Brigitte Schumacher

Comparative performance of uncoated, self-expanding metal biliary stents of different designs in 2 diameters: final results of an international multicenter, randomized, controlled trial.

BACKGROUND The Wallstent has remained the industry standard for biliary self-expanding metal stents (SEMSs). Recently, stents of differing designs, compositions, and diameters have been developed. OBJECTIVE To compare the new nitinol 6-mm and 10-mm Zilver stents with the 10-mm stainless steel Wallstent and determine the mechanism of obstruction. DESIGN Randomized, prospective, controlled study. SETTING Nine centers experienced in SEMS placement during ERCP. PATIENTS A total of 241 patients presenting between September 2003 and December 2005 with unresectable malignant biliary strictures at least 2 cm distal to the bifurcation. MAIN OUTCOME MEASUREMENT Stent occlusions requiring reintervention and death. RESULTS At interim analysis, a significant increase in occlusions was noted in the 6-mm Zilver group at the P = .04 level, resulting in arm closure but continued follow-up. Final study arms were 64, 88, and 89 patients receiving a 6-mm Zilver, 10-mm Zilver, and 10-mm Wallstent, respectively. Stent occlusions occurred in 25 (39.1%) of the patients in the 6-mm Zilver arm, 21 (23.9%) of the patients in the 10-mm Zilver arm, and 19 (21.4%) of the patients in the 10-mm Wallstent arm (P = .02). The mean number of days of stent patency were 142.9, 185.8, and 186.7, respectively (P = .057). No differences were noted in secondary endpoints, and the study was ended at the 95% censored study endpoints. Biopsy specimens of ingrowth occlusive tissue revealed that 56% were caused by benign epithelial hyperplasia. CONCLUSIONS SEMS occlusions were much more frequent with a 6-mm diameter SEMS and equivalent in the two 10-mm arms despite major differences in stent design, material, and expansion, suggesting that diameter is the critical feature. Malignant tumor ingrowth produced only a minority of the documented occlusions.

Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II)

Objective Focal endoscopic resection (ER) followed by radiofrequency ablation (RFA) safely and effectively eradicates Barretts oesophagus (BO) containing high-grade dysplasia (HGD) and/or early cancer (EC) in smaller studies with limited follow-up. Herein, we report long-term outcomes of combined ER and RFA for BO (HGD and/or EC) from a single-arm multicentre interventional study. Design In 13 European centres, patients with BO≤12 cm with HGD and/or EC on 2 separate endoscopies were eligible for inclusion. Visible lesions (<2 cm length; <50% circumference) were removed with ER, followed by serial RFA every 3 months (max 5 sessions). Follow-up endoscopy was scheduled at 6 months after the first negative post-treatment endoscopic control and annually thereafter. Outcomes: complete eradication of neoplasia (CE-neo) and intestinal metaplasia (CE-IM); durability of CE-neo and CE-IM (once achieved) during follow-up. Biopsy and resection specimens underwent centralised pathology review. Results 132 patients with median BO length C3M6 were included. After entry-ER in 119 patients (90%) and a median of 3 RFA (IQR 3–4) treatments, CE-neo was achieved in 121/132 (92%) and CE-IM in 115/132 patients (87%), per intention-to-treat analysis. Per-protocol analysis, CE-neo and CE-IM were achieved in 98% and 93%, respectively. After a median of 27 months following the first negative post-treatment endoscopic control, neoplasia and IM recurred in 4% and 8%, respectively. Mild-to-moderate adverse events occurred in 25 patients (19%); all managed conservatively or endoscopically. Conclusions In patients with early Barretts neoplasia, intensive multimodality endotherapy consisting of ER combined with RFA is safe and highly effective, and the treatment effect appears to be durable during mid-term follow-up. Trial registration number NTR 1211, http://www.trialregister.nl.

Prospective comparison of endoscopic ultrasound-guided fine-needle aspiration and surgical histology in upper gastrointestinal submucosal tumors

STUDY AIM To assess the accuracy of ultrasound-guided fine-needle aspiration biopsy in the differential diagnosis of gastrointestinal stroma cell tumors (GIST) from other submucosal tumors, using both cytology and histology. PATIENTS AND METHODS We conducted a prospective study from May 2005 to September 2008 in all patients presenting with upper gastrointestinal submucosal tumors. Only patients in whom surgical resection was carried out were included in the final analysis. In cases of mesenchymal tumor, immunocytochemistry was attempted for further differentiation between GIST and non-GIST. Surgical histopathology served as the gold standard. RESULTS A total of 47 patients were analyzable, with a final histologic diagnosis of 35 mesenchymal tumors. Sufficient tissue for conventional cytologic diagnosis was obtained only in the 35 patients with mesenchymal tumors; in this subgroup, immunocytochemistry was possible in 46 %. If and only if enough material was available for immunocytochemistry, the sensitivity for (correct recognition of) GIST tumors was 93 %. In all 12 patients with nonmesenchymal tumors and lesions, cytology was nondiagnostic and the diagnosis had to be based on clinical suspicion and the appearance on endoscopy and endoscopic ultrasound (EUS). On an intention-to-diagnose basis, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) had a positive predictive value for mesenchymal tumors of 100 %, but no value for the diagnosis of other lesions; using immunocytochemistry, a GIST tumor was recognized among the mesenchymal tumors with a sensitivity of 58 % and a specificity of 8 %. CONCLUSIONS EUS-FNA-based cytology is safe and has only limited value for the differential diagnosis of submucosal tumors, mainly because insufficient material is harvested. Better tissue acquisition techniques are necessary for better differential diagnosis.

Endoscopic submucosal dissection plus radiofrequency ablation of neoplastic Barrett's esophagus.

BACKGROUND AND STUDY AIMS Endoscopic submucosal dissection (ESD) of early gastrointestinal tumors has been shown to achieve complete resection rates superior to endoscopic mucosal resection (EMR), but at the cost of higher risk. The aim of this study was to prospectively assess the feasibility and oncological results of ESD in patients with neoplastic Barretts esophagus in conjunction with subsequent radiofrequency ablation (RFA). METHODS Patients with Barretts esophagus who had visible lesions containing high grade intraepithelial neoplasia (HGIN) or mucosal adenocarcinoma (MAC) up to 3 cm in diameter were included in the study. ESD was performed using a new waterjet-assisted system (WESD) with a HybridKnife (Erbe Elektromedizin GmbH, Tübingen, Germany). Primary outcome was the rate of complete tumor resection. RFA of residual intestinal metaplasia was offered to all patients with at least two negative follow-up endoscopies. RESULTS Of 30 patients (m:f = 21:9; median age 60 years) with biopsy-proven MAC (n = 24) or HGIN (n = 6) with a median diameter of 2 cm, complete resection of the targeted area was achieved in 29 patients (96.7 %; 95 % confidence interval [CI] 82 % - 99 %); en bloc resection was achieved in 27 of these patients (90.0 %; 95 %CI 74 % - 97 %). Minor delayed bleedings occurred in two patients. One patient died due to a sudden cardiac death 7 days after an uneventful WESD. Specimen histology (n = 29) revealed no neoplasia in 3 patients, HGIN in 2, MAC in 21, and submucosal cancer in 3; complete resection was histologically confirmed in only 10 of the 26 patients with HGIN or adenocarcinoma (38.5 %; 95 %CI 22 % - 57 %). However, endoscopic follow-up (median 17 months) showed complete remission of neoplasia in 27 /28 (96.4 %; 95 %CI 81 % - 99 %) patients who underwent successful WESD and were alive at 30 days. One patient underwent EMR of residual tumor. All Barretts tissue was eradicated by ESD alone in 15 cases and by additional RFA in 8 /10 cases (not done in three patients). CONCLUSIONS ESD of Barretts neoplasia is feasible and safe, but does not achieve sufficient R0 resection rates to warrant its recommended use over piecemeal EMR. In combination with RFA it can achieve complete eradication of neoplastic and non-neoplastic Barretts epithelium. The discrepancy between insufficient oncological resection and good medium-term results needs to be studied further.

A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett’s neoplasia

Background For endoscopic resection of early GI neoplasia, endoscopic submucosal dissection (ESD) achieves higher rates of complete resection (R0) than endoscopic mucosal resection (EMR). However, ESD is technically more difficult and evidence from randomised trial is missing. Objective We compared the efficacy and safety of ESD and EMR in patients with neoplastic Barretts oesophagus (BO). Design BO patients with a focal lesion of high-grade intraepithelial neoplasia (HGIN) or early adenocarcinoma (EAC) ≤3 cm were randomised to either ESD or EMR. Primary outcome was R0 resection; secondary outcomes were complete remission from neoplasia, recurrences and adverse events (AEs). Results There were no significant differences in patient and lesion characteristics between the groups randomised to ESD (n=20) or EMR (n=20). Histology of the resected specimen showed HGIN or EAC in all but six cases. Although R0 resection defined as margins free of HGIN/EAC was achieved more frequently with ESD (10/17 vs 2/17, p=0.01), there was no difference in complete remission from neoplasia at 3 months (ESD 15/16 vs EMR 16/17, p=1.0). During a mean follow-up period of 23.1±6.4 months, recurrent EAC was observed in one case in the ESD group. Elective surgery was performed in four and three cases after ESD and EMR, respectively (p=1.0). Two severe AEs were recorded for ESD and none for EMR (p=0.49). Conclusions In terms of need for surgery, neoplasia remission and recurrence, ESD and EMR are both highly effective for endoscopic resection of early BO neoplasia. ESD achieves a higher R0 resection rate, but for most BO patients this bears little clinical relevance. ESD is, however, more time consuming and may cause severe AE. Trial registration number NCT1871636

Standardized Long-Term Follow-Up After Endoscopic Resection of Large, Nonpedunculated Colorectal Lesions: A Prospective Two-Center Study

OBJECTIVES:Endoscopic removal of large, nonpedunculated colorectal lesions is challenging. Long-term outcome data based on standardized protocols, including detailed inspection of the resection site, are scarce. The aims of the present study were to evaluate the safety and efficacy of endoscopic resection (ER) of large, nonpedunculated lesions (LNLs; >20 mm) and to assess the long-term recurrence rate afterward.METHODS:A total of 243 consecutive patients (141 men, 102 women) with 252 adenomas (>20 mm) was followed up using a standardized protocol after complete ER. After endoscopic treatment, the patients received standardized follow-up examinations after 3–6 months and 12 months. The postpolypectomy scar was re-examined, assessed for residual neoplasia, and biopsied at each follow-up colonoscopy.RESULTS:Evident residual neoplasia was noted after 3–6 months in 58 of 183 lesions (31.69%). After 12 months, 126 LNLs were examined, with 19 late recurrences (16.37%). Twenty-one (6.5%) postpolypectomy scars were not detected during 321 surveillance examinations. Biopsy evidence of residual/recurrent lesions was found in 16 of 228 macroscopically inconspicuous polypectomy scars (7%). All residual adenomas were treated using ER and/or argon plasma coagulation. There were 43 complications with the 252 lesions (17%), including 20 major complications (7.9%), all managed conservatively.CONCLUSIONS:A detailed study design with systematic biopsies of inconspicuous scars reveals a significant number of residual adenomas after completed resection. However, these residual neoplasias can be effectively treated at follow-up colonoscopies.

Endoscopic submucosal dissection of early gastric neoplasia with a water jet–assisted knife: a Western, single-center experience

BACKGROUND Endoscopic submucosal dissection (ESD) of early gastric neoplasia has not yet been established in Western countries because of a lack of data and the difficult, time-consuming, and hazardous nature of the method. Some of the technical limitations may be overcome by use of a water jet-assisted knife, which allows a combination of a high-pressure water jet and electrosurgical interventions. OBJECTIVE To evaluate the efficacy and safety of water jet-assisted ESD (WESD) with a water jet-assisted knife in selected patients with early gastric neoplasia. DESIGN Single-center, prospective study. PATIENTS This study involved 29 consecutive patients (13 female; median age 61 years; age range 35-93 years) with early gastric neoplasia that met the expanded criteria of the Japanese Gastric Cancer Association. Histology of biopsies had shown gastric adenocarcinoma in 21 cases, adenoma in 8 case, and suspicion of a GI stromal tumor in 1 case. The median maximal diameter of the lesions was 20 mm (range 10-40 mm). INTERVENTION All procedures were done with patients under sedation with propofol. The water jet-assisted knife was used for setting coagulation markers around the neoplastic lesions, then for circumferential incision and dissection in combination with repeated submucosal injection of saline solution with a water jet system. Bleeding was treated with diathermia by use of the water jet-assisted knife or hemostatic forceps in case of failure or larger vessels. Clips were used for closure of perforations. MAIN OUTCOME MEASUREMENTS Complete resection of neoplasia, procedure time, complication and recurrence rates. RESULTS According to endoscopic criteria, complete resection of the targeted area could be achieved in all cases, with an en bloc resection rate of 90%. The median procedure duration was 74 minutes (range 15-402 minutes). Exchange of the device was needed in only 10 cases because of severe bleeding from larger vessels, which could be managed by use of hemostatic forceps. The 30-day morbidity rate was 4 of 30 (13.8%) because of postprocedure pain in 3 cases and delayed bleeding in 1 case. A 93-year-old patient died the night after WESD without evidence of a procedure-related complication. Histology of the resected specimens showed adenocarcinoma in 20 cases, adenoma in 7, no neoplasia in 2, and a plasmacytoma in 1. Complete resection (R0) was histologically confirmed in 18 of 28 patients (64.3%) with resected neoplastic specimens. A horizontal or vertical neoplasia-free margin could not be confirmed in 9 cases and 1 case, respectively. Complete local remission of neoplasia was achieved in 25 of 28 patients (89.3%) who were followed over a median period of 22 months (range 6-44 months). In 1 patient, a metachronous gastric adenocarcinoma was identified 54 weeks after initial WESD. LIMITATIONS Noncontrolled study with a limited number of patients. CONCLUSION The use of a water jet-assisted knife simplifies ESD because exchange of devices is rarely needed. WESD promises to be effective and safe. The study demonstrates that the high rates of en bloc resection of early gastric neoplasia reported in Asia can be reproduced in Western referral centers. However, histology may not always confirm complete resection of horizontal tumor margins. In spite of the unfavorable histology results, the high rate of complete local remission of neoplasia promises that surgical treatment of early gastric neoplasia can be avoided in the majority of cases.

Forward-viewing versus oblique-viewing echoendoscopes in transluminal drainage of pancreatic fluid collections: a multicenter, randomized, controlled trial

BACKGROUND EUS-guided drainage of pancreatic fluid collections (PFCs) is commonly performed with oblique-viewing echoendoscopes. However, accessing the PFC under an oblique angle can make drainage difficult. These difficulties might be overcome by using a forward-viewing echoendoscope. OBJECTIVE To compare endoscopic PFC drainage with an oblique-viewing versus a forward-viewing echoendoscope with emphasis on ease of endoscopic drainage. DESIGN Multicenter, randomized, controlled trial. SETTING Four tertiary-care referral centers. PATIENTS This study involved 58 patients with PFCs. INTERVENTION Patients with PFCs (≥ 6 cm) in whom drainage was indicated were randomized to receive EUS-guided drainage with a forward-viewing echoendoscope or an oblique-viewing echoendoscope. In cases of failed drainage, patients were crossed over to the other study arm. MAIN OUTCOME MEASUREMENTS Ease of EUS-guided drainage measured by procedure time. Secondary endpoints included technical success, EUS endoscope preference, clinical success, and adverse events. RESULTS Fifty-eight consecutive patients underwent randomization, of whom 52 were available for primary endpoint analysis. All 26 EUS-guided procedures done with the oblique-viewing echoendoscope and 24 of the 26 procedures done with the forward-viewing echoendoscope were technically successful. Mean (± standard deviation) procedure time was 24:55 ± 9:58 minutes in the forward-viewing echoendoscope group and 27:04 ± 9:58 minutes in the oblique-viewing echoendoscope group (P = .44). Median overall procedure ease was graded as equal (easy) in both groups. Drainage-related adverse events occurred in 2 patients (8%) in the forward-viewing echoendoscope group versus none in the oblique-viewing echoendoscope group (P = .56). Overall clinical success was achieved in 82% of patients (95% confidence interval, 69%-91%). LIMITATIONS Derived main outcome parameter and highly specialized endoscopists in tertiary-care referral centers. CONCLUSION This multicenter, randomized, controlled trial comparing the performance of oblique-viewing echoendoscopes and forward-viewing echoendoscopes in draining PFCs did not show a difference in ease of EUS-guided drainage or procedure safety and efficacy between the forward-viewing echoendoscope and the oblique-viewing echoendoscope. Clinical success was achieved in 82% of patients.

Treatment of malignant gastroduodenal obstruction with a nitinol self-expanding metal stent: an international prospective multicentre registry.

BACKGROUND Duodenal stenting has become a broadly accepted first line of treatment for patients with advanced malignant gastroduodenal obstruction as these patients are difficult to treat and are poor surgical candidates. AIMS To document duodenal stent performance for palliative management of malignant gastroduodenal obstruction. METHODS Multicentre, single arm, prospective registry documenting peroral endoscopic duodenal stenting procedures in 202 patients. RESULTS Technical success achieved in 98% (CI, 95%, 99%) of stent placements. Increase of Gastric Outlet Obstruction Score by at least 1 point compared to baseline was achieved in 91% (CI, 86%, 95%) of patients persisting for a median of 184 days (CI, 109, 266). By day 5 (CI, 4, 6) after stent placement, 50% of patients experienced a score increase of at least 1 point. Improvement from 14% of patients at baseline tolerating soft solids or low residue/normal diet to 84% at 15 days, 86% at 30 days, 81% at 90 days, 79% at 180 days, and 70% at 270 days. Complications included stent ingrowth and/or overgrowth (12.4%), transient periprocedural symptoms (3%), bleeding (3%), stent migration (1.5%), and perforation (0.5%). CONCLUSIONS Safety and effectiveness of duodenal stenting for palliation of malignant gastroduodenal obstruction was confirmed in the largest international prospective series to date.

Reduced medication dependency and improved symptoms and quality of life 12 months after enteryx implantation for gastroesophageal reflux.

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 ≥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.