Introduction

Per-Oral Endoscopic Myotomy (POEM) was introduced in clinical practice few years ago, and quickly become one of the first line treatments of esophageal motility disorders. We report on the outcomes of the first 1000 patients treated with POEM in a single tertiary referral center during 11 years.

Aims & Methods

The first 1000 patients treated with POEM between May 2011 and September 2022 were identified from a prospective database and included in this study.
Demographics, clinical and technical aspects and follow-up data were collected and analysed. After treatment, patients underwent a regular follow-up, after 6 month, 2 years, 5 years and 10 years. Additional follow-up visits were performed, if clinically indicated. Timed Barium Esophagram, EGD, and esophageal manometry were performed before endoscopic treatment and during post-operative follow-up; a 24-hour esophageal pH monitoring study was performed 6 months after POEM.
Clinical failure was defined by and Eckardt score > 3 and by the need for additional treatments.

Results

Mean age of patients was 51.5 years; 36 patients were younger than 18 years and 157 older than 70 years. Four-hundred ninety-eight patients were male. One hundred seventy-seven patients had received previous treatments for achalasia (110 pneumodilation, 46 surgical myotomy; 21 botulinum toxin injection).
A total of 141 patients had a type I achalasia, 626 a type II, 111% a type III, 30 non-achalasia spastic esophageal motility disorders; in 92 patients achalasia type were not adequately classified. A sigmoid-type esophagus was present in 45 patients.
Mean symptoms duration before POEM was 24±64.6 months.
POEM was technically successful in 979 patients.
The median length of myotomy was 8.0 cm (range 4-22 cm) in the esophagus and 3.1 cm (range 0-7 cm) in the stomach. An anterior myotomy was performed in the 83% of patients. Mean operative time was 50.4 minutes (11–180 minutes).
Length of hospital stay was a mean of 2.5 days (range 1 to 48 days) after POEM.
Mild or moderate complications occurred in 28 patients (2.8%) and were managed conservatively. Severe complications occurred in 2 patients and required prolongation of hospital stay and other interventional treatment. There were no perioperative deaths in our series.
A mean follow-up of 30.4 months (3–130 months) was available for 93.8% of patients. Overall clinical success rate (Eckardt score ≤ 3) was 95.1%. Clinical success was 97.3%, 95.2%, 90.8% and 82% after 6 months, 2 years, 5 years and 10 years, respectively.
Thirty-three patients (70.2 %) with clinical failure underwent pneumodilation (78.8% with persisting clinical benefits); 5 patients (10.6% underwent surgery), one (2.1%) underwent re-POEM.
Clinical success was 93.4% in achalasia-patients and 83.3% in those with spastic motility disorders (p=0.1742).
An altered esophageal pH-study was documented in 32.6% patients; esophagitis rate was 34% (88% grade A/B; 12% grade C/D). At the date of the last follow-up, 38% of patients was receiving daily proton-pump inhibitors for gastroesophageal reflux. Two patients underwent antireflux surgery. Non cases of post-operative Barrett esophagus were identified.

Conclusion

Our results confirm the efficacy of POEM in a large cohort of patients. Benefits of POEM seem durable; adverse events are rare and no specific mortality was reported. Prevalence of GERD is relatively high, but well controlled by medications in the vast majority of patients.

Introduction

Clinical trials are ongoing to develop novel therapies for ulcerative colitis (UC), aiming to break the existing therapeutic ceiling. Mirikizumab, a monoclonal antibody targeting the p-19 subunit of IL-23, was evaluated in a phase-II clinical trial for the treatment of moderate-to-severe UC. Identifying predictive variables for response to therapy is still an unmet need and would serve as a valuable asset in clinical trials and clinical practice to guide therapeutic strategies.

Aims & Methods

This post-hoc data analysis aimed to identify variables predicting response to mirikizumab in UC patients from a phase II clinical trial. One-hundred and six randomly selected patients from the induction phase were considered: 26 (24.5%) were assigned to receive mirikizumab 50mg IV Q4W, 37 to 200mg IV Q4W (34.9%), 30 to 600mg IV Q4W (28.3%) and 13 to placebo (12.3%). In the maintenance phase, 44 received 200mg SC Q12W (42.3%), 47 received 200mg SC Q4W (45.2%), and 13 received placebo (12.5%). Patients who did not achieve clinical remission (14, 13.2%) were excluded from the analysis related to the maintenance phase. A stepwise analysis was conducted, initially using a principal coordinate analysis (PCoA) with permutational multivariate analysis of the variance (PERMANOVA), followed by a univariate analysis (Fisher’s or Wilcoxon signed-rank test) to select significant variables (p<.05). Further, a country-nested, three-visit repeated-measured generalized mixed ordinal logistic regression model (GLM) using significant PCoA variables was conducted. For both models the endpoint was histological remission at weeks 12 and 52, defined as Geboes score <2.

Results

At week 12, histological remission was achieved in 34 patients (32.1%) while at week 52 in 42 patients (39.6%). PCoA, PERMANOVA and univariate analysis considered histological remission to be significantly predicted by faecal calprotectin, endoscopic remission (Mayo 0, UCEIS <1) and induction therapy at weeks 12 and 52 (p<.05). Also, at week 52, the 32-IBD Questionnaire (systemic symptoms and social function), Physician Global Assessment, partial and total Mayo scores, and maintenance treatment were significant. Considering these as explanatory variables for the GLM, we confirmed the following as significant predictors of histological remission: faecal calprotectin <250 µg/g (Odds Ratio 0.26; 95% CI 0.12-0.58; p<0.001), endoscopic remission (OR 0.16; 95% CI 0.04-0.57; p=.005), induction treatment with mirikizumab 200mg IV Q4W (OR 0.09; 95% CI 0.02- 0.45; p=.004), 600 mg IV Q4W (OR 0.09; 95% CI 0.01-0.50; p=.006) and maintenance with 200 mg SC Q4W (OR 0.05; 95% CI 0.01-0.30; p=.001). A more severe Physician Global Assessment predicted histological activity (OR 2.29; 95% CI 1.03- 5.11; p=.043).

Conclusion

Our predictive model identified faecal calprotectin, endoscopic remission, and Physician Global Assessment as predictive factors for response to therapy. Notably, our model identified the most effective therapeutic strategies to achieve histological remission during induction and maintenance phases, showing promising ability to guide therapeutic choices in clinical trials and clinical practice. Additional investigation utilizing a larger clinical dataset would further enhance the ability of this model to identify variables predictive of response to therapy.

Introduction

Renal disorders are among the extra-intestinal manifestations of inflammatory bowel disease (IBD), and treatments may also lead to renal failure. However, the incidence of end-stage renal disease (ESRD), defined as the need for renal replacement therapy (dialysis and/or renal transplantation (RT)), is poorly known. The primary objective of our study was to assess the incidence of ESRD in IBD patients, and to compare it with the general health insurance scheme population.

Aims & Methods

We conducted a prognostic cohort study based on data from the French National Health Insurance Database(SNDS). Prevalent cases of IBD affiliated to the general health insurance scheme during the period 2011-2020 were identified on the basis of declarations long-term diseases ALD 24 or the presence of 2 hospital stays for IBD with ICD-10 codes or a single stay with reimbursement of specific treatments. Incident cases of ESRD were identified on the basis of a stay with a RT or a period with dialysis sessions for at least 45 days. Crude incidence rates of ESRD were calculated over the period for the IBD and the non-IBD population, with their 95% confidence intervals.

Results

A total of 280,283 IBD patients were included in the study over the period 2011-2020, 134,567 with ulcerative colitis(UC) and 145,716 with Crohn’s disease(CD). The mean age at study inclusion was 39.8 (± 17.1) years. The M/F sex ratio was 0.9. The mean age at incidence of ESRD in the non-IBD population was 65.0 (±17.0) years, the M/F sex ratio cases was 1.7.
Among IBD patients, 534 patients began replacement therapy by dialysis or RT, they were younger than non-IBD patients (60.3(±16.7)years, P<0.001).The mean incidence rate of ESRD over the period was 26.4 per 100,000 person-years (IC95% 23.1-29.6), 480 (89.9%) patients entered ESRD by dialysis, and 54 (10.1%) by preemptive RT. In the non-IBD population the mean rate of ESRD was 15.9 per 100,000 person-years (IC95% 14.8- 17.1; P<0.0001 compared with IBD): 79,606 (94.5%) patients entered ESRD by dialysis, and 4,634 (5.5%) by RT (as compared with IBD,P<0.001). In subgroup analysis, the mean incidence rate of ESRD was 22.8 per 100,000 person-years (IC95% 18.9-26.7) in UC patients and 29.5 (IC95% 25.3-33.6) in CD patients (P<0,0001). The rates of preemptive RT were 12.4% in UC patients (87.6% dialysis) and 8.6% in CD patients (91.4% dialysis).
Over a median follow-up of 6.8 years, the survival rate after ESRD was 40.8% in ESRD-IBD patients VS 34.2% in ESRD non-IBD patients (P<0.001). This difference remained significant for patients under 65 (p<0.0073).
No significant difference for the risk of re-hospitalization after RT (p=0.84), of retransplantation during the follow-up period in RT patients (p=0.67), or for the risk of hospitalization for severe infection (p=0.97) after RT in patients from the general population compared with IBD patients. The same was true for the type of severe infections after RT (p= 0.068) and for the risk of solid and haematological cancer after RT (p=0.48). However, there was a significant difference in the type of first severe infection after RT(p=0.003), but we are waiting for the results to tell us which one.

Conclusion

The incidence of ESRD is significantly higher in IBD than in the general data base population, confirming the need for regular monitoring of renal function in our patients.
Survival after ESRD onset, is higher in IBD patients.
The high incidence of RT in the IBD population confirms that access to transplantation is not restricted in this
population.

References

Kirchgesner et al, Gastroenterology 2018
Meyer et al, Aliment Pharmacol Ther. 2020
Tuppin et al, Nephrol Ther 2016

Introduction

PEUGIC (Post-Endoscopy Upper Gastrointestinal Cancer) is defined as carcinoma in the upper gastrointestinal (GI) tract which was preceded by negative upper endoscopy in the last 3 years. According to current knowledge, the rate of PEUGIC is an important parameter of quality and should not exceed 10 %. The aim of this study was to evaluate the occurrence and risk factors of PEUGIC at non-university hospital in Frydek-Mistek (Czech Republic) between 2013 and 2023.

Aims & Methods

This is a retrospective analysis of the patients diagnosed with upper GI cancer from January 2013 to December 2023. The data analyzed included family history of upper GI cancer, indications of the examination, therapy, tumor location and histological type. Risk factors for PEUGIC were calculated using the Chi-squared test and Fisher's exact test, with p <0,05 considered significant.

Results

During the study period, a total of 22727 gastroscopies were performed in total, and 122 patients were diagnosed with upper GI cancer (88 men and 34 women), including 35 esophageal tumors, 80 gastric tumors, and 7 duodenal tumors. Family history of upper GI tumor was reported in 10 patients. PEUGIC was identified in 12 patients (9,84%, 9 men and 3 women, mean age 69,25 years), including 6 in the esophagus, 5 in the stomach, and 1 in the duodenum. Two patients had early detection as part of adequate surveillance (Barrett's esophagus, post-polypectomy). Thus, we can evaluate 10 patients as true PEUGIC (8,20%). The rate of PEUGIC was 17,14 % (6/35) in the esophagus, 6,25 % (5/80) in the stomach, and 14,3 % (1/7) in the duodenum. Tumor location (for esophagus p=0,086, for stomach p=0,065, for duodenum p=0,525), histology (for adenocarcinoma p=0,332, for spinocelular cancer p=0,402, for neuroendocrine tumor p=0,25), male gender (p=0,815), or family history of upper GI tumor (p=0,335) were not statistically significant risk factors for detecting PEUGIC.

Conclusion

The overall rate of PEUGIC at our institution over the 11-year study period was 9,86 %, without early detected lesions as part of adequate surveillance, it was 8,20 %. Early detection of PEUGIC, which indicate poorer endoscopy quality, need to be distinguished from early detection of carcinoma within adequate surveillance.

Introduction

Most of the data concerning the epidemiology of inflammatory bowel disease (IBD) in Asia originated from the Eastern population and there are limited studies conducted in the Middle East. We aimed to describe the clinical phenotype, disease course, and medication usage of IBD cases from Iran in the middle east.

Aims & Methods

We conducted a cross-sectional study of registered IBD patients in the Iranian Registry of Crohn’s and Colitis (IRCC) recruited from 2017 until 2022. IRCC is a nationwide registry with at least one center in every province of Iran.¹ More than 400 gastroenterologists collaborated with IRCC, which was reported as approximately 87% of total gastroenterologists working in Iran. Demographics characteristics, past medical history, family history of IBD, disease extent and location, clinical behavior, extraintestinal manifestations, IBD medications, IBD activity using the IBD-control-8 questionnaire and the Manitoba IBD index, admissions in the past 3 months, emergency visits in the past 12 months, history of colon cancer, and IBD-related surgeries were gathered.

Results

Overall, 9746 patients with confirmed IBD, including 7793 patients with ulcerative colitis (UC) and 1953 patients with Crohn’s disease (CD) were reported. The ratio of UC to CD patients was 3.99. The median age at diagnosis was 29.2 (IQR: 22.6,37.6) and 27.6 (IQR: 20.6,37.6) for patients with UC and CD, respectively. 17.9% of patients with UC had a positive family history. Majority of patients with UC had pancolitis (47%). The most common treatment received by patients was 5-ASA (93.5%) followed by immunomodulator, prednisolone, and anti-TNF. Among patients who received immunomodulators, 96.2% was azathioprine followed by 6-mercaptopurine (2.8%) and methotrexate (1%). Of patients who used anti-TNF, 68.8% were adalimumab and 31.2% were infliximab. Among patients with CD, only one peak was observed in the distribution of age at diagnosis at 30-40 years. Male to female ratio was 1.28 in patients with CD. Patients with CD most commonly had ileocolonic involvement (43.7%) and stricturing behavior prevalence was 4.6%. Moreover, 38.4% of patients with CD had been treated with anti-TNF. Among patients who received immunomodulators, 90.4% was azathioprine followed by 6-mercaptopurine (4.6%) and methotrexate (5%). Of patients who used anti-TNF, 71.9% were adalimumab and 28.1% were infliximab.

Conclusion

This first report of IBD behavior, clinical outcome, and medication usage from the Iranian Registry of Crohn’s and Colitis as a representative population of the Middle East highlights the differences in IBD characteristics based on geographical location.

References

1. Malekzadeh MM, Sima A, Alatab S, et al. Iranian Registry of Crohn's and Colitis: study profile of first nation-wide inflammatory bowel disease registry in Middle East. Intest Res. 2019;17(3):330-339

Introduction

Non-alcoholic Fatty Liver Disease (NAFLD), is a state of hyperinflammation which is associated with release of pro-inflammatory cytokines. Obesity, diabetes and metabolic syndrome, which are usually accompanied by hepatosteatosis, are risk factors for severe Covid-19 infection.

Aims & Methods

We aimed to investigate the association of hepatosteatosis and liver fibrosis by non-invasive markers (FIB-4 and APRI) with the prognosis of Covid-19 disease among hospitalized patients. In this retrospective and observational study, 500 patients with the diagnosis of Covid-19 between March 2020 and March 2022 and underwent Thorax Computed Tomography (CT) were included. Demographics, clinical characteristics and laboratory data at admission were recorded. Liver-spleen attenuation value difference (CT _L-S) was obtained from CT images and non-invasive fibrosis markers as APRI and FIB-4 scores were calculated (1). Advanced fibrosis was defined as FIB-4>2.67, APRI≥1. Severe outcomes were defined as either intensive care unit (ICU) admission or mortality.

Results

Among the patients, 129 (25.8%) were admitted to the ICU, and mortality occurred in 53 (10.3%) cases. According to CT _L-S value, hepatosteatosis was in 32.6% of the cases. 82.8% of cases with hepatosteatosis were male, mean age was 52.6±13.5, 82% were overweight or obese. Hypertension and diabetes were the most common comorbidities. Among ICU patients, hepatosteatosis was found in 41.8% and ICU admission was associated with hepatosteatosis (p=0.002). Of the patients with hepatosteatosis, 58% of patients have FIB-4>1.3 and of these, FIB-4 and APRI score were significantly high in patients with ICU admission and mortality (p=0,001). Of the patients both with hepatosteatosis and advanced fibrosis, 71% were admitted to the ICU, mortality was seen in 32.5%. Mortality was significantly higher in patients with hepatosteatosis and advanced fibrosis according to the FIB-4 score (p=0.001). In the ROC analysis, combination of FIB-4 score and attenuation had highest sensitivity (sensitivity: 88.37%; Negative Predictive Value 90.85%; p=0.001) in determining the need for ICU need. The need for ICU follow-up was found to be 5 times higher in patients with a high FIB-4 score and low attenuation value [(Odds ratio (OR) 5.101; 95% Confidence Interval (CI): 2.865-9.083)]. The risk factors for the need for intensive care in patients with hepatosteatosis were advanced age, presence of fibrosis, high ferritin and IL-6 level in univariate analysis, whilst only high ferritin level was defined as a risk factor in multivariate analysis. Inflammation markers such as IL-6 and ferritin were significantly higher in patients with hepatosteatosis and fibrosis.

Conclusion

Hepatosteatosis and fibrosis determined by non-invasive tests were found to be associated with severe Covid-19 infection. Hepatosteatosis and fibrosis may increase inflammation-related markers such as ferritin and IL-6 and may create a synergistic effect with infectious conditions. Likewise high ferritin level in Covid-19 patients with hepatosteatosis is a risk factor for severe disease. CT_L-S and fibrosis scores have strong negative predictive value in the diagnostic evaluation for severity of Covid-19 disease.

References

1. Byun J, Lee SS, Sung YS, Shin Y, Yun J, Kim HS, et al. CT indices for the diagnosis of hepatic steatosis using non-enhanced CT images: development and validation of diagnostic cut-off values in a large cohort with pathological reference standard. European Radiology. 2019 Aug 1; 29(8):4427–35.

Introduction

Transient elastography (TE) by Fibroscan® is a widespread method for non-invasive evaluation of liver stiffness measurement (LSM). Point-shear wave elastography (pSWE) is an alternative non-invasive method for this type of assessment. Transient elastography is also able to evaluate hepatic steatosis by the function Controlled Attenuation Parameter (CAP).

Aims & Methods

We aimed to compare the results of TE and pSWE for fibrosis assessment in patients with non-alcoholic steatohepatitis (NASH), stratified by the degree of steatosis.
​Consecutive patients with established diagnosis of NASH attending our Gaastroenterology Unit underwent liver stiffness measurement (LSM) by both TE and pSWE. Liver steatosis was measured by CAP and the severity was graded into S0-S3. At least 10 measurements were performed and results were expressed as median with interquartile range. Statistical analysis was conducted by Pearson’s test for correlation and linear regression. Bland-Altman graphs with bias and ROC curves with estimation of sensitivity, specificity, and area under the curve (AUC) were drawn.

Results

Seventy-seven patients were recruited (17 females, 60 males, aging 54.1 ± 13.9). The overall correlation between TE and pSWE was moderate (r=0,63, p < 0.001). Linear regression showed a “b” coefficient of 0.99 ± 0.033. The Bland-Altman plot found a bias of -0,52 and only six valued exceeded the 95% CI limits. When considering patients with mild steatosis (S1), we found a strong correlation (r=0.81, 95% CI 0.39-0.95, p=0.003). The highest correlation between TE and pSWE was recorded for S2 subjects: r=0.90 (95% CI, 0.64-0.98, p<0.001). The correlation was low in S3 patients (r=0.42, 95% CI, 0.09-0.67, p=0.001). A cut-off of 11.15 kPa of pSWE had sensitivity=87,50 % and specificity=97,10% to detect relevant fibrosis, with an AUC=0.98 compared to TE.

Conclusion

pSWE and TE showed comparable LSM in NASH. A good concordance was observed in patients with mild or moderate liver steatosis, while in S3 patients we observed a weaker agreement between the two techniques.