Risk stratification of patients with Barrett’s esophagus (BE) is based on diagnosis of low-grade dysplasia (LGD). LGD has a poor interobserver agreement and a limited value for prediction of ...progression to high-grade dysplasia or esophageal adenocarcinoma. Specific reproducible histologic criteria may improve the predictive value of LGD. Four gastrointestinal pathologists examined 12 histologic criteria associated with LGD in 84 BE patients with LGD (15 progressors and 69 nonprogressors). The criteria with at least a moderate (kappa, 0.4 to 0.6) interobserver agreement were validated in an independent cohort of 98 BE patients with LGD (30 progressors and 68 nonprogressors). Hazard ratios (HR) were calculated by Cox proportional hazard regression analysis using time-dependent covariates correcting for multiple endoscopies during follow-up. Agreement was moderate or good for 4 criteria, that is, loss of maturation, mucin depletion, nuclear enlargement, and increase of mitosis. Combination of the criteria differentiated high-risk and low-risk group amongst patients with LGD diagnosis (P<0.001). When ≥2 criteria were present, a significantly higher progression rate to high-grade dysplasia or esophageal adenocarcinoma was observed (discovery setHR, 5.47; 95% confidence interval CI, 1.81-17; P=0.002; validation setHR, 3.52; 95% CI, 1.56-7.97; P=0.003). Implementation of p53 immunohistochemistry and histologic criteria optimized the prediction of progression (area under the curve, 0.768; 95% CI, 0.656-0.881). We identified and validated a clinically applicable panel of 4 histologic criteria, segregating BE patients with LGD diagnosis into defined prognostic groups. This histologic panel can be used to improve clinical decision making, although additional studies are warranted.
The efficacy of local treatment of vulvar intraepithelial neoplasia with imiquimod, an immune-response modifier, was tested in a double-blind, randomized trial. As compared with placebo, imiquimod ...cream was effective in reducing or eliminating the lesion, relieving symptoms, and clearing the lesion of human papillomavirus.
Imiquimod cream was effective in reducing or eliminating vulvar intraepithelial neoplasia, relieving symptoms, and clearing the lesion of human papillomavirus.
Surgery, the treatment of choice for vulvar intraepithelial neoplasia, removes all visible lesions, with the aim of relieving symptoms and preventing vulvar cancer.
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However, there are limitations to surgery. The percentage of lesions with positive surgical margins ranges from 24 to 68%.
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Recurrences are common, because surgery does not eliminate human papillomavirus (HPV), the cause of most vulvar intraepithelial neoplasia.
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Progression is not influenced by radical excision,
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and surgery can mutilate the vulva, thereby causing psychosexual distress.
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Thus, alternative treatments are needed.
Vulvar intraepithelial neoplasia is caused by HPV,
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which has prompted the use of imiquimod . . .
IMPORTANCE Barrett esophagus containing low-grade dysplasia is associated with an increased risk of developing esophageal adenocarcinoma, a cancer with a rapidly increasing incidence in the western ...world. OBJECTIVE To investigate whether endoscopic radiofrequency ablation could decrease the rate of neoplastic progression. DESIGN, SETTING, AND PARTICIPANTS Multicenter randomized clinical trial that enrolled 136 patients with a confirmed diagnosis of Barrett esophagus containing low-grade dysplasia at 9 European sites between June 2007 and June 2011. Patient follow-up ended May 2013. INTERVENTIONS Eligible patients were randomly assigned in a 1:1 ratio to either endoscopic treatment with radiofrequency ablation (ablation) or endoscopic surveillance (control). Ablation was performed with the balloon device for circumferential ablation of the esophagus or the focal device for targeted ablation, with a maximum of 5 sessions allowed. MAIN OUTCOMES AND MEASURES The primary outcome was neoplastic progression to high-grade dysplasia or adenocarcinoma during a 3-year follow-up since randomization. Secondary outcomes were complete eradication of dysplasia and intestinal metaplasia and adverse events. RESULTS Sixty-eight patients were randomized to receive ablation and 68 to receive control. Ablation reduced the risk of progression to high-grade dysplasia or adenocarcinoma by 25.0% (1.5% for ablation vs 26.5% for control; 95% CI, 14.1%-35.9%; P < .001) and the risk of progression to adenocarcinoma by 7.4% (1.5% for ablation vs 8.8% for control; 95% CI, 0%-14.7%; P = .03). Among patients in the ablation group, complete eradication occurred in 92.6% for dysplasia and 88.2% for intestinal metaplasia compared with 27.9% for dysplasia and 0.0% for intestinal metaplasia among patients in the control group (P < .001). Treatment-related adverse events occurred in 19.1% of patients receiving ablation (P < .001). The most common adverse event was stricture, occurring in 8 patients receiving ablation (11.8%), all resolved by endoscopic dilation (median, 1 session). The data and safety monitoring board recommended early termination of the trial due to superiority of ablation for the primary outcome and the potential for patient safety issues if the trial continued. CONCLUSIONS AND RELEVANCE In this randomized trial of patients with Barrett esophagus and a confirmed diagnosis of low-grade dysplasia, radiofrequency ablation resulted in a reduced risk of neoplastic progression over 3 years of follow-up. TRIAL REGISTRATION trialregister.nl Identifier: NTR1198
This study compared extended transthoracic resection with limited transhiatal resection for adenocarcinoma of the esophagus or gastric cardia. The five-year survival rates in the two groups were not ...significantly different, but a nonsignificant trend in overall survival favored transthoracic resection in later years.
In this study of resection for adenocarcinoma, a trend in survival favored transthoracic resection.
Long-term survival after surgery with curative intent for adenocarcinoma of the distal esophagus and gastric cardia is only 20 percent.
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Surgery is generally considered to offer the best chance for cure, but opinions differ on how to improve survival by surgery. One strategy aims at decreasing early postoperative risk by the use of limited cervicoabdominal (transhiatal) esophagectomy without formal lymphadenectomy. Another is intended to improve long-term survival by performing a combined cervicothoracoabdominal resection, with wide excision of the tumor and peritumoral tissues and extended lymph-node dissection in the posterior mediastinum and the upper abdomen (transthoracic esophagectomy with extended en . . .
Background The detection of the mucosal morphology (ie, mucosal and vascular patterns) in Barrett's esophagus (BE) by magnifying (chromo)endoscopy may improve the distinction of high-grade ...intraepithelial neoplasia (HGIN) from nondysplastic specialized intestinal metaplasia (SIM). Narrow band imaging (NBI) is a new technique that uses optical filters to enhance the mucosal contrast without the need for chromoendoscopy. Objective To use NBI for the characterization and the classification of the mucosal morphology in nondysplastic BE and in BE with HGIN. Design Descriptive study. Setting Single-center study in a tertiary referral center for the diagnosis and treatment of patients with BE. Patients We used NBI with magnifying endoscopy to image and biopsy randomly selected areas in 63 patients with BE. A systematic image and a biopsy specimen evaluation process was followed, including unblinded assessment of an exploratory set of images and biopsy specimens, and blinded evaluation of learning and validation sets. Main Outcome Measurements The relationship between the mucosal morphology and the presence of SIM and HGIN. Results SIM was characterized by either villous/gyrus-forming patterns (80%), which were mostly regular and had regular vascular patterns, or a flat mucosa with regular normal-appearing long branching vessels (20%). HGIN was characterized by 3 abnormalities: irregular/disrupted mucosal patterns, irregular vascular patterns, and abnormal blood vessels. All areas with HGIN had at least 1 abnormality, and 85% had 2 or more abnormalities. The frequency of abnormalities showed a significant rise with increasing grades of dysplasia. The magnified NBI images had a sensitivity of 94%, a specificity of 76%, a positive predictive value of 64%, and a negative predictive value of 98% for HGIN. Limitations No data on observer agreement. Conclusions NBI with magnification reveals the mucosal morphology characteristics of NDBE and HGIN, without the need for staining and has a relatively high diagnostic value for HGIN when used for targeted detailed examination of areas of interest.
After focal endoscopic resection (ER) of high-grade dysplasia (HGD) or early cancer (EC) in Barrett's oesophagus (BO), eradication of all remaining BO reduces the recurrence risk. The aim of this ...study was to compare the safety of stepwise radical ER (SRER) versus focal ER followed by radiofrequency ablation (RFA) for complete eradication of BO containing HGD/EC.
A multicentre randomised clinical trial was carried out in three tertiary centres. Patients with BO ≤ 5 cm containing HGD/EC were randomised to SRER or ER/RFA. Patients in the SRER group underwent piecemeal ER of 50% of BO followed by serial ER. Patients in the ER/RFA group underwent focal ER for visible lesions followed by serial RFA. Follow-up endoscopy with biopsies (four-quadrant/2 cm BO) was performed at 6 and 12 months and then annually. The main outcome measures were: stenosis rate; complications; complete histological response for neoplasia (CR-neoplasia); and complete histological response for intestinal metaplasia (CR-IM).
CR-neoplasia was achieved in 25/25 (100%) SRER and in 21/22 (96%) ER/RFA patients. CR-IM was achieved in 23 (92%) SRER and 21 (96%) ER/RFA patients. The stenosis rate was significantly higher in SRER (88%) versus ER/RFA (14%; p<0.001), resulting in more therapeutic sessions in SRER (6 vs 3; p<0.001) due to dilations. After median 24 months follow-up, one SRER patient had recurrence of EC, requiring ER.
In patients with BO ≤ 5 cm containing HGD/EC, SRER and ER/RFA achieved comparably high rates of CR-IM and CR-neoplasia. However, SRER was associated with a higher number of complications and therapeutic sessions. For these patients, a combined endoscopic approach of focal ER followed by RFA may thus be preferred over SRER. Clinical trial number NTR1337.
Barrett's esophagus (BE) is associated with an increased risk of developing esophageal adenocarcinoma (EAC). Patients with a known diagnosis of BE are usually advised to participate in an endoscopic ...surveillance program, but its clinical value is unproven. Our objective was to compare patients participating in a surveillance program for BE before EAC diagnosis with those not participating in such a program, and to determine predictive factors for mortality from EAC.
All patients diagnosed with EAC between 1999 and 2009 were identified in the nationwide Netherlands Cancer Registry. These data were linked to Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief, the Dutch Pathology Registry. Prior surveillance was evaluated, and multivariable Cox proportional hazards regression analysis was performed to identify predictors for all-cause mortality at 2-year and 5-year follow-up.
In total, 9,780 EAC patients were included. Of these, 791 (8%) patients were known with a prior diagnosis of BE, of which 452 (57%) patients participated in an adequate endoscopic surveillance program, 120 (15%) patients in an inadequate program, and 219 (28%) patients had a prior BE diagnosis without participating. Two-year (and five-year) mortality rates were lower in patients undergoing adequate surveillance (adjusted hazard ratio (HR)=0.79, 95% confidence interval (CI)=0.64-0.92) when compared with patients with a prior BE diagnosis who were not participating. Other factors associated with lower mortality from EAC were lower tumor stage (stage I vs. IV, HR=0.19, 95% CI=0.16-0.23) and combining surgery with neoadjuvant chemo/radiotherapy (HR=0.66, 95% CI=0.58-0.76).
Participation in a surveillance program for BE, but only if adequately performed, reduces mortality from EAC. Nevertheless, it remains to be determined whether such a program is cost-effective, as more than 90% of all EAC patients were not known to have BE before diagnosis.
Adenocarcinoma of the esophagus, or GEJ, has a poor prognosis. Early lesions i.e. high grade dysplasia (HGD) or T1-carcinoma are potentially curable. Local endoscopic therapies are promising ...treatment options for superficial lesions; however, for deeper lesions, surgical resection is considered to be the treatment of choice. To contribute to therapeutic decision-making, we retrospectively analysed the outcome of transhiatal esophagectomy in 120 patients with pathologically proven HGD (n=13) or T1-adenocarcinoma (n=107) of the distal esophagus or gastro-esophageal junction (GEJ). Tumors were subdivided into six different depths of invasion ('T1-mucosal' m1-m3, 'T1-submucosal' sm1-sm3), and the frequency of lymphatic dissemination and time to locoregional and/or distant recurrence were analysed. Only one of the 79 T1m1-3/sm1 tumors (1%) showed lymph node metastases as compared with 18 out of 41 T1sm2-3 tumors (44%). There was a significant difference in recurrence-free period between T1m1-m3/sm1 versus T1sm2-sm3 tumor patients (P log rank <0.0001), with 5-year recurrence-free percentages of 97% and 57%, respectively. In multivariate analysis including age, gender, tumor differentiation grade, N-stage and depth of invasion, only N-stage was an independent prognostic factor for recurrence-free period (hazard rate=5.9, 95% CI 1.7-20.7). However, if N-stage was excluded from analysis, only depth of invasion (T1sm2-3 versus T1m1-m3/sm1) was an independent prognostic factor for recurrence-free period (hazard rate=7.5, 95% CI 2.0-27.7). These data indicate that T1m1-m3/sm1 adenocarcinomas of esophagus or GEJ show a very low risk of lymphatic dissemination and are therefore eligible for local endoscopic therapy. After transhiatal surgical resection, almost half of the patients with T1sm2-sm3 lesions develop recurrent disease within 5 years, and therefore need additional therapy to improve survival.
Background & Aims Radiofrequency ablation (RFA), with or without endoscopic resection effectively eradicates Barrett’s esophagus (BE) containing high-grade intraepithelial neoplasia and/or ...early-stage cancer. We followed patients who received RFA for BE containing high-grade intraepithelial neoplasia and/or early-stage cancer for 5 years to determine the durability of treatment response. Methods We followed 54 patients with BE (2−12 cm), previously enrolled in 4 consecutive cohort studies in which they underwent focal endoscopic resection in case of visible lesions (n = 40 72%), followed by serial RFA every 3 months. Patients underwent high-resolution endoscopy with narrow-band imaging at 6 and 12 months after treatment and then annually for 5 years (median, 61 months; interquartile range, 53−65 months); random biopsy samples were collected from neosquamous epithelium and gastric cardia. After 5 years, endoscopic ultrasound and endoscopic resection of neosquamous epithelium were performed. Outcomes included sustained complete remission of neoplasia or intestinal metaplasia (IM), IM in gastric cardia, or buried glands in neosquamous epithelium. Results After 5 years, Kaplan-Meier analysis showed sustained complete remission of neoplasia and intestinal metaplasia in 90% of patients; neoplasia recurred in 3 patients and was managed endoscopically. Focal IM in the cardia was found in 19 of 54 patients (35%), in 53 of 1143 gastric cardia biopsies (4.6%). The incidence of IM of the cardia did not increase over time; and IM was diagnosed based on only a single biopsy in 89% of patients. Buried glands were detected in 3 of 3543 neosquamous epithelium biopsies (0.08%, from 3 patients). No endoscopic resection samples had buried glands. Conclusions Among patients who have undergone RFA with or without endoscopic resection for neoplastic BE, 90% remain in remission at 5-year follow-up, with all recurrences managed endoscopically. This treatment approach is therefore an effective and durable alternative to esophagectomy; www.trialregister.nl number, NTR2938.
Background Endoscopic resection (ER) is an important treatment for high-grade intraepithelial neoplasia and early cancer in Barrett's 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 Barrett's 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 Barrett's 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 Barrett's neoplasia. (Clinical trial registration number: NTR1435.)
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