Introduction

Prucalopride, a 5-HT4 agonist approved for the treatment of refractory chronic constipation has been shown to reduce oesophageal acid exposure in healthy volunteers (Kessing BF, 2014) and improve oesophageal motility in gastroesophageal reflux (GER) patients with ineffective oesophageal motility (Lei W-Y, 2018). To date, no studies have evaluated its effect in patients with dysphagia and oesophageal dysmotility.

Aims & Methods

Our aim was therefore to evaluate the effect of prucalopride on dysphagia symptoms and to assess which, if any, motility or GERD diagnosis influenced outcome in patients with gastroscopy negative dysphagia. Clinical records, together with oesophageal high-resolution manometry (HRM) and available 24hr pH-monitoring (pH-MII) reports of patients referred for dysphagia to a single Neurogastroenterology Clinic between April 2017 and March 2024 were retrospectively reviewed. All patients had a previous negative gastroscopy with oesophageal biopsies, were not responsive to PPIs and were prescribed prucalopride as an add-on treatment at the initial dosage of 1 mg/daily with the possibility to increase to 2 mg/daily after one week in case of no response. A standardized template was used to collect clinical data and patient-reported response to treatment. Clinical response was defined as a self-reported improvement in dysphagia symptoms associated with a reduction in Eckardt score of at least one point. Data are expressed as median (QR).

Results

Thirty-five patients [median age 62 (28) years; 19 (54%) female] were included. Mean duration of follow-up was 12 (19) months. Twenty-two (63%) patients responded to Prucalopride with a significant improvement in the Eckardt score before to after treatment [3.5 (2.3) vs 1 (1.8); p<0.001)]. Six patients (27.3% of responders) responded to 1 mg, with the rest increasing to 2mg/daily. Response was maintained for a median of 14.5 (16) months.Thirteen (37.1%) patients did not respond, of which four (11.4%) experienced adverse events (diarrhoea, headache, abdominal pain) leading to an early treatment discontinuation. In these patients the Eckardt score did not change before to after the treatment [3 (3) vs 3.5 (2.3), respectively; p=0.85)]. None of the clinical (data not shown) or key manometric parameters were associated with treatment response [median basal distal contractile integral 283 (425) vs 340 (470)mmHg/s/cm; p=0.71 and median integrated relaxation pressure 6.2 (8) vs 8.4 (9.4)mmHg; p=0.13 in responders and non-responders, respectively]. However, there were trends for more patients with absent contractility to be non-responders, and more patients with EGJOO to be responders to prucalopride. Normal acid exposure time and number of reflux events were associated with a positive response to treatment (Table 1).

Table 1 – HRM and pH-monitoring characteristics of responder and non-responder patients at baseline.

Conclusion

Our study suggests Prucalopride might be a well-tolerated and useful treatment for dysphagia in patients with dysmotility disorders, mainly in the absence of pathological reflux. However, prospective randomized controlled studies are needed to confirm these data.

Introduction

The proportion of patients who take opioid based analgesics and cannabis has not been studied in a large cohort of patients with cyclical vomiting syndrome (CVS) in the UK. It is also unclear whether the efficacy of prophylactic tricyclic antidepressants (TCAs) is impacted by ongoing opioid or cannabis use.

Aims & Methods

(A) To study the burden of opioid and cannabis use in patients with CVS.
(B) To study the clinical response to prophylactic TCA and whether this was augmented by opioid/cannabis intake.
Clinical characteristics and healthcare outcomes of patients diagnosed with ROME IV CVS in a single neurogastroenterology clinic between January 2016 to December 2023 were retrospectively collected. A standardised clinic template was used to collect data relating to age, sex, gastrointestinal symptoms, medication usage, and patient-reported response to TCA. Patients commenced 10mg TCA for 60 days which was up titrated by 10 mg at each routine outpatient consultation (unless poorly tolerated) until clinical remission was achieved or the maxmum dose (50 mg daily) was prescribed. Clinical remission was defined as the absence of stereotypical episodes of vomiting for at least 6 months prior to the last clinic consultation.

Results

95 patients (male 21%, mean age 30.8±11.8 years) were identified and 84 (88%) were seen on at least two or more occasions with a median duration of follow-up of 22 (IQR: 5, 39) months. The treatment outcomes for all patients treated with TCA are outlined in table 1. At the initial consultation, 35 (37%) and 16 (17%) patients took prescribed opioid analgesics and cannabis, respectively. All were provided with drug cessation advice and were prescribed a TCA: only 12/35 (34%) and 11/16 (69%) of patients adhered to drug cessation advice. On follow-up, 100% of patients who adhered to recommendations to stop opioids and cannabis responded to TCA whilst 0% of patients who continued to take opioids/cannabis responded to TCA. Illicit drugs were found at urine drug screening in 5 patients who failed to respond to TCA (cocaine n=2 and heroin n=3).

Conclusion

This is the first UK study reporting the impact of opioid usage and illicit drugs in patients with CVS. TCAs are useful in treating CVS patients providing they do not consume prescribed opioids or illicit drugs.

Clinical Case Summary

54-year-old male, with gastroesophageal reflux disease medicated with PPIs, was admitted due to acute exacerbation of watery chronic-diarrhea (>10 bowel movements/day). The patient was dehydrated, hypotensive and presented acute-kidney-injury AKIN-3. Abdominal CT-scan identified diffuse gastric wall-thickening and a 20 mm nodule at the gastroduodenal junction. Due to suspicion of Zollinger-Ellison Syndrome (ZES), the PPI-dose was optimized with symptomatic improvement. Subsequently, for hormonal assay, PPI was switched to an H2 blocker. Approximately 72h after the switch, melena with hemodynamic instability was identified, and upper-endoscopy revealed extensive duodenal peptic ulcer disease (Forrest-IIc and III ulcers). After 72h without PPI, gastrin 4390 ng/L and gastric-pH 2.9 were documented.
The hospitalization was marked by two episodes of upper gastrointestinal haemorrhage (UGIH), with hemodynamic instability and admission in the intensive care unit. Besides PPI and endoscopic-hemostatic-therapy (EHT), octreotide was initiated. PET-DOTATOC-Ga-68 scan revealed nodal metastasis. The patient underwent antrectomy with Y-Roux-reconstruction (neuroendocrine-tumor, mitotic-index < 1/2mm², ki67 <3%, pT2N1-R2). On the 2nd postoperative-day, UGIH recurrence with hemodynamic instability occurred, leading to re-laparotomy and intraoperative retrograde-enteroscopy with EHT (Over-the-scope-Clip) and gastroduodenal artery ligation. The patient remained stable, without UGIH, and gastrin 20 ng/L. After 2-months, he was discharged and referred to Oncology (N1R2).
ZES caused by gastrinomas, is a rare condition requiring high clinical suspicion and symptoms typically begin years before diagnosis. Metastatic disease determines prognosis, but complications are associated with considerable morbimortality. This case illustrates the diagnostic/treatment dilemmas of ZES and gastrinoma staging/treatment, as well as the therapeutic challenge of one of its most feared complications, UGIH.

References

Image 1 - Abdominopelvic CT scan showing gastric wall thickening and a nodule in the gastrinoma triangle.
Image 2 - Upper gastrointestinal endoscopy – upper gastrointestinal haemorrhage.
Image 3 - PET-DOTATOC-Ga-68 scan result – tumor and nodal metastasis
Image 4 - Histopathological study of the surgical specimen compatible with neuroendocrine tumor - H&E as well as neuroendocrine markers.

Disclosure

Nothing to declare

Introduction

The only effective treatment for celiac disease (CD) is lifelong compliance with a gluten-free diet. Lactobacilli and Bifidobacterium spp. may play a role in the breakdown of gluten. Ithas been demonstrated that Lactobacilli can detoxify gliadin peptides after partial digestion by human proteases. These findings could suggest the use of probiotics as complementary therapy for CD.

Aims & Methods

We designed a study to determine the potential effect of a combination of Lactobacillus (acidophilus HA-122, casei HA-108) and Bifidobacterium bifidum HA-132 on perception of symptoms and on the inflammatory-immunological markers in patients with active CD.
25 adult patients were randomized to receive bid of a probiotic combination of Lactobacilus and Biffidobacter for six weeks (13 pts) va a placebo group (12 pts) while being on gluten-free diet. Laboratory studies included routine blood tests, CD specific antibodies, determination of IL-1b, IL-6 and TNF-alpha. CD serology and duodenal histology were performed at baseline, at the end of treatment and at 30 days after therapy. Histological damage in intestinal biopsy samples was graded according to the Marsh modified classification. At baseline and follow-up visit, patients completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. Histological damage in intestinal biopsy samples was graded according to the Marsh modified classification.

Results

25 pacients, 13 in the probiotic associated arm, 12 in the placebo arm, with median age of 40, BMI 21.2, 18 with symptomatic CD (equal distribuited) and 7 with sublinical CD (4 in the probiotic arm, 9 in the placebo arm). Baseline serology: IGA tTG 1986.6 (group A) vs 1507.1 (placebo group). Baseline hystology (Marsh classification)- Marsh 3a 1 pacient in probiotic group, 2 in the placebo arm. 5 pts Mars 3b3 in group A and 2 in the placebo arm and 17 pts Marsh 3c (9 pts probiotic, 8 pts placebo). IELs density (mean range) was 44.5 in the first group vs 42.5
After treatment: clinical aleviation of indigestion and diareea (p=0.002), constipation (p=0. 0396), gastro-esophageal reflux (p=0.0493) and abdominal pain (p=0.0378)-superior in the probiotic associated treatment.
Serologic parameters: IgA tTG 0,96 in the probiotic arm vs 1,16 in the placebo (p=0.048), IgA EMA 1,05 vs 0,97 (p=0.028), IgG DGP 0,91 vs 1,12 (p=0.21).
Improvement of the inflamatory status: decrease of IL-1b, IL 6 and TNF-a was superior in the probiotic associated group (p=0.071, p=0.083, p=0.078).
Regarding the histologic response: IELs 0,83 vs 1.07 in the placebo arm (p=0.049).

Conclusion

Tests and the lymphocyte infiltrates in the mucosal biopsy specimen in uur study suggests that prebiotic/probiotic treatment may improve symptoms and serology in celiac disease.

Disclosure

I don t have any conflict of interest to declare