Introduction

The diagnosis of Coeliac Disease (CD) in adults still continues to rely heavily on duodenal histology, in spite of several studies demonstrating a positive predictive value (PPV) of 100% for Marsh 3 histology when anti-tissue transglutaminase (TTG) exceeds 10x upper limit of normal. The majority of these studies come from tertiary centres and the slow uptake of the non biopsy approach may be as a result of limited data on the histological outcome of positive serology originating in the primary care setting.

Aims & Methods

To determine the PPV of primary care-based TTG testing with concurrent anti-endomysial antibody (EMA) positivity for histological diagnosis of CD.
The immunology lab in our institution performs reflex EMA testing on all newly positive and newly borderline positive TTG samples from the West of Ireland (TTG≥5U/ml Celikey by Phadia). Over a 6 year period (2018-2023), 1,361 index TTG positive samples also proved positive when tested for EMA. Following electronic medical record review, we excluded all samples from patients who were <16 years old, had a previous diagnosis of CD made elsewhere, lacked biopsy data, or had biopsies that predated the serological test. Patients who had their coeliac serology testing requested by any hospital-based physician were also excluded to ensure that only patients identified by primary care-based screening were included in the outcome analysis. In this manner, 335 adult patients who had serology screening performed by their primary care physician were eligible for further analysis. These eligible patients were then stratified by TTG levels ( ≤20, 21-69, and ≥70 U/ml). PPV was calculated for each stratum. Logistic regression assessed the relationship between TTG values and biopsy results. Additional analyses examined influence of interval between serology and biopsy.

Results

Chi-square analysis confirmed significant association between TTG levels and biopsy results (p<0.00001). For each 10 U/ml increase in TTG, odds of positive biopsy increased by 18% (OR 1.18, 95% CI: 1.10-1.26). For TTG 21-69 U/ml, PPV declined with longer serology-to-biopsy intervals: 100% for ≤47 days versus 45.2% for >203 days. High TTG values maintained excellent PPV regardless of interval. Long-term follow-up of initially biopsy-negative patients revealed subsequent CD diagnosis in 19/40 (47.5%) in the low titre group, 11/30 (36.7%) in the intermediate group, and 7/11 (63.6%) in the high titre group.

Conclusion

TTG titre significantly predicts biopsy-confirmed CD, with TTG ≥70 U/ml having 90.4% PPV. The predictive value of intermediate TTG diminishes with increasing interval between serology and biopsy. A substantial portion of initially biopsy-negative patients across all TTG strata were subsequently diagnosed with CD during follow-up. These findings support TTG in risk-stratifying CD patients, suggest prompt biopsies for intermediate TTG values, and highlight the importance of long-term monitoring even in patients with negative initial biopsies.

References

1. Husby S, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136-60.
2. Penny HA, et al. Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts. Gut. 2021;70(5):876-883.

Introduction

Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for Irritable Bowel Syndrome (IBS), demonstrating long-term improvements in symptoms and quality of life (QOL). However, its implementation is hindered by the complexity of treatment protocols, high time and financial costs, and limited accessibility in Japan.

Aims & Methods

This study aimed to develop a smartphone-based CBT application and evaluate its effectiveness in alleviating IBS symptoms.
Adults aged 18 or older who met the Rome IV criteria for IBS and scored ≥110 on the Japanese version of the IBS Symptom Severity Index (IBSSI-J) were enrolled. Twenty-six participants were randomly assigned to either the intervention group (n = 14) or the waiting-list control group (n = 12). Outcome measures included the IBSSI-J, Japanese versions of the IBS-QOL (IBS-QOL-J), Pain Catastrophizing Scale (PCS-J), and Visceral Sensitivity Index (VSI-J). A two-way ANOVA was conducted with group (intervention vs. control) and time (pre, mid, post, follow-up 1) as independent variables.
The intervention group used the app for 5–10 minutes daily over two months. The app included three components: psychoeducation, cognitive restructuring, and exposure. Psychoeducation consisted of educational materials and follow-up quizzes. Cognitive restructuring used gamified multiple-choice content (135 items), replacing conventional thought records. Exposure involved users creating individual anxiety hierarchies and recording their thoughts before and after exercises. The app visualized anxiety changes and progress via graphs.

Table 1.
Intervention module of the application

Results

Eleven participants in the intervention group and eight in the control group completed the program. Significant group × time interactions were observed for all outcome measures. For the IBSSI-J, the interaction was significant (F(3, 51) = 4.41, p < .001), with the intervention group showing greater improvement at mid-point (F(1, 17) = 5.54, p = .03, η² = .25). For the IBS-QOL-J, a significant interaction was found (F(3, 51) = 8.00, p < .001), with improvement evident at follow-up 1 (F(1, 17) = 6.65, p = .02, η² = .28). For the PCS-J, the interaction was significant (F(3, 51) = 3.83, p = .02), with improvements at post (F(1, 17) = 9.26, p = .01, η² = .35) and follow-up 1 (F(1, 17) = 5.83, p = .03, η² = .26). For the VSI-J, the interaction also reached significance (F(3, 51) = 3.32, p = .05).

Conclusion

The CBT-based app was effective in reducing IBS symptom severity. Its effects persisted after the intervention and extended to improvements in QOL, visceral anxiety, and pain catastrophizing—psychological factors associated with the maintenance and exacerbation of IBS. It is assumed that the cognitive restructuring component of the app facilitated cognitive diversification among participants. By empirically challenging the plausibility of these diversified cognitions through behavioral experiments in the form of exposure tasks, participants were able to further develop more adaptive thoughts. This process is considered to have contributed to the improvement of symptoms and enhancement of QOL. This digital approach may offer a viable solution to current barriers in CBT access.

Clinical Case Summary

A female patient (born 1974) presented with chronic diarrhea (up to 16 times/day, including nocturnal episodes), bloating, periumbilical pain, fatigue, general weakness, and 10 kg weight loss. Since childhood, the patient had been under observation for chronic iron-deficiency anemia of unknown origin without prior gastrointestinal evaluation. Symptoms progressively worsened over two years due to the lack of therapeutic effect at the outpatient stage, leading to hospitalization in July 2022. Histology revealed total duodenal villous atrophy (celiac disease: Marsh 3C, Corazza-Villanacci B2; 30-40 IELs/100 epithelial cells) and lymphocytic microscopic colitis (MC) of the colon (60-70 IELs/100 epithelial cells). Other examinations (abdominal CT, enterography, stool analysis) were normal; labs showed mild iron-deficiency anemia, with protein markers within normal ranges. She was diagnosed with celiac disease combined with lymphocytic MC. A gluten-free diet, iron supplementation, and budesonide (9 mg/day for 3 months) were initiated, leading to clinical improvement. However, diarrhea recurred (up to 10 times/day) one month after stopping budesonide, despite adherence to the gluten-free diet. Duodenal histology improved (Marsh I, IELs ≤20/100 cells), confirming dietary effectiveness for celiac disease. Colonic histology showed ongoing lymphocytic MC activity (25-30 IELs/100 cells). The relapse was attributed to persistent MC. A prolonged regimen of budesonide (9 mg/day for 3 months, tapering to 6 mg/day for 6 months) was prescribed. This clinical case of celiac disease combined with lymphocytic MC demonstrates that significant improvement in small intestine structure can be achieved with a gluten-free diet and prolonged budesonide therapy. However, the recurrent diarrheal syndrome in this case was associated with the persistent course of MC. Literature emphasizes increased MC prevalence in celiac patients, reinforcing the need for timely recognition and combined therapy.

References

1. Miehlke S., Guagnozzi D., Zabana Y., Tontini G.E., Kanstrup Fiehn A.M., Wildt S., Bohr J., Bonderup O., Bouma G., D’Amato M., Heiberg Engel P.J., Fernandez-Banares F., Macaigne G., Hjortswang H., Hultgren-Hörnquist E., Koulaouzidis A., Kupcinskas J., Landolfi S., Latella G., Lucendo A., Lyutakov I., Madisch A., Magro F., Marlicz W., Mihaly E., Munck L.K., Ostvik A.E., Patai Á.V., Penchev P., Skonieczna-Żydecka K., Verhaegh B., Münch A. European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations. United European Gastroenterol J. 2021 Feb 22;9(1):13–37. doi: 10.1177/2050640620951905. Epub ahead of print. PMID: 33619914; PMCID: PMC8259259.

2. Calabrese C., Gionchetti P., Liguori G., Areni A., Fornarini G.S., Campieri M., Rizzello F. Clinical course of microscopic colitis in a single-center cohort study. J Crohns Colitis. 2011 Jun;5(3):218-21. doi: 10.1016/j.crohns.2011.01.004. Epub 2011 Feb 18. PMID: 21575884.

3. Microscopic Colitis: A Concise Review for Clinicians. June Tome MD, Amrit K. Kamboj MD, Darrell S. Pardi MD MS. DOI: https://doi.org/10.1016/j.mayocp.2021.03.022.

4. Tome M.D., Kamboj A.K., Pardi D.S. Microscopic Colitis: A Concise Review for Clinicians. Mayo Clinic Proceedings. 2021;96(5):1212-1222. DOI: https://doi.org/10.1016/j.mayocp.2021.03.022.

Introduction

Avoidant/restrictive eating is common in people with neurogastroenterology disorders including functional dyspepsia (FD). There is debate on whether avoidant/restrictive food intake disorder (ARFID) is an expected response to severe symptoms or simply a common comorbid disorder. To address this, among adults with FD, we aimed to contrast those with and without ARFID on FD symptoms, quality of life, psychosocial factors, nutrient tolerance, and gut transit.

Aims & Methods

Adults with Rome-IV confirmed FD and healthy controls (HC) from an ongoing study participated. ARFID diagnosis was assigned based on a semi-structured DSM-5 diagnostic interview. Surveys: Patient Assessment of GI Disorders Symptom Severity Index (PAGI-SYM), Short Form Nepean Dyspepsia Inventory (SF-NDI), Nine-Item ARFID Screen (NIAS), Fear of Food Questionnaire (FFQ), Visceral Sensitivity Index (VSI), and Hospital Anxiety/Depression Scale (HADS). Nutrient Drink Test (NDT) measured gastric tolerance—liquid nutrient ingestion at 30mL/minute until subject reported unbearable fullness. Wireless Motility Capsule (WMC) measured gut transit. Height/weight was measured for body mass index (BMI).

Results

Sample (80% female, M_age=37.1±14.4y) included 37 FD+ARFID, 14 FD only, and 18 HC. Groups did not significantly differ in sex or age. Adjusted pairwise comparisons showed small (r=.1-.2) non-significant differences between FD and FD+ARFID on FD symptoms by PAGI-SYM and SF-NDI (Table 1). However, FD+ARFID had significantly worse scores compared to FD with medium effects (r=.3-.4) on: FD-related quality of life by SF-NDI, Fear of Food by NIAS-Fear and FFQ, GI-anxiety by VSI, and anxiety by HADS. FD+ARFID vs FD also had small differences (rs=.2) on: feeling more bothered by FD symptoms on SF-NDI, worse depression by HADS, lower BMI, and less NDT consumption. Compared to HC, FD and FD+ARFID had significantly worse survey scores with large effects for FD+ARFID (r=.6-.8) and medium effects for FD vs HC (r=.3-4). For the NDT, FD+ARFID consumed significantly less than HC with large effect (r=.6) but with a trend medium effect for FD consuming less than HC (r=.3). Groups did not significantly differ in WMC transit times.

Conclusion

Our findings suggest ARFID, when present in FD, does not reflect a response to more severe FD symptoms. Thus, ARFID is a legitimate secondary condition in FD. ARFID may reflect more profoundly altered distress around symptoms (e.g., fear of symptoms, anxiety sensitivity) and greater negative impacts (e.g., FD-related quality of life, lower liquid nutrient tolerance).

Introduction

The rising number of patients with intraductal papillary mucinous neoplasms (IPMNs) in countries with aging populations in the near future is predictable considering that the incidence of pancreatic cystic tumors is positively correlated with patient age and that IPMNs occur most frequently among multifocal pancreatic cystic tumors. Although the majority of IPMNs detected incidentally through various imaging tests have a tumor diameter ≤10 mm and are thus deemed low-risk for carcinogenesis, the possibility of malignant transformation persists. Thus, such IPMNs are subject to periodic follow-up diagnostic imaging. Therefore, an appropriate surveillance system must be established to effectively and efficiently identify cases of IPMN-related malignant transformation, which develops only in few IPMN cases, under the constraints of limited national healthcare funding.

Aims & Methods

In the current study, we analyzed the clinical background observed at initial patient presentation that affect long-term prognosis and tried to narrow the population for whom continued evaluation is inevitable. The study included 1645 patients with IPMNs (776 men and 869 women) treated at our hospital since 2010. We examined the types and timing of medical intervention (surgical resection or pancreatic carcinogenesis) selected mainly in terms of worrisome features (WF) as advocated by the international guidelines (Pancreatology, 2024:24;255–70) for IPMN treatment. Statistical analysis was performed using the chi-square test, log-rank test, and Cox proportional hazards model, with statistical significance set at α = 0.05.

Results

During the entire observation period, 123 patients (7.5%) had IPMN-derived carcinoma (IPMN-DC), whereas 41 patients (2.5%) had concomitant pancreatic ductal adenocarcinoma (PDAC), which required medical intervention. The proportion of cases with c-Stage I, II, III, and IV (UICC 8th edition) at the time of diagnosis were 52.0%, 43.9%, 0.8%, and 3.3%, respectively, for IPMN-DC and 39.0%, 31.7%, 9.8%, and 19.5%, respectively for PDAC. A significantly higher proportion of PDAC cases were diagnosed with an advanced disease stage that developed earlier in time. Factors with significantly shorter time for IPMN-DC medical intervention were: maximum cyst diameter ≥30 mm, non-branched type, main pancreatic duct diameter ≥5 mm, and septal nodal structure for IPMN-DC. For PDAC, these factors were maximum cyst diameter ≥30 mm, main duct type, main pancreatic duct diameter ≥5 mm, septal nodal structure, cyst enlargement (≥2.5 mm/year), and abnormally high levels of CA19-9. Both groups could be significantly stratified by the number of WFs. However, the difference was more distinct in IPMN-DC, whereas <1% (9/1190) medical intervention from the group with 0 WFs was noted in PDAC. Relative risk (hazard ratio, HR) analysis of WF in which proportional hazard was maintained revealed that the presence of septal nodular structure (HR 5.2), maximum cyst diameter ≥30 mm (HR 3.3), and main pancreatic duct diameter ≥5 mm (HR 2.6) were significant factors for IPMN-DC, whereas abnormally high CA19-9 levels (HR 5.0) and septal nodular structure (HR 4.8) were significant for PDAC. Conversely, a significantly higher percentage of patients who exhibited these factors at initial presentation also later developed IPMN-DC or PDAC.

Conclusion

Ten percent of IPMN cases will develop IPMN-DC or PDAC, thereby requiring careful follow-up, especially in cases with septal nodules, abnormally high CA19-9 levels, and cysts with a maximum diameter of ≥30 mm.

Introduction

Primary sclerosing cholangitis (PSC) is known to present characteristic cholangiographic findings; however, detailed observations using peroral cholangioscopy (POCS) have rarely been reported. We previously reported that POCS findings in PSC can be classified into three types: active (inflammatory), chronic (scarring), and tumorous (tumor-like). These findings may aid in the differential diagnosis of PSC and may be useful in predicting prognosis.

Aims & Methods

We aimed to analyze POCS findings in PSC in detail based on this classification and to clarify their characteristics by evaluating the frequency of each finding, their temporal changes, and comparisons with other biliary diseases.
We retrospectively reviewed 22 patients with PSC who underwent POCS between February 2018 and February 2023. For comparison, we included 19 cases of hepatolithiasis, 25 cases of cholangiocarcinoma, and 3 cases of IgG4-related sclerosing cholangitis (IgG4-SC). Twelve POCS findings were categorized into three types: active (mucosal erythema, ulcers, fibrous white exudates, irregular surface), chronic (longitudinal scarring, annular scarring, pseudodiverticula, stenosis), and tumorous (dilated vessels, tortuous vessels, friability, mass formation). In addition, we included “punched-out lesion (POL)” as an original finding. Each finding was graded on a 5-point scale (0–4) based on the extent or number of lesions, and scores were calculated for each type. We conducted three analyses: (1) correlation between cholangiographic and POCS findings in PSC, (2) temporal changes in POCS findings in PSC, and (3) comparison of POCS findings between PSC and other biliary diseases.

Results

In the first analysis, annular scarring (100%), stenosis (89%), POL (89%), and longitudinal scarring (86%) were frequently observed in PSC. Annular scarring was identified in all cases with a shaggy appearance on cholangiography, and stenosis were present in all ducts with band-like stricture. In ducts showing diverticulum-like outpouchings, longitudinal and annular scarring, pseudodiverticula, and POL were consistently seen, whereas other findings were absent. In the second analysis, active and tumorous scores varied over time even within the same case, whereas chronic scores remained stable or showed a progressive increase. A negative correlation was observed between active and chronic scores (p-value <0.001, r =-0.702). In the third analysis, chronic findings and POL were significantly more common in PSC compared to other diseases (p-value <0.001). Pseudodiverticula were seen exclusively in PSC, while dilated and tortuous vessels and friability were significantly more frequent in cholangiocarcinoma and IgG4-SC (p-value <0.001).

Conclusion

These findings suggest that the characteristic cholangiographic findings of PSC are mainly formed by chronic scarring. Diverticulum-like outpouchings reflect only fibrotic changes. Furthermore, the coexistence of inflammation and fibrosis, along with the time-dependent progression of fibrosis, is a unique feature of PSC, although active inflammation may obscure chronic findings. Finally, longitudinal scarring and POL were particularly prominent in PSC, and pseudodiverticula were highly specific to this disease, suggesting their usefulness in differential diagnosis. In conclusion, chronic findings on POCS are characteristic of PSC and may serve as a helpful tool in its diagnosis and differentiation from other biliary diseases.

References

T Fujisawa, M Ushio, S Takahashi, et al., Role of Peroral Cholangioscopy in the Diagnosis of Primary Sclerosing Cholangitis. Diagnostics (Basel), 2020. 10(5).
T Itoi, T Kamisawa, Y Igarashi, et al., The role of peroral video cholangioscopy in patients with IgG4-related sclerosing cholangitis. J Gastroenterol, 2013. 48(4): p. 504-14.
T H Karlsen, T Folseraas, D Thorburn, et al., Primary sclerosing cholangitis - a comprehensive review. J Hepatol, 2017. 67(6): p. 1298-1323.
T Nakazawa, K Notohara, S Tazuma, et al., The 2016 diagnostic criteria for primary sclerosing cholangitis. J Gastroenterol, 2017. 52(7): p. 838-844.
T Nakazawa, H Ohara, H Sano, et al., Cholangiography can discriminate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis. Gastrointest Endosc, 2004. 60(6): p. 937-44.
H Isayama, S Tazuma, N Kokudo, et al., Clinical guidelines for primary sclerosing cholangitis 2017. J Gastroenterol, 2018. 53(9): p. 1006-1034.
W L Campbell, M S Peterson, M P Federle, et al., Using CT and cholangiography to diagnose biliary tract carcinoma complicating primary sclerosing cholangitis. AJR Am J Roentgenol, 2001. 177(5): p. 1095-100.

Introduction

Endoscopic scores are crucial for assessing Crohn's disease (CD) severity, guiding therapy, and monitoring progression. The Simplified Endoscopic Score for Crohn's Disease (SES-CD) is widely used for this purpose [1]. Accurate scoring is vital for patient care. Recently, artificial intelligence has demonstrated potential in medical image interpretation [2]. This study aims to evaluate ChatGPT's effectiveness in rating the SES-CD.

Aims & Methods

This retrospective study evaluated ChatGPT's accuracy in assessing CD endoscopic activity using the SES-CD. One representative still image was selected for each bowel segment, and stricture degrees were provided separately if present. ChatGPT scored the SES-CD based on these images. The IBD expert's ratings were validated by calculating the intra-class correlation coefficient (ICC) with clinical trial central readers. The ICC between the IBD expert and ChatGPT scores was calculated to determine ChatGPT's reliability in SES-CD scoring.

Results

Nine (mean age 32.0 ± 11.8 years, 77.8% male) were included, with 45 bowel segments. Three (33.4%), 5 (55.6%), and 1 (11.1%) had nonstricturing nonpenetrating, structuring, and penetrating disease, respectively. Four (44.4%) had ileal disease and 5 (55.6%) had ileocolonic disease. Five (55.6%) had previous IBD surgery.
The SES-CD scores of the participants, rated by IBD expert in the hospital, revealed the following mean and standard deviation for each segment of the bowel: 6.9 ± 2.3 in the ileum, 1.3 ± 2.6 in the right colon, 1.6 ± 2.4 in the transverse colon, 1.3 ± 2.6 in the left colon, and 1.3 ± 2.6 in the rectum. The total SES-CD score was 12.4 ± 10.9. The score reliability of the institute IBD expert was tested compared to the clinical trial central reader and an intraclass correlation coefficient was calculated and found to be 0.96 (95% CI, 0.84-0.99) which is considered extremely correlated.
The mean and standard deviation of ChatGPT score in each segment were: 6.4 ± 2.4 in the ileum, 2.4 ± 3.8 in the right colon, 0.9 ± 2.7 in the transverse colon, 0.3 ± 1.0 in the left colon, 0.6 ± 1.3 in the rectum, with total SES-CD score of 10.6 ± 6.8. The calculated ICC between the expert and ChatGPT obtained SES-CD scores was 0.80 (95% IC, 0.64- 0.89) which is considered highly correlated.

Conclusion

Despite being based on only one photo per segment, ChatGPT demonstrated satisfactory performance in estimating endoscopic activity in CD. The differences between the IBD expert obtained scores and ChatGPT scores were acceptable, suggesting that artificial intelligence has the potential to be a useful tool in clinical and research settings, providing an accurate estimation of disease severity based on limited visual data.

References

1- Daperno M, D'Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505-512.
2- Levartovsky A, Albshesh A, Grinman A, et al. Enhancing diagnostics: ChatGPT-4 performance in ulcerative colitis endoscopic assessment. Endosc Int Open. 2025;13:a25420943. Published 2025 Mar 14.