Introduction

We previously reported 6 months results of a prospective, randomized and sham-controlled trial comparing endoscopic pyloromyotomy (G-POEM) with a sham procedure in patients with gastroparesis (GREG, 1). G-POEM was superior to a sham procedure in terms of both symptoms improvement and gastric emptying rate. Moreover, cross-over G-POEM, which was performed after a sham procedure was effective in 75% of patients. All patients have been prospectively followed according to an original protocol. Here, we report the long-term results. Unblinding of patients occurred 6 months after the originally allocated procedure (G-POEM or sham).

Aims & Methods

In GREG trial, G-POEM has been compared to a sham procedure in patients with refractory and severe gastroparesis (gastroparesis cardinal symptom index (GCSI) > 2.3, duration of symptoms of at least 6 months, with no adequate response to conservative measures). Patients randomized to the sham group with persistent symptoms were offered cross-over G-POEM. Symptoms were assessed in all enrolled patients (including those with a sham procedure only) at 12, 24 and 36 months, gastric emptying study and upper GI endoscopy were repeated at 12 months only in patients who underwent G-POEM (either primary or cross-over). The main outcomes were proportion of patients with treatment success and recurrences. Kaplan-Meier curve has been constructed to analyze the long-term effects.

Results

From a total of 41 randomized patients with gastroparesis (17 diabetic, 13 postsurgical, 11 idiopathic; 46% male), 33 patients received G-POEM (21 primary, 12 cross-over). Among these, median follow-up was 24 months and treatments success rates evolved from 72% (95% CI: 59%-90%) at 6 months to 67% (95% CI 52%-85%) at 12 months, 64% (49%-82%) at 24 months and 36 months. The corresponding numbers for diabetic, postsurgical and idiopathic gastroparesis at 36 months were 71% (51%-100%), 36% (17%-80%) and 78% (55%-100%). Overall, 3 patients (2 diabetic, 1 postsurgical) with previous treatment success experienced a recurrence of symptoms, however none of these patients required further intervention yet. One female patient with a primary treatment failure underwent redo G-POEM with treatment success (post-surgical etiology). Median gastric retention at 4 hours did not change between 3- and 12-months follow-up (6.7% to 10.0%). Seven patients underwent a sham procedure only, 4 achieving treatment success at 6 months. There were no symptomatic recurrencies up to 36 months follow-up. Among three “only sham” patients without a treatment success, one patient died from other reason and two patients who initially refused cross-over G-POEM decided to undergo this procedure later (one with treatment success, one is scheduled).

Conclusion

Endoscopic pyloromyotomy leads to a sustained improvement in approximately two thirds of patients with refractory GP and the rate of recurrencies is low. Diabetic and idiopathic GP showed a trend towards a higher long-term effect compared to postsurgical GP. Significant improvement of symptoms after sham procedure was infrequent but long-lasting.

References

Martinek J, Hustak R, Mares J, et al. Endoscopic pyloromyotomy for the treatment of severe and refractory gastroparesis: a pilot, randomised, sham-controlled trial. Gut 2022;71:2170–8.

Introduction

Glucose breath test (GBT) is the most commonly used method for the diagnosis of small intestinal bacterial overgrowth (SIBO). SIBO is a common condition with very unspecific symptoms (bloating, abdominal pain, diarrhea or constipation). Recently, American and European recommandations have been published to standardize the indications and the conditions to perform these tests.^1,2 However, some discrepancies remain between the European and American recommandations, and many statements were supported by low quality of evidence.^1,2 Moreover, several counfounding factors related to the patient’s condition may impact the result of the test, leading to a difficult interpretation.

Aims & Methods

This study aimed to assess the factors that could impact the results of a GBT. Therefore, we retrospectively reviewed the results of the GBT performed in our physiology department from 2013 to 2023. The test was performed after ingestion of 75g of glucose, with breath samples collected every 15min during 2 hours. The result was considered positive for hydrogen (H₂) if a rise ≥ 20ppm was observed or positive for methane (CH4) if a rise ≥ 10ppm was observed. Demographic data were collected, such as symptoms and questionnaires during the exam including Rome questionnaire, and the Gastro-Intestinal Quality of Life Index (GIQLI). Severity of symptoms was based on the GIQLI questionnaire, where a higher score represents a better condition. Medical and surgery history, such as drug treatments were then retrospectively collected from medical records, using a computerized research.

Results

A total of 2373 tests from different patients were included. The mean age was 46.0 ± 15.8 years old, with 1727 females (73.7%). The number of positive GBT was 576 tests (24.3%), with 294 tests positive for H₂ only, 214 tests positive for CH₄ only, and 69 tests positive for both. In univariate analysis, a higher age, female sex, and a lower body mass index (BMI) were associated with a positive GBT (Table). A history of diabetes, and a previous gastric surgery (sleeve, or bypass) were associated with a positive test, while proton pump inhibitors (PPI) or opioids intake did not change the outcome (Table). Regarding the symptoms, more severe abdominal bloating and constipation were associated with a positive test (1.28 ± 1.0 vs 1.41 ± 1.1; p=0.02, and 2.67 ± 1.3 vs 2.82 ± 1.2; p=0.03), while abdominal pain and diarrhea were not statistically different (1.57 ± 1.1 vs 1.67 ± 1.1; p=0.07; and 2.23 ± 1.3 vs 2.33 vs 1.4; p=0.14). In multivariate analysis, age (Odds Ratio (OR) = 1.02 [1.01 – 1.03]; p<0.001), BMI (OR=0.93 [0.90 – 0.96]; p<0.001), a previous gastric surgery (OR=9.32 [3.74 – 24.86]; p<0.001) and more severe constipation (OR=0.88 [0.79 – 0.98]; p=0.02) were associated with a positive GBT.

Conclusion

The result of GBT is more likely to be positive in patients with constipation. A previous gastric surgery is a cofounding factor, leading to a non-interpretable result of the test. A diagnosis of irritable bowel syndrome or functional dyspepsia did not change the result of the test, such as PPI or opioid intake.

References

1. Hammer HF, Fox MR, Keller J, et al. European guideline on indications, performance, and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Neurogastroenterology and Motility, and European Society for Paediatric Gastroenterology Hepatology and Nutrition consensus. United European Gastroenterol J 2022;10:15-40.
2. Pimentel M, Saad RJ, Long MD, et al. ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth. Am J Gastroenterol 2020;115:165-178.

Clinical Case Summary

Amyloidosis is a systemic disease that results from the extracellular accumulation of a pathological protein - amyloid, which can be present with its light chain associated protein (AL) ^[1]. AL amyloidosis can be presented with two insoluble fibrils - the light chain immunoglobulin κ or λ. Acute liver failure with liver amyloidosis is reported extremely rarely ^[2]. Usually the symptoms of liver involvement are mild, but in rare cases acute liver failure can be noted. The characteristic clinical presentation of liver involvement is hepatomegaly, cholestasis, and jaundice ^[3].
We present a case of a 57 years old male patient admitted to Mikaelyan University Hospital, Yerevan, Armenia with jaundice, weakness, bloating and dyspnea. His past medical history is notable for bladder cancer, without distant metastasis. Upon admission, his ALP level was 722 U/L, GGT 779 U/L, ALT 37 U/L, AST 151 U/L, total bilirubin 229 umol/L, INR 2.17. Viral hepatitis serological markers were negative. Contrast computer tomography (figure 1) unveiled portal hypertension, ascites and hepatosplenomegaly with liver craniocaudal size 23 cm. A decision was made to perform a liver biopsy, which was complicated with bleeding. The liver histology(figure 2) showed positive Congo red staining and the к chain of AL amyloid was predominant to the λ chain. There was 0.25 g/L proteinuria. Serum and urine paraproteinemia tests were negative. An electrocardiogram revealed decreased voltage in all leads. Because of deteriorating condition, the patient was transferred to intensive care unit (ICU) where liver enzyme levels continued to rise, creatinine level was 430 umol/L, 24 h urine was 150 ml, total Ca level 2.9 mmol/L. Patient died 13 days after admission to the hospital.
This unusual case emphasizes that hematological diseases, like amyloidosis play an important role in liver injury, fibrosis and should be included in differential diagnosis of liver pathology.

References

1. Ueno H, Douhara A, Osaki Y, Koizumi A, Yorioka N, Ueda S, Tsutsumi M, Yoshiji H. Liver Biopsy-confirmed Primary Hepatic Amyloidosis with Only Jaundice As the Initial Symptom: An Autopsy Case Report. Intern Med. 2022 Oct 1;61(19):2877-2881. doi: 10.2169/internalmedicine.9189-21. Epub 2022 Feb 26. PMID: 35228432; PMCID: PMC9593147.
2. Kim HJ, Tomaszewski M, Lam EC, Xiong W, Moosavi S. Amyloidosis: A Rare Cause of Severe Cholestasis and Acute Liver Failure. ACG Case Rep J. 2020 Dec 4;7(12):e00479. doi: 10.14309/crj.0000000000000479. PMID: 34604435; PMCID: PMC8483873.
3. Premkumar M, Rangegowda D, Vyas T, Kulkarni A, Grover S, Mahiwall R, Sarin SK. Primary Hepatic Amyloidosis Presenting as Acute-on-Chronic Liver Failure. ACG Case Rep J. 2017 Feb 15;4:e22. doi: 10.14309/crj.2017.22. PMID: 28286788; PMCID: PMC5340654.

Figure 1- CT scan of patients abdomen.
Figure 2- Liver biopsy, Congo red positive.

Introduction

Nephrolithiasis (NL) is a common extra-intestinal complication of inflammatory bowel diseases (IBD) with significant morbidity and mortality¹. Its pathogenesis and risk factors still need to be completely elucidated. Because of intestinal malabsorption, enteric hyperoxaluria is a critical pathogenic mechanism responsible for the development of NL in IBD patients². Growing evidence has highlighted the association between gut microbiota and NL, particularly emphasising the role of some oxalate-degrading bacteria, such as Oxalobacter formigenes, representing the mainstay of the so-called “gut-kidney axis”³. More recent studies also hypothesize the involvement of urinary microbiota⁴, but no data on IBD patients are currently available. Thus, our study aims to analyse the urinary lithogenic profile in IBD patients and its relationship with gut and urinary microbiota.

Aims & Methods

Consecutive adult patients with IBD were prospectively enrolled. The presence of ileoanal pouch, ileostomy, colostomy or short-bowel syndrome were exclusion criteria. Demographic and clinical data, including previous episodes of NL, were collected. Disease activity was evaluated using Harvey-Bradshaw index for Crohn’s disease (CD) and Mayo score for ulcerative colitis (UC). All patients underwent abdominal ultrasound for NL detection. Blood tests of kidney function (notably creatinine, blood urea nitrogen, creatinine clearance, and electrolytes) were also measured, together with a 24h-urine collection for lithogenic profile analysis, including calcium oxalate relative saturation ratio (RSRCaOx). In a subgroup of patients, urinary and faecal microbiota were also analysed through 16S rRNA sequencing.

Results

48 patients (52.1% men, mean age 42.6±17.4 years) were enrolled. Twenty-five patients were affected by CD and 23 by UC and 10 presented active disease at enrollement. NL was more frequent in CD than in UC (32% vs. 13%). In CD, 24-h urinary volume was lower and 24-h oxaluria was higher than in UC. Moreover, 24-h oxaluria was higher in patients with previous or present NL. Gut microbiota analysis was performed on 22 patients, stratified based on median RSRCaOx (higher or lower than the median). Significantly different β-diversity was observed between the two groups (p =0.025) and patients with an elevated RSRCaOx showed a higher relative abundance of Bacteroidetes and a lower abundance of Firmicutes (p value <0.05). No statistically significant difference was found in urinary microbiota composition between patients with high or low levels of RSRCaOx.

Conclusion

NL is more common in CD patients, who generally present lower urine volume and higher 24-h oxaluria than UC patients. Furthermore, NL is more frequent in IBD patients with higher oxaluria levels, confirming oxalate excretion's crucial role in NL pathogenesis. Again, our study reports an association between urinary stone development and Firmicutes/Bacteroidetes imbalance in the gut microbiota, suggesting possible further studies to identify patients at higher risk of NL.

References

1. Varda BK, McNabb-Baltar J, Sood A, et al. Urolithiasis and urinary tract infection among patients with inflammatory bowel disease: a review of US emergency department visits between 2006 and 2009. Urology. 2015;85(4):764-770. doi:10.1016/j.urology.2014.12.011
2. Witting C, Langman CB, Assimos D, et al. Pathophysiology and Treatment of Enteric Hyperoxaluria. Clin J Am Soc Nephrol. 2021;16(3):487-495. doi:10.2215/CJN.08000520
3. Ticinesi A, Milani C, Guerra A, et al. Understanding the gut-kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers. Gut. 2018;67(12):2097-2106. doi:10.1136/gutjnl-2017-315734
4. Xie J, Huang JS, Huang XJ, et al. Profiling the urinary microbiome in men with calcium-based kidney stones. BMC Microbiol. 2020;20(1):41. doi:10.1186/s12866-020-01734-6

Introduction

Patients with Hypermobile Ehlers Danlos Syndrome (hEDS) have a high prevalence of Disorders of Gut-Brain Interaction (DGBI) and pose complex nutritional challenges in gastroenterology clinic. Despite this, little is known regarding nutrient intake and adequacy in hEDS.

Aims & Methods

Our aim was to assess nutrient intake and adequacy of patients with hEDS, as well as to determine which factors, including co-existent DGBI, are associated with poor intake. We conducted a cross sectional survey of patients with hEDS from two tertiary neurogastroenterology clinics as well as the Ehlers-Danlos Support UK. Inclusion criteria were adults with hEDS, exclusion criteria were those currently or previously using artificial nutrition. Patients completed the validated semi-quantitative Scottish Collaboration Group Food Frequency Questionnaire (FFQ) alongside questionnaires characterising: demographics, DGBIs (Rome IV), gastrointestinal, mood, somatic and autonomic symptoms, past history of eating disorders and screen for Avoidant Restrictive Food Intake Disorder (ARFID) using the Nine Item Avoidant-Restrictive Scale (NIAS). Nutrient intake was calculated from the FFQ and nutrient adequacy was calculated by comparison with UK daily reference values (DRVs) for age and sex. Unpaired t-tests were performed to compare nutrient intakes among patients with and without comorbidities, including the most common DGBIs.

Results

425 participants were included in the final analysis (mean: 41 years, 96% female). Only 48.5% reported BMI in the normal range, whereas 5.2% were underweight (BMI <18.5 kg/m²)and46.4% were overweight/obese (BMI >25 kg/m²). Only one third met their estimated average requirements (EAR) for energy (kcal/d). The majority met their reference nutrient intake (RNI) for protein (87.3%) and fat (72.5%), in contrast to only 21.2% for carbohydrate. Fibre intakes were very low (AOAC mean 23.7g/day (SD: 12.7) with only 24.7% meeting the RNI of 30 g/d. More than 58% of participants met/exceeded their DRV for micronutrients (zinc, magnesium, copper, manganese and selenium) and >95% for vitamins. Patients with functional nausea (n=157) were less likely to meet their protein requirements compared to those without (82.2% vs. 90.3%, p=0.015) and also had lower intakes for sodium (p=0.02), magnesium (p=0.02), calcium (p=0.01), zinc (p=0.002), selenium (p=0.03), folic acid (p=0.02) and vitamin C (p=0.05). Patients with previous eating disorders were less likely to meet nutrient requirements for thiamine (p=0.01) and vitamin B12 (p=0.04). Patients with ARFID (n=110) were less likely to meet requirements for all nutrients (except fat, calcium, vitamin D, vitamin B12) compared to patients without.

Conclusion

Patients with hEDS are rarely underweight and tend to consume high protein, high fat diets that are low in fibre. Functional nausea is the single most important DGBI impacting nutrient intake, as well as previous eating disorders and disordered eating (ARFID). These factors should be considered by clinicians and dietitians when assessing nutrient intake in this complex patient group.

Disclosure

RT, AF and QA have received a grant from EDS-UK to conduct this study. AF undergoes consulting work for Abbvie.
KW has received research funding from Almond Board of California, Danone, International Nut & Dried Fruit Council, and has a patent for volatile organic compounds in the detection and management of IBS.
QA undergoes consulting work for Takeda Pharmacueticals, and Classado Biosciences Ltd.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, food and/or aeroallergen-mediated inflammatory disease , characterized by esophageal dysfunction and eosinophil inflammation of the esophageal mucosa. The incidence of EoE has increased in recent years, including Japan. Pathogenesis of EoE is incomplete, and the data on microbiome related with EoE are limited. The aim of this study was to identify the esophageal and salivary microbiome in patients with EoE.

Aims & Methods

Patients either with EoE or non-EOE patients with symptoms of esophageal dysfunction who underwent esophagogastroduodenoscopy(EGD) at Kawasaki Medical School hospital between April 2021 and April 2023 were enrolled. The endoscopic reference score (EREFS) is used to determine severity of endoscopic findings. EoE patients were classified as the active group, if the presence of esophageal eosinophilia greater than or equal to 15 eosinophils per high-power field were detected during the endoscopy. , Saliva and Esophageal mucous taken from esophagus using brushing samples and saliva were used to investigate microbiome in EoE patients and controls. The microbiota of samples was profiled using the Illumina MiSeq platform.

Results

Total 24 patients were enrolled including8 active EoE patients, 5 inactive EoE patients, and 11 controls.
There were no significant differences in age, PPI use, history of gastroesophageal reflux disease and H. pylori infection among the three groups.The comparative analysis of the taxonomic composition at the genus level among esophageal mucous samples indicated that Streptococcus were less abundant in the active EoE group compared to the other groups, and Stomatobaculum were more abundant in the inactive EoE group than in the controls. On salivary, The abundance of the genera Megasphaera were significantly more prevalent in the inactive EoE group than in the other groups.The abundance of the genera Streptococcus was negatively correlated with ERFFS scores.

Conclusion

Streptococcus might be involved in the pathogenesis of EOE.

Introduction

EUS-guided portal pressure gradient measurement (EUS-PPGm) would be a useful procedure in patients with liver diseases (1). However, there is scarcely data on the clinical relevance of this EUS-guided procedure.

Aims & Methods

We report our experience on EUS-PPGm focus on safety, clinical relevant findings, technical drawbacks and how to overcome them.
We used a therapeutic echoendoscope and a 25G dedicated needle as previously reported (1, 2). To minimize the risk of infection, periprocedural antibiotherapy was administered and the working channel of the echoendoscope was flushed with povidone-iodine.

Results

EUS-PPGm was performed in 30 patients, median age 42±3 yo. Indications: assessment of NAFLD, 25 patients; idiopathic portal hypertension, 3 patients; evaluation for curative therapy in hepatocellular carcinoma (HCC), 2 patients. Anticoagulants were withdrawn in 4 patients. EUS-guided bilobar liver biopsies (EUS-BLB) were also immediately performed in 26 patients (87%) with a 19G needle. EUS-PPGm was successfully obtained in 25/30 patients (83%). EUS-PPGm was >5 mmHg in 14/25 cases (56%). In idiopathic portal hypertension 3/3 patients. In NAFLD 10/22 patients (45%) without endoscopic and/or ultrasonographic signs of portal hypertension and without liver fibrosis on EUS-BLB. Mean time to obtain EUS-PPGm was 21±2 minutes. Mean time for EUS-PPGm plus EUS-BLB was 45±2 minutes. Idiopathic portal hypertension was assessed by this procedure with the complementary information given by the EUS-BLB. In the 2 patients with HCC, one patient did not have reliable results and, in the other, EUS-PPGm was useful ruling out portal hypertension and the patient was referred to curative surgery that was successfully carried out.
Technical drawbacks: In 5 cases (17%) EUS-PPGm was not obtained due to non-reliable measurements in 4 cases probably due to excesive use of the elevator and up&down wheel of the echoendoscope and bending of the needle, that would be avoided. In the fifth case the EUS-PPGm was not performed for exacerbating breathing movements that precluded the procedure for safety concerns. We experienced difficulty in punctioning the hepatic and the portal vein in one and two cases, respectively, having to transverse these vessels and repositioning the needle in the lumen of these veins. In one case the 25G needle passed in close proximity to the hepatic artery. We think dedicated 25G needles have more flexibility and penetrability than larger caliber needles and, probably could lead for a safer and easier procedure and could be more accurate in the puncture of narrow vessels in liver cirrhosis (3).
Adverse events: A self-limited bleeding from the cardias was immediately observed after one EUS-PPGm in a patient with idiopathic portal hypertension. One mild epigastric pain 2 day after a combined procedure was observed. No other adverse events were registered one month later.

Conclusion

EUS-guided PPGm, even when combined with EUS-BLB, seems safe providing useful clinical information. Almost half of patients affected with NAFLD have portal hypertension diagnosed precociously in reversible stages providing a useful tool in precision Medicine, especially in the setting of obesity pandemic. Idiopathic portal hypertension was confirmed by this procedure with the complementary information provided by the EUS-BLB. In the patient with HCC, EUS-PPGm rule out portal hypertension and allowed for curative surgery. There are technical aspects related to the needle and the position of the echoendoscope that could be useful to know to improve the safety and accuracy of this procedure.

References

(1) Samarasena J, Chang KJ. Endo-hepatology: A new paradigm. Endosc Ultrasound. 72018. p. 219-22.
(2) Hashimoto R, Chang KJ. Endoscopic ultrasound guided hepatic interventions. Dig Endosc. 2021;33(1):54-65.
(3) Romero-Castro, R; Carmona-Soria, I; Jimenez-Garcia, VA; et al. Endoscopic ultrasound-guided portal pressure gradient measurement: Improving its safety overcoming technical drawbacks. Endoscopy (In press).

Disclosure

Rafael Romero-Castro is consultant to Cook Medical since February, 28th, 2023.