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.

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

Post-ERCP pancreatitis (PEP) is the most frequent adverse event (AE) following ERCP with a 3.5-9.7% overall incidence across studies. ERCP is performed also to treat post-liver transplantation (LT) biliary complications. The occurrence of PEP in LT patients is not well studied, however in some series a slight increase in PEP incidence has been described.
The aim of this study is to perform a case-control study to evaluate the risk for PEP in post-LT patients.

Aims & Methods

This is a case-control retrospective study performed at a single high-volume endoscopy center. All consecutive patients undergoing ERCP for the first time (native papilla) for post-LT biliary complications from January 2015 to September 2022, were reviewed from a prospectively maintained ERCP database. The control group consisted of patients with native papilla undergoing ERCP for indications different than post-LT biliary complications at the same unit from January 2019 to December 2019. Demographic data, technical data, and post-ERCP AEs were recorded. Rectal indomethacin was administrated in all cases as PEP prophylaxis. General anesthesia or deep sedation was used in all cases. Statistical analysis was performed with SPSS 20 software. Descriptive data are reported as mean/median ± standard deviation/range, or percentage. Categorical data were compared using the χ₂ test. P values <0.05 were considered statistically significant.

Results

One hundred and six post-LT patients were included in the “case” group and 452 in the “control” group. Patients’ characteristics are summarized in Table 1. PEP prevalence was significantly higher in the case group (8/106, 7.5%) compared with the control group (15/452, 3.5%) (OR: 2.37, 95% CI: 0.98-5.75, P= 0.048). Double guide-wire cannulation prevalence (considered a criterion of difficult cannulation) was significantly higher in the case group (21/106, 19.8%) compared with the control group (54/442, 12.2%) (OR: 1.78, 95% CI: 1.02-3.10, P= 0.041). PEP prevalence resulted still higher in LT patients (OR: 4.19, 95% CI: 1.01-6.06, P= 0.04) after exclusion from the control group of pancreatic cancer patients (n=104), considered at lower risk for PEP assuming pancreatic duct obstruction as a protective factor.

Table 1: Patients characteristics (n: number, LT: liver transplantation, AEs: adverse events, PEP: post-ERCP pancreatitis).

Conclusion

LT patients are at higher risk of PEP when compared with patients undergoing ERCP for other indication. Biliary cannulation seems to be more difficult in LT patients and this could explain the higher risk of PEP. The main limitations of this study are the retrospective design and the presence of a historic cohort group as controls. Prospective studies are needed to confirm these data.

References

[1] Kochar B, Akshintala VS, Afghani E, et al. Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials. Gastrointest Endosc 2015; 81: 143-149.e9.
[2] Moy BT, Birk JW. A review on the management of biliary complications after orthotopic liver transplantation. Journal of clinical and translational hepatology. 2019 Mar 28;7(1):61.
[3] Kochhar G, Parungao JM, Hanouneh IA, Parsi MA. Biliary complications following liver transplantation. World J Gastroenterol. Published online 2013. doi:10.3748/wjg.v19.i19.284.

Introduction

Upper gastrointestinal bleeding (UGIB) continues to pose a significant threat to patients presenting at the emergency department, especially if the patients present with hemodynamic instability. There are still some uncertainties in the guidelines about the stepwise assessment and management for those patients before undergoing endoscopy.

Aims & Methods

Our study aims to report practice patterns to better understand the pre-endoscopic assessment for patients presenting with acute UGIB. This is an international online survey that included a prospective two-phase data collection. The distribution was conducted from April 2023 to November 2023. The target population was active physicians with clinical practices focusing on the management of patients with UGIB. Study data were collected and managed using Research Electronic Data Capture (REDCap), an electronic data collection tool. The survey included four main sections (demographics and clinical practice, definition of hemodynamic instability, pre-endoscopy assessment, and optimal time for endoscopy) with a total of 33 relevant questions. The survey was endorsed by several national and international gastroenterology societies. The primary analysis was a descriptive assessment of individual survey response items in different domains. Descriptive statistics were reported as proportions. Secondary analysis evaluated differences in survey responses according to the years of clinical experience, type of practice location, and the estimated number of UGIB patients presented annually.

Results

In total, 533 clinicians completed our survey from 50 countries. Over half of the respondents work at university-based hospitals (54.6%) and have over 100 UGIB patients hospitalized annually (67.7%). In terms of clinical experience, 55.7% reported less than 10 years and 44.3% with more than 10 years. In 29.1% of the hospitals, there was no specific protocol or guideline for the initial assessment of patients with suspected UGIB, and in 44.7%, there were no emergency on-call interventional radiology services for such cases. Among the respondents, 39.6% do not use any risk stratification scores at the time of patient presentation. Both 0.9% saline (40.9%) and balanced crystalloid fluid (39.5%) were almost equally chosen as initial fluid resuscitation. However, the rate of fluid resuscitation was dependent on the hemodynamic status of 40.2% of the answers. In 40.7% of the answers, clinicians do not use any major hemorrhagic protocol for patients with severe ongoing bleeding and at risk of exsanguination. Prokinetics were generally little or never used prior to endoscopy in patients with UGIB (34.3%) or even in those with known gastric emptying problems (27.6%). The most chosen optimal time for endoscopy was within 24 hours for stable patients with non-variceal bleeding and within 12 hours for variceal bleeding. If patients were unstable but responding to resuscitation, the most chosen time was within 6 hours regardless of the source of bleeding and within 2 hours for those with persistent hemodynamic instability.

Conclusion

Adherence to international gastroenterology guidelines is low. There is a significant variability in different assessment approaches among respondents. Based on our data, the optimal time for endoscopy seems to be dependent on the hemodynamic status of patients with acute UGIB in both variceal and non-variceal bleeding. Our study highlights opportunities for improving consistency in reporting data and identifies potential areas for research.