Introduction

Cholecystectomy (CCE) is commonly performed for treatment of gallstone disease. However, CCE may result in post-CCE syndrome (PCS) and diarrhea (PCD) in a subgroup of patients. In addition, epidemiological association of CCE with colorectal cancer (CRC) and metabolic-associated fatty liver disease (MAFLD) has raised concerns. CCE is expected to affect the enterohepatic circulation and result in gut microbiome changes. Such changes may account for clinical symptoms and risk for CRC and MAFLD. However, the spectrum and type of gut microbiome changes post-CCE has not been fully quantified and results have been inconsistent.

Aims & Methods

This systematic review aimed to clarify the effect of CCE on gut microbiome composition and the clinical impact. A systematic search was conducted on PubMed, Web of Science and Scopus in March 2024, combining keywords such as “cholecystectomy” or “post-cholecystectomy” with “gut microbiome” or “gut dysbiosis”. Reference and citation searches were conducted on included articles. Original articles irrespective of study design that described gut microbiome changes post-CCE were included. Articles were independently reviewed by two authors and data were extracted and synthesized using narrative review. The quality of studies was assessed using the Newcastle-Ottawa scale.

Results

A total of 1373 articles (after excluding duplicates) were initially selected, and after review of the titles and abstracts, 14 eligible studies were identified and the full text reviewed. There were 3 prospective cohort and 11 cross-sectional/ case control cohort studies, of which 13 examined the bacteria microbiome using 16S rRNA gene sequencing, and 1 cross-sectional study examined the fungal microbiome using ITS1 rDNA gene sequencing. Changes in microbiome diversity indices and relative abundances were inconsistent. Among 3 prospective cohort studies, an increase in phylum Bacteroidetes was observed in a study with post-CCE interval more than 3 months, but not in the study with 3-month post-CCE interval. One study reported no change at the phylum level, but an effect for the class Clostridia and the orders Clostridiales and Coriobacteriales within 3 days of CCE. An increase in phylum Bacteroidetes post-CCE was also seen in 3 other cross-sectional studies. Five studies attempted to correlate post-CCE microbiome changes with symptoms. A decreased Firmicutes/ Bacteroidetes (F/B) ratio was observed in patients with PCS/ PCD in 3 out of 5 studies. Although changes in relative abundances of taxa correlated with symptoms, these were inconsistent, with an increase in genus Prevotella being the only common finding in 2 out of these 5 studies. Other significant observations post-CCE included a decrease of the potentially beneficial genus Faecalibacterium and an increase in the opportunistic pathogen Escherichia/Shigella, as well as an attenuated aging-associated intestinal microbiota. The single cross-sectional study that examined post-CCE fungal microbiome changes found that the relative abundance of Candida glabrata and Aspergillus were enriched, and Candida albicans was depleted.

Conclusion

CCE is associated with significant changes in gut microbiome diversity and relative abundances of taxa. Such changes have been correlated with clinical symptoms. These microbiome changes may potentially explain the risk of CRC and MAFLD noted in epidemiological studies. Discordant results between studies may relate to differences in patient populations and study methodologies.

Introduction

Observational studies have associated cholecystectomy with cardiometabolic disorders and colorectal cancer. This is of clinical importance as the case volume of cholecystectomy has increased exponentially and cardiometabolic disorders pose a significant health burden. Understanding post-cholecystectomy gut microbiome changes may help clarify some of these observations. Published data on cholecystectomy-related gut microbiome changes are limited and mainly cross-sectional in study design, lack adequate taxonomic resolution or prediction of functional pathways as 16S rRNA sequencing rather than shotgun metagenomics sequencing was used, and observed microbiome changes have not been correlated with concomitant changes in the metabolome¹.

Aims & Methods

This exploratory prospective cohort study aimed to examine the changes in gut microbiome and systemic metabolome post-cholecystectomy. Subjects aged 21 to 65 years undergoing cholecystectomy for treatment of symptomatic gallstone disease were enrolled. Exclusion criteria included the use of antibiotics or probiotics within one month, appendicectomy, bowel surgery and inflammatory bowel disease. Biospecimens (stool, plasma and urine) were collected at baseline and one-month post-cholecystectomy. Stool microbiome was analysed by shotgun metagenomics sequencing, with assessment of 𝜔² effect size (derived from weighted Jaccard distance), α (Mann-Whitney U test for unpaired and Wilcoxon signed-rank test for paired tests) and β diversity indices (PCoA and PERMANOVA), as well as differentially abundant bacterial taxa and functional pathways (Maaslin2 R package, using false discovery rate [FDR] < 0.1). Systemic metabolome (plasma, stool and urine) was examined by targeted liquid chromatography-mass spectrometry, and Orthogonal Partial Least Squares Discriminant Analysis was performed to identify metabolites that were different post-cholecystectomy, using paired t-tests and FDR < 0.1. Correlation analysis of changes in stool microbiome and metabolome was performed.

Results

A total of 26 subjects were enrolled. The mean age was 47 years (12), with 62% (16/26) male and mean body mass index (BMI) 25.57 kg/m² (3.75). Other clinical meta-data were smoking in 15.4% (4/26), alcohol consumption in 11.5% (3/26), use of proton pump inhibitors (PPI) in 7.7% (2/26), statins usage in 23.1% (6/26), and presence of fatty liver in 15.4% (4/26). The microbiome profile of the enrolled cohort was similar to matched asymptomatic controls with intact gallbladder (with or without gallstones). One-month post-cholecystectomy, the 𝜔² effect size was 0.006 (80% power, α < 0.05). Significant differences were observed for β diversity indices after controlling for drinking status, presence of fatty liver and use of PPI. There were 32 differentially abundant bacterial taxa and 124 differentially abundant functional pathways. Analysis of observed microbiome and systemic metabolome changes revealed correlation of 9 species with plasma bile acid (chenodeoxycholic acid [CDAC]), 20 species with plasma lipids, 3 species with stool bile acids (CDCA), 9 species with stool carboxylic acids and 2 species with urinary trimethylamine N-oxide.

Conclusion

Cholecystectomy resulted in significant changes in the stool microbiome and systemic metabolome. Such changes may help explain the epidemiological association with cardiometabolic disorders. Further larger scale prospective cohort studies with longer duration of follow-up are needed to confirm these observations.

References

1. Ang TL, Koo SH, Ang D, Tan CK, Wang LM, Wong SH, Chow PKH. Postcholecystectomy Gut Microbiome Changes and the Clinical Impact: A Systematic Review With Narrative Synthesis. J Gastroenterol Hepatol. 2025 Mar;40(3):574-583.

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.

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

Percutaneous transesophageal gastrotubing (PTEG) was established as an alternative route to access the gastrointestinal tract for the patients that Percutaneous Endoscopic Gastrostomy was contraindicated. PTEG will be an ideal method of tube feeding for the patients without indication of PEG.

Aims & Methods

The aim of this study is to evaluate the clinical usefulness of PTEG for the patients who need tube feeding. A rupture-free balloon (RFB) catheter is inserted into the upper esophagus. Percutaneous balloon puncture with a specialized needle is then performed from the left side of patient’s neck under ultrasonographic control. A guide wire is inserted through the needle into the RFB, followed by a dilator and sheath. A placement tube is then inserted through the sheath, and the sheath is removed. Double Balloons equipped Over tube type RFB were used instead of primary RFB in thirty-five cases that the puncture needle is punctured into the over tube trough the balloon. We perform PTEG in a total of 115 patients (78 men and 37 women, mean age 77.7 years) in whom PEG was not feasible for nutrition. Sixty-one patients had prior gastrectomy , 30 patients had gastric herniation into the thoracic cavity , 6 patients had there stomach located behind the colon , 4 patients had ventriculo-peritoneal shunt tube in front of the stomach and 4 patients had peritoneal carcinoma.

Results

Satisfactory results were achieved in all 115 patients. Median follow-up was 322.0 days. There were no patients who needed a nasogastric tube after PTEG. Seven of 115 patients were able to free from tube feeding due to PTEG tube feeding support. About the complications, there was 1 patient with severe bleeding requiring blood transfusion, one patient had tracheal penetration, which was managed conservatively. Other complications were minor oozing bleeding in seven patients that did not require blood transfusion, subcutaneous emphysema in two patients, which were managed conservatively. Complication rate was 10.4%. No patient required surgical treatment or died after PTEG.

Conclusion

PTEG is feasible, safe, and useful　for long-term nutrition for the patient who is contraindicated to PEG. PTEG may become the only procedure of the liberation from nasogastric tube for the patient who is contraindicated to PEG PTEG is the ideal solution for the patients with PEG contraindicated in the tube feeding.

Disclosure

Nothing to disclose

Introduction

Capsule endoscopy is the first-line examination for digestive bleeding with likely origin in the small bowel, in hemodynamically stable patients. In the 2022 update, ESGE guidelines recommend that, in the context of overt bleeding, capsule enteroscopy should be performed as soon as possible, ideally within the first 48 hours. In the previous guidelines, published in 2015, the recommended window was 14 days.

Aims & Methods

This study aimed to evaluate the improvement in yield offered by the new recommendations regarding the timing of urgent capsule enteroscopy. Patients with suspected overt middle gastrointestinal bleeding between January 2005 and November 2022 were retrospectively analyzed. Diagnostic and therapeutic yield, rebleeding rate, and mortality were compared when capsule enteroscopy was performed within the first 48 hours, within the first 14 days, or between the 3rd and 14th day after admission.

Results

A total of 138 patients were included (58.7% men, median age 66 years), 87 of whom (63.0%) underwent capsule enteroscopy within the first 48 hours after hospital admission. The median follow-up was 55 months (5-180). The diagnostic yield (presence of blood or lesions with bleeding potential) was slightly higher when capsule enteroscopy was performed within the first 48 hours (81.6% versus 76.5%, p=0.349). On the other hand, capsule enteroscopy within the first 48 hours was significantly associated with higher therapeutic yield (endoscopic, radiologic, or surgical treatment) - 54.0% versus 39.2%, p=0.02. The rebleeding rate was significantly lower in patients undergoing enteroscopy within 48 hours after admission (19.5% versus 29.4%, p=0.04). On the other hand, overall mortality at 36 months did not differ between strategies (21.8% and 25.5%, p=0.401).

Conclusion

Performing capsule endoscopy within the first 48 hours, as recommended by recently published guidelines, is associated with favourable short- and long-term clinical outcomes.