Introduction

A good bowel preparation for colonoscopy is fundamental to improve the quality of the examination, reduce procedural complications and achieve optimal polyp detection. Among possible strategies to enhance bowel preparation, visual booklets have been proposed with conflicting results. Therefore we aimed to perform a systematic review with meta-analysis of randomized controlled studies (RCT) to ascertain whether booklets may be useful in this setting.

Aims & Methods

Literature search was performed in July 2022, in main databases (PUBMED, SCOPUS, ScienceDirect, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov). only RCTs were selected. The primary outcome was the quality of bowel preparation. Further outcomes were the adenoma detection rate (ADR), number of polyps detected per patient, rate of cecal intubation, time of insertion and withdrawal, adverse events, willingness to repeat preparation and colonoscopy. We estimated odd ratios (OR) for dichotomous outcomes. mean differences (MD) or standardized mean differences (SMD) were used for continuous outcomes. We estimated heterogeneity among studies with the Chi2 (Cochran Q) and the I2 statistics. In case of high heterogeneity, a random effect model was used, otherwise a fixed effects model was preferred. All analyses were performed using RevMan version 5.4.1.

Results

Six studies were selected, enrolling overall 1755 patients (857 in the booklet and 898 in the control group). Adequate bowel preparation was achieved in the 86.7% (743 out of 857) of booklet preparation versus the 77.5% (696 out of 898) in the control group, with an OR of 2.31 in favour of booklet (95% CI 1.20-4.45, p = 0.01). Booklet was more effective than control in the transverse colon (MD = 0.37, 95% CI 0.01-0.72, p = 0.03), while no differences were found in right colon and left colon. In four studies a 4-L PEG-based preparation was used and the pooled analysis did not find any difference compared to controls, while when sodium phosphate and magnesium citrate or sodium phosphate or PEG were used, preparation with booklet was better than in controls (OR = 5.10, 95% CI 1.82-14.27, p = 0.002). Two studies were performed in inpatient setting, without difference between booklet and controls while in outpatients patients receiving booklets were better prepared than controls (OR = 7.13, 95% CI 5.39-9.45, p < 0.001). ADR was similar between the two groups, with an OR = 0.93 (95% CI 0.75-1.16, p = 0.53). The mean number of polyps per patient did not differ between the two groups (MD = 0.22, 95% CI -0.14-0.58, p = 0.23).

Conclusion

The present meta-analysis demonstrated that booklets are useful to enhance bowel preparation. Outpatients and non PEG-based preparations seem to benefit more from booklets, while no effect on ADR has been observed.

Introduction

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, predominantly diagnosed in patients with chronic liver diseases. The absence of specific biomarkers and the typically asymptomatic progression of the disease lead to delayed diagnosis. Patients with liver disease, including HCC, exhibit alterations in the gut microbiome and increased bacterial permeability, factors that may influence disease progression and patient outcomes. In recent years, there has been a growing interest in exploring circulating microbiome signatures as potential indicators of liver disease stutus, providing a new avenue for understanding HCC.

Aims & Methods

Aims: To identify the signatures of the circulating blood microbiome associated with hepatocellular carcinoma, response to treatment and disease prognosis.
Methods: This study conducted a post-hoc analysis of the SORAMIC clinical trial utilizing peripheral blood plasma samples. For this analysis, blood plasma samples from a cohort of 71 patients with HCC were examined (25 treated with Sorafenib and 46 with SIRT/Sorafenib). Peripheral blood samples were collected at two time points: baseline (prior to the initiation of anti-tumor therapy) with all 71 patients included, and post-therapy (7 to 9 weeks after treatment) with 39 patients included. Additionally, peripheral blood samples were obtained from 52 control subjects, who were endoscopically diagnosed with colonic diverticulosis, to compare against the patient group. The composition of the circulating blood microbiome was assessed through 16S rRNA gene sequencing, targeting the V1-V2 hypervariable regions. Subsequent analyses focused on identifying associations with potential novel biomarkers for diagnosis, prognosis, and response to treatment.

Results

Patients with HCC had significantly diminished α-diversity of the circulating blood microbiome as compared to controls. Significant differences were also observed in between microbial communities of these two cohorts based on Bray-Curtis dissimilarity index. Patients with HCC had significantly higher levels of Proteobacteria and Bacteroidetes and lower levels of Firmicutes and Campylobacterota. Differential abundance analysis revealed that families of Gordoniaceae, Cryomorphaceae, Burkholderiaceae, Comamonadaceae, Enterobacteriaceae were significantly enriched in patients with HCC. At the genus level, patients with HCC had higher levels of Gordonia, Fluviicola, Burholderia, Limnohabitans and Escherichia/Shigella and lower levels of Corynebacterium. HCC patients, who responded to treatment with SIRT/Sorafenib showed an increase in blood bacterial diversity, enrichment of families Burkholderiales incertae sedis, Arcobacteraceae, Peptostreptococcaceae, Moraxellaceae, genera Sphaerotilus, Aliacrobacter, Rhodoluna, Giesbergeria, Microbacterium, Romboutsia, Arcicella, Pseudorhodoferax and depletion in families Gordoniaceae, Cryomorphaceae and genera Cloacibacterium, Gordonia, Limnohabitans, Fluviicola after the treatment. Levels of Acinetobacter, Enhydrobacter and Micrococcus in the blood before the HCC treatment were associated with patient prognosis.

Conclusion

Patients with HCC exhibit a unique circulating blood microbiome profile characterized by reduced bacterial diversity. Response to treatment is linked to an increase in α-diversity and changes in the circulating microbiome profile. Specific members of the circulating microbiome show potential prognostic capabilities, suggesting their utility as biomarkers for predicting disease progression and treatment outcomes in HCC.

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

Clinical Case Summary

Management of bleeding GIST is challenging, especially in metastatic disease. Emergent surgery for bleeding GIST lesions has a high rate of morbility and mortality in comparison to elective procedures (1). A safe and accurate method to obtain a permanent hemostasis is needed. Several endoscopic procedures are available although with limited efficacy due to the complex neoangiogenesis of these tumours that remains out of reach of contact endoscopic techniques (2). EUS-guided therapy of bleeding GIST injecting cyanoacrylate or ethanol has been published. After one adverse event of spurting bleeding after EUS-guided injection of cyanoacryalte, our group first reported the EUS-guided coil puls cyanoacrylate injection therapy for bleeding GIST in two patients (3). We report our experience in five consecutive cases of bleeding GIST successfully treated under EUS-guidance (Table 1). Given the rich network of arteries in some cases, we aim to deploy coils into de tumor .
One adverse event was observed. An intratumoral bleeding after the punction of a 22G needle, successfully managed by EUS-guided deployment of a coil plus CYA. The clinical outcome in these five patients was uneventful until scheduled surgery was performed or palliative therapy in the fifth patient with a metastatic GIST with oncologic progression disease.

CASE	AGE	LOCALZATION SIZE OF THE ARTERY	CLINICAL PRESENTATION	EUS-GUIDED PROCEDURE NEEDLE CYANOACRYLATE/COILS	ADVERSE EVENTS	CLINICAL OUTCOME SCHEDULED SURGERY
1	82	Duodenal Bulb 2 mm	Recurrent melena Two unsuccessful endoscopic injection and clipping therapy	22 gauge 1 mL CYA	None	Uneventful 4 years
2	72	Fundus 5 mm	Hematemesis and hypovolemic shock	22 gauge 1 mL CYA 19 gauge 1 coil (6 mm/20cm long) 2 mL CYA	Bleeding after injection of 1 mL CYA Hemostasis after deployment of 1 coil and 2 mL CYA	Uventful 3 years
3	79	Fundus 4 mm	Hematemesis and hypovolemic shock	19 gauge 1 coil (6mm/14 mm long)	None	Uneventful
4	43	Fundus 3 mm	Melena	19 gauge 3 coils (3 mm/14cm long) 2 mL CYA	None	Uneventful 2 years
5	63	Body Metastatic GIST with oncologic progressiion Several 4 mm arteries	Hypovolemic shock	19 gauge 1 session: 5 coils (14mm/14 cm long) plus 2 mL CYA 2 session (anemia): 6 coils (6 mm/14 cm) plus 1 mL CYA	None	Uneventful on palliative care 6 weeks

EUS-guided therapy of bleeding GIST was effective in these five cases and could be another safe and accurate endoscopic procedure in bleeding GIST aiming to obtain hemostasis until scheduled surgical therapy is carried out or as palliative therapy. In these cases there were not observed recurrent bleeding in spite of a rich network of arterial vessels.

References

(1) Liu Q, Kong F, Zhou J, et al. Management of hemorrhage in gastrointestinal stromal tumors: a review. Cancer Manag Res. 2018;10:735-43.
(2) Venezia G, Asnaghi G, Manca A, et al. Successful use of Hemospray as a bridge to surgery in life-threatening bleeding from a gastrointestinal stromal tumor of the stomach. Endoscopy 2016;48:E232-E233.
(3) Romero-Castro R, Jimenez-Garcia VA, Irisawa A, et al. Endoscopic ultrasound-guided angiotherapy in bleeding gastrointestinal stromal tumors with coil deployment and cyanoacrylate injection. Endoscopy. 2021;53(4):E124-E5.

Disclosure

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

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a widespread chronic liver condition closely associated with obesity, insulin resistance, and dyslipidemia. Recent evidence points to gut microbiota dysbiosis as a key player in MASLD pathogenesis, affecting intestinal barrier function and systemic inflammation.

Aims & Methods

The aim was to investigate gut microbiota composition in patients with MASLD and assess its association with disease progression and gut barrier dysfunction. A total of 152 MASLD patients and 150 matched controls without liver pathology were examined. Diagnosis was confirmed by ultrasound and steatometry, alongside assessment of cardiometabolic risk factors. Gut microbiota composition was analyzed using real-time PCR, focusing on Bacteroidetes, Firmicutes, and Actinobacteria. Hydrogen breath testing was used to diagnose small intestinal bacterial overgrowth (SIBO), and the presence of Akkermansia muciniphila was evaluated as a marker of gut barrier integrity.

Results

MASLD patients demonstrated a significant increase in Firmicutes (50.3%) and Actinobacteria (15.3%) proportions compared to controls, with a higher Firmicutes/Bacteroidetes (F/B) ratio. SIBO was detected in 52% of MASLD patients versus 40.5% in controls (p<0.05). The presence of Akkermansia muciniphila was notably lower in MASLD patients (33%) compared to controls (63%), suggesting impaired gut barrier function. Strong positive correlations were observed between Actinobacteria abundance and the F/B index (r=0.75, p<0.05), while Akkermansia muciniphila presence negatively correlated with MASLD development (r=–0.69, p<0.05).

Conclusion

Gut microbiota dysbiosis, characterized by elevated Firmicutes and Actinobacteria and reduced Akkermansia muciniphila, is closely associated with MASLD pathogenesis. The findings highlight the potential of microbiota-targeted interventions for improving gut barrier function and modifying disease progression in MASLD patients.

Introduction

Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative strategy for chronic hepatitis B (CHB), but data on optimal biomarkers for post-treatment monitoring is limited.

Aims & Methods

With the aim to investigate whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR), this retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase (ALT) > 80 U/L with recurrent viremia. During follow-up, serum HBcrAg was evaluated as a time-varying variable in the Cox proportional hazard model.

Results

The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.1% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5-40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7-67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1% ‐ 62.4%). Time-varying HBcrAg levels were a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.43 per log U/mL; 95% CI, 1.16-1.76) in the multivariable model adjusted for EOT HBsAg level, anti-HBe antibody, and EOT ALT. During follow-up, HBcrAg < 1,000 U/mL predicted a low risk of subsequent CR (aHR, 0.31; 95% CI, 0.17-0.57).

Conclusion

Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be used to guide posttreatment monitoring.

References

1. Mak LY, Wong DK, Cheung KS, Seto WK, Lai CL, Yuen MF. Review article: Hepatitis B core-related antigen (HBcrAg): an emerging marker for chronic hepatitis B virus infection. Aliment Pharmacol Ther. 2018;47(1):43-54.
2. Hsu YC, Nguyen MH, Mo LR, Wu MS, Yang TH, Chen CC, et al. Combining hepatitis B core-related and surface antigens at end of nucleos(t)ide analogue treatment to predict off-therapy relapse risk. Aliment Pharmacol Ther. 2019;49(1):107-15.
3. Sonneveld MJ, Park JY, Kaewdech A, Seto WK, Tanaka Y, Carey I, et al. CREATE Study Group. Prediction of Sustained Response After Nucleo(s)tide Analogue Cessation Using HBsAg and HBcrAg Levels: A Multicenter Study (CREATE). Clin Gastroenterol Hepatol. 2022 Apr;20(4):e784-e793

Introduction

The outcome of ESD in early gastrointestinal neoplasia in Japan is well established. However, in the west, ESD practice is variable given different disease prevalence in UGI tract and also the volume and experience of each centre.

Aims & Methods

We aim to evaluate ESD practice and outcomes in the UK and hence, multi centre registry was set up. This is a prospective observational study for patients undergoing ESD for early GI neoplasia. All technical and outcomes data was prospectively collected onto REDCap.

Results

There were 451 UGI ESD cases recruited between August 2016 to August 2023 from 6 large tertiary referral centres in the UK. Mean age of the patients was 70.8 years (range: 24-94 years) with male preponderance (318 males vs. 133 females). Majority were in oesophagus: 282 (62.53%), stomach: 159 (35.25%) and duodenum: 10 (2.22%).
Of 282 oesophageal ESDs, 277 (98.23%) were technically successful with en-bloc resection rate of 96%. There were 3 intraprocedural complications (2 oesophageal perforations and 1 oral laceration from overtube). All of them were managed endoscopically. There were 29 (10.28%) post ESD strictures requiring endoscopic dilatations. 3 (1.06%) delayed bleeding were noted and 3 were readmitted for decompensation of underlying co-morbidities.
There were 204/282 (72.34%) Barrett’s cases with average length of C3 M5 and mean size 34.5mm. 34 cases (16.67%) had previous ESD or ablation at the same site. Post ESD resection showed deep submucosal (SM) invasion in 21 patients (deep R0 achieved in 42.9% and lateral R0 in 76.2%), 23 pT1bSM1 (deep R0 in 87.0% and lateral R0 in 87%), 107 pT1a (deep R0 in 89.7% and lateral R0 in 85.1%), 31 high grade dysplasia (HGD) (R0 in 97%) and 9 low grade dysplasia (LGD) (R0 in 78%) as shown in Table 1.
There were 44 squamous cell carcinoma (SCC), 26 gastro-oesophageal junctional neoplasia and 8 others (submucosal lesion and granular cell tumours). Of 44 SCC, there were 8 pT1b (5 achieved deep R0, 7 achieved lateral R0), 10 pT1a (all achieved both deep and lateral R0), 22 HGD (81.8% achieved R0), 3 LGD (all achieved R0) as shown in Table 1.
There were 160 gastric ESDs with completion rate of 96.25% and en-bloc rate of 95.5%. There were 8 (5%) intra-procedural perforation which required endoscopic clippings. There were 7 (4.36%) delayed bleeds which were managed endoscopically. Of 160 cases, 138 were epithelial neoplasia, 11 were submucosal lesions while 4 were large hyperplastic polyps. As shown in Table 1, of 138 epithelial neoplasia, 10 had deep SM invasion (7 achieved deep R0, 8 lateral R0), 14 pT1bSM1 (7 achieved deep R0, 10 lateral R0), 50 pT1a (90% achieved deep R0, 80% lateral R0), 35 HGD (94.3% R0) and 27 LGD (77.8% R0).

	Deep SM invasion (n)	Deep R0 (%)	Lateral R0 (%)	pT1b SM1 (n)	Deep R0 (%)	Lateral R0 (%)	IMC (n)	Deep R0 (%)	Lateral R0 (%)	HGD (n)	R0 (%)	LGD (n)	R0 (%)
Barrett’s neoplasia	21	42.9	76.2	23	87.0	87.0	107	89.7	85.1	31	97.0	9	78.0
Oesophageal SCC	3	66.7	100.0	5	60.0	80.0	10	100.0	100.0	22	81.8	3	100.0
Gastric neoplasia	10	70.0	80.0	14	50.0	71.4	50	90.0	80.0	35	94.3	27	77.9
Table 1. Post ESD histology outcome in UGI tract

Conclusion

Unlike in the East, most ESDs in our study were performed in Barrett’s oesophagus rather than the stomach. Our data demonstrates the feasibility and safety of UGI ESD in Western setting with high en-bloc rate and low complication rates. We found that within indication of ESD, complete resection (R0) rate is high but lesions with deep submucosal invasion have poor R0 rate.

Disclosure

Professor Bhandari has received research grants or is the advisory board for Fujifilm, Boston, Olympus, Pentax, 3-D matrix, NEC (Japan), Medtronic.