Introduction

There are no agreed guidelines to inform the approach to previously-treated achalasia patients presenting with recurrent symptoms. The decision to proceed to re-intervention is often based mainly on the clinical presentation and data arising from barium swallow studies and upper gastrointestinal endoscopy.

Aims & Methods

We evaluated Endoluminal functional luminal imaging probe (EndoFLIP) and High Resolution Manometry (HRM) value in such a setting. We selected patients from a prospectively-kept database with previously-treated achalasia (including Per Oral Esophageal Myotomy (POEM), Heller myotomy (LHM), pneumatic balloon dilatation (PBD) and botulinum toxin injection (BTX; only if submitted the last six months) presenting with symptom recurrence during an 8-year period (11/2015-2/2023). Only those with assessable EndoFLIP data (distensibility index (DI) at 40ml balloon inflation volume) and planned for re-intervention with POEM according to clinical judgment were included in the study. Baseline data were analyzed retrospectively. Consecutive naïve-to-treatment patients formed the control group.

Results

N=70 patients (25 treated vs 45 naïve) were included in the study (F=38; mean age 43 (17-78yrs). The majority of patients were previously submitted to pneumatic balloon dilatation (n=13), 5 were submitted to POEM A to Heller myotomy and 3 had botox treatment during the last six months before assessment. Table 1 lists the main demographic and investigative parameters. DI of treated patients was significantly decreased among patients without barium clearance at 5 min (1.8±0.9 vs 2.5±1.6, p=0.017) and was correlated to height of barium column (r=-0.439, p=0.015), fact not observed for IRP (29.1±13.5 vs 21.5±8.8, p=0.017 and r=0.266, p=0.319, respectively). DI was not correlated to IRP4s in treated patients (r=-0.168, p=0.374) in comparison to naïve (r=-0.227, p=0.046). Neither DI, IRP, nor barium column at 5 min were correlated to patients Eckardt score among treated patients (p=0.494, p=0.998, p=0.734 respectively).

Conclusion

DI is impaired and correlated to height of barium swallow in 5 minutes in previously treated achalasia patients presenting with symptom recurrence and can be used as an objective metric to tailor re-intervention in conjunction to barium swallow. DI is significantly reduced among treated in comparison to naïve achalasia patients. HRM cannot with certainty navigate treatment decisions in approximately half of treated patients. Future studies that may define specific diagnostic DI cut-offs for patients with recurrence of achalasia symptoms needing re-intervention are needed.

Introduction

The first-line treatment for patients hospitalized with Acute severe ulcerative colitis (ASUC) is intravenous corticosteroid therapy, but 30% require second-line 'rescue' infliximab (IFX) therapy or colon resection due to incomplete response. Identifying patients with acute severe ulcerative colitis who are refractory to corticosteroid therapy remains challenging, as physicians have no markers to predict non-response to steroids on admission. This study aims to investigate whether the CRP/albumin ratio on days 1 and 3 of hospitalization could predict early response to intravenous steroids.

Aims & Methods

Data from all admissions for acute severe ulcerative colitis over 4 years from January 2019 to December 2022 were retrospectively collected.
All patients initially received intravenous corticosteroids. Demographic, clinical, biological, and endoscopic data were collected; C-reactive protein (CRP) and albumin levels were recorded at baseline and during hospitalization. Receiver operating characteristic statistics were used to determine the optimal stool frequency, Lichtiger index, CRP, albumin, and CRP/albumin ratio (CAR) to predict steroid response.

Results

A total of 81 ASUC patients were admitted. Sixty-six patients (81.5%) were steroid responsive, 8 patients (10%) received rescue IFX and 7 patients (8.6%) required colectomy. By comparing two groups of patients (steroid-responsive and steroid-refractory), baseline stool frequency, Lichtiger index, CRP and CRP/Albumin ratio data didn’t show any significant difference between the two groups. While baseline albumin was lower in the steroid-refractory group (Median 26, IQR 18-36, p=0.041).
Day 3 stool frequency and Lichtiger index were significantly higher in the steroid refractory group (p<0.001).
By receiver operating characteristic statistics, day 3 CAR was a more accurate marker of steroid responsiveness than day 3 CRP or day 3 albumin alone [area under curve=0.911 (P<0.001)]. The optimal CAR to predict response to steroids on day 3 was 2.67 (sensitivity 80%, specificity 91%).

Conclusion

An elevated CRP and low albumin level on day 3 is an early predictor of steroid-refractory ASUC. When combined in a ratio, their predictive ability improves. In patients with predicted steroid nonresponse, early introduction of rescue IFX at this stage may be more effective, before serum albumin falls profoundly.

Introduction

Endoscopic suturing offers a novel minimally invasive technique for deploying full thickness sutures in the gastrointestinal (GI) tract. Indications range from defect closure, post operative leaks, fistula repair, stent fixation and tissue plication for endoscopic sleeve gastroplasty.
Here we report our updated experience of endoscopic suturing for non-bariatric applications in the upper GI tract using the Apollo OverStitch^TM device (Apollo Endosurgery, Austin, Texas). This represents the largest and most diverse case series in a UK cohort of patients.

Aims & Methods

We retrospectively evaluated cases where the Apollo OverStitch^TM device was used at our tertiary upper GI centre. The primary outcomes were immediate technical and clinical success. Technical success was defined as the successful application of sutures. Immediate clinical success was defined according to indication. For defect closure this was evaluated using on the table fluoroscopy/endoscopic visualisation. For stent fixation it was determined by the absence of stent migration at follow up endoscopy.
Secondary outcomes included defect recurrence at follow up investigation. We also evaluated long term clinical success by assessing for resolution of the index clinical issue at the time of latest follow up.

Results

The Apollo OverStitch ^TM device was used 56 times across 35 patients (57% female) between August 2018 and March 2023. The mean age of patients at the time of the index procedure was 58 (+/-17.3 years). Outcomes according to indication are highlighted below (Table 1).
There were five cases (5/56, 8.9%) of technical failure. Three (3/5, 60%) involved iatrogenic perforations at the junction between D1/D2. Three cases (3/37, 8.1%) of immediate clinical failure were reported for the defect closure cohort. In the defect closure cohort there was a recurrence rate of 61.8% (21/34), with a long term clinical success rate of 68.2% (15/22). 14 cases of stent fixation were conducted with a stent migration rate of 35.7% (5/14).
There were two (2/56, 3.6%) cases of bleeding following endoscopic suturing. In both cases bleeding was stemmed endoscopically on the table and prior to the end of the procedure.

Conclusion

Our case series suggests that the Apollo OverStitch^TM device can be used for a diverse range of indications with high rates of immediate technical and clinical success.
We note a high recurrence rate reflecting that many defects require repeat suturing attempts to achieve durable long term closure. We postulate that this may be related tissue epithelisation and/or friability impacting opposition. Furthermore, technical failure occurred most with perforations at the D1/D2 junction. This is likely related to acute angulation which impedes the ability to deploy sutures.
The heterogenous follow up data from this case series impacts the ability to draw firm conclusions regarding long term outcomes. There is an ongoing prospective multicentre registry which will assist in evaluating long term outcomes.

Clinical Case Summary

There are limited available rescue therapy options for refractory acute severe ulcerative colitis (ASUC). Cyclosporine is used in steroid refractory and steroid resistant ASUC patients and based on our report, may also help steroid intolerant patients. Here, we describe the case of a 22-year-old male with left sided UC who presented with ASUC to our tertiary IBD center in Abu Dhabi in the United Arab Emirates. In clinic, our patient reported 20 watery bowel movements per day associated with nocturnal episodes mixed with blood, abdominal cramps.He had lost 12 kg over 6 months. He reported having failed escalating doses of infliximab and adalimumab in the past. Additionally, he had developed severe peripheral neuropathy on steroids and had to stop taking them. On examination, vital signs were normal with generalized abdominal tenderness. The patient was admitted to the hospital. Labs revealed severe anemia, low albumin, elevated CRP, ESR and fecal calprotectin. His abdominal X-ray was unremarkable. Stool for C diff and blood CMV DNA by PCR were negative. On flexible sigmoidoscopy, he had severe contiguous inflammation to a Mayo endoscopic score of 3. Subsequent biopsies confirmed severe active chronic colitis without CMV infection. On the day of admission, we induced him with vedolizumab 300 mg intravenous infusion, started intravenous cyclosporine and placed him concurrently on oral azathioprine. Over the next week, he had responded. By day 12, he was in clinical remission and discharge home. When followed in clinic 1 week post discharge, he remained in clinical remission on vedolizumab, oral cyclosporine and oral azathioprine. At week 6 post discharge, he was in clinical remission as well on the same regimen. In conclusion, this report is a good example of the possibility of using combination of cyclosporine, vedolizumab and azathioprine as concurrent induction therapy for patients with ASUC.

References

Gisbert JP, García MJ, Chaparro M. Rescue therapies for steroid-refractory acute severe ulcerative colitis: A review. Journal of Crohn's and Colitis. 2023 Jan 18
Dai C, Huang YH, Jiang M. Combination therapy in inflammatory bowel disease: Current evidence and perspectives. International Immunopharmacology. 2023 Jan 1;114:109545.
Pellet G, Stefanescu C, Carbonnel F, Peyrin-Biroulet L, Roblin X, Allimant C, Nachury M, Nancey S, Filippi J, Altwegg R, Brixi H. Efficacy and safety of induction therapy with calcineurin inhibitors in combination with vedolizumab in patients with refractory ulcerative colitis. Clinical Gastroenterology and Hepatology. 2019 Feb 1;17(3):494-501.

Introduction

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by abdominal pain and changes in bowel habits. Small intestinal bacterial overgrowth (SIBO) refers to a group of gastrointestinal syndromes caused by an excessive number of bacteria in the small intestine. Up to now, the relationship between IBS and SIBO remains contentious. So we set out to investigate the differences between these two conditions.

Aims & Methods

Participants who met the Rome III diagnostic criteria for IBS and had a negative lactulose hydrogen and methane breath test (LHMBT) were diagnosed with IBS. Those who presented with gastrointestinal symptoms and had a positive LHMBT were diagnosed with SIBO. Overlapping cases were excluded. Participants who had a negative LHMBT and no significant abdominal symptoms were classified as healthy controls (HC). All participants were instructed to provide fecal samples for 16S rRNA sequencing.

Results

Our results showed that a history of enteritis was more common in IBS patients, and the severity of gastrointestinal symptoms was significantly higher in IBS and SIBO groups compared to healthy controls. IBS patients also reported more severe symptoms than SIBO. Additionally, IBS patients were more affected by their symptoms, while the SIBO group reported more dissatisfaction with bowel habits. We observed differences in dietary intake between the groups, with IBS patients having the highest total energy and protein intake, and the lowest dietary fiber intake. SIBO patients had higher fat intake and significantly lower carbohydrate intake compared to the other two groups. Regarding the fecal microbiome, both IBS and SIBO patients had higher structural diversity and lower functional diversity than the HC group. The abundance of Firmicutes/Bacteroidetes in the IBS group was significantly higher than in the other two groups. Our analyses indicated that the fecal microbiome could significantly distinguish the three groups, and specific bacterial species were associated with different symptoms in each group. In SIBO, Thalassospira and Christensenellaceae_group were associated with intestinal motility abnormalities, while Ruminococcaceae_group, Butyricimonas, and Oscillospira were associated with gas production. In the IBS group, Klebsiella and Mitsuokella were associated with abdominal pain, and other bacteria such as Escherichia_Shigella and Enterobacter were generally associated with enteritis infection, abdominal pain, and diarrhea. We also found that the predicted KEGG pathways were enriched in various nutrient metabolism pathways, with potential implications for elevated blood folate levels and vitamin B12 deficiency in SIBO patients.Protein bacterial motility and biofilm formation_ Escherichia coli, were mainly enhanced in IBS, and these functions were related to the mucosal barrier damage.

Conclusion

Our study shows that although IBS and SIBO share similar symptom spectra, they may be two distinct diseases. Despite the potential differences in the fecal flora of small intestinal flora in SIBO group, significant differences were found between IBS and SIBO in terms of clinical phenotype and fecal microbiome. Further exclusion of SIBO using lactulose hydrogen and methane breath testing in patients who meet the diagnostic criteria for IBS is warranted, as the differences suggest that different treatment strategies may be needed for these two populations. Future studies are needed to explore the underlying mechanisms and potential therapies for these conditions, which may ultimately benefit patients with IBS and SIBO.

References

1. Quigley EMM, Murray JA, Pimentel M. AGA Clinical Practice Update on Small Intestinal Bacterial Overgrowth: Expert Review. Gastroenterology. 2020; 159(4):1526-1532. DOI: 10.1053/j.gastro.2020.06.090
2. Bushyhead D, Quigley EMM. Small Intestinal Bacterial Overgrowth-Pathophysiology and Its Implications for Definition and Management. Gastroenterology. 2022; 163(3):593-607. DOI: 10.1053/j.gastro.2022.04.002
3. Ghoshal UC, Nehra A, Mathur A, Rai S. A meta-analysis on small intestinal bacterial overgrowth in patients with different subtypes of irritable bowel syndrome. J Gastroenterol Hepatol. 2020; 35(6):922-931. DOI: 10.1111/jgh.14938
4. Mearin F,Lacy BE,Chang L, et al. BowelDisorders[J].Gastroenterology,2016;150;1393-1407.
5. Zhu L, Huang D, Shi L, et al.Intestinal symptoms and psychological factors jointly affect quality of life of patients with irritable bowel syndrome with diarrhea.Health
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6. Sperber AD,Dumitrascu D, Fukudo S, et al.Gut 2017;66:1075–1082
7. Jindong Zhang, Jiao Liu, Shiwei Zhu, Ben Wang, Qiong Jia, Qihua He, Lijin Song, Yuan Fang, Baoli Zhu, Liping Duan. Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation. Acta Pharmacologica Sinica，Accepted 2020

Clinical Case Summary

Introduction: Primary epiploic appendagitis (PEA) is a rare cause of acute abdominal pain. The clinical is non-specific, making the diagnosis difficult; hence the interest of CT scan. The preferred treatment is essentially medical.
Objectives: Focus on the particularities of this entity, which can mimic the picture of an acute surgical abdomen, in order to minimize the risk of an unnecessary surgery.
Materials and methods: We present a retrospective and descriptive study of 4 cases diagnosed with PEA, managed in the hepatogastroenterology department in collaboration with the visceral surgery department 2, during the year 2021.
Results:
- The average age of the patients was 50.75 years, with a male predominance.
- Obesity was a predisposing factor for PEA; three patients were overweight.
- The clinical picture was dominated by abdominal pain, found in all patients.
- Associated signs (nausea, vomiting, transit disorders) were rare or absent, found respectively in 2 patients and one patient.
- The clinical examination revealed abdominal tenderness in 3 patients, defensiveness in only one patient, and a temperature higher than 37.3 °Cin 3 patients.
- Laboratory examinations showed hyperleukocytosis in 2 patients and a moderate increase in C-reactive protein in 3 patients.
- CT scan was the key examination for the diagnosis of PEA, performed in all patients.
- Three patients benefited from conservative management, only one patient was operated on.
- The evolution was favorable; no case of recurrence or complication was noted.
Conclusion: PEA is a condition that should be kept in mind as it is managed medically and to spare patients unnecessary surgery or hospitalization.