Introduction

Endoscopic biliary drainage (BD) in patients with altered anatomy is a challenging scenario reducing the chance of clinical success compared to standard anatomy. The choice between different BD approaches is still not standardized and relies on local availability and expertise.

Aims & Methods

Aim of this study was to explore the type and the number of endoscopic BD approach in patients with altered anatomy in different Italian centers. This was a retrospective multicenter cohort study within the i-EUS network of biliopancreatic endoscopy. All adult patients with upper GI surgical altered anatomy who underwent endoscopic BD for any indication in the last 5 years were enrolled. Patients with Billroth-I or sleeve gastrectomy were excluded. Patients with duodenopancreasectomy were grouped with patients with BillrothII reconstruction for the statistical analysis. Fisher’s exact test and Mann-Whitney test were used when appropriate.

Results

21 centers participated in the study. All centers were equipped for interventional endoscopic ultrasound (EUS) whereas only 7 centers had also the availability of device-assisted enteroscopy (DAE). 428 patients were enrolled. Clinical and BD techniques characteristics of patients are described in table 1. Indication to BD was not different between patients with Billroth-II (B-II, N=263) or Roux-en-Y (RY, N=165) reconstructions. 16% of patients had at least one previous failed BD attempt. B-II anatomies were more frequently managed transpapillary with a duodenoscope or a forward viewing scope (85%), whereas in case of RY reconstruction BD approach was more heterogeneous. In 68% of RY cases endoscopic BD was performed with a luminal approach (in 43% of cases with standard scopes). In patients who underwent to EUS-BD, hepaticogastrostomy or antegrade stenting were performed in 74% of cases mostly for malignant indications (90%). Type of surgical reconstruction did not affect the clinical success (84% in BII and 79% in RY, p=ns). Interventional EUS demonstrated a higher clinical success compared to DAE (94% vs 73%, p=0.004). The total number of procedures to achieve clinical success was similar between B-II and RY patients. Patients who failed endoscopic BD for whom follow-up was available were managed by PTBD or surgery in 71% and 15% of cases respectively.

Conclusion

Endoscopic BD in altered anatomy has a sub-optimal clinical success compared to standard anatomy. A relevant proportion of patients requires more than one endoscopic attempt to achieve the clinical success. Despite the recent advent, interventional EUS is optioned in a significant proportion of patients and demonstrated a high efficacy in patients with surgically altered anatomy.

Introduction

Mirikizumab (MIRI) has shown promising results in ulcerative colitis (UC) based on the data from the pivotal clinical trials (LUCENT). However, these results still need to be validated in clinical practice.

Aims & Methods

This study aims to assess the short-term real-world effectiveness and safety of MIRI in patients with UC.
All patients with UC who received MIRI and without previous colectomy included in the prospectively-maintained ENEIDA registry were included. Clinical disease activity was assessed by partial Mayo score (pMS). The primary outcome was clinical remission (defined as pMS ≤2 with no subscore >1 and no rectal bleeding) at week 8 and 12, alongside its safety profile.

Results

A total of 171 patients from 43 Spanish hospitals were included (mean age of 49.5 years [SD 18], 54% male, median disease duration of 128 months [SD 97], 55% non-smokers, 62% extensive colitis. Concomitant therapy at baseline included 44% with steroids and 7.6% with immunosuppressants. Prior advanced therapies exposure was: 89% Anti-TNF, 69% vedolizumab, 54% ustekinumab, and 40% JAK inhibitors, with 54% exposed to > 2 mechanisms of action (MoA). At baseline patients had a median pMS 5 (IQR, 4-7) and faecal calprotectin of 557 ug/g (IQR, 120-1000). All but one patient started MIRI 300 mg iv every 4 weeks. Mean follow-up was 5.3 (SD 4.4) months. Clinical response and clinical remission at week 8 were 44% and 26%, respectively, and this increased up to 45% and 30% at week 12. Clinical remission rate at week 12 was higher among those with prior exposure to 1 MoA vs 2 or more than 2 (65%, 25%, 27% respectively, p=0.04, p=0.02). Previous exposure to ustekinumab was associated with a numerically lower, not statistically significant, rate of clinical remission at week 12 (28% vs. 38%, p=0.4). Faecal calprotectin significantly decreased at week 12 (160 ug/g [IQR, 54-852], p=0.001). The overall hospitalization and colectomy rates were 5.8% and 1.7% respectively. MIRI was generally well tolerated, with 10% of patients reporting at least one adverse event, but only one of them categorized as severe.

Conclusion

MIRI demonstrated its real-life effectiveness in the short-term, even in a highly-refractory cohort. Prior advanced therapy exposure to more than one MoA significantly impacts the effectiveness of MIRI during the induction. Safety was consistent with the known profile of this drug.

Introduction

Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass. Primary sarcopenia is associated with aging, while secondary sarcopenia is caused by various factors, including inflammatory conditions such as inflammatory bowel disease (IBD). The complex interaction between inflammation, intestinal dysbiosis, and malnutrition in IBD patients is referred to as the gut-muscle axis. High levels of cytokines and intestinal dysbiosis in IBD activate pathways that disrupt muscle protein synthesis. However, molecular and microbial mechanisms of sarcopenia in IBD are not extensively studied as well as therapeutic approaches.

Aims & Methods

A murine model of DSS-induced colitis was used. To detect sarcopenia, physical performance assessment on a rotarod was conducted. In this model, muscle was studied using immunohistochemistry, fiber counting per field, and cross-sectional area evaluation. Subsequently, intestinal microbiota and serum LPS detection were assessed. Additionally, an in vitro model of muscle cells was created using the immortalized murine cell line C2C12. Cells were exposed for 30 Min and 6 h to treatments including exposure to pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6), lipopolysaccharides (LPS), drugs (Infliximab, Upadacitinib, Tofacitinib), and probiotics (L. plantarum, L. rhamnosus).

Results

The murine model showed decreased body weight and muscle function alongside increased expression of muscle atrophy markers (myostatin and Murf-1) in colitic mouse muscle. Furthermore, there was an upregulation of the STAT3-pSTAT3 pathway associated with muscle wasting and a decrease in pAKT, a pathway associated with muscle growth. Surprisingly, DSS-induced colitis in mice resulted in intestinal dysbiosis characterized by reduced Roseburia genus and increased Sutterella, Turicibacter, and Bacteroides in the DSS group, as well as increased serum LPS levels.
In vitro, Upadacitinib and Tofacitinib, in the presence of inflammatory cytokines, reduced the expression of pathways associated with muscle atrophy (STAT3, pSTAT3, and NFκB) and increased pAKT expression, a protein associated with muscle synthesis. When cells were treated with LPS, NFκB expression did not decrease with the addition of the drugs, suggesting that LPS can activate NFκB independently of the JAK/STAT pathway.
Treatment with probiotics reduced STAT3 and pSTAT3 signals, suggesting potential positive modulation by all probiotics.

Conclusion

These data open new avenues for the gut-muscle axis as a promising research area for managing sarcopenia in IBD. Considering microbiota and LPS along with inflammatory cytokines may provide a more comprehensive understanding, especially as LPS-induced signaling appears to be only partially controlled by drugs and potentially positively influenced by probiotics.

Introduction

​​​​​PSC is chronic infammatory disease of bile ducts leading to strictures of bile duct and eventually to liver cirrhosis. Chronic inflammation is associated with markedly increased risk of cholangiocancer (CCA). In addition, gall bladder abnormalities are common in patients with PSC¹ such as cholecystitis, gallstones, polys and gallbladder carcinoma (GBCA). Increased fasting gallbladder volume has been reported with normal gallbladder emptying². Due to the increased risk of GBCA³ cholecystectomy is recommended in PSC with gallbladder polyps ≥8 mm and smaller polyps growing⁴. However, cholecystectomy has been associated with impaired PSC outcome. A study consisting of 11 PSC patients with cholecystectomy suggested protective role of gallbladder based on MRCP changes and elevated AST levels in patients with cholecystectomy. No significant difference in serum bile acids was observed in patients with or w/o cholecystectomy⁵. Another small study including five PSC patients with cholecystectomy showed that cholecystectomy was associated with worse Mayo scores and an elevated FIB4⁶. More than 50% of PSC have enlarged gallbladder which is suspected to be caused by hyperpressure in the biliary tract⁵. Cholecystectomy may thus eliminate this reserve function and lead to progression of bile duct strictures.

Aims & Methods

To evaluate the impact of cholecystectomy on liver enzyme levels, biliary bile acid composition, bile duct disease progression, and overall outcomes in a large PSC patient cohort, we analyzed data from 1,009 individuals enrolled in the prospective Helsinki PSC registry. Of these, 114 patients (11.3%) had undergone cholecystectomy—34 prior to and 80 following the PSC diagnosis. Patients with gallbladder cancer were excluded. Clinical and laboratory parameters were collected, along with data on disease progression based on sequential ERC examinations scored by the Helsinki ERC score⁷. Additionally, bile composition was analyzed in a subgroup of 157 patients receiving UDCA therapy, 32 of whom had undergone cholecystectomy.

Results

Demographics, liver function tests, and outcomes stratified by cholecystectomy, are presented in the table. We found no differences between the three groups (no cholecystectomy, cholecystectomy done prior or after PSC dg) regarding the progression of bile duct disease or its severity, liver function tests, development of biliary dysplasia or need for dilatation, Mayo- and MELD-scores. The cumulative incidence of the composite end point (= transplantation, liver related death, HCC or CCA) did not differ between groups. The molar-% of phospholipids were lower and cholic acid and deoxycholic acid (mg) elevated in bile in patients with cholecystectomy, whereas no differences were found in UDCA content.

Conclusion

In this large study investigating the impact of cholecystectomy on PSC outcomes, we found no effect on liver enzyme levels, prognostic indices, bile duct disease progression, or overall prognosis, regardless of whether the procedure was performed before or after the PSC diagnosis.

References

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