Introduction

Dominant stricture (DS) in Primary Sclerosing Cholangitis (PSC) is associated with a increased risk for Cholangiocarcinoma (CC)^1,2. The traditional definiton for DS (TDS) has been narrowing <1mm of common hepatic duct (CHD) and ducts <2cm within the bifurcation or <1,5mm of the common bile duct³. A new definition (NDS) has replaced TDS, including elevated cholestatic lab values (ALP, bil) and/or symptoms and response to treatment of the stricture (dilatation and/or stenting)⁴.

Aims & Methods

To compare clinical charasteristics of PSC patients and ocurance of biliary neoplasia with DS defined by either traditional (TDS) or new criteria (NDS).
In this longitudinal prospective cohort study, all patients who underwent Endoscopic Retrograde Cholangiography (ERC) for confirming of the diagnosis or screening for biliary dysplasia between October 2021 - 2022 were recruited. Laboratory values (P-ALP, P-Bil) and symptoms of cholestasis were collected before ERC. Bile duct disease severity was assesedby using Helsinki score⁵ and patients were classified as having no DS, TDS or NDS. Markers of biliary inflammation (IL-8, calprotectine) and biliary brush cytology were collected at time of ERC and laboratory values (P-ALP, P-Bil) 4 weeks after treatment of stricture. Ordinal variables were presented as median and interquartile range (IQR) and categorical variables as number and percentage. Fisher´s exact test, Chi-square test and Mann-Whitney tests were used when applicable.

Results

In total, 228 patients underwent 248 ERC:s: 28 (11%) to confirm the diagnosis and 216 (89%) for screening biliary dysplasia. TDS was detected in 62 (25%; 58 individual patients) and NDS in 43 (17%; 36 individual patients) ERC:s respectively; in the remaining 143 ERC:s no DS was seen. No differences were seen in disease duration (median 8 years), patient’s age or gender.
Not unexpectedly, patients with NDS had more symptoms (TDS 1, 2%; NDS 17, 40%; p < 0.001) and more frequently elevated cholestatic liver enzymes (TDS ALP med 94 U/l, IQR 74-129; NDS 288 U/l, IQR 233-419; p < 0.001).
Also, patients with NDS had more advanced bile duct disease based on Helsinki-score, see table.
Markers of biliary inflammation, biliary IL-8 and calprotectin were higher in NDS.
Patients with NDS needed more dilatation (81%) and stenting (21%) than those with TDS (60% and 5%, respectively).
No difference in amount of dysplasia were observed between NDS and TDS.

Conclusion

Patients with DS based on the new definition have significantly higher cholestatic lab values and are more often symptomatic. Patients with NDS present with more advanced bile duct disease and increased markers of biliary inflammation.

References

1. Rudolph G et al, J. Hepatol. 2010; 53(2):313-7.
2. Chapman MH, Eur J Gastroenterol Hepatol. 2012;24(9):1051-8.
3. Stiehl A et al. J Heptatol. 2002;36(2):151-156.
4. Ponsionen C. et al, Gastroenterology, 2021;161(6):1764-1775.
5. Boyd S. et al, Endoscopy 2016; 48(05): 432-439

Introduction

According to the latest clinical practice guidelines, the empirical antimicrobial therapy used for managmente of patients with acute cholangitis should be established according to its level of severity. However, this recommendation have been highly questioned in those settings where the prevalence of broad spectrum beta-lactamase (ESBL) producing E.coli or Klebsiella exceeds 10-20%, and some experts recommend starting with a broader coverage in a systematic way.

Aims & Methods

To evaluate the prevalence of multidrug-resistant cholangitis in our hospital setting, identify possible predictors and antibiotic adequacy.
We made a retrospective analysis of 331 patients diagnosed with acute cholangitis (gathering demographic, clinical, analytical and microbiological data) admitted to the Hospital del Mar during the period from 2018 to 2021.

Results

After assessing the baseline characteristics of theses sample, we obtained a mean age of 78 years, and 53% male. Blood cultures were extracted in 92% of the patients, of which 49% were positive (149 patients) and of these, 12% had multiresistant germs (19 patients, with 17 cases positive for BLEE). The most frequent empirical regimens were amoxicillin-clavulanic acid (112 cases) and cephalosporins with metronidazole (120 cases) with 94.8% and 96.1% of therapeutic adequacy, respectively. The bacteria identified were mainly: E.coli (88%), Enterobacter spp (16%) and Klebsiella spp (21%). Previous colonization by multidrug-resistant germs (3.9%) and institutionalized patients (5.14%) were the only variables related to the presence of cholangitis due to multidrug-resistant germs, but in the multivariate analysis only colonization was a predictor factor (OR 6.69, CI 1.16-38.35). No analytical or hemodynamic variables were found to be associated to bacteremia due to multidrug-resistant germs. Otherwise, bacteremia due to multidrug-resistant germs didn't correlate with a higher mortality.

Conclusion

The prevalence of multidrug-resistant cholangitis in our setting is considerable. However, high antibiotic adequacy is achieved with amoxicillin-clavulanic acid or third generation cephalosporins in most cases. In patients with history of infection or previous colonization by conflicting germs, a broad-spectrum antibiotic coverage including multidrug-resistant germs should be considered empirically.

Introduction

Individuals with Lynch syndrome (LS) have an increased risk of developing gastric cancer (GC) and duodenal cancer (DC), particularly individuals with MLH1 and MSH2 pathogenic variants (PVs). Lack of consensus exists whether individuals with LS benefit from esophagogastroduodenoscopy (EGD) surveillance. In order to gain further insight in GC and DC risk in LS individuals, we studied tumor characteristics and cumulative incidence of GC and DC in a large Dutch cohort of LS individuals.

Aims & Methods

Clinical data of LS individuals registered between 1985-2021 at the Dutch Hereditary Cancer Registry (StOET) was retrospectively matched with pathology reports filed between 1989-2021 by the Dutch Pathology Registry. All pathology reports describing results of gastric or duodenal tissue specimens were reviewed for presence of GC and DC. Cumulative incidences of GC and DC were estimated for individuals with high-risk (MLH1, MSH2 and EpCAM) and low-risk (MSH6 and PMS2) PVs using a competing risk model with death as competing risk. Standardized incidence ratios (SIR) were determined by dividing the observed number of carcinomas in the study cohort by the expected number of carcinomas per age group based on the GC and DC incidence in the general Dutch population.

Results

Among the 1002 individuals with high-risk and 765 individuals with low-risk PVs registered at the StOET, 29 cases of GC (1.6%) and 39 cases of DC (2.2%) were diagnosed. The median age at diagnosis was 68 (IQR 58–74) years for GC and 59 (IQR 53–66) years for DC. Cumulative incidence of GC and DC were higher in individuals with high-risk compared to individuals with low-risk PVs (Table 1; HR 3.60 [95% CI 1.45–8.92], p=0.006 and HR 2.56 [95% CI 1.25–5.26], p=0.01, respectively). Cumulative risk of GC and DC under the age of 50 years was very low (≤1%) for individuals with both high and low-risk PVs. At age 70 years and lifetime, cumulative risk for individuals with high-risk PVs was 3% and 8% for GC and 5% and 6% for DC, respectively. Individuals with low-risk PVs had 1% and 3% cumulative incidence of GC and 1% and 5% cumulative incidence of DC at the age of 70 and lifetime, respectively. The cumulative risk of GC and DC combined at age 70 and lifetime was 8% and 14% for high-risk and 2% and 8% for low-risk PVs, respectively. Primary tumor resection could be performed in the majority of GC (62%) and DC (77%) patients. UICC 8^th TNM stage 1 was found in 56% of resected GCs. Stage 2 was found in 56% of resected DCs. Individuals with LS had a 4.9 (SIR, 95% CI 3.3–7.0) and 250 (SIR, 95% CI 178-290) times higher risk of GC and DC, respectively, compared to the general Dutch population.

Conclusion

This retrospective nationwide cohort study shows that individuals with MLH1, MSH2 and EpCAM mutations have a substantial risk of developing GC and DC at the age of 70 years, but that this risk is negligible before the age of 50 years. The majority of GC and DC were detected at a relatively early stage. Yield of GC, DC and their precursor lesions during surveillance and cost-effectiveness should be determined in future studies.