Search

Background: The European Society of Gastroenterology and Endoscopy recommends a primarily flexible endoscopic approach for the treatment of Zenker's diverticulum. Due to the rarity of the disorder, evidence for its effectiveness and safety comes mainly from small, retrospective, single-center studies., Methods: In this retrospective, observational, multicenter cohort study, data from six German tertiary referral centers were analyzed. The primary outcome parameters were technical and clinical success; among the secondary outcomes, the rates of adverse events (AE) and re-admission with symptomatic recurrence and mortality were the most relevant., Results: Between 2003 and 2024, 384 treatments were performed in 327 patients (61.8% male, mean age 74.70 (± 10.60)). Incision methods/techniques were 250 needle knives, 44 ESD knives, 64 stag beetle knives, 24 staplers, one APC-probe, and one Z-POEM. The Zenker's diverticulum overtube was used in 65.1%, prophylactic clipping in 30.2%, and antibiotic therapy in 25.3% of treatments. The rates of technical and clinical success were 99.2% and 97.4%, and the rates of AE and re-admission with symptomatic recurrence were 11.2% and 16.7%, respectively. Mortality was 0.3%. Comparative subgroup analyses of 312 diverticula without prior treatment versus 72 symptomatic recurrences and incision methods/techniques showed no significant differences in outcome parameters. The use of additional devices and prophylactic measures (clipping, antibiotic therapy) were not independent predictors of technical/clinical success or AE in uni-/multivariable regression analysis., Conclusions: Flexible endoscopic Zenker's diverticulotomy is a safe and effective minimally invasive treatment. Recurrences can be treated by flexible endoscopy with comparable results. None of the cutting methods, ancillary devices, or prophylactic measures showed superiority in effectiveness or safety., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Endoscopic resection is accepted as standard treatment for intramucosal esophageal adenocarcinoma (EAC) that is well or moderately differentiated. Poor differentiation (PD) is judged as a risk factor for lymph node metastasis (LNM), and surgery is recommended. However, the evidence for this recommendation is weak. The aim of this study was to analyze the clinical course of patients after endoscopic resection of EAC with PD., Methods: Patients undergoing endoscopic submucosal dissection for EAC were included from 16 German centers. Inclusion criteria were PD in the resection specimen, R0 resection, and endoscopic follow-up. Primary outcome was the metastasis rate during follow-up. Analysis was performed retrospectively in a prospectively collected database., Results: Twenty-five patients with PD as single risk factor (group A) and 15 patients with PD and additional risk factors (submucosal invasion and/or lymphovascular invasion) (group B) were included. The metastasis rate was was 1 of 25 (4.0%; 95% CI, .4%-17.2%) in group A and 3 of 15 (20.0%; 95% CI, 6.0%-44.4%) in group B, respectively (P = .293). The rate of EAC-associated deaths was 1 of 25 (4%; 95% CI, .4%-17.2%) versus 3 of 15 (20%; 95% CI, 6.0%-44.4%) in group B (P = .293). The overall death rate was 7 of 25 (28.0%; 95% CI, 13.5%-47.3%) versus 3 of 15 (20%; 95% CI, 6.0%-44.4%) (P = .715). Median follow-up was 30 months (interquartile range, 15-53 months)., Conclusions: During long-term follow-up, the risk of metastasis is low after endoscopic resection of mucosal EAC with PD as a single risk factor. A conservative approach seems justified in this small patient group. However, the treatment strategy must be determined on an individualized basis until further prospective data are available., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and aims: Endoscopic submucosal dissection (ESD) has become a standard treatment for early gastric cancer (EGC), often fulfilling guideline criteria (GC) or expanded criteria (EC). When lesions exceed the EC, surgical resection is recommended. However, a subgroup of these patients are not treated surgically. The aim of this study was to investigate the long-term follow-up of patients after ESD for EGC outside the EC (out of indication; OI). Methods: Patients who were included in the prospective German ESD registry were analyzed when ESD was performed for EGC. Patients were stratified in three groups according to histopathological features (GC, EC and OI). The results were evaluated in terms of patient characteristics, procedure characteristics and follow-up data. Results: Over a 48-month period, 195 patients from 14 German centers were included. In total, 71 lesions (36.4%) met the guideline criteria, 70 lesions (35.9%) corresponded to the expanded criteria and 54 lesions (27.7%) turned out to be OI. The R0 resection rate was significantly higher for the GC and EC groups than for the OI group (94.4% vs. 84.3% vs. 55.6%, p < 0.001). Additional surgery was not performed in 72% (39/54) of patients in the OI group. During a mean follow-up of 37 months, overall survival showed no significant difference between the EC and OI groups when endoscopic follow-up was performed without additional surgery ( p = 0.064). Conclusions: The results show that a good long-term survival can be achieved after ESD for patients with OI lesions without additional surgery. The treatment decision has to be made on an individual basis, taking the patient's comorbidities and the risk of surgical resection into account.

Background & Aims: Endoscopic mucosal resection (EMR) is standard therapy for nonpedunculated colorectal polyps ≥20 mm. It has been suggested recently that polyp resection without current (cold resection) may be superior to the standard technique using cutting/coagulation current (hot resection) by reducing adverse events (AEs), but evidence from a randomized trial is missing., Methods: In this randomized controlled multicentric trial involving 19 centers, nonpedunculated colorectal polyps ≥20 mm were randomly assigned to cold or hot EMR. The primary outcome was major AE (eg, perforation or postendoscopic bleeding). Among secondary outcomes, major AE subcategories, postpolypectomy syndrome, and residual adenoma were most relevant., Results: Between 2021 and 2023, there were 396 polyps in 363 patients (48.2% were female) enrolled for the intention-to-treat analysis. Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001; odds ratio [OR], 0.12; 95% CI, 0.03-0.54). Rates for perforation and postendoscopic bleeding were significantly lower in the cold group, with 0% vs 3.9% (P = .007) and 1.0% vs 4.4% (P = .040). Postpolypectomy syndrome occurred with similar frequency (3.1% vs 4.4%; P = .490). After cold resection, residual adenoma was found more frequently, with 23.7% vs 13.8% (P = .020; OR, 1.94; 95% CI, 1.12-3.38). In multivariable analysis, lesion diameter of ≥4 cm was an independent predictor both for major AEs (OR, 3.37) and residual adenoma (OR, 2.47) and high-grade dysplasia/cancer for residual adenoma (OR, 2.92)., Conclusions: Cold resection of large, nonpedunculated colorectal polyps appears to be considerably safer than hot EMR; however, at the cost of a higher residual adenoma rate. Further studies have to confirm to what extent polyp size and histology can determine an individualized approach. German Clinical Trials Registry (Deutsches Register Klinischer Studien), Number DRKS00025170., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Goals: The therapy of buried bumper syndrome (BBS) is difficult. The aim of this retrospective multicenter study was to analyze the treatment methods with focus on effectiveness and safety of endoscopic techniques., Methods: The analysis of all therapies and a comparison of the papillotome technique (PT) and needle knife-based nonpapillotome technique (NPT) were performed. Primary endpoint was technical success in one session, secondary endpoints overall technical success, number and duration of treatment sessions, SAE, and mortality., Results: The primary treatment of 160 BBS cases, diagnosed between 2003 and 2021, was NPT in 60 (37.5%), PT in 43 (26.9%), push/pull technique (PPT) in 40 (25.0%), no removal in 9 (5.6%), laparotomy in 7 (4.4%) cases, and external incision in 1 (0.6%) case. For PT and NPT rates of technical success in one session were 95.5% and 45.0% (P<0.01), rates of overall technical success 100% and 88.3% (P=0.02), and mean number and duration of treatment sessions 1.05 (±0.21) versus 1.70 (±0.91) (P<0.01) and 32.17 (±21.73) versus 98,00 (±62.28) minutes (P<0.01), respectively. No significant differences between PT and NPT were found for SAE (15.9% vs. 25.0%) and mortality (2.3% vs. 1.7%). For PPT, laparotomy and external incision rates of technical success in one session and overall technical success were 100%, rates of SAE 2.5%, 50.0%, and 0% and mortality 0%, 10.0%, and 0%., Conclusions: Endoscopic therapy of BBS is treatment of choice in most cases with removal of incomplete BB by PPT. In case of complete BB PT appears more effective than NPT., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: For an adequate educational strategy of ESD in non-Asian settings with prevalence-based indication it is essential to define adequate lesions, suitable for the beginner without on-site expert-supervision., Aims: We analyzed possible predictors for outcome parameters of effectiveness and safety during the initial learning curve., Methods: The first 120 ESDs of four operators (n = 480), performed between 2007 and 2020 in four tertiary hospitals, were enrolled. Uni-/multivariable regression analysis was done with sex, age, pretreated lesion, lesion size, organ, and organ-based localization as possible independent predictors for en bloc resection (EBR), complication, and resection speed., Results: Rates of EBR, complication, and resection speed were 84.5%, 14.2%, and 6.20 (± 4.45) cm 2 /h. Independent predictors for EBR were pretreated lesion (OR 0.27 [0.13-0.57], p < 0.001) and non-colonic ESD (OR 2.29 [1.26-4.17] (rectum)/5.72 [2.36-13.89] (stomach)/7.80 [2.60-23.42] (esophagus), p < 0.001), for complication pretreated lesion (OR 3.04 [1.46-6.34], p < 0.001) and lesion size (OR 1.02 [1.004-1.04], p = 0.012) and for resection speed pretreated lesion (RC - 3.10 [- 4.39 to - 1.81], p < 0.001), lesion size (RC 0.13 [0.11-0.16], p < 0.001) and male patient (RC - 1.11 [- 1.85 to - 0.37], p < 0.001). We found no significant difference in the incidence of technically unsuccessful resections in esophageal (1/84), gastric (3/113), rectal (7/181), and colonic (3/101) ESDs (p = 0.76). Technical failure was mainly caused by complication and fibrosis/pretreatment., Conclusion: During the initial learning curve of an unsupervised ESD program with prevalence-based indication, pretreated lesions and colonic ESDs should be avoided. In contrast, lesion size and organ-based localizations have less predictive value for the outcome., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The development of capsule endoscopy and device-assisted enteroscopy (DAE) revolutionized minimally invasive examination and treatment of small bowel diseases. Limitations of DAE are a great time expenditure and low rates of complete enteroscopy. Recently motorized spiral enteroscopy (MSE) was introduced with shorter procedure times and concurrently greater insertion depths. MSE is also the first device that opens up the possibility to achieve complete enteroscopy in a relevant number of cases by the unidirectional, peroral approach.To our knowledge we present the first published case of complete enteroscopy by retrograde MSE in a 35-year-old female without prior abdominal surgery with direct endoscopic visualization of the pyloric ring. The patient suffered from colonic polyposis syndrome. For the exploration of both colorectum and the small bowel we performed retrograde MSE under propofol sedation. After 60 minutes of advancement, we achieved complete enteroscopy by retrograde identification of the pyloric ring. The procedure could be finished after withdrawal of the endoscope and cold snare polypectomy of 3 small colonic adenomas without any adverse events. Total procedure time was 82 minutes. The patient was discharged one day after the procedure without complaints.It has been proven already that great insertion depths are achievable by retrograde MSE, but this case shows for the first time that even a complete enteroscopy is possible. In conclusion, primary retrograde MSE with no need of tracheal intubation might be a key to more effective, time-preserving, and cost-effective concepts of small-bowel endoscopy in the future., Competing Interests: Lecture fees from Olympus Medical., (Thieme. All rights reserved.)

Background: Iatrogenic colorectal perforation is a rare event with a relevant mortality and the need for surgical therapy in around ¾ of cases., Methods: In this retrospective multicentric cohort study iatrogenic colorectal perforations from 2004 to 2021 were analyzed. Primary outcome parameters were incidence and clinical success of 1st line endoscopic treatment. Comparative analysis of interventional and non-interventional perforations was performed and predictors for clinical success of endoscopic therapy were identified., Results: From 103,570 colonoscopies 213 (0.2%) iatrogenic perforations were identified. 68.4% were interventional (80 during polypectomy/EMR, 54 during ESD and 11 for other reasons) and 31.6% non-interventional perforations (39 by the tip, 19 by the shaft, 7 by inversion, two by biopsy and one by distension). Incidence of 1st line endoscopic therapy was 61.0% and clinical success 81.5%. Other non-surgical therapies were conducted in 8.9% with clinical success in 94.7% of cases. In interventional perforations both incidence and clinical success of 1st line endoscopic therapy were significantly higher compared to non-interventional perforations [71.7% vs. 38.2% (p < 0.01) resp. 86.5% vs. 61.5% (p < 0.01)]. Mortality was 2.3% and significantly lower in the group of interventional perforations (0.7% vs. 5.9%, p = 0.037). Multivariable analysis revealed perforation size < 5 mm as only independent predictor for clinical success of 1st line endoscopic treatment [OR 14.85 (1.57-140.69), p = 0.019]., Conclusions: Endoscopic therapy is treatment of choice in the majority of iatrogenic colorectal perforations. In case of interventional perforations it is highly effective but only a minority of non-interventional perforations are good candidates for endoscopic treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: As there is still no consensus about the adequate training strategy for ESD in Western countries, we evaluated unsupervised prevalence-based learning curves including detailed organ-specific subgroup analysis., Methods: The first 120 ESDs of four operators (n = 480) were divided into three groups (1: ESD 1-40, 2: ESD 41-80, 3: ESD 81-120). Outcome parameters were rates of technical success, en bloc and R0 resection, the resection speed, rates of conversion to EMR, curative resection, adverse events, surgery due to adverse events, and recurrence. In addition, we analyzed the achievement of quality benchmarks indicating levels of expertise., Results: After exclusion of pretreated lesions, 438 procedures were enrolled in the final analysis. Technical success rates were > 96% with significant improvements regarding rate of en bloc resection (from 82.6 to 91.2%), resection speed (from 4.54 to 7.63 cm 2 /h), and rate of conversion to EMR (from 22.0 to 8.1%). No significant differences could be observed for rates of R0 resection (65.9 vs. 69.6%), curative resection (55.8 vs. 55.7%), adverse events (16.3 vs. 11.7%), surgery due to adverse events (1.5 vs. 1.3%), and recurrence (12.5 vs. 4.5%). Subgroup and benchmark analysis revealed an improvement in esophageal, gastric, and rectal ESD with achievement of competence levels for the esophagus and stomach within 80 and most of the benchmarks for proficiency level within 120 procedures. Some of the benchmarks could also be achieved in rectal ESD., Conclusions: This trial confirms safety and feasibility of unsupervised ESD along the initial learning curve with prevalence-based indication and exclusion of colonic cases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Endoscopic submucosal dissection (ESD) enables the curative resection of early malignant lesions and is associated with reduced recurrence risk. Due to the lack of comprehensive ESD data in the West, the German ESD registry was set up to evaluate relevant outcomes of ESD., Methods: The German ESD registry is a prospective uncontrolled multicenter study. During a 35-month period, 20 centers included 1000 ESDs of neoplastic lesions. The results were evaluated in terms of en bloc, R0, curative resection rates, and recurrence rate after a 3-month and 12-month follow-up. Additionally, participating centers were grouped into low-volume (≤20 ESDs/y), middle-volume (20-50/y), and high-volume centers (>50/y). A multivariate analysis investigating risk factors for noncurative resection was performed., Results: Overall, en bloc, R0, and curative resection rates of 92.4% (95% confidence interval [CI], 0.90-0.94), 78.8% (95% CI, 0.76-0.81), and 72.3% (95% CI, 0.69-0.75) were achieved, respectively. The overall complication rate was 8.3% (95% CI, 0.067-0.102), whereas the recurrence rate after 12 months was 2.1%. High-volume centers had significantly higher en bloc, R0, curative resection rates, and recurrence rates and lower complication rates than middle- or low-volume centers. The lesion size, hybrid ESD, age, stage T1b carcinoma, and treatment outside high-volume centers were identified as risk factors for noncurative ESD., Conclusion: In Germany, ESD achieves excellent en bloc resection rates but only modest curative resection rates. ESD requires a high level of expertise, and results vary significantly depending on the center's yearly case volume., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Aims: Although various methods of treatment have been tried, treatment options for advanced hepatocellular carcinoma (HCC) remain limited. Expression of the platelet-derived growth factor has been shown in HCC, which may derive from hepatic stem cells that express the c-kit proto-oncogene. Because of the promising results of imatinib and the key role played by c-kit in gastrointestinal stromal tumours and other solid tumours, the aim of this study was to determine the prevalence of c-kit (CD117) overexpression in patients with HCC., Materials and Methods: A retrospective study of 258 archival specimens of subjects with histologically confirmed HCC was carried out. Expression of the c-kit proto-oncogene was evaluated by immunohistochemistry using rabbit anti-CD117 antibody A4502., Results: The overall percentage of positive immunohistochemical staining of HCCs was 2.3% (6/258)., Conclusions: Our results suggest that CD117 is not significantly overexpressed in HCC and there seems to be no role for the use of imatinib.

Unlabelled: Although numerous treatment modalities have been explored in patients with advanced HCC, the therapeutic options are still limited. Somatostatin has been shown to have antimitotic activity in endocrine as well as in a variety of nonendocrine tumors. Expression of somatostatin receptors is found in HCCs, but the efficacy of the somatostatin analogue octreotide remains controversial. Therefore, a randomized double-blind placebo-controlled multicenter trial was performed to assess the efficacy of long-acting octreotide for the treatment of advanced HCC. One hundred twenty untreated patients with histologically confirmed HCC were randomized to receive either long-acting octreotide (Sandostation LAR 30 mg) intramuscularly every 4 weeks or placebo. The study groups were comparable with respect to clinical characteristics. There was no difference in the cumulative survival. The median survival time was 4.7 months in the octreotide group compared with 5.3 months in the control group. Six-month survival rates were 41% for octreotide patients and 42% for control patients, respectively. The unadjusted relative risk for mortality in the octreotide group compared with patients in the control group was 1.11 (95% CI 0.76-1.63; P = 0.59). When adjusted for Okuda, CTP, and Cancer of the Liver Italian Program (CLIP) scores, the relative risk for octreotide did not change markedly and was 1.05 (95% CI 0.71-1.55; P = 0.83). The CLIP score seems to predict survival better than both Okuda and CTP score., Conclusion: The randomized controlled double-blind HECTOR trial showed no survival benefit for HCC patients treated with long-acting octreotide compared with placebo.

Background: Hepatopulmonary syndrome (HPS) is a rare complication of liver diseases of different etiologies and may indicate a poor prognosis. Therefore, a simple non-invasive screening method to detect HPS would be highly desirable. In this study pulse oximetry was evaluated to identify patients with HPS., Methods: In 316 consecutive patients with liver cirrhosis (n = 245), chronic hepatitis (n = 69) or non-cirrhotic portal hypertension (n = 2) arterial oxygen saturation (SaO2) was determined using a pulse oximeter. In patients with SaO2 < or = 92% in supine position and/or a decrease of > or = 4% after change from supine to upright position further diagnostic procedures were performed, including contrast-enhanced echocardiography and perfusion lung scan., Results: Seventeen patients (5.4%) had a pathological SaO2. Four patients (1.3%) had HPS. HPS patients had a significant lower mean SaO2 in supine (89.7%, SD 5.4 vs. 96.0%, SD 2.3; p = 0.003) and upright position (84.3%, SD 5.0 vs. 96.0%, SD 2.4; p = 0.001) and had a lower mean PaO2 (56.2 mm Hg, SD 15.2 vs. 71.2 mm Hg, SD 20.2; p = 0.02) as compared to patients without HPS. The mean deltaSaO2 (difference between supine and upright position) was 5.50 (SD 7) in HPS patients compared to non-HPS patients who showed no change (p = 0.001). There was a strong correlation between shunt volume and the SaO2 values (R = -0.94)., Conclusion: Arterial SaO2 determination in supine and upright position is a useful non-invasive screening test for HPS and correlates well with the intrapulmonary shunt volume.

Background/aims: Local ablation methods are an effective treatment for hepatocellular carcinoma (HCC). The rate of recurrence or development of intra-hepatic metastases may be lowered by antitumoral immune responses. Since HCCs are in general only weakly immunogenic, cell injury induced by local tumor ablation (PEI/RFTA) may increase HCC immunogenicity and may release endogenous adjuvants that activate dendritic cells (DC). The aim of the study, therefore, was the analysis whether PEI or RFTA induced injury results in an adjuvant effect for immune responses to HCCs., Methods: Eight HCC patients were treated with PEI or RFTA and serially analyzed for 4 weeks. Plasmocytoid (PDC) and myeloid dendritic cells (MDC) were analyzed directly ex vivo and in vitro using FACS and proliferation assays., Results: HCC ablation induced a functional transient activation of MDC but not of PDC associated with increased serum levels of TNF-alpha and IL-1beta., Conclusions: These findings suggest that the combination of PEI or RFTA and active antigen specific immunotherapeutic approaches using DCs is a promising approach for the induction of sustained antitumoral immune responses aiming at the reduction of tumor recurrence and metastases in HCC patients.

Aim: To assess whether the effectiveness of a combination of transarterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) in the treatment of unresectable hepatocellular carcinoma (HCC) is superior to TACE alone a randomized controlled trial was performed., Methods: The effect of combination therapy on long-term survival rates and duration of hospitalization was evaluated in 52 previously untreated HCCs, randomly allocated to TACE-PEI (27 pts) or TACE alone (25 pts)., Results: The cumulative survival rate of the TACE group was 75.8% at 6 mo, 62.9% at 12 mo, and 18.0% at 24 mo and of the TACE-PEI group 76.9%, 61.5%, and 38.7%, respectively. Comparison of overall survival in both groups showed no statistically significant difference. Regarding the patients with HCCs Okuda stage I (n = 26), the median survival of the TACE-PEI group was significantly longer (>24 mo, median not yet reached in the study period) compared to the TACE group (18.4 mo [range 11.6-21.7 mo]; P = 0.04). TACE-PEI reduced the relative risk for mortality to 0.4 (95%CI 0.15-0.96) compared to patients who received TACE alone. Median survival in patients with HCCs Okuda stage II or III was 5.0 mo in the TACE group (1.7 mo-not defined) compared to 10.4 mo in the TACE-PEI group., Conclusion: The combination TACE-PEI improved survival time compared to TACE alone. Our study revealed a statistically significant improved survival in HCCs Okuda stage I. Side effects were minor and the combination therapy did not prolong duration of hospitalization considerably.

Background: While the Wnt pathway has been widely implicated in hepatocarcinogenesis, the role of cyclin D1 as a direct downstream target gene of beta-catenin-lymphoid enhancer factor-1 (LEF-1)/T-cell factor (TCF) signaling is controversely discussed., Methods: By immunohistochemical analyses we studied the subcellular localization of LEF-1/TCF and cyclin D1 in 162 hepatocellular carcinoma (HCC). Single- and double-label imaging by brightfield and confocal laser scanning microscopy was quantitated and correlated with beta-catenin, the Ki67(+) proliferation fraction (PF), tumor size, grade, the Okuda stage and patient survival., Results: The frequency of nuclear cyclin D1 expression was 28% and closely correlated with LEF-1/TCF (P<0.0001) and the Ki67(+) PF (P=0.03). Nuclear LEF-1/TCF expression was observed in 52% of all cases, but was also present in 42% of cyclin D1(-) cases. Nuclear beta-catenin was identified in 37% of all HCCs and correlated with LEF-1/TCF (P=0.04). The expression of cyclin D1, LEF-1/TCF or beta-catenin did not correlate with other clinico-pathological data., Conclusions: A large proportion of HCCs does not appear to be linked to a deregulation of cyclin D1. However, the coordinated expression of cyclin D1 and LEF-1/TCF in some cases suggests the role of cyclin D1 as a Wnt target gene in a subset of HCCs.

Background: The need is well recognized for additional data on endoluminal therapies for gastroesophageal reflux disease (GERD). This prospective multicenter clinical trial was designed to assess safety and effectiveness of Enteryx, a nonresorbable copolymer implanted into the lower esophagus, in reducing usage of proton pump inhibitors (PPIs) and improving reflux symptoms and quality of life., Methods: Enteryx implantation was performed under fluoroscopic visualization without general anesthesia in 93 patients with symptomatic GERD responsive to and relapsing upon cessation of PPI therapy. Subjective and objective data were collected up to 12 months postprocedure. The criterion for treatment success was reduction in PPI dosage of > or =50%., Results: At 12 months, treatment success was attained in 86% (confidence interval, 77%-93%) of 74 evaluable patients and elimination of PPI therapy in 65% (confidence interval, 53%-76%). The treatment success rate by intent-to-treat analysis was 69% (confidence interval, 58%-78%). Reflux-related heartburn (P < 0.0001), regurgitation symptoms (P = 0.0005), and physical (P < 0.0001) and mental quality of life (P = 0.0012) scores improved. The most frequent complications were chest pain (77%), dysphagia/odynophagia (27%), and sensation of fever (26%)., Conclusions: Enteryx implantation provides an effective and safe alternative for management of gastroesophageal reflux, reducing medication dependency and symptoms and enhancing quality of life.

The cellular retinol-binding protein-1 (CRBP-1) plays a key role in the esterification and intercellular transfer of retinol. By in situ hybridization, immunohistochemistry, and confocal laser scanning microscopy (CLSM), we show that, in normal liver, CRBP-1 is strongly expressed in the cytoplasm of hepatic stellate cells (HSCs) and myofibroblasts (MFs) with only low CRBP-1 levels in hepatocytes. By contrast, in 196 hepatocellular carcinoma (HCC) specimens CRBP-1 expression in MFs was down-regulated in 83%. Patients with high CRBP-1 expression in MFs had a significantly higher 2-year survival as compared with patients with low CRBP-1 expression (52% vs. 29%, respectively; P =.034). An aberrant nuclear CRBP-1 accumulation resulting from cytoplasmic invagination was found in 29% of HCCs. Nuclear CRBP-1 staining correlated positively with a favorable tumor stage (Okuda stage I; P =.01) and negatively with the Ki-67(+) proliferation fraction (PF). A Ki-67(+) PF of > or =10% was associated with a lower 2-year survival probability as compared with patients with a Ki-67(+) PF of <10% (12% vs. 40%, respectively; P =.015). Prognosis did not correlate with the nuclear beta-catenin expression. There was, however, a close correlation between nuclear CRBP-1 inclusions and nuclear beta-catenin staining in HCCs (P =.008), suggesting a cross talk between CRBP-1 and the Wnt/wingless signal transduction pathway. In conclusion, our findings demonstrate that CRBP-1 detection may be useful for the discrimination between nonneoplastic and neoplastic liver cells and suggest that modulation of CRBP-1 expression in HCCs contributes to tumor growth and progression via retinoid-mediated signaling and disruption of cellular vitamin A homeostasis.

Purpose: To compare the effectiveness of radio-frequency (RF) thermal ablation with that of percutaneous ethanol injection (PEI) for the treatment of small hepatocellular carcinoma (HCC) in patients with cirrhosis., Materials and Methods: A series of 102 patients with hepatic cirrhosis and either single HCC 5 cm in diameter or smaller or as many as three HCCs each 3 cm or smaller (overall number of lesions, 142) randomly received either RF ablation (n = 52) or PEI (n = 50) as the sole first-line anticancer treatment. Mean follow-up was 22.9 months +/- 9.4 (SD) in the RF group and 22.4 months +/- 8.6 in the PEI group. Prognostic value of treatment techniques was assessed with univariate and multivariate Cox proportional hazards regression models., Results: One- and 2-year survival rates were 100% and 98% in the RF group and 96% and 88% in the PEI group, respectively (univariate relative risk [RR] = 0.20; 95% CI: 0.02, 1.69; P =.138). One- and 2-year local recurrence-free survival rates were 98% and 96% in the RF group and 83% and 62% in the PEI group, respectively (univariate RR = 0.17; 95% CI: 0.06, 0.51; P =.002). One- and 2-year event-free survival rates were 86% and 64% for the RF group and 77% and 43% for the PEI group, respectively (univariate RR = 0.48; 95% CI: 0.27, 0.85; P =.012). RF treatment was confirmed as an independent prognostic factor for local recurrence-free survival rates with multivariate analysis (adjusted RR = 0.20; 95% CI: 0.05, 0.73; P =.015)., Conclusion: RF ablation is superior to PEI with respect to local recurrence-free survival rates.

Background: Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases of unknown etiology. Unspecific immunosuppressive therapy represents current standard treatment and is often associated with severe side effects. Several treatment regimens have been evaluated to identify alternative therapeutic options. Among these different diet therapies were investigated. Objective of this paper is to review the results of diet therapy in chronic inflammatory bowel disease on the basis of randomised controlled trials and meta-analysis of randomised controlled trials., Methods: Medline and Cochrane Library were searched for meta-analysis and randomised controlled trials investigating this question. Additionally reference lists of identified articles and text books were checked for further trials., Results: Four meta-analyses investigated the treatment of acute Crohn's disease with elemental-, semi-elemental-, and polymeric diets in comparison to corticosteroids or to another form of enteral diet. All meta-analyses show a superiority of corticosteroids and no difference in the effect of the compared enteral diets. Randomised controlled trials investigating diet therapy in ulcerative colitis have not been summarised in a meta-analysis yet. Eleven randomised trials were identified which evaluated diets in ulcerative colitis patients: Dietary supplementation with n-3-fatty acids (6 trials), elemental diet [2], dietary supplementation with dietary fiber [1], elimination diet [1], and dietary supplementation with olestra [1]. Only for the elimination diet a significant positive effect on the course of disease was found in one trial which investigated only 18 patients., Conclusions: Enteral nutritional therapy of acute Crohn's disease is less effective than treatment with corticosteroids. In case of severe steroid induced side effects diet treatment can present a promising alternative. Superiority of one of the investigated different formulations was not found. Meta-analyses of randomised trials provide a clear and easy to understand presentation of the effect of this intervention. Eleven published trials investigating the effect of diets in ulcerative colitis show only for elimination diet a positive treatment effect. The trials do find a positive effect of one of the other interventions but the trials are very small and cannot exclude a treatment effect. Meta-analysis of these trials would be helpful for a better presentation and understanding of these results.

Background: Malignant biliary obstruction, which requires endoscopic stenting as palliative therapy, is often complicated by clogging of the stent with subsequent jaundice and/or cholangitis. Stent clogging may be caused by microbiological adhesion and biliary stasis. Therefore, antibiotics and choleretic agents like ursodeoxycholic acid (UDCA) have been investigated to see whether they prolong stent patency., Objectives: To evaluate if UDCA and/or antibiotics may prolong stent patency and survival in patients with strictures of the biliary tract and endoscopically inserted stents., Search Strategy: The Trials Register of The Cochrane Hepato-Biliary Group, The Cochrane Library, MEDLINE, Current Contents, EMBASE, and CancerLit were searched until June 2001. Reference lists of the identified articles were checked for further trials., Selection Criteria: All randomised or quasi-randomised clinical trials investigating UDCA and/or antibiotics in patients with biliary stents were considered for inclusion, regardless of blinding, language, and publication status., Data Collection and Analysis: Trial inclusion, quality assessment, and data extraction were performed independently by two reviewers. Principal investigators were contacted for further information. Survival data were combined by using hazard ratios (with 95% confidence interval (95% CI))., Main Results: Five non-blinded randomised trials with 258 patients with malignant strictures treated with polyethylene stents were included. Three trials, including 152 patients, investigated a combination of UDCA and antibiotics versus no treatment. The meta-analysis of these three trials does not show a significant treatment effect on the duration of stent patency (hazard ratio (random effects model) 0.58, 95% CI 0.22 to 1.54) or mortality (hazard ratio (fixed effect model) 0.99, 95% CI 0.68 to 1.43). Two trials with 106 patients compared antibiotics with no treatment, one of these trials used a combination of antibiotics and rowachol (an 'alternative' drug of the 'mint' family). The pooled results of these two trials do not show significant effects of antibiotics on the duration of stent patency (hazard ratio (fixed effect model) 0.69 (95% CI 0.37 to 1.30)) or mortality (hazard ratio (fixed effect model) 1.23 (95% CI 0.72 to 2.08). Data concerning duration of hospital stay, frequency of cholangitis, and rate of infectious complications due to selection of antibiotic resistant bacteria strains were not available., Reviewer's Conclusions: Treatment with UDCA and/or antibiotics to prevent clogging of biliary stents in patients with malignant stricture of the biliary tract cannot be recommended routinely on the basis of the existing randomised clinical trials. Further trials are needed with rigorous methodology and sufficient statistical power.

Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide. Due to advanced or decompensated liver cirrhosis, comorbidity and multicentricity of the tumor lesions, 70-80% of HCC patients are inoperable at the time of diagnosis. Radiofrequency thermal ablation (RFTA) is a new minimally invasive and sage technique for the nonsurgical treatment of HCCs. Similar to other ablation techniques, the treatment strategy depends on several factors, including the patient's clinical status, the stage of liver cirrhosis and of the HCC. RFTA can be performed percutaneously, laparoscopically or after laparotomy. Advanced RFTA equipment, refined techniques of modifying tumor tissue response to RFTA, and combined treatment strategies should lead to better response rates even in larger HCCs., (Copyright 2002 S. Karger AG, Basel)

This report presents a 46-year-old man who was treated for hypertension with the angiotensin-converting-enzyme (ACE) inhibitor enalapril. After 3 years of continuous treatment he presented with jaundice and progressive liver failure that continued despite withdrawal of the medication. The patient was taking no other medication. All known causes of acute liver failure could be excluded indicating a drug-induced liver damage after long-term treatment with enalapril. Analysis of liver biopsies revealed a pathomorphological pattern comparable to than observed in severe halothane hepatitis. Serological studies including T-cell stimulation with enalapril and a broad spectrum of tests for autoimmunity including autoantibodies against calreticulin, the major Ca2+ and Zn2+ binding protein of the endoplasmic reticulum and suggested to be involved in the pathogenesis of halothane hepatitis were negative. Thus, the mechanism of enalapril-induced liver injury remains obscure. Liver failure progressed and finally led to orthotopic liver transplantation. To our knowledge, this is the longest duration of chronic treatment with an ACE inhibitor before liver failure occurred. In addition, liver failure progressed despite withdrawal of the medication. It is concluded that even after long-term treatment with an ACE inhibitor liver failure may be induced. Therefore, regular monitoring of liver enzymes should be considered.

Purpose: To evaluate the usefulness of percutaneous radio-frequency (RF) thermal ablation of nonresectable hepatocellular carcinoma (HCC) after occlusion of the tumor arterial supply., Materials and Methods: Sixty-two patients with cirrhosis and biopsy-proved HCC underwent RF ablation after interruption of the tumor arterial supply by means of occlusion of either the hepatic artery with a balloon catheter (40 patients) or the feeding arteries with gelatin sponge particles (22 patients)., Results: After a single RF procedure in 56 patients and after two procedures in six patients, spiral computed tomography (CT) demonstrated a nonenhancing area corresponding in shape to the previously identified HCC, which was suggestive of complete necrosis. No major complications occurred. Two patients subsequently underwent surgical resection; the remaining 60 patients were followed up with spiral CT. During a mean follow-up of 12.1 months, 11 HCC nodules showed areas of local progression; 49 were identified as nonenhancing areas with a 40%-75% reduction in maximum diameter. The 1-year estimate of failure risk was 19% for local recurrence and 45% for overall intrahepatic recurrence. The estimated 1-year survival was 87%. Histopathologic analysis of one autopsy and two surgical specimens revealed more than 90% necrosis in one specimen and 100% necrosis in two., Conclusion: HCC nodules 3.5-8.5 cm in diameter can be ablated in one or two RF sessions after occlusion of the tumor arterial supply.

Pancreaticobiliary tumors are mostly adenocarcinomas with a poor 5-year survival of less than 2%. Early diagnosis of resectable tumors improves outcome. Conventional ultrasound (US) is non-invasive and is the first modality employed on suspicion of these tumors. With adequate skills and equipment, pancreatic tumors from 1.5 cm in diameter can be detected. By contrast, US is less sensitive in the detection of lymph node involvement and infiltration of blood vessels. Depending on the location tumors of the biliary tract appear as a mass lesion intrahepatically or within the gallbladder. Perihilar and extrahepatic bile duct carcinomas cause proximal duct dilatation which is readily detected by US. Again, sensitivity in the detection of lymph node metastases or portal vein invasion is limited. Endoscopic ultrasound (EUS) has emerged as the method of choice in detecting small pancreatic tumors (e.g. < 2 cm in diameter). An accuracy of over 90% in T-staging and blood vessel infiltration can be achieved whereas lymph node metastases are correctly diagnosed in only 67% of cases. EUS-guided biopsy is readily performed using a curved array scanner. This technique enables neurolysis of the coeliac plexus in patients with heavy pain. EUS adds valuable information in cases of distal extrahepatic bile duct cancer. The role of EUS is limited in perihilar and intrahepatic cholangiocarcinoma. Staging and palliative therapy of perihilar carcinoma is still a domain of endoscopic retrograde cholangiography. Intraductal EUS is restricted to specialized centers and plays no role for routine purposes.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) requires selective cannulation of the common bile duct and pancreatic duct. Selective common bile and pancreatic duct cannulation with standard techniques can be achieved in most but not all cases even in experienced centers. To facilitate selective cannulation, sphincterotomes can be used., Methods: A prospective randomized study aimed at selective deep cannulation of the common bile and pancreatic ducts comparing different ERCP procedures was performed. One hundred patients were randomly assigned to undergo cannulation with a standard catheter or with a guidewire sphincterotome (GS) without guidewire., Results: The primary success rate of selective common bile duct cannulation was significantly higher in the GS group (84%) as compared with the standard catheter group (62%) (p = 0.023). In patients with primary standard catheter failure, selective common bile duct cannulation was possible in 16 patients using a GS which increased the total success rate in the standard catheter group to 94% (p < 0.001). In GS failures selective common bile duct cannulation was possible in two patients using a standard catheter and increased the total success rate from 84% to 88%. The frequency of postinterventional pancreatitis did not differ significantly between the two groups., Conclusions: ERCP using a GS without guidewire has a significantly higher primary success rate for selective common bile duct cannulation then ERCP using a standard catheter. The use of a GS should be considered to optimize selective cannulation of the common bile duct before resorting to precut techniques.

In the majority of patients hepatocellular carcinoma (HCC) is associated with liver cirrhosis. Advanced or decompensated liver cirrhosis, comorbidity and multicentricity make 70-80% of HCCs inoperable at the time of diagnosis. Therefore, percutaneous ethanol injection (PEI) and radiofrequency thermal ablation (RFTA) are non-surgical therapeutic options for patients with small HCCs. In patients with advanced tumor stage transarterial chemoembolization (TACE) and its variants showed no survival benefit on the basis of randomized trials. In several studies, however, combined treatment strategies like TACE and PEI or RFTA after occlusion of tumor blood supply in the treatment of advanced HCC seems to result in a survival benefit. All HCC patients should be included in randomized treatment studies.

Manometry of the esophagus is essential in the diagnostic workup of patients with motility disorders of the esophagus. Before manometry organic diseases causing the symptoms should be excluded by a esophago-gastroscopy and/or a barium swallow meal. Indications for manometry are noncardiac chest pain, dysphagia of unknown origin, primary or secondary motility disorders of the esophagus and preoperative assessment before antireflux surgery.

Tumors of the papilla of Vater are very rare. Despite advanced imaging techniques the distinction between benign and malignant tumors remains very difficult. Because most ampullary and periampullary tumors are malignant, primary management is surgical. Here we report the case of a 65-year-old man with biliary obstruction caused by an ampullary hamartoma simulating cancer. The correct diagnosis was not established until surgery.

Hepatocellular carcinoma (HCC) is one of the most severe sequelae of chronic liver disease. The only potentially curative therapeutic options are surgical resection and orthotopic liver transplantation. In most HCC patients, however, at clinical presentation the tumors are unresectable because of multicentricity or poor hepatic functional reserve due to pre-existing cirrhosis or not transplantable because of too advanced tumor stage or severe co-morbidity. In clinical practice, therefore, percutaneous ethanol injection (PEI) and transarterial chemoembolization (TACE) are widely used non-surgical therapeutic strategies. We prospectively analyzed the clinical factors determining the prognosis of 132 inoperable HCC patients and assessed the feasibility, therapeutic efficacy and safety of PEI, TACE and a combination thereof. Mean age of patients was 64 years; 95% of patients had liver cirrhosis and 39% were Okuda stage I, 48% stage II and 13% stage III. Fifteen patients were treated by PEI (group 1), 33 by TACE (group 2), 39 by TACE and PEI (group 3) and 45 received best supportive care (group 4). Survival correlated with the Child-Pugh class of liver cirrhosis and the Okuda stage of HCC. Favorable prognostic parameters were alpha-fetoprotein (AFP) levels <100 ng/ml and absence of portal vein thrombosis. Median survival time was 18 months in group 1 [interquartile range (IQR) 10-19], 8 months in group 2 (IQR 5-15), 25 months in group 3 (IQR 13-36) and 2 months in group 4 (IQR 1-9). Multivariate analysis revealed that patients treated with a combination of TACE and PEI have a significantly better survival than patients receiving either PEI or TACE only (p = 0.001). Patients with inoperable HCCs treated by the combination of TACE and PEI have a clear survival benefit. A favorable outcome can be expected in patients with compensated cirrhosis, a low Okuda stage, a baseline AFP level <100 ng/ml and absence of portal vein thrombosis.

The therapeutic modalities in patients with hepatocellular carcinoma (HCC) depend on the number, size and location of the lesions as well as the stage of the underlying liver disease and the physical condition of the patients. In patients with small and solitary lesions resection, liver resection and in selected cases liver transplantation can be curative. In more advanced stages of the disease with larger or multiple lesions PEI and/or transarterial chemotherapy with or without embolisation (TACE or TAC) can slow the progression of the disease. In disseminated disease, a radio-therapeutic approach can be taken in selected cases. The therapeutic strategy in patients with HCCs has to be individualized, frequently using a combination of therapeutic modalities. Different from the earlier unfavourable prognosis, today for most HCC patients a therapeutic strategy can be offered that results in a prolongation of life and in some cases even cure.

The hepatopulmonary syndrome (HPS) is a reversible pulmonary insufficiency in association with liver disease, most frequently liver cirrhosis. The pathogenesis of HPS is poorly understood. HPS is characterized by arterial hypoxemia caused by intrapulmonary arteriovenous shunts or marked vasodilatation of the pulmonary vessels and ventilation-perfusion mismatch in the absence of intrinsic heart or lung disease. Typical clinical signs are dyspnea in the upright position which improves in supine position (platypnoe) and decrease of arterial pO2 in the upright position (orthodeoxia). The diagnosis of HPS is based on clinical features, arterial blood gas analyses in supine and upright position, contrast echocardiography and lung perfusion scanning. Arteriovenous fistula can be excluded by pulmonary angiography. There is no established medical treatment of HPS. New medical and noninvasive therapies, such as transjugular intrahepatic Stent-shunt (TIPS), lead to improvement of HPS. These treatment modalities need further elucidation. HPS was shown to be reversible after orthotopic liver transplantation (OLTx) in some cases. Severe HPS, therefore, may be an indication rather than a contraindication for OLTx.

Indications for a local non-surgical therapy of focal liver lesions are the hepatocellular carcinoma (HCC) and metastases. The HCC is one of the most frequent malignant tumors worldwide with an incidence of 1 million cases per year. The prognosis of the untreated HCC is poor. For non-surgical cases there are local and systemic therapies available. A number of studies involving thousands of patients, have used treatment by PEI. Several of these studies have shown an increased survival in the PEI-treated patients. For patients primarily not treatable with PEI transarterial chemoembolization (TACE) with lipiodol in combination with a chemotherapeutic drug and gelfoam is a possibility. Studies of patients treated with PEI or TACE show a variability in survival, however, the trend is to prolonged survival. Improvement in efficacy of treatment and decreases in toxicities could be achieved through a combination of different interventions and an optimal patient selection. Both surgical and those cases unsuitable to local therapy should be treated with tamoxifen.

The therapeutic modalities in patients with hepatocellular carcinoma (HCC) depend on the number, size and location of the lesions as well as the stage of the underlying liver disease and the physical condition of the patient. In patients with small and solitary lesions, resection, liver transplantation and in some cases percutaneous ethanol injection (PEI) can be curative. In more advanced stages of the disease with larger or multiple lesions, PEI and/or transarterial chemotherapy with or without embolization (TACE or TAC) can slow the progression of the disease. In disseminated disease, a radiotherapeutic approach can be taken in selected cases. The therapeutic strategy in patients with HCCs should be individualized, frequently involving a combination of therapeutic modalities. In contrast to the earlier dismal prognosis, for most HCC patients there is today a therapeutic strategy that results in prolongation of life and in some cases even cure.

Hepatocellular carcinoma (HCC) is a frequent complication of chronic liver disease. The major causes of chronic liver diseases are hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, as well as chronic alcohol misuse. The clinical presentations of HCC patients are unspecific, with signs and symptoms of chronic liver disease. Early diagnosis of HCC in an asymptomatic and potentially curable stage is of highest priority. The present strategy for the detection of early HCC in patients with chronic liver disease is 6-monthly determination of alpha-fetoprotein (AFP) and ultrasound study of the liver. If these are abnormal, further diagnostic steps include computer tomography, magnetic resonance tomography, lipiodol-angiography and histopathology. By this sequential diagnostic strategy it should be possible to identify HCC in patients with chronic liver disease at an early and potentially curable stage.