Introduction

Biologic therapies are commonly used for inflammatory bowel disease (IBD) patients. Multiple biologic medicines can now be given both intravenously and subcutaneously. The different administration routes present provide different advantages regarding dose escalation, healthcare resource utilisation, pharmacokinetics, convenience, and safety.^1,2 Comparator effectiveness studies between intravenous and subcutaneous administration are lacking.

Aims & Methods

Our primary outcome was to compare the effectiveness between intravenous (IV) and subcutaneous (SC) biologics in rates of clinical remission. We performed a systematic review and meta-analysis to include all relevant articles from MEDLINE (Ovid), EMBASE, PubMed, and Cochrane central register of controlled trials from January 1^st, 1946 to January 28th, 2024. Studies that compared intravenous and subcutaneous administration of the same biologic therapy in IBD patients and reported effectiveness outcomes were included. Eligible studies had to include one of the following outcomes: [a] Clinical remission or response with a formalised clinical scoring system as defined by each study; [b] CRP remission; [c] faecal calprotectin remission. This study was registered on PROSPERO (CRD42023442675).

Results

Twenty studies met the inclusion criteria for the systematic review. There were only two randomised controlled trials and therefore were not analysed. There were eighteen cohort studies. One study was a prospective clinical trial switch from IV to SC vedolizumab. Twelve were prospective cohort studies. Five were retrospective cohort studies. Ten studies compared vedolizumab, seven studies compared infliximaband one study compared ustekinumab. We excluded the ustekinumab study given it was the only study evaluating ustekinumab. Of the 17 included studies, 15 were whole cohort switches from IV to SC formulations, with only 2 studies having both IV and SC arms. Nine vedolizumab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between IV and SC administration (RR 0.99; 95% CI 0.88, 1.11). Six infliximab cohort studies were meta-analysed for clinical remission and no difference was found in rates of clinical remission between IV and SC administration (RR 0.91; 95% CI 0.77, 1.08). Four studies reported CRP remission rates (1 infliximab study and 3 vedolizumab studies), and the vedolizumab studies were meta-analysed. Seventy one percent (159/224) of the SC group and 71% (207/291) of the IV group were in CRP remission. The pooled RR was 0.88 (95% CI 0.88, 1.07; p=0.09). We observed a high degree of heterogeneity (I² = 76%). Four studies, all studying vedolizumab, reported faecal calprotectin remission, and they were meta-analysed. Seventy six percent (158/207) of the SC group and 76% (140/183) of the IV group were in faecal calprotectin remission. The pooled RR was 0.99 (95% CI 0.90, 1.09). We observed no heterogeneity (I² = 0%). The quality of the cohort studies was high, with no studies found to be at a high risk of bias.

Conclusion

There was no difference in the effectiveness between subcutaneous and intravenous administration of infliximab and vedolizumab respectively. However, further high-quality studies, particularly head-to-head studies are required to confirm this finding.

References

1. Little RD, Ward MG, Wright E, Jois AJ, Boussioutas A, Hold GL, Gibson PR, Sparrow MP. Therapeutic Drug Monitoring of Subcutaneous Infliximab in Inflammatory Bowel Disease-Understanding Pharmacokinetics and Exposure Response Relationships in a New Era of Subcutaneous Biologics. J Clin Med. 2022 Oct 19;11(20):6173. doi: 10.3390/jcm11206173. PMID: 36294494; PMCID: PMC9605309.
2. Heald A, Bramham-Jones S, Davies M. Comparing cost of intravenous infusion and subcutaneous biologics in COVID-19 pandemic care pathways for rheumatoid arthritis and inflammatory bowel disease: A brief UK stakeholder survey. Int J Clin Pract. 2021 Sep;75(9):e14341. doi: 10.1111/ijcp.14341. Epub 2021 Jul 8. PMID: 33963659; PMCID: PMC8236906.

Disclosure

Dr. Alexander Elford is supported by the Australian Commonwealth government via a Research Training Program Scholarship. Dr Shahed Kamal and Miss Rishni Heldt have no conflicts of interest. A/Prof Christensen has received speaking fees from Abbvie, Janssen, Pfizer, Takeda and Ferring; research grants from Janssen and Ferring Pharmaceuticals and served on the advisory board of Gilead and Novartis. A/Prof. Jonathan P. Segal received speaker fees for Takeda and Abbvie, BMS and Falk Pharma and has a non-restricted grant from Tillots.

Introduction

Afferent loop syndrome is a rare complication after surgical gastrojejunostomy reconstruction due to mechanical obstruction of the afferent limb. It poses a dismal prognosis, especially in cases of local cancer recurrence. Standard surgical and endoscopic treatment is often unsatisfactory. Due to poor performance status, patients frequently require immediate and less invasive treatment. Transmural stenting with lumen-apposing metal stents/LAMS/ is a new alternative to surgery and transluminal endoscopic treatment. We present our single-center experience in the management of malignant afferent loop syndrome/MALS/ with endoscopic ultrasound-guided gastroenterostomy/EUS GE/.

Aims & Methods

To evaluate the efficacy and safety of EUS GE in malignant afferent loop syndrome in cases of emergency.Methods: Two cases of MALS and severe cholangitis,managed by EUS GE in a single tertiary center.

Results

Patient 1: In the first case, a 39-year-old patient was referred to our center for recurrent episodes of severe cholangitis. He had a previous gastrojejunostomy in a different hospital, as chronic pancreatitis was suspected. After evaluation of the patient, a locally advanced pancreatic cancer with peritoneal carcinomatosis was found. Due to the poor performance status and after multidisciplinary discussion, we performed a single-step EUS GE with HOT AXIOS 15mm/10mm/Boston Scientific Marlborough, Massachusetts, USA /. After the procedure, there was complete resolution of symptoms of cholangitis and the patient started palliative chemotherapy. The patient died 56 days after the procedure due to disease progression.
Patient 2: 57 years old male, who underwent a Whipple procedure due to pancreatic cancer in 2022. During follow - up local recurrence was found. He was admitted with signs of severe cholangitis with renal and respiratory failure. Computed tomography revealed an extremely dilated afferent loop. An EUS GE was performed with,, off - label,, application of HOT SPAXUS 8mm/20mm/Taewoong/. After the procedure, the septic state was resolved, and shortly after discharge, the patient continued with regular courses of systemic chemotherapy. There are no episodes of recurrence during the current follow-up/210 days after the procedure/.
In both cases, there were no events of misdeployment. We found clinical success in both patients with fast resolution of symptoms due to cholangitis. No episodes of recurrence were found during follow-up. We didn't experience any adverse events/AE/ during either procedure, with no AE in the postprocedural period. The mean procedure time was 20 minutes. In both cases, an electro-cautery enhanced lumen apposing metal stent was used, which allowed us to create a single-step endoscopic anastomosis and obtain an internal drainage of the dilated afferent loop into the stomach.

Conclusion

Endoscopic ultrasound-guided gastroenterostomy offers a highly efficient, convenient, and safe alternative for patients presenting with malignant ALS. In our cases, no need for reintervention was found. It could be offered as a fast approach to selected patients, especially those unfit for surgery and with poor performance status.

Disclosure

No conflict of interest

Introduction

Volatile organic compounds (VOC) in stool samples may reflect functional activity of gut microbiome. Previous studies showed that gut flora may influence transient relaxations of lower esophageal sphincter through short-chain fatty acids production and thus - participate in pathogenesis of gastroesophageal reflux disease (GERD). However, the role of VOC in pathogenesis of GERD is poorly studied yet.

Aims & Methods

The aim of this study (FGMF-2025-0003) was to perform correlation analysis between concentrations of VOC in stool samples and GERD-Q score.
We enrolled willing to participate patients referred to perform multichannel 24-h pH-impedance recording (Ohmega, Laborie). According to the Lyon 2.0 criteria patients were allocated to the GERD or the control group. GERD-Q questionnaire was filled in by the participants on the same day as stool samples were collected. Thermo TSQ 8000 triple quadrupole mass-spectrometer (GC/MS) was used for the measurement of VOCs in stool samples were analyzed with. Correlation analysis (Spearman rank R) was performed between values of 80 VOCs in stool samples and the results of GERD-Q questionnaire.

Results

Data of 76 patients were eligible: 42 with GERD and 34 - of the control group. Participants in the GERD group were older (54.7±12.2 y.o. vs 46±14.9 y.o., P<0.05) and their BMI was greater (30.9±5.2 vs 27.2±6.5 kg/m², P<0.05). GERD-Q score was logically greater in GERD group (11.0±2.5 vs 5.2±1.2, p<0.01). Correlation analysis revealed significant correlations between GERD-Q score and concentrations of 2-methylbutyric acid (Spearman R =-0.31), caproic acid (0.34) and enantiic acid (0.396) in stool samples.

Conclusion

GERD-Q score positively correlates with concentrations of Caproic acid (0.34) and Enantiic acid (0.396) in stool samples and negatively – with 2-Methylbutyric acid. The data of this pilot study may serve as a basis for further research on the role of functional activity of gut microbiome in pathogenesis of GERD.

Clinical Case Summary

A 67 old male patient with Hx of DM, HTN, IHD and previous repair of paraumbilical hernial defect. He had history of multiple previous ERCP with difficult stone extraction and stent placement to secure biliary drainage.
He presented with fever and abdominal pain mainly at re-herniated defect at paraumbilical region. By examination we found ulcerated skin over the hernial sac with a small foreign body protruding from it. He was sent for radiology and performed abdominal CT examination which commented on a mispositioned/slipped biliary stent along with CBD dilatation. Initial labs showed elevated TLC and bilirubin. he admitted that he neglected the instructions to make an appointment for stent exchange after 3 months as he was told after the last ERCP 2 years ago.
Surgical consultation was done to inspect the ectopic stent, they removed it and recommended for follow up of the fistulous opening only as the CT didn't show serious injuries or any abdominal free fluid.
The ectopic stent was impacted inside an intestinal loop inside the hernial sac and couldn't take the natural pathway out of the body with the excreta.
When we saw the slipped stent that punctured its own way out through the hernia out of the patient's body, we thought that this strange finding was the only surprise that the patient can give us.
Patient was planned for ERCP to secure biliary drainage.
After cannulation while performing ERCP, the cholangiogram revealed another surprise, The patient had another hidden stent, an internally migrated one.
It was removed by balloon sweeping and another new double pigtail stent was inserted to ensure more stability.
Upon our request we brought the previous ERCP reports to be revised. We found that the last procedure 2 years ago reported a missed stent already and he put a new one. This means that the hernial stent was the older slipped one and kept in place for this whole time till it decided to get out and the newer stent was internally migrated.

Clinical Case Summary

A 45 y/o female patient complained from fatigue and dyspnea, her CBC showed MHA (Hb 6.5 g/dl, MCV 62 fl/cell) with normal WBCs and PLTs and she denied any apparent bleeding or menstrual abnormalities. Upon investigating, her virology profile was negative, she had +ve FOB, low levels of iron (25.6 ug/dl), low ferritin (10.3 ng/ml) and high Reticulocyte count (3.5%). She underwent upper and lower GI endoscopies without significant findings. She received packed RBCs to correct her general condition but the symptoms recurred. Repeated upper and lower endoscopies didn’t show any source of bleeding. Capsule enteroscopy was ordered and showed multiple red spots, dilated vessels and small varices. We thought of angiodysplasia so we ordered CT enterography but the scan couldn’t detect vascular abnormalities in small intestinal wall and showed an aneurismal dilation at portal vein confluence (3x3.7cm) along with dilated both portal vein and splenic vein. The interventional radiology team described the aneurysm as fusiform not saccular, so it wasn’t suitable for coiling and embolization.
Portal vein aneurysm (PVA) was discovered incidentally in this case. The turbulence of the portal blood flow is believed to be causing congestion in the drained intestinal segments. As a result, we found the described spots and dilated vessels in the jejunum. DBE was suggested to apply APC to the telangiectatic spots, but this won’t address the dilated veins that’s why we preferred consulting intervention radiology to deal with both the intestinal lesions and the aneurysm itself as the main cause of this condition, but unfortunately no definitive intestinal lesions were seen in the angiography CT and the aneurysmal anatomy wasn’t suitable for intervention, also endovascular surgical consultation declined the portal vein reconstruction possibilities due to the difficulty and procedural risks. We advised the patient to continue on supportive treatment and blood transfusion when needed.

References

Kurtcehajic, A., Zerem, E., Alibegovic, E., Kunosic, S., Hujdurovic, A. and Fejzic, J.A., 2023. Portal vein aneurysm-etiology, multimodal imaging and current management. World Journal of Clinical Cases, 11(4), p.725.

Clinical Case Summary

The endoscopic removal of polyps located at the appendiceal orifice is a challenge, particularly when extending inside the appendiceal lumen, due to its anatomic difficulty and risk of complications.
The endoscopic full-thickness resection (FTR) technique has become an non-surgical option for these lesions but with a non negligible risk of appendicitis.
With the present case we explore an alternative technique.
A 75-year-old man with iron deficiency anemia underwent upper digestive endoscopy and colonoscopy.
The upper digestive endoscopy was normal.
In the colonoscopy angiectasias were found in the cecum and multiple polyps in the left colon (the largest measuring 30 mm). The inspection of the appendix revealed an intra-appendiceal orifice lesion (Image A).
Only after inversion of the appendix it was possible to accurately assess the lesion: an approximately 15 mm sessile polyp (Images B, C).
We applied argon plasma for ectasias ablation and removed the left colon polyps by endoscopic mucosal resection.
Intra-appendiceal orifice polyp resection was performed underwater with a diathermic loop (Image D), with no immediate or late complications.
Histology revealed a sessile serrated adenoma with low-grade dysplasia.
The described technique, being a simpler, faster and cheaper option than the endoscopic-FTR is a valid and a cost effective one.