Angelika Behrens

Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus.

Objective: Endoscopic therapy is increasingly being used in the treatment of high-grade intraepithelial neoplasia (HGIN) and mucosal adenocarcinoma (BC) in patients with Barrett’s oesophagus. This report provides 5 year follow-up data from a large prospective study investigating the efficacy and safety of endoscopic treatment in these patients and analysing risk factors for recurrence. Design: Prospective case series. Setting: Academic tertiary care centre. Patients: Between October 1996 and September 2002, 61 patients with HGIN and 288 with BC were included (173 with short-segment and 176 with long-segment Barrett’s oesophagus) from a total of 486 patients presenting with Barrett’s neoplasia. Patients with submucosal or more advanced cancer were excluded. Interventions: Endoscopic therapy. Main outcome measures: Rate of complete remission and recurrence rate, tumour-associated death. Results: Endoscopic resection was performed in 279 patients, photodynamic therapy in 55, and both procedures in 13; two patients received argon plasma coagulation. The mean follow-up period was 63.6 (SD 23.1) months. Complete response (CR) was achieved in 337 patients (96.6%); surgery was necessary in 13 (3.7%) after endoscopic therapy failed. Metachronous lesions developed during the follow-up in 74 patients (21.5%); 56 died of concomitant disease, but none died of BC. The calculated 5 year survival rate was 84%. The risk factors most frequently associated with recurrence were piecemeal resection, long-segment Barrett’s oesophagus, no ablative therapy of Barrett’s oesophagus after CR, time until CR achieved >10 months and multifocal neoplasia. Conclusions: This study showed that endoscopic therapy was highly effective and safe, with an excellent long-term survival rate. The risk factors identified may help stratify patients who are at risk for recurrence and those requiring more intensified follow-up.

Long-term Efficacy and Safety of Endoscopic Resection for Patients With Mucosal Adenocarcinoma of the Esophagus

BACKGROUND & AIMS Barretts esophagus-associated high-grade dysplasia is commonly treated by endoscopy. However, most guidelines offer no recommendations for endoscopic treatment of mucosal adenocarcinoma of the esophagus (mAC). We investigated the efficacy and safety of endoscopic resection in a large series of patients with mAC. METHODS We collected data from 1000 consecutive patients (mean age, 69.1 ± 10.7 years; 861 men) with mAC (481 with short-segment and 519 with long-segment Barretts esophagus) who presented at a tertiary care center from October 1996 to September 2010. Patients with low-grade and high-grade dysplasia and submucosal or more advanced cancer were excluded. All patients underwent endoscopic resection of mACs. Patients found to have submucosal cancer at their first endoscopy examination were excluded from the analysis. RESULTS After a mean follow-up period of 56.6 ± 33.4 months, 963 patients (96.3%) had achieved a complete response; surgery was necessary in 12 patients (3.7%) after endoscopic therapy failed. Metachronous lesions or recurrence of cancer developed during the follow-up period in 140 patients (14.5%) but endoscopic re-treatment was successful in 115, resulting in a long-term complete remission rate of 93.8%; 111 died of concomitant disease and 2 of Barretts esophagus-associated cancer. The calculated 10-year survival rate of patients who underwent endoscopic resection of mACs was 75%. Major complications developed in 15 patients (1.5%) but could be managed conservatively. CONCLUSIONS Endoscopic therapy is highly effective and safe for patients with mAC, with excellent long-term results. In an almost 5-year follow-up of 1000 patients treated with endoscopic resection, there was no mortality and less than 2% had major complications. Endoscopic therapy should become the standard of care for patients with mAC.

Efficacy, Safety, and Long-term Results of Endoscopic Treatment for Early Stage Adenocarcinoma of the Esophagus With Low-risk sm1 Invasion

BACKGROUND & AIMS Patients with early-stage mucosal (T1a) esophageal adenocarcinoma (EAC) are increasingly treated by endoscopic resection. EACs limited to the upper third of the submucosa (pT1b sm1) could also be treated by endoscopy. We assessed the efficacy, safety, and long-term effects of endoscopic therapy for these patients. METHODS We analyzed data from 66 patients with sm1 low-risk lesions (macroscopically polypoid or flat, with a histologic pattern of sm1 invasion, good-to-moderate differentiation [G1/2], and no invasion into lymph vessels or veins) treated by endoscopic therapy at the HSK Hospital Wiesbaden from 1996 through 2010. The efficacy of endoscopic therapy was assessed on the basis of rates of complete endoluminal remission (CER), metachronous neoplasia, lymph node events, and long-term remission (LTR). Safety was assessed on the basis of rate of complications. RESULTS Remissions were assessed in 61 of the 66 patients; 53 of the 61 achieved CER (87%). Of patients with small focal neoplasias ≤2 cm, 97% achieved CER (for those with tumors ≥2 cm, 77%; P = .026). Metachronous neoplasias were observed in 10 of 53 patients (19%; 9 of the 10 underwent repeat endoscopic resection). One patient developed a lymph node metastasis (1.9%). Fifty-one patients achieved LTR (84%); 90% of those with focal lesions ≤2 cm achieved LTR after a mean follow-up period of 47 ± 29.1 months (range, 8-120 months). No tumor-associated deaths were observed, and the estimated 5-year survival rate was 84%. The rate of major complications from endoscopic resection was 1.5%, and no patients died. CONCLUSIONS Endoscopic therapy appears to be a good alternative to esophagectomy for patients with pT1b sm1 EAC, on the basis of macroscopic and histologic analyses. The risk of developing lymph node metastases after endoscopic resection for sm1 EAC is lower than the risk of surgery.

Water Infusion for Cecal Intubation Increases Patient Tolerance, but Does Not Improve Intubation of Unsedated Colonoscopies

BACKGROUND & AIMS Several studies have indicated that water infusion, instead of air insufflation, enhances cecal intubation in selected patients undergoing unsedated colonoscopy. We performed a prospective, randomized, controlled trial to investigate whether the water technique increases the proportion of patients that are able to complete unsedated colonoscopy. METHODS We analyzed data from 116 consecutive outpatients who were willing to start colonoscopy without sedation; 58 were each randomly assigned to groups given water infusion or air insufflation during the insertion phase. Sedation and analgesia were administered on demand. RESULTS Fewer patients requested sedation in the water group (8.6%) than in the air group (34.5%; P = .003) and their maximum pain scores were lower (2.8 ± 1.9 vs 4.2 ± 2.3 in the air group; P = .011). However, differences in percentages of patients who received complete, unsedated colonoscopy between the water group (74.1%) and air group (62.1%) did not reach statistical significance (P = .23); the percentage of successful cecal intubations was lower in the water group (82.8%) than in the air group (96.5%; P = .03) because of poor visibility. Failed procedures in the water group were completed successfully after air insufflation. The cecal intubation time was shorter in the air group (6.2 ± 3.4 min) than in the water group (8.1 ± 3.0 min; P = .01). CONCLUSIONS In patients willing to undergo unsedated colonoscopy, water infusion improves patient tolerance for cecal intubation, compared with air insufflation. However, it does not increase the overall percentage of successful cecal intubations because suboptimal bowel preparation interferes with visibility.

Ablation of residual Barrett's epithelium after endoscopic resection: a randomized long-term follow-up study of argon plasma coagulation vs. surveillance (APE study).

BACKGROUND AND STUDY AIM It is commonly assumed that ablation of any remaining Barretts epithelium after endoscopic resection of early Barretts neoplasia improves outcome by reducing the rate of metachronous lesions, but this has not yet been evaluated in a randomized trial. The aim of this study was to compare argon plasma coagulation (APC) with surveillance only for the management of residual Barretts epithelium following endoscopic resection. PATIENTS AND METHODS Patients in whom focal early Barretts neoplasia (high grade intraepithelial neoplasia [HGIN] or mucosal cancer) had been curatively resected by endoscopy were randomly assigned to undergo ablation of the residual Barretts segment by APC or surveillance only; pH-metry-adjusted proton pump inhibitor therapy was administered in both groups. The main outcome parameter was recurrence-free survival. Follow-up endoscopies with biopsies in cases of further residual Barretts epithelium were carried out at 6-monthly intervals in both groups. RESULTS A total of 63 patients (57 male [90.5%]) were included in the study (ablation group n=33; surveillance group n=30). For complete Barretts ablation, a mean number of 4±1.6 APC sessions were required (range 2-7). The mean follow-up duration did not differ significantly between ablation (28.2±13.7 months, range 0-44) and surveillance patients (24.7±14.8 months, range 0-45; P=0.159). The number of secondary lesions was 1 in the ablation group (3%), and 11 in the surveillance group (36.7%), leading to significantly higher recurrence-free survival for the patients undergoing ablation (P=0.005). CONCLUSIONS Thermal ablation of residual Barretts epithelium leads to a significant reduction in neoplasia recurrence rate compared with a surveillance strategy during a limited follow-up of 2 years. A longer follow-up duration may have led to a relatively higher rate of secondary neoplasia in both groups of patients.

Barrett’s Adenocarcinoma of the Esophagus: Better Outcomes Through New Methods of Diagnosis and Treatment

BACKGROUND Esophageal adenocarcinoma has attracted more attention among gastroenterologists recently because of its rapidly rising incidence in Western countries. Many new epidemiological findings have been published, and there have been numerous technical advances in diagnostic procedures and in multimodal treatment based on the staging of the disease. METHODS In this paper, we selectively review the literature on esophageal adenocarcinoma, also considering the evidence-based recommendations contained in the guidelines of the German Society for Digestive and Metabolic Diseases (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten, DGVS) as well as the latest data from our own research team. RESULTS AND CONCLUSION here have been major recent advances in the diagnosis and treatment of esophageal adenocarcinoma. New refinements in endoscopic techniques now make endoscopic treatment possible for early esophageal carcinoma. New surgical techniques and new strategies of neoadjuvant chemotherapy have lowered the morbidity and improved the outcome of patients with locally advanced disease. Molecular therapies, too, have shown promising initial results.

Prospective randomized comparison of short-access mother-baby cholangioscopy versus direct cholangioscopy with ultraslim gastroscopes

BACKGROUND Mother-baby technologies, the criterion standard for cholangioscopy, have several limitations. A novel, short-access, mother-baby (SAMBA) system may improve this technique. Direct cholangioscopy (DC) was recently developed as an alternative to mother-baby cholangioscopy. OBJECTIVE Comparison of success rates with SAMBA and DC. DESIGN Single-center, randomized, controlled trial. SETTING Academic tertiary-care referral center. PATIENTS Sixty patients with suspected cholangiopathies randomized to either SAMBA (n = 30) or DC (n = 30). INTERVENTION Cholangioscopy under deep sedation. MAIN OUTCOME MEASUREMENTS Technical success rate of diagnostic or therapeutic procedure. RESULTS A total of 24 and 21 diagnostic procedures were performed in the SAMBA and DC groups, respectively. There were no significant differences in the overall technical success rates between SAMBA (90.0%) and DC (86.7%) (P = 1.0). There was better correlation between the endoscopic prediction and histologic findings in DC (P = .013). Procedure times were shorter in DC (P < .03). In patients without significant stenoses, SAMBA allowed intrahepatic bile duct exploration in all cases, compared with 10.5% of cases in DC (P < .01). No differences regarding adverse event rates between the groups occurred (10.0% both groups). LIMITATIONS Small sample size. Heterogeneous indications for cholangioscopy. DC requires advanced skills of the endoscopist. The study is not replicable. CONCLUSION SAMBA and DC offer high technical success rates for diagnostic and therapeutic interventions. The advantages of DC consist of superior imaging, shorter total procedure time, and a wider working channel for adequate tissue sampling. SAMBA is better than DC with regard to intraductal stability and accessibility of the intrahepatic bile ducts.

Verrucous Oesophageal Carcinoma: Single Case Report and Case Series Including 15 Patients - Issues for Consideration of Therapeutic Strategies

Background: Verrucous carcinomas (VC) of the oesophagus are a rarity. Due to their histological resemblance to squamous cell carcinoma, the diagnostic and treatment standards applicable to the latter have so far also been applied to VC as a disease entity. Quite limited data are available including two case series of 5 or 11 patients. The present study reports on a single case treated by local endoscopic therapy and a series of 15 patients, 9 of whom received local endoscopic therapy. Methods: The data for patients diagnosed with VC of the oesophagus who had been treated from January 1999 to May 2011 were analysed retrospectively. Results: 15 patients with the diagnosis of oesophageal VC were included. The male-female ratio was 3:1. 9 of 11 pT1-VC patients presented with the cardinal symptom dysphagia or odynophagia. For the majority of the patients, the growth pattern is one of extensive superficial expansion showing a median length of 9 cm (range: 2-22 cm). Surprisingly, none of the VC patients showed lymph node or distant metastasis. 9 of 15 VC patients received local endoscopic therapy; 4 were treated with curative intent and 5 were treated palliatively. 3 patients underwent oesophageal resection, and definitive chemoradiotherapy was administered in a further 3 patients. One severe complication, consisting of a postoperative anastomotic insufficiency with a fatal outcome, occurred in this group of patients. Conclusion: This is the largest published study describing patients diagnosed with VC of the oesophagus so far. The option of local endoscopic therapy and its results in 9 patients are reported for the first time. The superficial growth pattern of the tumour and the frequent absence of lymph node or distant metastasis suggest that endoscopic resection can be carried out as a diagnostic and/or therapeutic approach. Due to the rarity of this entity, the case numbers are unfortunately so limited that evidence-based recommendations are unlikely to become available even in the future.

Inter- and Intraobserver Variability in High Resolution Chromoendoscopy with Acetic Acid for the Detection of Intestinal Metaplasia and Early Neoplasia in Barrett's Esophagus

Interand Intraobserver Variability in High Resolution Chromoendoscopy with Acetic Acid for the Detection of Intestinal Metaplasia and Early Neoplasia in Barrett’s Esophagus Liebwin Gossner, Oliver Pech, Andrea May, Thomas Rabenstein, Hendrik Manner, Angelika Behrens, Christian Ell Specialized intestinal metaplasia (SIM) in Barrett’s esophagus (BE) embodies the risk of malignant transformation. Optically guided, ‘‘smart’’ biopsies using chromoendoscopy with acetic acid (AA) are a fascinating option in surveillance procedures for BE. Methods: Consecutive patients with GERD, suspicious of SIM or early neoplasia in BE referred to our center were enclosed in this prospective study. They were studied using Fujinon high resolution endoscopes (EG HR485ZW5, EG HR490ZW5). The distal esophagus was sprayed with a solution of 1.5% acetic acid. Esophageal columnar mucosal patterns were characterized after AA spraying: Dotted round pits representing cardiac mucosa (pattern I), villous and ridged surface pattern (pattern II) for SIM and an irregular, distorted mucosal pattern (pattern III) representing neoplasia in SIM. The observed surface patterns were digitally stored on PC. All digitally stored images were reassessed by 6 blinded endoscopists. Intraand interobserver variations of the investigators were evaluated by using kappa statistics. Results: 394 endoscopic pictures of 96 patients were studied. SIM could be predicted with a sensitivity of 92%, high-grade intraepithelial neoplasia (HGIN) or early mucosal cancer in 89% respectively. The mean kappa for interobserver agreement was 0.959, whereas intraobserver agreement showed a mean kappa of 1.0. Conclusions: High resolution endoscopy with acetic acid is an accurate method for visually predicting SIM and early neoplasia in BE with very low interand intraobserver variability. Abstracts

Perioperative and Palliative Chemotherapy for Esophageal Cancer

Perioperative and palliative chemotherapy for esophageal carcinoma has undergone substantial changes in recent years. The implementation of trastuzumab in the treatment of HER2-positive advanced adenocarcinoma is a milestone as it marked the introduction of the first molecularly targeted treatment of gastric cancer. Current studies are investigating whether anti-HER2-directed treatment also proves effective in the perioperative setting. Data from the CROSS study on neoadjuvant radio-/chemotherapy with paclitaxel and carboplatin have helped to establish a new standard of care for the treatment of localized esophageal cancer. Finally, preliminary experience in potentially curative treatment approaches for oligometastatic tumor stages may offer new treatment options for patients with stage IV gastric cancer. However, some of these innovative approaches urgently require validation in larger, prospective, and controlled multicenter studies. Highly active forms of radiotherapy, radio-/chemotherapy, or chemoimmunotherapy can achieve complete tumor remissions in some patients. Despite these advances, life expectancy unfortunately continues to be very limited in the majority of patients with locally advanced or metastatic esophageal carcinoma.