Introduction

The incidence of type I gastric neuroendocrine neoplasms (gNEN) has increased substantially over the past 50 years, although studies evaluating the association with chronic autoimmune gastritis (AIG) in the long term have been inconsistent.

Aims & Methods

The main aim was to evaluate the incidence of type I gNENs in a cohort of AIG patients enrolled from October 2020 to May 2022, with a histologic diagnosis of CAAG; circulating levels of chromogranin A (CgA) and gastrin were assessed at enrollment. Included patients underwent regular endoscopic follow-up, to assess for gastric neoplastic lesions, enterochromaffin-like (ECL) cell hyperplasia, and the development of gNEN.

Results

We included 176 patients [142 women, median age 64 years (51-41)], diagnosed with AIG from January 1990 to June 2022. At enrollment, 116 patients (65.9%) had ECL hyperplasia, of which 29.5% had simple/linear, 30.7% had micronodular, and 5.7% had macronodular. The median follow-up was 5 years (3-7.5). After 1032 person-years, 33 patients developed a total of 33 gNEN type I, with an incidence rate of 0.032 person-years, corresponding to an annual cumulative incidence of 3.2%. Circulating gastrin levels were significantly higher in AIG patients who developed gNENs [median 992 pg/mL IQR=449-1500 vs 688 pg/mL IQR =423-1200, p=0.03]; similarly, circulating CgA levels were significantly higher in patients with gNENs [median 227 ng/mL IQR=124-421 vs 174 ng/mL IQR= 77-265, p=0.01].

Conclusion

Type I gNENs represent a non-negligible complication in patients with AIG, and they are related to hypergastrinemia. Also elevated circulating CgA levels are associated with the presence of gNENs.

References

1. Massironi S, Zilli A, Elvevi A,et al. The changing face of chronic autoimmune atrophic gastritis: an updated comprehensive perspective. Autoimmun Rev. 2019;18:215-22.
2. Rugge M, Bricca L, Guzzinati S, et al. Autoimmune gastritis: long-term natural history in naïve Helicobacter pylori-negative patients. Gut. 2023;72:30-8.
3. Shah SC, Piazuelo MB, Kuipers EJ, et al. AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology. 2021;161:1325-32.
4. Dixon MF, Genta RM, Yardley JH, et al. Classification and grading of gastritis. The updated Sydney System. Am J Surg Pathol. 1996;20:1161-81.
5. Delle Fave G, O'Toole D, Sundin A, et al. ENETS Consensus Guidelines Update for Gastroduodenal Neuroendocrine Neoplasms. Neuroendocrinology. 2016;103:119-24.
6. Yue H, Shan L, Bin L. The significance of OLGA and OLGIM staging systems in the risk assessment of gastric cancer: a systematic review and meta-analysis. Gastric Cancer. 2018;21:579-87.
7. Nagtegaal ID, Odze RD, Klimstra D, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76:182-8.
8. Capurso G, Gaujoux S, Pescatori LC, et al. The ENETS TNM staging and grading system accurately predict prognosis in patients with rectal NENs. Dig Liver Dis. 2019;51:1725-30.

Introduction

Despite being a frequent step in clinical practice, there is little real world evidence supporting the benefit of optimizing mesalamine in ulcerative colitis (UC) patients who have a mild to moderate flare. The aim of this study was to assess the role of optimizing 5-ASA in patients in clinical remission (CR) who suffer clinical relapse.

Aims & Methods

Patients in CR who developed a mild to moderate flare treated with 5-ASA optimization from 2015 to 2023 were included. Patients under immunosuppression were excluded, as well as flares treated with oral or topical corticosteroids (CS). The primary outcome was corticosteroid-free clinical remission (CFCR) at six months. Secondary outcomes were need for CS at six months and deep remission (DR) defined as fecal calprotectin <250 ug/g or Mayo endoscopic score of 0.

Results

From 908 UC patients screened, 116 flares met the inclusion criteria. The average disease duration was 9.1±7.0 years. The majority were under oral therapy (91%), 6% topical therapy and the remainder combined therapy. Most flares were mild (81.9%). Optimization of 5-ASA recaptured CR in 72.4% and 37.1% of those were in DR at six months. Around 15% required CS at six months. The absence of a flare in the previous year (OR 13.5; p<0.01) and lower PRO-2 score (OR 2.07; p=0.020) were identified as predictive factors for CFCR at six months, as well as both DR and need for CS at six months. Non-extensive UC (E1/E2) was also a predictive factor for DR and need for CS at six months (p<0.05). The type or formulation of 5-ASA (granules vs tablet), pre-flare or optimized 5-ASA dose were not associated with primary or secondary outcomes.

Conclusion

Optimizing 5-ASA therapy recaptured CR in a significant number of patients. Those with extensive UC, previous flares and with higher symptom burden should be closely monitored.

Disclosure

The authors declare that there are no conflicts of interest related to this study.

Introduction

Corpus Atrophic Gastritis (CAG) is a precancerous inflammatory condition of the oxyntic mucosa. Up today, two types of CAG are distinguished: 1) autoimmune (corpus-restricted), defined for CAG sparing the antrum 2) Helicobacter pylori (Hp)-related (multifocal), which involves antrum too.
Antrum involvement/sparing is crucial for both CAG definition as autoimmune and gastric cancer risk level, which is increased in case of pan-atrophy/pan-metaplasia, according to OLGA and OLGIM scores. CAG natural history is still poorly known, especially regarding antrum evolution. In cases with previous antral involvement, possible antrum healing after cure of Hp infection was formerly described. So, given the importance of the criterium antrum-sparing, we aimed to assess antral mucosa changes at long-term follow-up(FU) beside baseline in a cohort of CAG patients.

Aims & Methods

Given the importance of the criterium antrum-spared, we aimed to assess antral mucosa changes at long-term follow-up(FU) beside baseline in a cohort of CAG patients.
We performed a retrospective study on 130 patients with CAG and antrum involvement according to updated Sydney System. Mean time of FU gastroscopy was 40.6(range 4-192) months. In 13 patients corpus atrophy was not confirmed at FU, so were excluded. At baseline, among the remaining 117 patients [mean age 63 (range 20-87) years; F 67.5%], 47 (40.2%) had antral non-atrophic and 70 (59.8%) had antral atrophic gastritis, metaplastic in 84.3%. Histologically diagnosed Hp infection was present in 27.3% of patients, all receiving eradication therapy, anti-parietal cells antibodies (APCA) were positive in 53.8%.

Results

At FU 29/117(24.8%) of patients with tout-court involved antrum showed a complete restitutio ad integrum of antral mucosa. In particular, on 70 cases with antral atrophy at baseline, atrophy regressed in 15 (21.4%). Hp infection at baseline was present in 38% of patients who reported complete antral healing at FU, cured in all but one. Both antral healing and atrophy regression were found to be similar in Hp-cured and not-cured/negatives (p>0.05). In 8 patients (6.8%) a worsening of antral histology at FU was reported: 5 developed antral atrophy, not present at baseline, and 3 antral atrophic patients developed intestinal metaplasia.

Conclusion

Nearly 25% of CAG patients with antral involvement showed complete antrum healing, with regression of baseline antral atrophy in 21.4%. Antral healing occurred also in patients without history of Hp infection and/or eradication. These data suggest that in CAG natural history, concomitant antral involvement may regress irrespective of Hp cure, implying cancer risk reduction and raising queries about histology as sole criteria diagnostic for autoimmune gastritis.

References

1. Lahner et al. Dig LIver Dis 2019
2. Sipponen P et al. Gastroenterology clinics of North America 2000
3. Annibale B Helicobacter 1997

Introduction

Peripheral musculoskeletal (MSK) symptoms are the most common extra intestinal manifestations (EIMs) in IBD patients, with substantial impact on quality of life. IBD related spondyloarthritis (IBD-SpA) often requires a multidisciplinary evaluation to enable optimal choice of treatment and patient care, but systematic rheumatological characterisation of this population is scarce [1].
Characterisation of IBD-SpA is challenged by the variety of MSK involvement (from arthralgia to ankylosing spondylitis), the co-existence of osteoarthritis, overuse enthesopathies or fibromyalgia, and by the heterogeneity in methodologies used to describe the SpA features. Recently developed recommendations for endpoints for EIMs in IBD trials [2] were applied in the present study.

Aims & Methods

To determine the prevalence and distribution of inflammatory lesions in peripheral joints and entheses in newly diagnosed IBD patients, assessed for presence of MSK symptoms, and by rheumatological and ultrasound (US) evaluation.
Patients from the IBD prognosis inception cohort (IBD-Pro) were consecutively included [2]. They reported MSK symptoms using a validated questionnaire (IBD-TASQ). A clinical examination was performed by rheumatologist, as was US examination (grey scale (GS) and colour Doppler (CD)) of 38 peripheral joints and 14 entheses, applying OMERACT-EULAR definitions and scoring systems for synovitis and enthesitis [3]. Synovitis was defined as GS score ≥2 and/or CD≥1 and entheseal inflammation was defined as presence of hypoechogenicity/thickening and/or CD score ≥1. Further, OMERACT-EULAR sum score (GLOESS) was calculated (0-114).

Results

110 newly diagnosed IBD patients (mean age 42, 39% male) were included (34% Crohn’s disease, 59% ulcerative colitis (UC), 5% unclassified IBD). The IBD disease activity scores indicated mild activity in UC patients (Simple Clinical Colitis Activity Index mean (SD) 6.7 (3.6), and low in Crohn's (Harvey-Bradshaw Index 4.5 (2.9)). Four patients received systemic glucocorticoids (2%) or biologics (2%) at the time of rheumatological evaluation. History of other SpA-associated features such as psoriasis was reported in 2% and uveitis in 5% of the patients.
40% of the patients reported positive history for ≥1 MSK symptom. Joint pain and swelling were the most common complaints (30%), followed by heel enthesitis (17%) and dactylitis in 20%. Patient pain VAS was low, mean (SD) 12(21).
Clinical examination revealed 52% of all patients had arthritis and/or enthesitis and 46% fulfilled ASAS classification criteria for peripheral SpA (25% ≥1 tender joint, 12% ≥1 swollen joint, 46% ≥1 tender enthesis (most affected sites were Achilles and lateral epicondyle).
US found inflammation in ≥1 joint or enthesis in 49% of the IBD patients - synovitis in 29%, mean GLOESS sum score 5.2 SD (4.6) and entheseal inflammation in 34% (US enthesitis sum, mean (SD) 2.6(2).
Among those patients reporting MSK symptoms, 69% had ≥1 tender/swollen joint and/or enthesis at clinical evaluation and 64% had joint/entheseal inflammation by US. Suggesting good overlap between patient-reported symptoms, clinical and US findings. 36% of the asymptomatic patients also had clinical and US signs of arthritis and/or enthesitis.

Conclusion

At the time of IBD diagnosis, more than half of the patients had musculoskeletal manifestations by clinical examination and half had objectively verified synovitis and/or enthesitis by ultrasound, indicating that SpA may be underdiagnosed among IBD patients.

References

1 Schwartzman M et al., RMD Open 2022
2 Guillo L et al., Lancet Gastroenterol Hepatol 2022
3 Bruyn GA et al., The Journal of Rheumatology 2019
4 Attauabi M, et al., BMJ Open 2022

Disclosure

no conflict of interest

Introduction

Ulcerative colitis (UC), a chronic inflammatory bowel disease, may require surgical intervention such as colectomy. Post-colectomy, an ileal pouch-anal anastomosis (IPAA) offers an alternative to a permanent ostomy. However, up to 50% of patients with an IPAA will experience pouchitis, which can cause symptoms similar to UC. More robust data is needed to establish effective treatments and assess their real-world effectiveness, especially in population-based cohorts.

Aims & Methods

The aim was to investigate the choice of treatments for pouchitis, their effectiveness, and pouch failure rates in UC patients who underwent IPAA at Copenhagen University Hospital Hvidovre between 11th November 1993 and 26th April 2021. Patients were screened through electronic medical records. Antibiotic treatment responses were defined as antibiotic dependent (needing 4+ courses/year), antibiotic refractory (courses of antibiotics lasting >28 days), and antibiotic responsive (not meeting the other criteria). Continuous or pro necessitate treatments were considered refractory (29 days), while courses without a stop date and no new symptoms were deemed responsive (14 days).

Results

A total of 239 UC patients underwent IPAA. After excluding 6 patients who did not receive ileostomy reversal, 233 were analysed with a median follow-up of 8.36 (IQR: 4.33–11.16) years. 529 pouchitis treatment courses were prescribed to 118 (50.64%) of the UC patients, with 474 (89.6%) being antibiotics. Ciprofloxacin and metronidazole were the most common prescribed antibiotics, while adalimumab and infliximab were the most common used biologics. The median duration of antibiotic treatment was 11 (IQR: 9-19 days) days.
Two-thirds of antibiotic courses were responsive, while one-third were refractory or dependent. This corresponded to, 46.4% of the 233 patients being antibiotic responsive, 14.6% dependent, and 16.3% refractory.
Survival rates for responsive, refractory, and dependent pouchitis treatments were as follows:
For responsive treatments, survival rates were 0.84 at 6 months, 0.77 at 12 months, 0.65 at 24 months, 0.56 at 60 months, and 0.49 at 120 months.
For refractory treatments, survival rates were 0.98 at 6 months, 0.97 at 12 months, 0.95 at 24 months, 0.89 at 60 months, and 0.80 at 120 months.
For dependent treatments, survival rates were 0.97 at 6 months, 0.94 at 12 months, 0.91 at 24 months, 0.86 at 60 months, and 0.83 at 120 months.
Pouch failure occurred in 13.8% (32) of patients. These patients experienced 36 pouch failures, where 12 (33.33%) were due to acute and chronic sepsis, 19 (52.78%) were caused by poor function for mechanical or functional reasons, 3 (8.33%) resulted from mucosal inflammation (pouchitis), and 2 (5.56%) were attributed to neoplastic transformation. Prior to pouch failure, 50.8% of the 32 patients had at least 1 responsive episode of pouchitis, 21.9% had dependent pouchitis, and 18.8% had refractory pouchitis.

Conclusion

This study provides insights into pouchitis treatment strategies, their effectiveness, and failure rates in UC patients who undergoes IPAA. The majority of pouchitis treatments were antibiotics, with ciprofloxacin and metronidazole being the most common. Antibiotic responsiveness varied among patients, with pouch failure observed in 13.8% of cases. These findings contribute to a better understanding of pouchitis management in real-world settings, emphasizing the need for further research to optimize treatment strategies and improve patient outcomes.

Disclosure

This study was supported by Takeda Pharma A/S.

Introduction

Functional bloating, a common gastrointestinal symptom marked by stomach discomfort and excessive gas production, presents a substantial problem for patients and healthcare practitioners. Fructose malabsorption is one of the main causes of functional bloating among the many other variables. When fructose is not well absorbed, it ferments in the colon, causing bloating and discomfort. The study examines the relationship between functional bloating and fructose malabsorption, emphasizing the significance of this relationship for diagnosis and treatment. Comprehending this correlation is crucial for executing focused measures to mitigate symptoms and enhance the well-being of impacted persons.

Aims & Methods

Aim: To study the frequency of fructose malabsorption in patients with functional bloating and its comparison to that in healthy controls.
Methods: We included 70 patients with functional bloating satisfying ROME III criteria and 35 healthy controls. Both the groups initially underwent a Glucose Hydrogen breath test(GHBT) to exclude Small intestinal bacterial overgrowth(SIBO). Subsequently, both groups underwent a fructose hydrogen breath test(FHBT) to assess for fructose malabsorption. 25 g of fructose in 250 ml of water was used. Breath hydrogen & methane concentrations were noted at baseline & every 15 min after administration of fructose for a total of 3 h. Persistent rise in breath hydrogen or methane > 20 ppm above basal was considered diagnostic of fructose malabsorption. Symptoms experienced during the test were noted.

Results

In our study, 20/70(29%) patients with functional bloating had evidence of fructose malabsorption compared to 1/35(3%) healthy controls(P-0.01). 51/105(48%) participants in our study had symptoms during FHBT. 16/21(76%) participants with positive FHBT had concomitant symptoms. Symptoms (suggestive of fructose intolerance) without the presence of malabsorption, occurred in 42%(35/84) of participants in our study. In univariate analysis, predictors of fructose malabsorption in patients with functional bloating were younger age, female gender, Bristol score >4, symptoms of epigastric discomfort, and mucus in stools(P<0.05). There was no
significant difference among patients with FM and those without FM for diet, duration of symptoms, severity of bloating, recent PPI usage, use of promotility drugs, or BMI (P-0.26, P-0.69, P-0.20, P- 0.07,P-0.24 and P-0.25 respectively). However, in the multivariate analysis, only female gender was significantly associated with a positive FHBT(P-0.02)

Conclusion

More than 1/4th of patients with functional bloating in our study had evidence of fructose malabsorption compared to healthy controls and this subset of patients with functional bloating might benefit from dietary restriction of fructose.