Introduction

Delayed Gastric Conduit Emptying (DGCE) after Esophagectomy with a gastric conduit is a complication that occurs in 15-39% of patients. It is associated with short and long-term complications and with a poor quality of life. Intra-Pyloric Injection of Botulinum Toxin (BT), Pyloric Pneumatic Dilation (PD), and a combination of these two techniques (BTPD) in the same session, represent the main endoscopic procedures, but comparative data are currently unavailable.

Aims & Methods

Retrospectively analyzed prospectively collected data on all consecutive patients with DGCE after esophagectomy, refractory to prokinetics drugs and treated endoscopically. with BT, PD, or BTPD from January 2014 to November 2023 in San Raffaele Hospital (Milan). International Society Disease of the Esophagus (ISDE) Diagnostic Criteria were used for DGCE diagnosis and classification. Gastric Outlet Obstruction Score (GOOS) was used for clinical staging at diagnosis and at discharge. All patients undergoing BT received 100 UI of toxin, while those undergoing PD were dilated with the same model of pneumatic balloon, progressively inflated from 18 to 20mm, and left in site for one minute for every different size. BTPD underwent BT and BD during the same procedure. Technical success (TS) was defined as the completion of the procedure, clinical success (CS) as the resolution of symptoms/resumption of feeding (soft solid, GOOS 2) at discharge or expanding dietary intake at any rate, without the need to replace the nasogastric tube. Recurrence was defined as symptom relapse after more than 15 days of well-being requiring endoscopic or surgical intervention. Adverse events (AEs) were classified using the AGREE classification.

Results

64 patients (81.2% male, ASA II 54.7%, 90.6% Ivor-Lewis esophagectomy, 77.4% adenocarcinoma), median age 62 years (IR 55-70), were enrolled: 18 (28.1%) in the BT group, 24 (37.5%) in the PD group and 22 (34.4%) in the BTPD group. No statistically significant differences were found in the baseline characteristics among the three groups and in indication, disease stage, neoadjuvant treatments, type of surgery with/without intraoperative pyloric surgical procedures, other surgical complications, and median follow-up. Despite identical TS success (100%), BTPD group exhibited a higher CS rate (100%) compared to the PD and BTPD groups (p=0.02). Among patients who achieved CS, BT group showed a higher recurrence rate (23.1%) compared to the other two groups but not statistically different (p=0.41). Kaplan-Meier dysfunction analysis revealed that the BTPD group was characterized by both a significatively shorter median time to refeeding of 1 day (IR 1-1) compared to the other two groups (log-rank test p=0.0049), and a shorter median time to discharge of 1 day (IR 1-4) (log-rank test p=0.02). No AEs procedures related were recorded.

Conclusion

Endoscopic management of DGCE is challenging and BT and PD represent the main available treatments. Our study shows that the same session combination approach (BTPD) could offer patients a higher rate of clinical efficacy and a shorter time to refeed and to be discharged, maintaining an equivalent safety profile. Further prospective studies are needed to validate these findings.

Introduction

Esophagogastric junction contractile integral (EGJ-CI) is a metric of EGJ barrier function on high-resolution manometry (HRM), which may be limited by measurement discrepancies and unclear clinical utility. Mean EGJ basal pressure is a novel, simple HRM metric assessing barrier function. We compared their performance to predict conclusive gastroesophageal reflux disease (GERD).

Aims & Methods

Consecutive patients (Nov 2022-Oct 2023) undergoing combined HRM and 24 hour pH-impedance testing OFF antisecretory therapy (except for Barrett's patients) for known or suspected GERD were eligible, all with prior upper endoscopy. Mean (between end-expiration and end-inspiration) basal EGJ pressure, referenced to mean intragastric pressure, was calculated manually using the isobaric contour tool. EGJ-CI was calculated using the smart box tool, with the isobaric contour set 2 mmHg above intragastric pressure, over three respiratory cycles and normalized for its duration. On pH-impedance testing, Lyon classification 2.0 was applied. Conclusive GERD was defined as acid exposure time (AET) >6% or histologically confirmed Barrett’s. Mann-Whitney U and Kruskal-Wallis test, with Bonferroni correction, were used. ROC curves were plotted.

Results

125 patients were included (mean age 51.6 ± 16.5 years, 60% males). Upon applying Lyon 2.0 classification, 45 (36%) patients had conclusive GERD (25 Barrett’s), 7 (6%) borderline GERD, 16 (13%) reflux hypersensitivity (RH), while 57 (45%) had functional symptoms. Patients with conclusive GERD, on HRM, had a significantly lower mean basal EGJ pressure (11.0 vs 18.5 mmHg; p<0.001) than patients without conclusive GERD, while EGJ-CI was not statistically different (26.1 vs 35.1 mmHg∙cm; p=0.101). Mean basal EGJ pressure was significantly different across Lyon v2.0 subgroups (median values in GERD: 11, borderline GERD: 16, RH: 19, FH: 20 mmHg; p<0.001), while EGJ-CI did not differ (p=0.283). Mean basal EGJ pressure (AUROC: 0.73, 95%CI 0.64-0.82) showed greater predictive performance of conclusive GERD than EGJ-CI (AUROC: 0.59, 95%CI 0.49-0.69). The optimal cut-off of 13 mmHg had 72% sensitivity and 62% specificity; a cut-off of 9.5 mmHg had 86% sensitivity, while a cut-off of 23.5 mmHg had 91% specificity.

Conclusion

Mean EGJ basal pressure is a simple HRM metric to predict conclusive GERD, well differentiating GERD phenotypes, with greater performance than EGJ-CI. This metric could be preferred over EGJ-CI as a useful adjunctive measure to support GERD diagnosis.

Introduction

Long-term maintenance treatment efficacy, safety and tolerability in eosinophilic esophagitis (EoE) is still partially understood. The aim of this study was to evaluate long-term outcomes of maintenance treatment for EoE with various drugs and dose regimens in real-world observational studies and randomized controlled trials (RCTs).

Aims & Methods

Systematic search was performed on Pubmed-MEDLINE, Embase and Cochrane Central Register of Controlled Trials from inception to October 2023. Studies reporting histologic success of maintenance therapy for EoE patients > 48 weeks, following 8-12 weeks of induction therapy with the same drug were included. Primary outcome was pooled histologic success (defined as < 15 eosinophils/HPF) at the end of follow-up for both study designs. Risk Difference (RD) or Odds Ratio (ORs) for histological success of maintenance therapy versus placebo (PBO) (for RCTs) and versus induction (for both study designs), pooled drug-related adverse events (AEs), endoscopic and clinical success rates were assessed as secondary outcomes. Random effects model metanalyses were performed. A-priori sub-group analyses were performed to address substantial inter-study heterogeneity (measured with I² statistic).

Results

From 3,916 full articles, 23 articles matched inclusion criteria (17 observational studies and 6 RCTs), 7 with pediatric patients only. Overall, 1,923 patients (M 70.1%; mean age 29.8±12.6 years). Mean follow-up time was 78.4 weeks. Budesonide (either oro-dispersible or viscous suspension) was administered in 7 studies (including 2 RCTs), PPI in 6 studies (all observational, 4 pediatric), Fluticasone in 5 studies (including 1 RCT with 4 cohorts), Dupilumab in 2 RCTs and Cendakimab in 1 RTC. Pooled rate of long-term histologic success for RCTs was 83% (95% CI, 77%-89%; I² 73.1%), while for observational studies attested at 53% (95% CI, 42%-65%; I² 93.5%) at a median follow-up of 97.8 weeks. Maintenance therapy in RCTs showed a RD of -0.71 (95% CI; -0.92-0.50; p<0.01; I² 88.9%) versus PBO, while a RD of -0.06 (95% CI; -0.11-0.01; p<0.016; I² 23.1%) compared with induction. Observational studies showed a non-significant (p=0.38) Odds Ratio (OR) of 1.37 (95% CI, 0.66-2.85; I² 81.3%) of losing histologic success during therapy de-escalation. Pooled clinical success among RCTs attested at 61% (95% CI, 51%-75%; I² 71.3%), comparable with observational studies (60% [95% CI, 42%-77%; I² 97.3%]). Biological therapy (either Dupilumab or Cendakimab at various regimens) ranked first for pooled histologic success rate among RCTs with 79% (95% CI; 71%-87%; I² 54.9%). In observational studies, PPI with histologic success of 64% (95% CI, 50%-78%; I² 88.7%) and clinical success of 79% (95% CI; 66%-93%; I² 85.2%) ranked first. Pooled rate of AEs among RCTs attested at 34% (95% CI; 22%-45%; I² 93.2%), with a pooled candidiasis infection rate of 6% (95% CI; 2%-10%; I² 61.9%), comparable with pooled AEs among observational studies (5% [95% CI, 2%-7%; I² 66.7%]). Pooled therapy discontinuation rate was 0.14 (95% CI, 0.073-0.210, I² 94.49%) in real-world data.

Conclusion

This is the first meta-analysis on efficacy and safety of long-term maintenance treatment (median 78 weeks) for EoE. All treatments showed good efficacy in maintaining long-term histological remission without clear disadvantage in de-escalating therapy during maintenance in real-word data. Biological therapies resulted the most effective in RCTs, while PPIs in observational studies. Low adverse events rates and low therapy discontinuation rates confirm long-term treatment is well tolerated.

References

1. Nistel M, Andrews R, Furuta GT, Atkins D. Elimination Diet or Swallowed Topical Steroid Treatment of Pediatric Eosinophilic Esophagitis: Five-Year Outcomes. J Allergy Clin Immunol Pract. 2023 Aug;11(8):2516-2523.e2. doi: 10.1016/j.jaip.2023.05.036. Epub 2023 May 30. PMID: 37263351; PMCID: PMC10525024.

Disclosure

ES has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapa-gos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Uni-farco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Nestlè, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Takeda, Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici.
Danese has served as a speaker, consultant and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Fer-ring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor.

Introduction

This paired biopsy study aimed to investigate the predictive value of various non-invasive scores for identifying the temporal evolution of hepatic fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).

Aims & Methods

A total of 69 patients with NAFLD who had undergone two paired liver biopsies (mean interval: 21.3 ± 9.7 months) were examined. Fibrosis progression and regression were defined as an increase or decrease of at least one stage in fibrosis between the initial and second biopsy. Fibrosis-4 index (FIB-4), NAFLD Fibrosis Score (NFS), Agile 3+ score, Agile 4 score, and FibroScan-AST (FAST) score were calculated at the time of the initial biopsy.

Results

Upon comparing the results of paired biopsies, 45% of the participants (n = 31) showed no change in fibrosis, 26% (n = 18) experienced fibrosis progression, and 29% (n = 20) had evidence of fibrosis regression. In multivariable logistic regression analysis, the only independent predictive factor for progressive fibrosis was the FAST score. The odds ratio for progressive fibrosis was found to increase by 19% (95% confidence interval: 8–38%, p < 0.05) with every unit increase in FAST score at the time of the initial biopsy. No independent predictors for fibrosis regression were identified.

Conclusion

Patients with higher baseline FAST scores were more likely to experience fibrosis progression independent of potential confounders. Consequently, FAST could serve not only as a diagnostic tool for screening fibrosis in NAFLD, but also as a prognostic indicator.

Introduction

In cirrhosis, several prognostic scores have been developed to predict overall and complication-free survival. The MELD (Model for End-Stage Liver Disease), MELD-Na and MELD3.0 scores have been proposed as a criteria for allocating organs.

Aims & Methods

The aim of our study was to assess the performance of these 3 scores for the prediction of overall and complication-free survival in decompensated Tunisian cirrhotic patients.
Methods: We conducted an observational, retrospective study involving all patients with decompensated cirrhosis managed in Gastroenterology department of Taher Maamouri hospital during the period from January 2010 to December 2021. Mortality was assessed using the Kaplan Meier model. The performance of the scores was assessed using the AUROC (Area under the Receiver Operating Characteristic curve).

Results

One hundred and fifty-two patients were included with an average age of 61 years. Viral liver cirrhosis was the most common (65.13%). The mean value of the MELD-Na and MELD3.0 scores was 17.74 and 19.4, respectively. The mean follow-up time was 17.1 months. The rate of complications and short-term mortality was 33.6% and 18.4% respectively.
The AUROC of the MELD3.0 score in predicting of the occurrence of further decompensation was the highest (0.775) compared to those of the MELD and MELD-Na score (0.743 and 0.756 respectively). The cut-off value of the MELD3.0 score in predicting further decompensation was 20 (sensitivity 60.7%, specificity 73.3%).
In the prediction of 3-month mortality, the AUROCs of the MELD, MELD-Na and MELD3.0 scores were 0.786; 0.841 and 0.850 respectively. The cut-off value of the MELD3.0 score was 24 (sensitivity 68%, specificity 88%). A statistically significant correlation was noted between the MELD3.0 score ≥24 and 3-month mortality (p=0.04).

Conclusion

The MELD3.0 score had the best predictive value for the occurrence of further decompensation and short-term mortality in decompensated cirrhotic patients. Those with a MELD 3.0 score ≥24 should be prioritized on waiting lists.

Introduction

Although Crohn’s disease (CD) patients are expected to be at high risk for developing NAFLD, because of their altered nutrition state and some CD medication, little is known about prevalence of this condition in this population.

Aims & Methods

The aim of our study was to describe the prevalence of hepatic steatosis and fibrosis in patients with Crohn's disease and to assess their risk factors.
This was a cross-sectional, descriptive study including patients with CD, diagnosed since at least one year. We excluded patients known to have chronic liver disease or a condition that could lead to it (chronic alcoholism, viral infection with hepatotropic viruses, portal thrombosis, etc.). Patients included were at least in clinical remission. Elastometry and Controlled Attenuation Parameter (CAP) measurement were made in all patients, using a fibroScan® with an XL probe. Data were collected and analyzed by SPSS software version 26.

Results

We included 100 patients, 55 men and 45 women with a mean age of 42 ± 12 years. Seven patients had diabetes and 4 had hypertension. Forty-one patients were smokers. The mean duration of CD was 11.09 years. The disease was ileal, colonic or ileocolic in 39%, 24% and 29% of cases respectively. An upper gastrointestinal tract’s involvement was observed in 7 patients and ano-perineal lesions was observed in 36 patients. The phenotype was inflammatory, stricturing and fistulizing in 55%, 21% and 24% of the patients respectively. Almost half of our patients (45%) had already received at least one course of corticosteroids. CAP measurement had shown S1, S2 and S3 stage steatosis in 8%, 3% and 7% of patients respectively. Factors associated with the presence of hepatic steatosis were diabetes (p=0.002, OR=15), presence of overweight or obesity (p=0.005, OR=4,71), age over 35 years at the time of study (p=0.038). ALT level greater than 10.75IU/L was also associated with the presence of hepatic steatosis (p=0.04). Several factors related to corticosteroid courses were associated with the presence of hepatic steatosis such as a duration shorter than 18 months since the last corticosteroid course (p=0.038), maximum achieved prednisolone dose of more than 55mg/d (p=0.04) and duration on full dose of corticosteroids exceeding 4.5 weeks (p=0.016). FibroScan® showed a fibrosis stage F1 in 4% and F2 in 7%. Elasticity in the remaining patients was less than 6 Kpa. The factors associated with the presence of F1 and/or F2 fibrosis were: diabetes (p=0.003, OR=16), age at the time of the study of more than 51.5 years (p=0.049) as well as an age of more than 36.5 years at diagnosis (p=0.020).

Conclusion

Apart from the known epidemiological factors associated with steatosis and hepatic fibrosis, our study showed that features related to corticosteroid therapy were associated with hepatic steatosis in patients with CD.

Introduction

Non-alcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver disease, ranging from simple steatosis to steatohepatitis, advanced fibrosis and liver cirrhosis, with histological features of alcohol induced liver disease. Despite the high morbidity and mortality burden of NAFLD, no definite treatment is established yet. Lifestyle modifications are one of the most valued measures for NAFLD amelioration. A lot of dietary regimens have been recommended with pro-ved weight loss, inflammation reduction, along with improved cardiovascular and metabolic markers. Many regimens have been suggested for NAFLD patients: caloric restriction, low carbohydrate high fat diet, or intermittent fasting diets (IF). Notably, in IF people are allowed to eat for a restricted time and abstain food and caloric fluids for another time. Remarkably, IF is capable of reversal of insulin resistance, leading to marvelous achievements in most resistant cases. Accordingly, IF is one of the most promising regimens suggested for improving the unhealthy NAFLD parameters. Being an Islamic pillar, Ramadan fasting (RF) might also be considered as a form of dry intermittent fasting. Despite the reported deleterious impacts of fasting on liver cirrhosis, fruitfully IF had been suggested to improve NAFLD patients.

Aims & Methods

Despite the ample flow of non-alcoholic fatty liver disease (NAFLD) drugs in the pipeline, lifestyle modifications are still the optimal solution of NAFLD. The aim of the study was to assess short term effects of Ramadan fasting (RF) as a sort of intermittent fasting (IF) on biochemical, radiological, and anthropometric parameters of NAFLD patients.
Ninety-eight NAFLD patients were recruited and voluntarily subjected to 16 hours daily fasting for an average of 22-29 days, without special dietary recommendations. Anthropometric, laboratory and radiological parameters were measured before, at 30 days, and one month after fasting (fasting and non-fasting phases).

Results

Patients were mostly rural (76%), hypertensive (34.7%), diabetic (43.9%), and female (76.8%), with overt criteria of metabolic syndrome (67.3%). Liver transaminases (ALT and AST) were ameliorated significantly after fasting (p ≤ 0.01), which continued in the following month (p ≤ 0.01) especially in those with elevated ALT before fasting (46%). Eleven patients (24.4%) experienced ALT normalization after one month of fasting, which was further increased to 15 (33.3%) one month later. Lipid profiles (cholesterol, triglycerides, HDL, LDL, cholesterol/HDL risk ratio) were significantly corrected following IF (p ≤ 0.01) and continuing in the next phase (p ≤ 0.010). Body mass index (BMI) lessened following the fasting (p ≤ 0.01), while no remarkable changes were noted regarding waist, hip, and triceps skin fold thickness (p ≤ 0.01). Glycemic indices (HbA1c, postprandial, HOMA-IR) and fibrosis markers (FIB-4 and APRI) were significantly ameliorated (p ≤ 0.01), while reduction in inflammatory markers was not long lasting (p ≤ 0.01).

Conclusion

Intermittent fasting led to momentous improvements in ultrasonographic, biochemical, and anthropometric parameters of NAFLD especially in early phases and prediabetics.

References

Badran H, Elsabaawy M, Sakr A, Eltahawy M, Elsayed M, Elsabaawy DM, Abdelkreem M. Impact of intermittent fasting on laboratory, radiological, and anthropometric parameters in NAFLD patients. Clin Exp Hepatol. 2022 Jun;8(2):118-124. doi: 10.5114/ceh.2022.115056. Epub 2022 May 30. PMID: 36092752; PMCID: PMC9442655.

Pubmed:
https://pubmed.ncbi.nlm.nih.gov/36092752/

Disclosure

No conflict of interest.