anti-enterocyte antibodies, and exclusion of drugs and infections, led to a diagnosis of seronegative CeD. A gluten-free diet was started, but after 1 year, symptoms improved only partially despite good adherence. OEGD showed persistent duodenal damage with increased intraepithelial lymphocytes (IELs), CD3+ and CD8+ T-cells with monoclonal TCR expression (fig. 1), consistent with RCeD type 1, despite no overt malabsorption. The patient began prednisone 50 mg/day, then switched to open-capsule budesonide, with some clinical benefit but persistent atrophy.
A year later, his daughter was diagnosed with CVID and a heterozygous STAT3 variant (c.1252T>C, p.Cys418Arg), somatically acquired in NK-cell leukemia. A luciferase assay confirmed its gain-of-function (GOF) effect (fig. 2). Family studies revealed the same germline variant in the patient. His diagnosis was revised to STAT3 GOF-associated enteropathy. Further investigations revealed hypogammaglobulinemia, splenomegaly, bronchiectasis, and emphysema. Treatment with Ruxolitinib (a JAK1/2 inhibitor) was started, resulting in clinical and histological remission (fig. 3).
STAT3 GOF enteropathy is a very rare condition (2,3) that should be considered in the differential diagnosis of seronegative villous atrophy. Anti-JAK therapy may be effective (4).

References

References of the images:
Figure 1: Histologic aspects at diagnosis
Figure 2: Luciferase assay of STAT3
Figure 3: Histologic aspects after 1 year of therapy

1. Schiepatti A, Sanders DS, Baiardi P, Caio G, Ciacci C, Kaukinen K, et al. Nomenclature and diagnosis of seronegative coeliac disease and chronic non-coeliac enteropathies in adults: the Paris consensus. Gut. 2022 Jun 8;71(11):2218–25.
2. Vogel TP, Leiding JW, Cooper MA, Forbes Satter LR. STAT3 gain-of-function syndrome. Vol. 10, Frontiers in Pediatrics. Frontiers Media SA; 2023.
3. Flanagan SE, Haapaniemi E, Russell MA, Caswell R, Allen HL, De Franco E, et al. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nat Genet. 2014;46(8):812–4.
4. Kaneko S, Sakura F, Tanita K, Shimbo A, Nambu R, Yoshida M, et al. Janus kinase inhibitors ameliorate clinical symptoms in patients with STAT3 gain-of-function. Immunotherapy Advances. 2023;3(1).

Introduction

Gastric intestinal metaplasia (IM), a precancerous lesion, requires precise assessment for surveillance. The Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) staging system, based on histopathology, is the international standard for IM risk stratification. ESGE guidelines recommend endoscopic surveillance for advanced IM (OLGIM stages 3/4). Developed as a substitute, the Endoscopic Grading of Gastric Intestinal Metaplasia (EGGIM) score assesses IM across five gastric regions using a 30% threshold. Two large-scale studies demonstrated excellent performance in predicting advanced IM (OLGIM stage 3/4).

Aims & Methods

To optimize the EGGIM scoring system by refining threshold criteria, incorporating IM morphology, and evaluating simplified scoring approaches.
In this retrospective cohort study, patients undergoing structured gastroscopy at the National Taiwan University Cancer Center were analyzed from February 2022 to September 2024. EGGIM scoring was performed using high-resolution white-light and narrow-band imaging, with histopathological confirmation per the updated Sydney protocol. Three modifications were proposed: (1) EGGIM-15, an extended scoring system with 0–3 per site (0: no IM; 1: IM <30%; 2: 30–60%; 3: >60%); (2) EGGIM-M, integrating morphology (small patches, large patches, carpet-like); and (3) EGGIM-S, a simplified version using only the angle and LC body,. Their diagnostic performance in predicting advanced IM (OLGIM stage 3/4) was evaluated and compared to the original EGGIM score.

Results

Among 944 patients (56% female; median age: 64 years), 64 (6.8%) had advanced IM. The original EGGIM score yielded an AUC of 0.83. EGGIM-15 achieved a similar AUC of 0.82. EGGIM-M reached an AUC of 0.83 in a random forest model, though feature importance remained highest for the original EGGIM (0.786). EGGIM-S demonstrated an AUC of 0.83, which is non-inferior to the original score, while using fewer assessed regions and achieving fewer false positives at a cutoff ≥4.

Conclusion

Neither expansion of scoring thresholds (EGGIM-15) nor inclusion of morphology (EGGIM-M) significantly improved diagnostic accuracy over the original EGGIM. However, the simplified model (EGGIM-S) offers similar performance with practical advantages in efficiency and applicability. This suggests potential for streamlined risk stratification in clinical settings without compromising diagnostic yield.

Introduction

Biomarkers associated with the progression from gastric intestinal metaplasia (GIM) to gastric adenocarcinoma (GA) could provide valuable insights into identifying patients with increased risk for GA. Currently, the discovery of effective GA biomarkers poses a challenge due to the complexity of predictive and actionable value. Rarely can tumorigenesis be attributed solely to an individual molecule, as GA arises from the complex interplay of various intrinsic and environmental factors and collective interactions among multiple molecules.

Aims & Methods

The aim of this study was to identify potential biomarkers for the GIM-to-GA progression and potential drug repurposing for GIM. Sixty-four surgical biopsies were collected from 16 patients (4 tissue biopsies per patient) at St. Olav’s Hospital, Norway. Transcriptome datasets of GIM, GA, and normal tissues were compared within the same stomachs. Computational platform ScType was used for cell-type identification based on given scRNA-seq data and a comprehensive cell marker database. Ingenuity pathway analysis, Pagerank centrality, GO and MSigDB enrichments, CopyKat, aneuploid analysis, docking analysis, pathology and immunohistochemistry (IHC) were used for data and pathway mining, protein-protein interaction (PPI), and molecular structure-based drug repurposing.

Results

GIM displayed 110 canonical pathways that exhibited a negative correlation with GA. Wnt/β-catenin, ERK/MAPK, mTOR, neuregulin, and BRCA1 pathways were activated in both GIM and GA. Conversely, pathways such as HIPPO, p53, toll-like receptor, aryl hydrocarbon receptor, LPS/IL-1-mediated inhibition of RXR function, and eIF2 were inactivated in GIM but activated in GA. GIM exhibited elevated gene expression compared to GA in tumor microenvironment-related cells. Particularly, RBP2 expression and goblet cell-related gene expression were found to be restricted in GIM, but not in GA. Chromosome instability occurred mainly in GA cells with high rates of gain or loss of chromosomes 1, 7, 12, 21 (gain), and 5, 7, 8, X (loss). CD44 IHC expression was expanded from the basal part of mucosa in normal and GIM stomachs to the upper part of the mucosa in GA stomachs. PPI analysis of 865 GIM-related proteins showed seven network nodes (i.e., drug targets) including epidermal growth factor receptor (EGFR), SRC (proto-oncogene tyrosine-protein kinase), paxillin (PXN), Jun proto-oncogene (JUN), breast cancer type 1 susceptibility protein (BRCA1), tumor protein P53 (TP53 or p53), mouse double minute 2 homolog (MDM2), and CD44. These network node proteins were also shown in The Human Protein Atlas and IHC, with the exception of SRC in GA. Computational drug repurposing of approved and investigational drugs/compounds (e.g., as found on www.clinicaltrials.gov) identified the following drugs as effective for GIM: dasatinib with or without erlotinib, nilotinib, afatinib on SRC, SM1-71 on SRC, JNJ-26483327 on EGFR, Afatinib on EGFR, ingenol mebutate on protein kinase C (PKC) family, amoxapine, benoxaprofen, avobenzone, amlexanox, alprazolam, praziquantel, ibuprofen piconol, tranilast, and restoril.

Conclusion

The druggable protein network associated with GIM progression toward GA was identified. The distinct phenotypic patterns between GIM and GA might challenge the notion that GIM serves as the primary precancerous lesion in GA tumorigenesis rather than shares a common cause with tissue-resident stem cells. Further validation of the druggable protein network is needed for the development of a cost-effective surveillance program and preventive treatment of the GIM-to-GA progression.

Introduction

Malnutrition and sarcopenia are highly prevalent in chronic gastrointestinal diseases, including short bowel syndrome (SBS, <2m of small bowel). While restoration of colonic continuity (RC) improves intestinal adaptation, the link with malnutrition and sarcopenia is unknown.

Aims & Methods

SBS patients were included at a single tertiary care expert centre. Malnutrition (GLIM-criteria) and sarcopenia (EWGSOP2-criteria) were assessed before and 6 months after RC. The primary outcome was the evolution of sarcopenia, defined as a reduced fat free mass index (FFMI, using bioimpedance analysis) and handgrip strength (HGS). Changes in C-reactive protein (CRP) and albumin were also studied with parametric analyses after testing for normality. Comparisons were done based on weaning off home-parenteral nutrition (HPN) and presence of a jejuno-colonic (JC) or jejuno-ileo-colonic (JIC) anastomosis.

Results

In total, 46 patients (23 female, mean age 59 ±15 years) were included. Complete weaning was seen in 21 (46%) patients after 6 months, with a mean caloric reduction (kcal/day) of 33% in the remaining 25 patients. Malnutrition was present in 16 (35%) patients before and 21 (46%) after RC (p= 0.29), with no significant change in BMI (table). Although proportions of reduced FFMI (42% vs. 34%, p= 0.51) and sarcopenia (16% vs. 11%, p= 0.48) were similar before and after RC, a trend for increased FFMI was found in all patients (table). Proportions of malnutrition (52% vs. 40%, p= 0.4) and sarcopenia (10% vs. 13%, p= 0.75) were also similar in those with or without complete weaning after 6 months. In contrast, a significant increase in HGS was found (table), but only in those with complete weaning (p= 0.04). While CRP decreased and albumin increased in both groups, levels were higher in case of complete weaning after 6 months (p= 0.02) with similar CRP. Results were similar between SBS-JC (n= 26) and SBS-JIC (n= 20) patients.

Conclusion

Restoration of colonic continuity allows a reduction of HPN in SBS, with stable rates of malnutrition and sarcopenia. Besides a potential effect on body composition (FFMI), muscle strength and albumin levels increased, especially in those with complete weaning. Further study of the role of the colon and use of these functional markers during adaptation is required.