Hansjoerg Ullerich

Double Balloon Enteroscopy: A Useful Tool for Diagnostic and Therapeutic Procedures in the Pancreaticobiliary System

OBJECTIVES:Diagnostic and therapeutic interventions in the biliary and pancreatic system in the previously operated patient by conventional endoscopic retrograde cholangiopancreaticography (ERCP) are difficult and, depending on the surgical procedure, in many cases unsuccessful. We describe our experience of ERCP performed with a double balloon enteroscope (DBE) as an alternative examination technique for these patients.METHODS:In a retrospective analysis of all DBE procedures at our department between November 2004 and June 2007, 11 patients were identified with various anatomic variations in whom ERCP was performed using a DBE.RESULTS:In 72% of the patients, previous conventional ERCP examinations failed (8/11). In these patients, DBE-ERCP was successful in 63%. The overall success rate of DBE-ERCP in all patients was 64% (7/11 patients). In those patients, interventions such as papillotomy, calculus extractions, as well as stent placement could be performed even though tools for DBE-ERCP are still very limited. Despite most of the DBE-ERCPs having included therapeutic interventions, no major complications occurred in our case series and minor side effects were restricted to meteorism and mild to moderate abdominal pain.CONCLUSIONS:DBE-ERCP is an alternative method for diagnostic as well as therapeutic interventions in the biliary as well pancreatic system in the operated patient. However, it should be limited to selected patients, e.g., with contraindications for PTC, as it is a time-consuming as well as a cost-intensive procedure.

Detection and differentiation of inflammatory versus fibromatous Crohn's disease strictures: prospective comparison of 18F-FDG-PET/CT, MR-enteroclysis, and transabdominal ultrasound versus endoscopic/histologic evaluation.

Background: Differentiation between inflammatory and fibromatous strictures in Crohns disease (CD) is difficult but crucial for therapeutic decisions. The aim of this study was to assess the best noninvasive imaging method for the detection and differentiation of inflammatory and fibromatous stenoses in CD in comparison to endoscopic and histologic evaluation. Methods: Patients with suspected CD strictures were included. According to a formalized endoscopic and histologic protocol, strictures were classified as inflammatory, mixed, and fibrostenotic. Strictures were further analyzed using fluorine 18‐labeled fluoro‐2‐deoxy‐D‐glucose (18FDG) / positron emission tomography (PET) low‐dose computed tomography (CT), magnetic resonance (MR) enteroclysis and transabdominal ultrasound using standardized scoring systems. Results: Thirty patients with 37 strictures were evaluated (inflamed n = 22; mixed n = 12, fibromatous n = 3). 18FDG‐PET/CT detected 81%, MR‐enteroclysis 81%, and ultrasound 68% of the strictures. Correct differentiation rates of strictures were 57% for MRE, 53% for 18FDG‐PET/CT, and 40% for ultrasound. Differences of detection rates and differentiation rates were not statistically significant. When combining transabdominal ultrasound with 18FDG‐PET/CT or MR‐enteroclysis all strictures that required invasive treatment were detected. Conclusions: Detection rates of the strictures were not significantly different between 18FDG‐PET/CT, MR‐enteroclysis, and ultrasound. Despite good stricture detection rates relating to our gold standard, 18FDG‐PET/CT nor MR‐enteroclysis nor ultrasound can accurately differentiate inflamed from fibrotic strictures. A combination of MR‐enteroclysis and ultrasound as well as a combination of 18FDG‐PET/CT and ultrasound resulted in a 100% detection rate of strictures requiring surgery or endoscopic dilation therapy, suggesting the combination of these methods as an alternative to endoscopy at least in the group of patients not able to perform an adequate bowel preparation. (Inflamm Bowel Dis 2012;)

Single-step versus multi-step transmural drainage of pancreatic pseudocysts: the use of cystostome is effective and timesaving.

Abstract Background and aims. Pancreatic pseudocysts are a major complication of chronic and acute pancreatitis and often require endoscopic intervention. Endoscopic single-step and multi-step transmural drainage techniques have been reported in the literature. The aim of this study was to evaluate and compare technical results and clinical outcome rates of the single-step versus multi-step endoscopic ultrasonography (EUS)-guided endoscopic transmural drainage in patients with symptomatic pancreatic pseudocysts of >4 cm size. Design. Retrospective study at an academic tertiary referral center. Patients and methods. A total of 38 consecutive patients comprising 42 interventions were studied: 16 patients with pancreatic pseudocysts (18 interventions) had undergone single-step EUS-guided transmural cystostome drainage between 2007 and 2010. Results were compared with a cohort of 22 patients who had submitted to multi-step EUS-guided transmural drainage of pancreatic pseudocysts in 24 cases between 2005 and 2007. Results. The technical success rate for using the single-step procedure was 94% compared with multi-step procedure with 83% (n.s.). Primary clinical success rate was 88% for single-step drainage and 90% for the multi-step approach (n.s.). The mean procedure time was 36 ± 9 min in the single-step group compared with 62 ± 12 min for the multi-step access (p < 0.001). Conclusions. The use of single-step cystostome appears useful in managing selected patients with symptomatic pancreatic pseudocysts as it is effective and timesaving.

CO2 insufflation during single-balloon enteroscopy: a multicenter randomized controlled trial.

BACKGROUND AND STUDY AIMS Carbon dioxide (CO2) insufflation has previously been shown to have advantages over air insufflation in terms of procedure-related pain and oral insertion depth during double-balloon enteroscopy. The aim of this prospective study was to evaluate the performance of CO2 vs. air insufflation during single-balloon enteroscopy. PATIENTS AND METHODS This study was a randomized European multicenter trial (ClinicalTrials.gov: NCT01524055). Patients and endoscopists were blinded to the type of insufflation gas used. Patient discomfort during and after the procedure was scored using a visual analog scale. RESULTS A total of 107 patients were enrolled in the study (52 in the CO2 group and 55 in the air group). Patient characteristics were comparable in both groups. The mean (±SD) oral intubation depth was not significantly deeper in the CO2 group vs. the air group (254±80 vs. 238±55 cm; P=0.726). However, in patients with previous abdominal surgery, oral intubation depth was significantly higher in the CO2 group compared with the air group (258±84 vs. 192±42 cm; P<0.05). In patients undergoing SBE via the anal approach, CO2 showed no significant difference in intubation depth compared with air insufflation (86±67 vs. 110±68 cm; P=0.155). The diagnostic yield was comparable (CO2 67%; air 73%). Procedure times, dosage of sedation, and therapeutic interventions did not differ between the two groups. Patients in the CO2 group reported less pain than those in the air group. CONCLUSIONS This study demonstrated an advantage of using CO2 insufflation during single-balloon enteroscopy in patients with a history of previous abdominal surgery. Overall, single-balloon enteroscopy was a well-tolerated procedure that may benefit from the use of CO2 insufflation to reduce post-procedural pain.

Ileal gallstone obstruction: Single-balloon enteroscopic removal.

Gallstone-induced ileus is a rare complication of cholelithiasis. Since localization of gallstones impacted in the small bowel, especially in the ileum, prevents access by conventional endoscopy in most cases, the mainstay of treatment remains surgical. Recent invention of double- and single-balloon enteroscopy has added much to the ability of imaging the small bowel and enables endoscopically directed therapy. Herein, for the first time, we report a successful endoscopic calculus removal via peroral single-balloon enteroscopy in an 81-year-old woman suffering from gallstone ileus of the ileum.

Direct peroral cholangioscopy with a new anchoring technique using the guide probe of Kautz – first clinical experiences

Background and study aims We present the first clinical results of a new tandem technique for direct peroral cholangioscopy using a standard ultraslim upper gastrointestinal endoscope and a guide probe that was originally developed for the non-transendoscopic placement of biliary endoprostheses (guide probe of Kautz; MTW, Wesel, Germany). Patients and methods Twenty direct peroral cholangioscopy procedures were performed with the new anchor-assisted method using the guide probe of Kautz in a single center and were retrospectively analyzed. Results  Indications for anchor-assisted cholangioscopy procedures included indeterminate bile duct strictures (n = 14), filling defects that remained after stone extraction (n = 4), and complex stone extractions (n = 2). Biliary access and visualization of the target region were achieved in 18/20 procedures (90 %). The interventional success rate was 85 % (11 /13 interventions). One case of postinterventional cholangitis occurred (5 %), along with one case of minor peri-interventional papillary bleeding (5 %). Conclusions The anchor-assisted cholangioscopy technique is feasible and safe for direct cholangioscopy and provides reliable success rates in clinical practice. This technique represents an alternative approach for direct cholangioscopy on a single-operator basis using standard endoscopes.

Safety, diagnostic accuracy and therapeutic efficacy of digital single-operator cholangioscopy:

Background Digital single-operator cholangioscopes (digital SOCs), equipped with an improved image quality, have been recently introduced. Objective The aim of this study is to evaluate the safety and diagnostic and therapeutic efficacy of digital SOCs (Spyglass™ DS). Methods Sixty-seven digital SOC procedures performed between 2015 and 2017 were retrospectively analyzed. Results The most frequent indications for examination were indeterminate biliary strictures (61.2%) and biliary stone disease (23.9%). In 25 patients (37.3), visual findings predicted malignancy with a sensitivity of 88.9%, a specificity of 97.6%, a positive predictive value (PPV) of 96.0% and a negative predictive value (NPV) of 92.9%. For histological analysis, forceps biopsies were performed in 29 patients (43.2%). Compared with visual findings, forceps biopsies yield a lower diagnostic efficacy in diagnosing malignancy (sensitivity 62.5%, specificity 90.0%, PPV 90.9%, NPV 60.0%). Therapeutic interventions were performed in 19 patients with a technical success rate of 89.4%. Adverse events were observed in 17 patients (25.4%). Of these, 11 patients (16.4%) suffered from severe adverse events (pancreatitis, cholangitis or major bleeding), which led to a prolonged hospital stay. Conclusion Digital SOCs have excellent diagnostic and therapeutic efficacies, but are accompanied by high rates of adverse events; therefore, physicians should use digital SOCs in carefully selected cases.

Digital single-operator cholangioscopy: a useful tool for selective guidewire placements across complex biliary strictures

BackgroundTreatment of biliary strictures is challenging. Digital single-operator cholangioscopes (SOCs) equipped with an improved imaging quality, were recently introduced and may be useful for selective guidewire placement in difficult biliary strictures.MethodsA total of 167 digital SOC procedures performed between 2015 and 2018 were retrospectively analyzed for successful guidewire placements across biliary strictures. Only cases with previous failed conventional guidewire placement approaches were included.ResultsIn total, 30 examinations with a digital SOC-assisted guidewire placement across biliary strictures, performed in 23 patients, were identified. In 52% of all patients, the stricture was benign with post-liver-transplant strictures (75%) as the most frequent finding; in 48% of all patients the stricture was malignant with cholangiocellular carcinoma as the most frequent type (64%). Guidewire placement was successful in 21 of 30 procedures (70%). According to a subgroup analysis, digital SOC-assisted guidewire placements were significantly more successful in patients with benign strictures than those in patients with malignant strictures (88.2% vs. 46.2%; p = 0.02). Furthermore, the technical success rate tended to be increased in cases of initial examinations (78.3%) than in patients with repeated examinations (42.9%; p = 0.15). Adverse events, such as post-interventional pancreatitis or cholangitis as well as severe bleeding occurred in 16.7% of all examinations.ConclusionsDigital SOC-assisted guidewire placements have high technical success rates, especially in benign biliary strictures. This technique can help to avoid more invasive procedures such as percutaneous transhepatic or endoscopic ultrasound-guided biliary drainage.

Circulating microRNA-99 family as liquid biopsy marker in pancreatic adenocarcinoma

PurposeRecently, we identified the microRNA-99 family as unfavorable prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to evaluate its value as circulating biomarker for PDAC.MethodsTissue and corresponding preoperative blood samples of 181 patients with PDAC UICC Stages I–IV (n = 90), intraductal papillary mucinous neoplasm (IPMN, n = 11), chronic pancreatitis (n = 40), pancreatic cystadenoma (n = 20), and age-matched healthy blood serum controls (n = 20) were collected between 2014 and 2017 prospectively. Expression of microRNA-21 as confirmatory marker and the microRNA-99 family, consisting of microRNA-99a, -99b, and -100, was analyzed by qRT-PCR. Target analysis of insulin-like growth factor 1 receptor (IGF1R) was performed using tissue array immunohistochemistry and Western blotting.ResultsExpression of microRNA-99 family members was significantly increased in macrodissected tumor tissue and corresponding blood serum samples (p < 0.05) of patients with PDAC of all stages. Correspondingly, its target protein IGF1R was upregulated (p < 0.001) in carcinoma tissue. Circulating and tissue-related microRNA-100 could well discriminate PDAC from healthy samples with area under the receiver operating characteristic (ROC) curve (AUC) values of 0.81 and 0.85, respectively. Low expression of circulating microRNA-100 was associated with significantly improved overall survival (p = 0.004) and recurrence-free survival (p = 0.03) in multivariate analyses. Circulating microRNA-21 was overexpressed in PDAC with fair discrimination between PDAC and healthy controls (AUC = 0.71) and decreased overall survival (p = 0.046) and recurrence-free survival (p = 0.03) in PDAC patients.ConclusionsMultivariate survival and ROC analyses identified circulating microRNA-100 as potential diagnostic and prognostic marker in PDAC patients.

The ambiguous role of microRNA-205 and its clinical potential in pancreatic ductal adenocarcinoma

PurposeEarly treatment of pancreatic ductal adenocarcinoma (PDAC) is significantly delayed due to the lack of liquid biopsy markers for early diagnosis at surgically resectable tumor stages. Recent studies suggest that microRNA-205 (miR-205) is involved in PDAC progression by post-transcriptional regulation of epithelial-to-mesenchymal transition (EMT). However, the clinical potential of miR-205 as diagnostic and prognostic marker remains undefined and its exact role in PDAC is still ambiguous. This retrospective study is a substantial contribution to this on-going scientific discussion.MethodsExpression analysis of miR-205 and its molecular targets in PDAC cell lines (n = 5), human tissue (n = 73), and blood serum samples (n = 85) by qRT-PCR, tissue microarray immunohistochemistry, and western blot. Descriptive and explorative statistical analysis of miR-205’s clinical potential for diagnosis and prognosis of PDAC.ResultsThe expression of miR-205 differs more than 2000-fold (p < 0.001) between epithelial and mesenchymal-like human PDAC cell lines correlating with EMT-marker expression of E-cadherin, vimentin, fibronectin, and ZEB-1. Expression of miR-205 is significantly upregulated in carcinoma tissue (eightfold, p = 0.028) and serum (2.3-fold, p = 0.023) of PDAC patients compared to age-matched healthy controls. In our patient collective circulating miR-205 in combination with CA.19-9 outperforms the diagnostic accuracy of CA.19-9 alone with an AUC of 0.890 (p < 0.001), sensitivity of 0.867, and specificity of 0.933. Though non-significant, low expression of circulating miR-205 is more frequent in advanced tumor stages combined with a worse overall survival (6.9 vs. 11.9 months, p = 0.176).ConclusionBesides its controversial role in carcinogenesis, miR-205 shows high potential as a solid and liquid biopsy marker in PDAC. This result is an urgent call for larger confirmatory multi-center studies.