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 Barrett's 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 < or = 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 Barrett's mucosa was achieved in 33 (89%) patients: 4 patients (all had undergone APC [argon plasma coagulation]) were found to have small isles of Barrett's 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 Barrett's 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 Barrett's mucosa. Methods for prevention of stenosis should be developed.     

Endoscopic mucosal resection for lesions with endoscopic features suggestive of malignancy and high-grade dysplasia within Barrett's esophagus

BACKGROUND: Endoscopic mucosal resection has been used in the treatment of superficial squamous cell cancers and gastric malignancies. Our aim was to determine whether endoscopic mucosal resection can be used in the diagnosis of lesions within Barrett's esophagus whose endoscopic appearances raise suspicion of carcinoma or high-grade dysplasia. METHODS: Twenty-five patients with such lesions within Barrett's esophagus underwent endoscopic mucosal resection for diagnostic and therapeutic purposes. All patients underwent endoscopic ultrasound to determine the feasibility of endoscopic resection. Only lesions found to be uT0 or uT1 underwent EMR. The lift and cut technique was used in 23 patients and a variceal ligating device was used on 2 patients. RESULTS: Endoscopic mucosal resection was performed because of a nodule or polyp within Barrett's esophagus in 11 patients (44%) and suspected superficial cancer or high-grade dysplasia in 14 patients (56%). Endoscopic mucosal resection diagnosed superficial adenocarcinoma in 13 patients (52%) and high-grade dysplasia in 4 (16%); it confirmed lesions in 8 patients (40%) to be of lower neoplastic risk. No complications occurred due to the procedure itself. CONCLUSIONS: Endoscopic mucosal resection is a technique with low morbidity and mortality. It has led to a change in diagnosis in patients with Barrett's esophagus and lesions with endoscopic features that suggest neoplasia. Its major advantages include simplicity and retrieval of the specimen en bloc.     

Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett's cancer and high-grade intraepithelial neoplasia

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has proven to be safe and effective in patients with early neoplasia in Barrett's esophagus. However, long-term results in patients with high-grade intraepithelial neoplasia (HGIN) or with early cancer are still lacking. METHODS: The aim of the study was to evaluate the efficacy of ALA-PDT and the survival of patients with early Barrett's neoplasia. ALA-PDT was carried out in 66 patients. Protoporphyrin IX induced by oral administration of ALA (60 mg/kg body weight orally applied 4-6 hours before PDT) was used as the photosensitizer. Acid suppression was maintained in all patients. RESULTS: Between September 1996 and September 2002, 667 patients with early neoplasia in Barrett's esophagus were referred for local endoscopic therapy. A total of 558 patients fulfilled the criteria for local endoscopic therapy, and 66 patients (mean [standard deviation] age 61.4 [10.2] years) with HGIN (group A; n = 35) and early adenocarcinoma (group B; n = 31) were treated by PDT. A total of 82 ALA-PDT were performed. A total of 34 of the 35 patients in group A (97%) and all patients in group B (100%) achieved a complete response during a median follow-up period of 37 months (interquartile range 23-55) (not significant). One local recurrence was observed in group A and 10 in group B (p < 0.005). Seven patients died during follow-up; but, all deaths were not tumor related. No major complications were observed. Disease-free survival in patients with HGIN was 89%, and, in patients with mucosal cancer, it was 68%. The calculated 5-year survival was 97% in group A and 80% in group B, but there occurred no death related to Barrett's neoplasia. CONCLUSIONS: The excellent long-term results of PDT with ALA in patients with HGIN or mucosal cancer might offer PDT with ALA as an alternative to surgical esophagectomy and endoscopic resection, especially in cases with multifocal Barrett's neoplasia.     

Local endoscopic therapy for intraepithelial high-grade neoplasia and early adenocarcinoma in Barrett's oesophagus: acute-phase and intermediate results of a new treatment approach

BACKGROUND: Radical oesophageal resection has until now been regarded as the gold standard for treatment in intraepithelial high-grade neoplasia or early adenocarcinoma of the oesophagus. However, the mortality and morbidity rates are substantial. DESIGN: A new therapeutic approach involving low-risk endoscopic therapy modalities was examined in the framework of a prospective study. PATIENTS: A total of 115 patients with intraepithelial high-grade neoplasia (19) and early adenocarcinoma (96) in Barrett's oesophagus. METHODS: Endoscopic mucosal resection (EMR) was used in 70 patients, and photodynamic therapy (PDT) was used in 32 patients. The two procedures were combined in ten patients. Three patients underwent primary treatment with argon plasma coagulation (APC). The average follow-up was 34 +/- 10 months (range 24-60 months). RESULTS: Complete local remission was achieved in 98%. The overall complication rate was 9.5%. Major complications, such as perforation and severe bleeding, did not occur. Minor complications included not haemoglobin relevant bleeding (drop of haemoglobin less than 2 g/dl) (5) and stenosis (3) after EMR, and long-lasting odynophagia (1) and sunburn (2) after PDT. In all, 13 patients have died so far, but in only one case due to the underlying disease. The calculated overall 3-year survival rate is 88%. During the follow-up period, a 30% rate of metachronous lesions was observed; endoscopic therapy was performed successfully in all but one of these patients. CONCLUSIONS: These good acute-phase and intermediate results, along with low morbidity rates and no mortality, suggest that the organ-preserving local endoscopic procedure including EMR and PDT is an attractive alternative to oesophageal resection. Therefore, endoscopic therapy might replace radical oesophageal resection in future in cases of intraepithelial high-grade neoplasia and early mucosal adenocarcinoma in Barrett's oesophagus.     

Endoscopic ablation of dysplastic Barrett's oesophagus comparing argon plasma coagulation and photodynamic therapy: a randomized prospective trial assessing efficacy and cost-effectiveness

OBJECTIVE: Endoscopic mucosal ablation is a promising technique that is used to treat dysplastic Barrett's oesophagus. The purpose of this study was to investigate the efficacy and cost-effectiveness of two promising techniques, argon plasma coagulation (APC) and photodynamic therapy (PDT), in the ablation of dysplastic Barrett's oesophagus. MATERIALS AND METHODS: Twenty-six patients with dysplastic Barrett's oesophagus (21 M, median age 60 years, median length 4 cm, 23 low-grade dysplasia (LGD), 3 high-grade dysplasia (HGD)) were randomized to APC: 13 patients, PDT: 13 patients. APC was performed at a power setting of 65 W and argon gas flow at 1.8 l/min in 1-6 sessions (mean 5). PDT was performed 48 h after intravenous injection of Photofrin 2 mg/kg with a 630 nm red laser light, 200 J/cm through a PDT balloon in one session. All patients received treatment with high-dose proton pump inhibitors. Cost analysis was undertaken and the results were assessed by endoscopy and biopsies at 4 months and 12 months after therapy. RESULTS: All patients in both groups showed a reduction in the length of Barrett's oesophagus. The median length of Barrett's oesophagus eradicated at the 4-month follow-up: APC 65%, PDT 57% and at the 12-month follow-up: APC 56%, PDT 60%. Dysplasia eradication at 4 months: APC 62%, PDT 77%, p = 0.03 (95% CI 0.66-0.96) and at 12 months APC 67%, PDT 77%. Buried columnar glands with intestinal metaplasia were seen in both groups, with one patient in the PDT arm developing adenocarcioma under the neo-squamous epithelium. Severe adverse events included APC 2/13 (15%) stricture, 1/13 (8%) odynophagia, chest pain and fever; PDT 2/13 (15%) photosensitivity, 2/13 (15%) stricture. PDT would cost an additional 266 pounds sterling for every percentage reduction in Barrett's length and 146 pounds sterling per percentage reduction in dysplasia compared with APC treatment. CONCLUSIONS: APC and PDT are equally effective in eradicating Barrett's mucosa, with PDT being the more expensive treatment. However, PDT is more effective in eradicating dysplasia and the extra benefits of PDT are generated at an extra cost. The occurrence of buried columnar glands and carcinoma warrants caution. Long-term follow-up is needed to assess cancer prevention and the durability of the neo-squamous epithelium to justify these interventions.     

New directions in endoscopic therapy of Barrett' s esophagus

The key to prevention and early treatment of esophageal adenocarcinoma is the detection and eradication of neoplasia found in patients with Barrett's esophagus (BE). The approach to the management in BE has rapidly evolved based on the paradigm shift towards endoscopic therapy, on improved detection of neoplasia with increased appreciation for subtle lesions and enhanced endoscopic imaging modalities, and on a new set of endoscopic therapeutic modalities. This review briefly outlines the evolution of the current approach to neoplasia in BE, the appreciation for improved techniques and technologies to detect neoplasia, and the specific modalities currently used in the endoscopic treatment of Barrett's neoplasia. The goals of endoscopic therapy of Barrett's neoplasia are to preserve the esophagus while ablating or removing the entire Barrett's segment. The therapeutic modalities highlighted are endoscopic resection (endoscopic mucosal resection and endoscopic submucosal dissection), photodynamic therapy, radiofrequency ablation, and cryotherapy. Endoscopic resection is a tool to accurately provide a histological diagnosis of lesions in addition to treat neoplasia. In addition, to treating the known neoplasia, it is also important to treat the remainder of the at-risk Barrett's epithelium to address synchronous and metachronous lesions. This treatment of the entire Barrett's epithelium may be achieved with one or more modalities. With multiple endoscopic tools available, it is important to appreciate how to optimally address neoplasia in BE.     

Present status of photodynamic therapy for high-grade dysplasia in Barrett's esophagus

GOALS: Review recent developments in Barrett's dysplasia including regulatory approval of porfimer sodium photodynamic therapy. BACKGROUND: Barrett's esophagus is thought to be the result of long-standing gastroesophageal reflux disease and is known to be the most important risk factor for the development of esophageal adenocarcinoma. The natural history of Barrett's esophagus is not well known, but the annual incidence of invasive adenocarcinoma is estimated to be 0.5% (reported range, 0.2%-2.0%). This represents an increased risk for esophageal cancer of 30 to 60 times higher than normal subjects. As for colorectal cancer, malignant degeneration is Barrett's esophagus is thought to occur through a continuum of histologic stages: metaplasia, dysplasia and neoplasia. Barrett's high-grade dysplasia (formerly referred to as carcinoma in situ) is the histologic stage of disease that immediately precedes the development of invasive carcinoma. CONCLUSIONS: Previously, Barrett's high-grade dysplasia patients were routinely referred for esophageal resection surgery based upon the assumption of inevitable progression to cancer, the high rate of undiagnosed synchronous cancers, and few treatment alternatives. Important developments in Barrett's high-grade dysplasia include recent publications regarding the natural history of Barrett's high-grade dysplasia and the regulatory approval for endoscopic ablation therapy using porfimer sodium photodynamic therapy (Photofrin PDT).     

Pathologic Validation of Endoscopic Ablative Therapy for Gastric Epithelial Neoplasia: A Randomized Controlled Trial

BackgroundThe effectiveness of endoscopic ablative therapy such as monopolar coagulation (MC) or argon plasma coagulation (APC) have not been validated histologically. The aim of this study was the histologic validation of endoscopic ablative therapy for gastric epithelial neoplasia.Methods: We designed a prospective randomized controlled trial involving patients with gastric low-grade dysplasia. Patients were randomly assigned to either the APC or the MC group. Endoscopic ablative therapy was followed by endoscopic submucosal dissection (ESD) for histologic evaluation. The main outcome was histologic completeness of endoscopic ablative therapy. Results: Sixty-eight patients were recruited, of whom 34 patients underwent APC and 34 patients underwent MC followed by ESD. The APC group showed significantly higher complete eradication rate compared to the MC group (55.9% vs. 11.8%, P < .001). APC was the only significant predictor of histologic complete eradication in multivariate analysis (OR: 7.66; 95% CI: 2.139-27.448). No adverse events related to the procedure occurred in either group.Conclusions: Although APC is a more effective treatment option than MC in the management of gastric epithelial neoplasia, the effectiveness of both methods was limited in eradicating gastric epithelial neoplasia completely. Therefore, endoscopic resection should be a first option for treatment of gastric epithelial neoplasia until the optimal method is established with further studies.     

Randomized trial of argon plasma coagulation vs. multipolar electrocoagulation for ablation of Barrett's esophagus

BACKGROUND: Endoscopic ablation of Barrett's esophagus has been described in which various thermocoagulation modalities are used in combination with a high dose of a proton pump inhibitor. No randomized comparison of ablation strategies has been published. METHODS: Referred patients were screened to identify those with Barrett's esophagus 2 to 7 cm in length, without high-grade dysplasia or cancer. Included patients received pantoprazole (40 mg twice a day), followed by randomization to treatment with argon plasma coagulation (APC) or multipolar electrocoagulation (MPEC). The primary outcome measure was the number of treatment sessions required for endoscopic ablation. RESULTS: Of 235 patients screened, 52 were randomized. The mean length of Barrett's esophagus was 3.1 cm in the MPEC group vs. 4.0 cm in the APC group (p = 0.03). Otherwise, the treatment groups were similar with regard to baseline characteristics. The mean number of treatment sessions required for endoscopic ablation was 2.9 for MPEC vs. 3.8 for APC (p = 0.04) in an intention-to-treat analysis (p = 0.249, after adjustment for the difference in length of Barrett's esophagus). The proportion of patients in which ablation was endoscopically achieved proximal to the gastroesophageal junction was 88% for the MPEC group vs. 81% for the APC group (p = 0.68) and histologically achieved in 81% for MPEC vs. 65% for APC (p = 0.21). The mean time required for the first treatment session was 6 minutes with MPEC vs. 10 minutes with APC (p = 0.01) in per protocol analysis. There was no serious adverse event, but transient moderate to severe upper-GI symptoms occurred after MPEC in 8% vs. 13% after APC (p = 0.64). Conclusions Although there were no statistically significant differences, ablation of Barrett's esophagus with pantoprazole and MPEC required numerically fewer treatment sessions, and endoscopic and histologic ablation was achieved in a greater proportion of patients compared with treatment with pantoprazole and APC.     

Combined endoscopic mucosal resection and photodynamic therapy versus esophagectomy for management of early adenocarcinoma in Barrett's esophagus.

BACKGROUND & AIMS: Although esophagectomy is the standard of care for treating early adenocarcinoma in Barrett's esophagus, the procedure is associated with significant morbidity and mortality. For these patients, the multimodal approach of endoscopic mucosal resection and photodynamic therapy (EMR/PDT) may be a viable, less invasive option. METHODS: A retrospective review (1996-2001) of all patients undergoing either combined EMR/PDT group or esophagectomy (SURG) for early-stage Barrett's adenocarcinoma was performed. Data were collected on patient demographics, tumor staging, procedure-related morbidity and mortality, persistence or recurrence of cancer, and cancer-related deaths after therapy. Differences in outcomes between the 2 groups were assessed. RESULTS: Twenty-four patients were identified in the EMR/PDT group and 64 in the SURG group. The SURG group was found to have a significantly higher procedure-related complication rate compared with the EMR/PDT group (31 vs. 4; P < 0.01). There were no procedure-related deaths in the EMR/PDT group, whereas one death occurred in the SURG group as a result of complications. Eighty-three percent of patients (20 of 24) in the EMR/PDT group and all patients in the SURG group remained free of cancer over a follow-up of 12 +/- 2 and 19 +/- 3 months, respectively. Four patients in the EMR/PDT group failed to respond to therapy; 2 of them underwent alternate therapies and are free of disease, whereas the other 2 died of unrelated causes. CONCLUSIONS: The combination of EMR/PDT seems to be a viable and less morbid alternative to standard esophagectomy in patients presenting with early Barrett's esophageal adenocarcinoma. A prospective randomized, controlled trial of EMR/PDT compared with esophagectomy for managing early adenocarcinoma in Barrett's esophagus may be warranted.     

The role of endoscopic resection and ablation therapy for early lesions

Endoscopic resection (ER) has gained more and more importance in the treatment of early neoplastic lesions in Barrett's oesophagus over the last few years. The choice of the different available techniques depends on the site, the macroscopic type of the tumour and the personal experience of the endoscopist. The 'suck-and-cut' technique with ligation device or cap should be favoured to normal strip biopsy in the oesophagus because of the size of the resected specimen and its technical feasibility. A recently described method of EMR comprises the circumferential mucosal incision with a special type of needle-knife and subsequent en-bloc resection following prior injection under the lesions, but only a few patients with early Barrett's cancer were treated so far. EMR should be considered as the treatment of choice for high-grade intraepithelial neoplasia (HGIN) and mucosal adenocarcinoma in Barrett's oesophagus. First mid- and long-term results of endoscopic therapy show promising results, disease-free survival is comparable to oesophagectomy. Studies with larger patient numbers proved the efficacy and safety of ER, major complications occur <1%. Photodynamic therapy and other ablation therapies, although they are comparably effective, have a decisive disadvantage in comparison with ER: they lack the opportunity for histological processing of the resected specimen and therefore, provide no information regarding the depth of invasion of the individual layers of the oesophageal wall, and regarding radicality of the resection. Curative endoscopic treatment of early neoplastic lesions in Barrett's oesophagus should only be carried out in centers with a high-volume.     

Endotherapy for Barrett's esophagus

Endotherapy is now the mainstay of therapy for Barrett's associated neoplasia. The approach should begin with confirmation of neoplasia by a gastrointestinal pathologist, patient counseling, and appropriate endoscopic work up. Detailed examination with high-resolution white light endoscopy is the most important tool for detection of neoplasia. Further validation studies are needed for many enhanced imaging modalities before being recommended as part of the standard work up and assessment of patients with Barrett's esophagus (BE). Endoscopic mucosal resection is required for any visible lesion in the setting of dysplasia for accurate histological diagnosis. The remainder of the epithelium may be treated with resection or ablative therapy, followed by adequate surveillance. Patients with nondysplastic Barrett's require further risk stratification before incorporation of ablative therapy for this population. The future will fortify the endoscopic role in Barrett's with validation trials for endoscopic assessment, further long-term results for each of the treatment modalities, potential risk stratification for patients with BE, and improved guidelines for surveillance after therapy.     

High recurrence rate of Barrett's epithelium during long-term follow-up after argon plasma coagulation

OBJECTIVE: Several studies have shown that argon plasma coagulation (APC) combined with proton-pump inhibitor (PPI) therapy is a suitable procedure to eradicate Barrett's epithelium for a short-term follow-up. The real impact of this kind of management with respect to cancer risk and durability of squamous regeneration remains unclear. We present the follow-up data for up to 51 months after eradication of Barrett's mucosa. MATERIAL AND METHODS: In 1998-2001, 25 patients with Barrett's esophagus were included in a prospective study. After baseline documentation, Barrett's epithelium was treated with repeated APC until complete squamous restoration was reached. Thereafter, all patients were continuously treated with high-dose PPIs. RESULTS: Each patient underwent a median of four APC sessions. Twenty-one (84%) of the patients had complete squamous regeneration at the end of treatment. During a follow-up of up to 51 months, Barrett's epithelium was found to have recurred in 14/21 (66%) patients. Including the patients with initially incomplete squamous restoration, a long-lasting and complete effect was achieved in only 7 patients (28%) after a mean follow-up period of 30 months. CONCLUSIONS: So far, it is still not proven whether coagulation-induced squamous regeneration reduces the risk of Barrett's carcinoma. Furthermore, the high relapse rate, the procedure-related risk, and the high costs incurred preclude the routine use of APC for the treatment of non-dysplastic Barrett's esophagus. The different recurrence rates between published studies may be due to technical differences and PPI schedule. We suggest that optimal conditions for the procedure must be defined before further studies are undertaken.     

Endoscopic therapy in patients with Barrett's esophagus and portal hypertension

BACKGROUND: Endoscopic mucosal resection has been used to stage and treat early neoplasia in Barrett's esophagus. The ability to do this in the setting of portal hypertension has not been reported. OBJECTIVE: Our purpose was to describe the feasibility and efficacy of endoscopic mucosal resection in patients with portal hypertension and Barrett's esophagus. DESIGN: Retrospective case series. SETTING: Two tertiary referral centers. PATIENTS: Patients with Barrett's esophagus and high-grade dysplasia or adenocarcinoma in the setting of portal hypertension. INTERVENTION: Endoscopic mucosal resection of endoscopically visible lesions. MAIN OUTCOME MEASUREMENTS: Complete resection of neoplastic lesion, lack of variceal bleeding. RESULTS: Four patients were treated with endoscopic mucosal resection a total of 5 times. Endoscopic mucosal resection was successfully performed without significant GI bleeding. LIMITATIONS: This preliminary case series describes feasibility of the procedure. Whether this can be generalized remains to be determined, although it may be an option in poor surgical candidates. CONCLUSIONS: Endoscopic mucosal resection appears to be relatively safe in selected patients with portal hypertension and Barrett's esophagus. Further studies are needed to confirm these findings.     

Stepwise radical endoscopic resection of the complete Barrett's esophagus with early neoplasia successfully eradicates pre-existing genetic abnormalities

OBJECTIVES: Malignant transformation of Barrett's mucosa is associated with the accumulation of genetic alterations. Stepwise radical endoscopic resection of the Barrett's 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 Barrett's 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 Barrett's esophagus with early neoplasia successfully eradicates pre-existing genetic abnormalities and results in neosquamous epithelium without these genetic abnormalities.     

Endoscopic resection techniques and ablative therapies for Barrett's neoplasia

Esophageal adenocarcinoma is the most rapidly increas- ing cancer in western countries.High-grade dysplasia (HGD)arising from Barrett’s esophagus(BE)is the most important risk factor for its development,and when it is present the reported incidence is up to 10% per patient-year.Adenocarcinoma in the setting of BE develops through a well known histological sequence,from non-dysplastic Barrett’s to low grade dysplasia and then HGD and cancer.Endoscopic surveillance programs have been established to detect the presence of neo- plasia at a potentially curative stage.Newly developed endoscopic treatments have dramatically changed the therapeutic approach of BE.When neoplasia is confined to the mucosal layer the risk for developing lymph node metastasis is negligible and can be successfully eradi- cated by an endoscopic approach,offering a curative in- tention treatment with minimal invasiveness.Endoscopic therapies include resection techniques,also known as tissue-acquiring modalities,and ablation therapies or non-tissue acquiring modalities.The aim of endoscopic treatment is to eradicate the whole Barrett’s segment,since the risk of developing synchronous and metachro- nous lesions due to the persistence of molecular aberra- tions in the residual epithelium is well established.     

Antireflux surgery followed by bipolar electrocoagulation in the treatment of Barrett's esophagus.

BACKGROUND: Management of Barrett's esophagus requires reduction of gastric acid secretion and screening for the development of adenocarcinoma. However, the current therapeutic options are ineffective in reducing the Barrett's mucosa. The aim of this study was to evaluate the effectiveness of endoscopic thermal coagulation of Barrett's mucosa as an alternative therapeutic approach and the recurrence of the disease in the long term. METHODS: Fourteen patients (11 men, 3 women; mean age 45.7 years) with Barrett's esophagus participated in the study. They underwent laparoscopic fundoplication and were symptom free with no defective fundoplication wraps before therapeutic endoscopy. Endoscopic thermocoagulation was performed with a flexible videoendoscope and a bipolar probe. Mucosal areas were treated once a month until the Barrett's mucosa disappeared. Endoscopy was performed 1 and 7 months after completion of the treatments and once a year thereafter. RESULTS: The mean follow-up period was 21.6 months (range 18 to 30 months). The mean length of Barrett's esophagus was 4.8 cm. Successful ablation of the columnar epithelium was achieved in 3.7 sessions, as defined by demonstration of normal squamous epithelium at histologic examination of biopsy samples collected after completion of the treatments and at follow-up evaluations. Three patients experienced short-term (10 days) odynophagia or dysphagia. All patients were symptom free with no evidence of Barrett's esophagus at the end of the study. CONCLUSIONS: Bipolar electrocoagulation after antireflux operations is effective in promoting regression of Barrett's esophagus and has few complications. Endoscopic thermal coagulation might reduce risk for adenocarcinoma among these patients.     

EUS in the management of the patient with dysplasia in Barrett's esophagus

Barrett's esophagus is the most important risk factor in the development of adenocarcinoma of the esophagus. Barrett's esophagus is generally regarded as the most significant complication of gastroesophageal reflux disease. Adenocarcinoma occurs more frequently in the setting of high-grade dysplasia. The prognosis of adenocarcinoma of the esophagus is strongly correlated with the stage of disease. The prognosis of late stage disease is extremely poor. Cure may be achieved when disease is found at an early stage. Esophagectomy has been the definitive treatment of limited stage adenocarcinoma of the esophagus. The morbidity and mortality rate for esophagectomy is high. Therefore, alternative endoscopic methods for curative treatments have gained popularity. The two main endoscopic therapies, photodynamic therapy and endoscopic mucosal resection, are both effective when applied to early-stage disease. Traditional evaluation of the patient with Barrett's esophagus with high-grade dysplasia includes esophago-gastro-duodenoscopy (EGD) with biopsy and computed tomography of the chest. Endoscopic ultrasound (EUS) has gained popularity in the evaluation of the patient with Barrett's esophagus and high-grade dysplasia because it is the only imaging technique capable of delineating the separate histologic layers of the gastrointestinal tract. The principal role of EUS in evaluating patients with Barrett's-associated dysplasia is to identify patients who may be candidates for endoscopic ablative (endoscopic mucosal resection, photodynamic therapy) therapies. EUS has been shown to be superior to computed tomography (including high resolution spiral CT) or magnetic resonance imaging for preoperative staging in patients with high-grade dysplasia and carcinoma. This review of the literature summarizes the ability of EUS to evaluate patients with Barrett's esophagus and high-grade dysplasia.     

Persistent genetic abnormalities in Barrett's esophagus after photodynamic therapy

BACKGROUND & AIMS: Photodynamic therapy (PDT) is a technique for nonsurgical treatment of patients with dysplasia in Barrett's esophagus. The primary endpoint for PDT has been resolution of dysplasia. We studied the effect of PDT at the genetic level. METHODS: Archival material from 3 patients who had initial improvement in dysplasia after PDT but occurrence of high-grade dysplasia during follow-up was used. Biopsy specimens were analyzed for increased proliferation, aneuploidy, p53 protein overexpression, p53 mutations, and p16 promoter hypermethylation. RESULTS: Patients developed high-grade dysplasia 16, 28, and 37 months after PDT. In all cases, one or more genetic markers were positive after PDT treatment, whereas histology was downstaged consistently after therapy. Increasing genetic abnormalities were noted by the end of follow-up. CONCLUSIONS: Genetic abnormalities may persist after PDT despite phenotypical improvement of dysplasia. These patients may progress to high-grade dysplasia or develop adenocarcinoma. Histologic improvement in dysplasia is an inadequate endpoint for PDT in patients with Barrett's esophagus.     

Histologic evaluation of resection specimens obtained at 293 endoscopic resections in Barrett's esophagus

BACKGROUND: Evidence-based selection criteria for endoscopic resection (ER) of Barrett's neoplasia are scarce. OBJECTIVE: To study the histopathology of ER specimens of Barrett's neoplasia and correlate this with endoscopic characteristics to make recommendations for patient management. DESIGN, SETTING, INTERVENTIONS: Histology and correlating endoscopy reports of specimens obtained at 293 consecutive ERs performed at a Dutch tertiary referral center between 2000 and 2006 were reviewed. MAIN OUTCOME MEASUREMENTS: Histologic findings in ER specimens and their relation with endoscopic characteristics. RESULTS: A total of 150 ERs were performed for focal lesions: 16% type 0-I, 23% 0-IIa, 7% 0-IIb, 3% 0-IIc, 9% 0-IIa-IIb, and 42% 0-IIa-IIc; and 143 for flat mucosa. Histology revealed no dysplasia in 57 ERs, low-grade intraepithelial neoplasia in 52, high-grade intraepithelial neoplasia in 104, T1m in 61, and T1sm in 17; in two cancers, infiltration depth was not assessable because of artifacts. Type 0-I and 0-IIc lesions significantly more often penetrated the submucosa (P = .009): 60% were G1 cancers, 23% were G2 cancers, and 18% were G3 cancers. G2-G3 cancers significantly more often invaded the submucosa (P < .001) or had positive vertical margins (P = .015). Histology of ER specimens led to a change in diagnosis in 49% of the focal lesions and a relevant change in treatment policy in 30%. LIMITATIONS: A retrospective study. CONCLUSIONS: ER is a valuable diagnostic tool that frequently leads to a change in treatment policy. Most endoscopically resected early Barrett's neoplasia are 0-II type, G1 mucosal neoplasia. Submucosal infiltration is more often encountered in type 0-I and 0-IIc lesions and in G2-G3 cancers.