Femke P. Peters

Endoscopic video autofluorescence imaging may improve the detection of early neoplasia in patients with Barrett's esophagus.

BACKGROUND The aim of this study was to investigate the feasibility of detecting high-grade dysplasia (HGD) and early cancer (EC) in Barretts esophagus (BE) with a prototype video autofluorescence endoscope. METHODS Sixty patients with BE were evaluated with a prototype, high-resolution videoendoscope that has separate charge-coupled devices for white light endoscopy (WLE) and autofluorescence imaging (AFI). Nondysplastic BE appears green on AFI, whereas potentially neoplastic areas appear blue/violet. The BE was first screened with WLE for visible abnormalities and then was examined by AFI to detect additional lesions. Lesions that raised a suspicion of neoplasia and control areas that were normal on AFI were sampled for histopathologic assessment. Finally, random 4-quadrant biopsy specimens were obtained at 2-cm intervals. RESULTS A diagnosis of HGD/EC was made in 22 patients; one patient had no visible abnormality, and 21 had endoscopically detectable areas with HGD/EC. In 6 of the latter 21 patients, the HGD/EC was detected with AFI alone; in another patient, HGD/EC was detected with AFI and random biopsies. In 14 patients, HGD/EC was detected with both WLE and AFI; in 3 of these 14 patients, additional lesions containing HGD/EC were detected by AFI alone. CONCLUSIONS The results of this study suggest that video AFI may improve the detection of HGD/EC in patients with BE.

Stepwise Radical Endoscopic Resection Is Effective for Complete Removal of Barrett's Esophagus with Early Neoplasia: A Prospective Study

OBJECTIVES:Endoscopic therapy for early neoplasia in Barretts esophagus (BE) is evolving rapidly. Aim of this study was to prospectively evaluate safety and efficacy of stepwise radical endoscopic resection (ER) of BE containing early neoplasia.METHODS:Patients with early neoplasia (i.e., high-grade intraepithelial neoplasia or early cancer) in BE ≤5 cm, without signs of submucosal infiltration or lymph node/distant metastases, were included. Patients underwent resection sessions (cap technique after submucosal lifting) with intervals of 6 wk.RESULTS:Between January 2003 and December 2004, 39 consecutive patients were included. Therapy was discontinued in two patients due to unrelated comorbidity. Complete eradication of early neoplasia was achieved in all 37 treated patients in a median number of three sessions. Complete removal of all Barretts mucosa was achieved in 33 (89%) patients: 4 patients (all had undergone APC [argon plasma coagulation]) were found to have small isles of Barretts mucosa underneath neosquamous mucosa. Complications occurred in two out of 88 (2%) ER procedures: one asymptomatic perforation, one delayed bleeding. Symptomatic stenosis occurred in 10 of 39 (26%) patients and was effectively treated by endoscopic bougienage. During a median follow-up of 11 months, no patients died and none had recurrence of neoplasia or Barretts mucosa.CONCLUSIONS:Stepwise radical ER is effective for selected patients with early neoplasia in BE; provides optimal histopathological diagnosis; and may reduce recurrence rate, since all mucosa at risk is effectively removed. Use of APC should be limited to prevent buried Barretts mucosa. Methods for prevention of stenosis should be developed.

Endoscopic treatment of high-grade dysplasia and early stage cancer in Barrett's esophagus

BACKGROUND The aim of this study was to prospectively evaluate endoscopic resection (ER) combined with photodynamic therapy (PDT) for the treatment of selected patients with early neoplasia in Barretts esophagus. METHODS Patients with Barretts esophagus and neoplastic lesions <2 cm in diameter and no sign of submucosal infiltration, positive lymph nodes, or distant metastasis underwent diagnostic ER (cap technique). Patients with a T1sm tumor in the resection specimen were referred for surgery; those with a T1m or a less invasive tumor underwent additional endoscopic therapy (ER, PDT, and/or argon plasma coagulation [APC]), or they were followed. PDT was performed with 5-aminolevulinic acid and a light dose of 100 J/cm 2 at lambda = 632 nm. RESULTS Thirty-three patients underwent diagnostic ER. Endoscopic treatment was not performed in 5 patients, who underwent surgery (4 T1sm; 1, patient preference). Five patients were immediately entered into a follow-up protocol, and 23 received additional endoscopic treatment (13 additional ER, 19 PDT, 3 APC). Endoscopic treatment was successful in 26/28 patients; no severe complication was observed. During follow-up (median 19 months, range 13-24 months), 5/26 patients had a recurrence of high-grade dysplasia: all were successfully re-treated with ER. At the end of follow-up, 26/33 originally enrolled patients (79%) and 26/28 endoscopically treated patients (93%) were in local remission. CONCLUSIONS Endoscopic therapy is safe and effective for selected patients with early stage neoplasia in Barretts esophagus.

Randomized trial on endoscopic resection-cap versus multiband mucosectomy for piecemeal endoscopic resection of early Barrett's neoplasia

BACKGROUND Endoscopic resection (ER) is an important treatment for high-grade intraepithelial neoplasia and early cancer in Barretts esophagus. ER-cap requires submucosal lifting and positioning of a snare in the cap, making it technically demanding and laborious. Multiband mucosectomy (MBM) uses a modified variceal band ligator and requires no submucosal lifting or positioning of a snare. OBJECTIVE To compare ER-cap and MBM for piecemeal ER of early Barretts neoplasia. DESIGN Randomized, controlled trial. SETTING Tertiary-care and community-care centers. PATIENTS This study involved 84 patients (64 men; median age 70 years) undergoing piecemeal ER of Barretts neoplasia. INTERVENTION Piecemeal ER was performed by using ER-cap (n = 42) or MBM (n = 42). MAIN OUTCOME MEASUREMENTS Safety, efficacy, procedure time, costs. RESULTS Procedure time (34 vs 50 minutes; P = .02) and costs (€240 vs €322; P < .01) were significantly less with MBM compared with ER-cap. MBM resulted in smaller resection specimens than ER-cap (18 ×13 mm vs 20 × 15 mm; P < .01). Maximum thicknesses of specimens and resected submucosa were not significantly different. There were no clinically relevant bleeding episodes. Four perforations occurred, 3 with ER-cap, 1 with MBM (P = not significant). LIMITATIONS Potential bias because of different levels of experience among participating endoscopists. CONCLUSION Piecemeal ER with MBM is faster and cheaper than with ER-cap. Despite the lack of submucosal lifting, MBM appears not to be associated with more perforations. Although MBM results in slightly smaller specimens, the clinical relevance of this may be limited because depth of resections does not differ between both techniques. MBM may thus be preferred for piecemeal ER of early Barretts neoplasia. ( CLINICAL TRIAL REGISTRATION NUMBER NTR1435.).

Multiband mucosectomy for endoscopic resection of Barrett's esophagus : feasibility study with matched historical controls

Background and aims Piece-meal endoscopic resection of early neoplastic lesions larger than 15–20 mm is a laborious procedure with the cap technique. Multiband mucosectomy is a new technique using a modified variceal band ligator. Submucosal lifting and prelooping of the snare in the cap is not necessary and multiple resections can be performed with a single snare. We prospectively evaluated the feasibility of multiband mucosectomy for widespread endoscopic resection in patients with a Barretts esophagus with early neoplasia and compared results retrospectively with prospectively registered endoscopic cap resection procedures. Results Eighty multiband mucosectomy procedures were performed in 40 patients and 86 endoscopic cap resection procedures in 53 patients. Median duration of the multiband mucosectomy procedures was 37 vs. 50 min for endoscopic cap resection procedures (P=0.06); median duration per resection was 6 vs. 12 min, respectively (P<0.001). Mean diameter of the specimens was 17 vs. 21 mm (P<0.001). One perforation in the endoscopic cap resection group was successfully treated conservatively. Mild bleeding occurred in 6% of multiband mucosectomy and 20% of endoscopic cap resection procedures (P=0.012). Technical difficulties during multiband mucosectomy procedures included a decreased visibility owing to the black bands and the releasing wires. Conclusions Multiband mucosectomy allows safe and easy widespread piece-meal resections in Barretts esophagus. Time and costs appear to be saved compared with the cap technique, and multiband mucosectomy appears to cause less bleeding during the endoscopic resection procedure. Multiband mucosectomy, however, results in smaller specimens and is, therefore, most suited for en-bloc resection of lesions smaller than 10 mm or for widespread resection of flat mucosa.

Surveillance history of endoscopically treated patients with early Barrett's neoplasia: nonadherence to the Seattle biopsy protocol leads to sampling error

SUMMARY The studys aim was to retrospectively evaluate the surveillance history of Barretts esophagus (BE) patients with endoscopically treated early neoplasia. All BE patients endoscopically treated for early cancer (EC) or high-grade intraepithelial neoplasia (HGIN) in a lesion or mass between 1998 and 2005 were included. Endoscopy and histology records were reviewed. Ninety-four patients (78 males, mean age 67 years, 24 HGIN, 70 EC) were included. In 36 (38%) patients, HGIN/EC was diagnosed at (or within 6 months after) initial endoscopy. The remaining 58 (62%) patients had a surveillance history (median duration 7 years, mean 6.7 endoscopies). Seventy-nine percent of these had low-grade intraepithelial neoplasia (LGIN) diagnosed at least once during their surveillance period with a median of seven endoscopies and a median number of biopsies that was 50% of what should have been taken according to the Seattle protocol. Patients without any dysplasia during earlier surveillance (n = 12, 21%) had undergone significantly less endoscopies (median four endoscopies, P = 0.02) and had a median biopsy percentage that was 23% of the Seattle protocol (P < 0.001 versus 50% in LGIN). In this selected cohort of patients with early Barretts neoplasia, 38% of patients were diagnosed at initial endoscopy. Of the patients with a surveillance history, 79% had shown LGIN prior to HGIN/EC diagnosis. Only 21% of patients had a surveillance history without any dysplasia, which in general encompassed endoscopies with an insufficient number of biopsies, suggesting sampling error. This underlines the importance of obtaining an adequate number of biopsies during surveillance endoscopies.

Learning to perform endoscopic resection of esophageal neoplasia is associated with significant complications even within a structured training program

BACKGROUND AND STUDY AIMS Endoscopic resection is the cornerstone of endoscopic treatment of esophageal high grade dysplasia or early cancer. Endoscopic resection is, however, a technically demanding procedure, which requires training and expertise. The aim of the current study was to prospectively evaluate efficacy and safety of the first 120 endoscopic resection procedures of early esophageal neoplasia performed by six endoscopists (20 endoscopic resections each) who were participating in an endoscopic resection training program. PATIENTS AND METHODS The program consisted of four tri-monthly 1-day courses with lectures, live-demonstrations, hands-on training on anesthetized pigs, and one-on-one hands-on training days. Gastroenterologists from centers with multidisciplinary expertise in upper gastrointestinal oncology participated, together with an endoscopy nurse and a pathologist. Outcome measures were complete endoscopic removal of the target area and acute complications. RESULTS A total of 120 consecutive esophageal endoscopic resection procedures (85 ER-cap, 35 multiband mucosectomy [MBM]) were performed by six endoscopists: 109 in Barretts esophagus, 11 for squamous neoplasia; 85 piecemeal endoscopic resections (median 3 specimens, interquartile range 2 - 4 specimens). Complete endoscopic removal was achieved in 111 /120 cases (92.5 %). Six perforations occurred (5.0 %): five were effectively treated endoscopically (clips, covered stent), and one patient underwent esophagectomy. There were 11 acute mild bleedings (9.2 %), which were managed endoscopically. Perforations occurred in ER-cap procedures performed by four participants (7.1 % ER-cap vs. 0 % MBM; P = 0.18), and in 1.7 % of the first 10 endoscopic resections and 8.3 % of the second 10 endoscopic resections per endoscopist (P = 0.26). CONCLUSION In this intense, structured training program, the first 120 esophageal endoscopic resections performed by six participants were associated with a 5.0 % perforation rate. Although perforations were adequately managed, performing 20 endoscopic resections may not be sufficient to reach the peak of the learning curve in endoscopic resection.

Quality of Barrett's surveillance in The Netherlands : a standardized review of endoscopy and pathology reports

Objective The quality of Barretts surveillance relies on an adequate endoscopic inspection, obtaining a sufficient number of biopsy specimens, good communication of the endoscopic findings to the pathologist, and an accurate description of the histological findings by the pathologist. The aim of this study was to assess the quality of Barretts surveillance in daily practice in The Netherlands. Materials and methods A structured scoring list was developed to evaluate systematically the quality of endoscopy and pathology reports. From 15 hospitals, endoscopy reports and corresponding pathology reports were selected randomly and evaluated by two observers. In case of disagreement, the observers re-evaluated the reports in a consensus meeting. Results One hundred and fifty cases were evaluated. The adherence to current standard biopsy protocols (four quadrant biopsies every 2 cm) decreased with increasing Barretts length: 0–5 cm: 79%; 5–10 cm: 50%; 10–15 cm: 30%. The indication for the endoscopy was mentioned in 28% of the pathology reports, in 4% the presence/absence of oesophagitis was communicated, and in 19% the location and/or aetiology of biopsies was described. The presence/absence of dysplasia was mentioned in 93% of pathology reports. Conclusion Endoscopy reports and pathology reports in current practice do not include all relevant information for an adequate Barretts surveillance. In short Barretts oesophagus, the adherence to current standard biopsy protocols is acceptable, but in longer segments (with a higher risk for neoplastic progression) this is clearly insufficient. The communication between endoscopists and pathologist is suboptimal.

Stepwise Radical Endoscopic Resection of the Complete Barrett's Esophagus With Early Neoplasia Successfully Eradicates Pre-Existing Genetic Abnormalities

OBJECTIVES: Malignant transformation of Barretts mucosa is associated with the accumulation of genetic alterations. Stepwise radical endoscopic resection of the Barretts segment with early neoplasia is a promising new treatment resulting in complete re-epithelialization of the esophagus with neosquamous epithelium. It is unknown whether radical resection also eradicates genetic abnormalities. The aim of this study was to prospectively evaluate whether genetic abnormalities as found in the Barretts segment before radical resection are effectively eradicated and absent in the neosquamous epithelium.METHODS: Nine patients with early neoplasia who successfully underwent radical resection were included. Immunohistochemistry (IHC) was performed to assess p53 protein overexpression. DNA fluorescent in-situ hybridization was (DNA-FISH) performed for evaluation of numerical abnormalities of chromosomes 1 and 9, and losses of p16 and p53. Immunohistochemistry and DNA-FISH were performed on endoscopic resection specimens of the neoplasia and on follow-up biopsies of the neosquamous epithelium.RESULTS: DNA-FISH and IHC showed alterations in the pretreatment samples of all patients. All showed aneusomy of chromosome 1 and 9. Loss of p16 and p53 were seen in 6 and 8 patients. IHC showed intense p53 nuclear staining in seven patients. Post-treatment biopsies showed neosquamous epithelium with a normal diploid signal count for all DNA-FISH probes and normal IHC stainings in all patients.CONCLUSIONS: Radical resection of Barretts esophagus with early neoplasia successfully eradicates pre-existing genetic abnormalities and results in neosquamous epithelium without these genetic abnormalities.