Biliary Candidiasis - Optimization of Diagnostics and Therapy

Study Overview
=================
Brief Summary
-----------------
Biliary obstruction and cholangitis are common problems in gastroenterology and need specific therapeutic interventions. Besides a variety of potential causes, infections of the biliary tract with Candida and other fungal species have increasingly been reported in the last few years. Especially interesting is the question, if patients with positive fungal cultures of bile samples should be treated or not and under which circumstances. The primary aim of the present study is to evaluate wether positive fungal cultures of bile samples indicate fungal infection of the biliary tract, rather colonization or simply contamination during endoscopic retrograde cholangiopancreatography (ERCP) procedure.

Detailed Description
-----------------
Background: Biliary obstruction and cholangitis are common problems in gastroenterology and need specific therapeutic interventions. Besides a variety of potential causes, infections of the biliary tract with Candida and other fungal species have increasingly been reported in the last few years [1-6]. Fungal infections can even lead to common bile duct (CBD) obstruction, as previously reported [7]. Because of the difficulty of gaining bile samples, little is known about the microbial flora of the bile. In a first prospective, observational study, 123 consecutive patients undergoing ERCP for various indications were screened for fungal species [8]. According to this data Candida species may be very frequently be detected in the bile (54/123 patients, 44 % of the cases). As significant risk factors immunosuppression and long-term antibiotic therapy were identified. The main issue in this context is whether positive diagnostic findings represent fungal infection or fungal colonization. Especially interesting is the question, if patients with positive fungal cultures of bile samples should be treated or not and under which circumstances. Study Aim: The primary aim of the present study is to evaluate wether positive fungal cultures of bile samples indicate fungal infection of the biliary tract, rather colonization or simply contamination during ERCP procedure. In addition to mycological analysis of bile samples, tissue samples of the common bile duct are collected to confirm fungal invasion. Study design: The study is designed as a single-center, non-randomized, observational study. The conducting center is the University Hospital of Muenster, Department of Medicine B, Gastroenterology. The examinations are performed by two experienced gastroenterologists (D. D., H. U.). Endoscopic Retrograde Cholangiopancreatography (ERCP) procedure: ERCP is performed using a conventional duodenoscope as described in the literature. To exclude contamination artefacts, smears of the endoscope working channel (elevator) will be taken before and after the examination. Furthermore buccal smears and stool samples will be taken to get an impression of the individual transient flora. Endoscopic transpapillary bile duct biopsy for diagnosing an invasive fungal infection will be performed. Transpapillary biopsies as confirmed by the present literature cause no increased risk for post-interventional bleeding and infection [9-12]. Additionally with routinely taken blood samples (hemoglobin and lipase), candida-antigen-serology and blood-cultures will be gained. Ethics: The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was a priori approved by the local ethics committee of the University of Muenster. Statistical methods: The data will be analyzed using standard statistical methods. As observational study, no power-analysis will reasonable - nevertheless data will be shown with confidence interval. All statistical analyses will be performed in cooperation with the Department of Medical Informatics and Biomathematics.

Official Title
-----------------
Biliary Candidiasis - Evaluation of Risk Factors, Implementation of an Algorithm in Diagnostics and Therapy

Conditions
-----------------
Secondary Cholangitis, Bile Duct Strictures of Unknown Origin

Intervention / Treatment
-----------------
* Procedure: ERCP


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Secondary cholangitis Bile duct strictures of unknown origin Age ≥ 18 years All individuals provide written informed consent before entering the trial Exclusion Criteria: Exclusion criteria and contraindications of the performed procedure Ineffective aspiration of bile samples Pregnant or breastfeeding patient Age < 18 years Missing informed consent Missing cooperation (language barrier, amblyacousia, psychiatric disease) Refusal of participation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| with biliary candidiasis<br>Patients with positive fungal cultures of bile samples. | Procedure: ERCP<br>* endoscopic retrograde cholangiopancreatography transpapillary biopsies<br>|
| without biliary candidiasis<br>Patients with negative fungal cultures of bile samples. | Procedure: ERCP<br>* endoscopic retrograde cholangiopancreatography transpapillary biopsies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis of an invasive fungal infection of the biliary tract | Diagnosis of an invasive fungal infection of the biliary tract | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of risk factors 2. Implementation of an algorithm in diagnostics and therapy | Risk factors | 12 month |