Philipp Lenz

Single- vs. double-balloon enteroscopy in small-bowel diagnostics: a randomized multicenter trial

BACKGROUND AND STUDY AIMS Double-balloon enteroscopy (DBE) is the first choice endoscopic technique for small-bowel visualization. However, preparation and handling of the double-balloon enteroscope is complex. Recently, a single-balloon enteroscopy (SBE) system has been introduced as being a simplified, less-complex balloon-assisted enteroscopy system. PATIENTS AND METHODS This study was a randomized international multicenter trial comparing two balloon-assisted enteroscopy systems: DBE vs. SBE. Consecutive patients referred for balloon-assisted enteroscopy were randomized to either DBE or SBE. Patients were blinded with regard to the type of instrument used. The primary study outcome was oral insertion depth. Secondary outcomes included complete small-bowel visualization, anal insertion depth, patient discomfort, and adverse events. Patient discomfort during and after the procedure was scored using a visual analog scale. RESULTS A total of 130 patients were included over 12 months: 65 with DBE and 65 with the SBE technique. Patient and procedure characteristics were comparable between the two groups. Mean oral intubation depth was 253 cm with DBE and 258 cm with SBE, showing noninferiority of SBE vs. DBE. Complete visualization of the small bowel was achieved in 18 % and 11 % of procedures in the DBE and SBE groups, respectively. Mean anal intubation depth was 107 cm in the DBE group and 118 cm in the SBE group. Diagnostic yield and mean pain scores during and after the procedures were similar in the two groups. No adverse events were observed during or after the examinations. CONCLUSIONS This head-to-head comparison study shows that DBE and SBE have a comparable performance and diagnostic yield for evaluation of the small bowel.

Undifferentiated embryonal sarcoma of the liver in adults

Undifferentiated embryonal sarcoma of the liver (UESL), a rare tumor that predominantly affects children, generally has been considered an aggressive neoplasm with an unfavorable prognosis. More recent reports have indicated that modern multimodal treatment and supportive care improve the survival of children with UESL. Data regarding the treatment and survival of adults have not been reviewed comprehensively, and only a few adult patients with UESL have been reported in the literature.

Quantitative Stain-Free and Continuous Multimodal Monitoring of Wound Healing In Vitro with Digital Holographic Microscopy

Impaired epithelial wound healing has significant pathophysiological implications in several conditions including gastrointestinal ulcers, anastomotic leakage and venous or diabetic skin ulcers. Promising drug candidates for accelerating wound closure are commonly evaluated in in vitro wound assays. However, staining procedures and discontinuous monitoring are major drawbacks hampering accurate assessment of wound assays. We therefore investigated digital holographic microscopy (DHM) to appropriately monitor wound healing in vitro and secondly, to provide multimodal quantitative information on morphological and functional cell alterations as well as on motility changes upon cytokine stimulation. Wound closure as reflected by proliferation and migration of Caco-2 cells in wound healing assays was studied and assessed in time-lapse series for 40 h in the presence of stimulating epidermal growth factor (EGF) and inhibiting mitomycin c. Therefore, digital holograms were recorded continuously every thirty minutes. Morphological changes including cell thickness, dry mass and tissue density were analyzed by data from quantitative digital holographic phase microscopy. Stimulation of Caco-2 cells with EGF or mitomycin c resulted in significant morphological changes during wound healing compared to control cells. In conclusion, DHM allows accurate, stain-free and continuous multimodal quantitative monitoring of wound healing in vitro and could be a promising new technique for assessment of wound healing.

Teaching ultrasound in a curricular course according to certified EFSUMB standards during undergraduate medical education: a prospective study

BackgroundAs a non-invasive and readily available diagnostic tool, ultrasound is one of the most important imaging techniques in medicine. Ultrasound is usually trained during residency preferable according to German Society of Ultrasound in Medicine (DEGUM) standards. Our curriculum calls for undergraduate training in ultrasound of medical students in their 4th year of undergraduate education. An explorative pilot study evaluated the acceptance of this teaching method, and compared it to other practical activities in medical education at Muenster University.Methods240 medical students in their 4th year of undergraduate medical education participated in the training and completed a pre- and post-questionnaire for self-assessment of technical knowledge, self-assurance of the procedure, and motivation in performing ultrasound using a Likert scale. Moreover, students were asked about their interest in pursuing a career in internal medicine. To compare this training to other educational activities a standardized online evaluation tool was used. A direct observation of procedural skills assessment (DOPS) for the first time applied on ultrasound aimed to independently assess the success of our teaching method.ResultsThere was a significant increase in technical knowledge and self-assurance (p < 0.001) of the students’ self-assessments. The clinical relevance and self-motivation of the teaching were evaluated positively. The students’ DOPS results demonstrated proficiency in the understanding of anatomic structures shown in ultrasonographic images, including terminology, machine settings, and transducer frequencies.ConclusionsTraining ultrasound according to certified DEGUM standards was successful and should be offered in undergraduate medical education. The evaluation of the course affirmed the necessity, quality and clinical relevance of the course with a top ranking score of hands-on training courses within the educational activities of the Medical Faculty of Muenster.

Prevalence, associations, and trends of biliary-tract candidiasis: a prospective observational study

BACKGROUND Biliary obstruction and cholangitis are common problems in gastroenterology. Infections of the biliary tract with Candida and other fungal species have increasingly been seen in the last few years. OBJECTIVE To investigate the prevalence, associations, and trends of biliary-tract candidiasis. DESIGN A prospective, observational, diagnostic study. SETTING University Hospital, Muenster, Germany. PATIENTS Consecutive patients undergoing ERCP for various indications. RESULTS In 54 of 123 patients, we found Candida species in bile samples (44%). In only 7 patients, candidiasis was suspected on endoscopy before mycologic proof. Only 4 of these 7 patients were correctly diagnosed with biliary candidiasis by simple morphologic aspects. The fungus was mainly differentiated as Candida albicans or Candida glabrata and rarely as Candida parapsilosis, Candida tropicalis, or other subspecies. Immunosuppression for various reasons was significantly associated with bile-duct candidiasis (P < .02). No significant association was found between positive fungal cultures and prior endoscopic sphincterotomy (P = .0824) or prior ERCP (P = .1152). Biliary candidiasis was neither associated with positive fungal cultures of buccal smears (P = .0722) nor with positive findings in stool samples (P = .0860). LIMITATIONS Highly selected patient population. Buccal smears and stool samples were not obtained from all patients. Contamination artifacts cannot totally be excluded with the ERCP procedure. CONCLUSIONS Candida species very frequently can be detected in the bile. Positive fungal cultures of bile samples are not just contamination artifacts. This has to be taken into account when designing an anti-infectious treatment for recurrent cholangitis or even more cholangiosepsis. Especially in immunosuppressed patients or recipients of long-term antibiotic therapy, physicians should screen for biliary-tract candidiasis during endoscopic examination.

Intraductal ultrasound substantiates diagnostics of bile duct strictures of uncertain etiology

AIM To report the largest patient cohort study investigating the diagnostic yield of intraductal ultrasound (IDUS) in indeterminate strictures of the common bile duct. METHODS A patient cohort with bile duct strictures of unknown etiology was examined by IDUS. Sensitivity, specificity and accuracy rates of IDUS were calculated relating to the definite diagnoses proved by histopathology or long-term follow-up in those patients who did not undergo surgery. Analysis of the endosonographic report allowed drawing conclusions with respect to the T and N staging in 147 patients. IDUS staging was compared to the postoperative histopathological staging data allowing calculation of sensitivity, specificity and accuracy rates for T and N stages. The endoscopic retrograde cholangio-pancreatography and IDUS procedures were performed under fluoroscopic guidance using a side-viewing duodenoscope (Olympus TJF 160, Olympus, Ltd., Tokyo, Japan). All procedures were performed under conscious sedation (propofol combined with pethidine) according to the German guidelines. For IDUS, a 6 F or 8 F ultrasound miniprobe was employed with a radial scanner of 15-20 MHz at the tip of the probe (Aloka Co., Tokyo, Japan). RESULTS A total of 397 patients (210 males, 187 females, mean age 61.43 ± 13 years) with indeterminate bile duct strictures were included. Two hundred and sixty-four patients were referred to the department of surgery for operative exploration, thus surgical histopathological correlation was available for those patients. Out of 264 patients, 174 had malignant disease proven by surgery, in 90 patients benign disease was found. In these patients decision for surgical exploration was made due to suspicion for malignant disease in multimodal diagnostics (computed tomography scan, endoscopic ultrasound or magnetic resonance imaging). Twenty benign bile duct strictures were misclassified by IDUS as malignant while 14 patients with malignant strictures were initially misdiagnosed by IDUS as benign resulting in sensitivity, specificity and accuracy rates of 93.2%, 89.5% and 91.4%, respectively. In the subgroup analysis of malignancy prediction, IDUS showed best performance in cholangiocellular carcinoma as underlying disease (sensitivity rate, 97.6%) followed by pancreatic carcinoma (93.8%), gallbladder cancer (88.9%) and ampullary cancer (80.8%). A total of 133 patients were not surgically explored. 32 patients had palliative therapy due to extended tumor disease in IDUS and other imaging modalities. Ninety-five patients had benign diagnosis by IDUS, forceps biopsy and radiographic imaging and were followed by a surveillance protocol with a follow-up of at least 12 mo; the mean follow-up was 39.7 mo. Tumor localization within the common bile duct did not have a significant influence on prediction of malignancy by IDUS. The accuracy rate for discriminating early T stage tumors (T1) was 84% while for T2 and T3 malignancies the accuracy rates were 73% and 71%, respectively. Relating to N0 and N1 staging, IDUS procedure achieved accuracy rates of 69% for N0 and N1, respectively. LIMITATIONS Pre-test likelihood of 52% may not rule out bias and over-interpretation due to the clinical scenario or other prior performed imaging tests. CONCLUSION IDUS shows good results for accurate diagnostics of bile duct strictures of uncertain etiology thus allowing for adequate further clinical management.

Clinical outcome and predictors of survival after TIPS insertion in patients with liver cirrhosis

AIM To determine the clinical outcome and predictors of survival after transjugular intrahepatic portosystemic stent shunt (TIPS) implantation in cirrhotic patients. METHODS Eighty-one patients with liver cirrhosis and consequential portal hypertension had TIPS implantation (bare metal) for either refractory ascites (RA) (n = 27) or variceal bleeding (VB) (n = 54). Endpoints for the study were: technical success, stent occlusion and stent stenosis, rebleeding, RA and mortality. Clinical records of patients were collected and analysed. Baseline characteristics [e.g., age, sex, CHILD score and the model for end-stage liver disease score (MELD score), underlying disease] were retrieved. The Kaplan-Meier method was employed to calculate survival from the time of TIPS implantation and comparisons were made by log rank test. A multivariate analysis of factors influencing survival was carried out using the Cox proportional hazards regression model. Results were expressed as medians and ranges. Comparisons between groups were performed by using the Mann-Whitney U-test and the χ2 test as appropriate. RESULTS No difference could be seen in terms of age, sex, underlying disease or degree of portal pressure gradient (PPG) reduction between the ascites and the bleeding group. The PPG significantly decreased from 23.4 ± 5.3 mmHg (VB) vs. 22.1 ± 5.5 mmHg (RA) before TIPS to 11.8 ± 4.0 vs. 11.7 ± 4.2 after TIPS implantation (P = 0.001 within each group). There was a tendency towards more patients with stage CHILD A in the bleeding group compared to the ascites group (24 vs 6, P = 0.052). The median survival for the ascites group was 29 mo compared to > 60 mo for the bleeding group (P = 0.009). The number of radiological controls for stent patency was 6.3 for bleeders and 3.8 for ascites patients (P = 0.029). Kaplan-Meier calculation indicated that stent occlusion at first control (P = 0.027), ascites prior to TIPS implantation (P = 0.009), CHILD stage (P = 0.013), MELD score (P = 0.001) and those patients not having undergone liver transplantation (P = 0.024) were significant predictors of survival. In the Cox regression model, stent occlusion (P = 0.022), RA (P = 0.043), CHILD stage (P = 0.015) and MELD score (P = 0.004) turned out to be independent prognostic factors of survival. The anticoagulation management (P = 0.097), the porto-systemic pressure gradient (P = 0.460) and rebleeding episodes (P = 0.765) had no significant effect on the overall survival. CONCLUSION RA, stent occlusion, initial CHILD stage and MELD score are independent predictors of survival in patients with TIPS, speaking for a close follow-up in these circumstances.

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.

Murine endoscopy for in vivo multimodal imaging of carcinogenesis and assessment of intestinal wound healing and inflammation.

Mouse models are widely used to study pathogenesis of human diseases and to evaluate diagnostic procedures as well as therapeutic interventions preclinically. However, valid assessment of pathological alterations often requires histological analysis, and when performed ex vivo, necessitates death of the animal. Therefore in conventional experimental settings, intra-individual follow-up examinations are rarely possible. Thus, development of murine endoscopy in live mice enables investigators for the first time to both directly visualize the gastrointestinal mucosa and also repeat the procedure to monitor for alterations. Numerous applications for in vivo murine endoscopy exist, including studying intestinal inflammation or wound healing, obtaining mucosal biopsies repeatedly, and to locally administer diagnostic or therapeutic agents using miniature injection catheters. Most recently, molecular imaging has extended diagnostic imaging modalities allowing specific detection of distinct target molecules using specific photoprobes. In conclusion, murine endoscopy has emerged as a novel cutting-edge technology for diagnostic experimental in vivo imaging and may significantly impact on preclinical research in various fields.

Detection of Early Murine Colorectal Cancer by MMP-2/-9-Guided Fluorescence Endoscopy.

Background:Patients with ulcerative colitis are at increased risk for colorectal cancer and endoscopic surveillance is mandatory. Matrix metalloproteinases (MMPs)-2 and -9 activities are increased in malignant colonic mucosa. The aim of the study was to evaluate molecular imaging of MMP-2/-9 by fluorescence endoscopy (FE) for early tumor detection. Methods:Colorectal cancer in mice (n = 28) was induced by azoxymethane and dextran sodium sulfate. Twenty-four hours after intravenous injection of a nonpeptidic, Cy5.5-labeled MMP-selective tracer, tumor development was assessed in vivo by white light endoscopy and FE. Topical administration of the tracer was also investigated (after 5 minutes and 24 hours). Colonic tumors were evaluated ex vivo by fluorescence reflectance imaging, immunohistochemistry, Western blot analysis, and zymography. Results:Imaging of MMP-2/-9 expression by FE achieved a significantly higher contrast of the fluorescence signal in colonic adenomas compared with the adjacent nonmalignant mucosa (P < 0.001). Fluorescence reflectance imaging detected a significantly higher tracer uptake in adenoma compared with healthy mucosa (P < 0.001) and revealed a tumor size–dependent increase of tracer uptake (P < 0.01). Topical tracer administration did not facilitate tumor detection. Immunohistochemistry, Western blot analysis, and zymography indicated higher levels of MMP-2 and -9 in high-grade dysplasia and pT1 tumors ex vivo. Conclusions:MMP-2/-9 expression was significantly increased in colorectal neoplasia. FE allows direct visualization of a prognostic parameter (here MMP-2/-9) on a molecular level and may improve the characterization of colorectal lesions and the adenoma detection rate in the future.