Long-term fear of cancer recurrence in patients treated endoscopically for early Barrett's neoplasia.

Previous studies on fear of cancer recurrence after endoscopic treatment for early Barrett's neoplasia focused on fear during a relatively short period after the intervention. The aim of this study was to explore whether fear of cancer (recurrence) persists during long-term follow-up in patients treated endoscopically for Barrett's neoplasia compared to patients treated surgically for a more advanced stage of esophageal adenocarcinoma. Participants previously participated in a prospective longitudinal study investigating quality of life and fear of cancer recurrence and were treated endoscopically for early Barrett's neoplasia (high-grade dysplasia-T1sm1N0M0) or surgically for a more advanced esophageal adenocarcinoma (T1N0M0-T3N1M0). For the present study, participants were again invited to complete a set of questionnaires including the fear of cancer recurrence scale (FORS), worry for cancer scale (WOCS), and the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS Anxiety). Thirty-nine patients were eligible in the endoscopy group and 28 in the surgical group. The median time between the baseline measurement (original study) and the long-term follow-up assessment was 4 years (interquartile range 3-5 years). Fear and worry for cancer recurrence and general anxiety diminished over time in both treatment groups. However, at long-term follow-up, endoscopically treated patients had significantly higher levels of worry for cancer and general anxiety than surgically treated patients. Fear of cancer recurrence did not significantly differ between endoscopically and surgically treated patients. We found that worry and fear of cancer recurrence and general anxiety in endoscopically treated patients declined over time, but not as much as in surgically treated patients.

Impact of ablation of Barrett's esophagus with low-grade dysplasia on patients' illness perception and quality of life: a multicenter randomized trial.

BACKGROUND AND AIMS: A previous multicenter randomized trial demonstrated that radiofrequency ablation (RFA) significantly reduced the risk of neoplastic progression compared with surveillance (1.5% vs 26.5%) in patients with Barrett's esophagus (BE) and low-grade dysplasia (LGD). In the same population, this study aimed to compare the quality of life (QOL) and illness perception (IP) among patients treated with RFA and patients kept under surveillance. METHODS: From June 2007 to June 2011, patients with BE and LGD were randomly assigned to RFA or surveillance. QOL and IP were assessed at baseline, 2, 9, 14, 26, and 38 months. Standardized questionnaires were used (SF-36, EORTC QLQ-C30, EORTC QLQ-OES18, and the brief Illness Perception Questionnaire [IPQ]). RESULTS: Forty-seven patients in the ablation group and 49 patients in the surveillance group completed the questionnaires (median follow-up, 36 months). Marginal differences were observed in the SF-36 and the EORTC-QLQ-C30. Based on the EORTC-QLQ-OES18, the ablation group reported more diarrhea (7.8 vs 4.0; P = .018), whereas the surveillance group reported more reflux (15.1 vs 9.0; P < .001) and more problems with speaking (4.3 vs 2.2; P = .019). The IPQ showed that patients in the ablation group perceived their disease lasted for a shorter period of time (P < .001), experienced fewer symptoms (P < .001), had fewer concerns about their condition (P < .001), and tended to be less emotionally affected by their condition (P = .012) than patients in the surveillance group. As a result, patients who underwent ablation experienced their condition as less threatening compared with patients in the surveillance group (P < .001). CONCLUSION: Patients treated with ablation for BE with LGD reported a QOL comparable with that of patients undergoing endoscopic surveillance; however, the patients in the ablation group had fewer concerns and a less-threatening view of their condition. (Clinical trial registration number [www.trialregister.nl]: NTR1198; 25-1-2008.).

Self-dilation for therapy-resistant benign esophageal strictures: towards a systematic approach.

BACKGROUND: Patients with therapy-resistant benign esophageal strictures (TRBES) suffer from chronic dysphagia and generally require repeated endoscopic dilations. For selected patients, esophageal self-dilation may improve patient's autonomy and reduce the number of endoscopic dilations. We evaluated the clinical course and outcomes of patients who started esophageal self-dilation at our institution. METHODS: This study was a retrospective case series of patients with TRBES who started esophageal self-dilation between 2012 and 2016 at the Academic Medical Center Amsterdam. To learn self-dilation using Savary-Gilliard bougie dilators, patients visited the outpatient clinic on a weekly basis where they were trained by a dedicated nurse. Endoscopic dilation was continued until patients were able to perform self-bougienage adequately. The primary outcome was the number of endoscopic dilation procedures before and after initiation of self-dilation. Secondary outcomes were technical success, final bougie size, dysphagia scores, and adverse events. RESULTS: Seventeen patients started with esophageal self-dilation mainly because of therapy-resistant post-surgical (41%) and caustic (35%) strictures. The technical success rate of learning self-bougienage was 94% (16/17). The median number of endoscopic dilation procedures dropped from 17 [interquartile range (IQR) 11-27] procedures during a median period of 9 (IQR 6-36) months to 1.5 (IQR 0-3) procedures after the start of self-dilation (p < 0.001). The median follow-up after initiation of self-dilation was 17.6 (IQR 11.5-33.3) months. The final bougie size achieved with self-bougienage had a median diameter of 14 (IQR 13-15) mm. All patients could tolerate solid foods (Ogilvie dysphagia score ≤ 1), making the clinical success rate 94% (16/17). One patient (6%) developed a single episode of hematemesis related to self-bougienage. CONCLUSIONS: In this small case series, esophageal self-dilation was found to be successful 94% of patients when conducted under strict guidance. All patients performing self-bougienage achieved a stable situation where they could tolerate solid foods without the need for endoscopic dilation.

The cost-effectiveness of radiofrequency ablation for Barrett's esophagus with low-grade dysplasia: results from a randomized controlled trial (SURF trial).

BACKGROUND AND AIMS: The Surveillance versus Radiofrequency Ablation (SURF) trial randomized 136 patients with Barrett's esophagus (BE) containing low-grade dysplasia (LGD), to receive radiofrequency ablation (ablation, n = 68) or endoscopic surveillance (control, n = 68). Ablation reduced the risk of neoplastic progression to high-grade dysplasia and esophageal adenocarcinoma (EAC) by 25% over 3 years (1.5% for ablation vs 26.5% for control). We performed a cost-effectiveness analysis from a provider perspective alongside this trial. METHODS: Patients were followed for 3 years to quantify their use of health care services, including therapeutic and surveillance endoscopies, treatment of adverse events, and medication. Costs for treatment of progression were analyzed separately. Incremental cost-effectiveness ratios (ICER) were calculated by dividing the difference in costs (excluding and including the downstream costs for treatment of progression) by the difference in prevented events of progression. Bootstrap analysis (1000 samples) was used to construct 95% confidence intervals (CIs). RESULTS: Patients who underwent ablation generated mean costs of U.S.$13,503 during the trial versus $2236 for controls (difference $11,267; 95% CI, $9996-$12,378), with an ICER per prevented event of progression of $45,066. Including the costs for treatment of progression, ablation patients generated mean costs of $13,523 versus $4,930 for controls (difference $8593; 95% CI, $6881-$10,153) with an ICER of $34,373. Based on the various ICER estimates derived from the bootstrap analysis, one can be reasonably certain (>75%) that ablation is efficient at a willingness to pay of $51,664 per prevented event of progression or $40,915 including downstream costs of progression. CONCLUSIONS: Ablation for patients with confirmed BE-LGD is more effective and more expensive than endoscopic surveillance in reducing the risk of progression to high-grade dysplasia/EAC. The increase in costs of ablation can be justified to avoid a serious event such as neoplastic progression. At a willingness to pay of $40,915 per prevented event of progression, one can be reasonably certain that ablation is efficient. (www.trialregister.nl number: NTR 1198.).

Quality of life and fear of cancer recurrence after endoscopic treatment for early Barrett's neoplasia: a prospective study.

Endoscopic therapy is the treatment of choice for high grade intraepithelial neoplasia (HGIN) or early cancer (≤T1sm1) in Barrett's esophagus (BE). We prospectively evaluated the effect of endoscopic treatment on quality of life (QOL) and fear of cancer (recurrence) and compared this with the effect of Barrett's surveillance or surgery. Patients treated endoscopically for early Barrett's neoplasia (n = 42, HGIN - T1sm1N0M0) were compared with three groups: patients with non-dysplastic BE undergoing surveillance (n = 44); patients treated surgically for early BE neoplasia (HGIN - T2N0M0, n = 21); patients treated surgically for advanced BE cancer (T1N1M0 - T3N1M0, n = 19). QOL (SF-36; EORTC-QLQ-C30; EORTC-QLQ-OES18) and fear of cancer recurrence (Worry of Cancer Scale [WOCS] and the Hospital Anxiety and Depression Scale [HADS]) were measured at baseline, 2 and 6 months after treatment. The endoscopic treatment group reported significantly better QOL in both physical and mental scales of SF-36 and EORTC-QLQ-C30 and less esophageal cancer related symptoms compared to both surgical groups. The endoscopic treatment group reported significant more worry for cancer recurrence (WOCS) compared to the early surgical group. Their scores on the WOCS were comparable with the scores of the advanced surgical group. Endoscopic treatment of early esophageal cancer has less negative impact on QOL and esophageal cancer symptoms than surgery. However, endoscopically treated patients worry as much about cancer recurrence as patients treated surgically for advanced cancer.

Derivation of genetic biomarkers for cancer risk stratification in Barrett's oesophagus: a prospective cohort study.

OBJECTIVE: The risk of developing adenocarcinoma in non-dysplastic Barrett's oesophagus is low and difficult to predict. Accurate tools for risk stratification are needed to increase the efficiency of surveillance. We aimed to develop a prediction model for progression using clinical variables and genetic markers. METHODS: In a prospective cohort of patients with non-dysplastic Barrett's oesophagus, we evaluated six molecular markers: p16, p53, Her-2/neu, 20q, MYC and aneusomy by DNA fluorescence in situ hybridisation on brush cytology specimens. Primary study outcomes were the development of high-grade dysplasia or oesophageal adenocarcinoma. The most predictive clinical variables and markers were determined using Cox proportional-hazards models, receiver operating characteristic curves and a leave-one-out analysis. RESULTS: A total of 428 patients participated (345 men; median age 60 years) with a cumulative follow-up of 2019 patient-years (median 45 months per patient). Of these patients, 22 progressed; nine developed high-grade dysplasia and 13 oesophageal adenocarcinoma. The clinical variables, age and circumferential Barrett's length, and the markers, p16 loss, MYC gain and aneusomy, were significantly associated with progression on univariate analysis. We defined an 'Abnormal Marker Count' that counted abnormalities in p16, MYC and aneusomy, which significantly improved risk prediction beyond using just age and Barrett's length. In multivariate analysis, these three factors identified a high-risk group with an 8.7-fold (95% CI 2.6 to 29.8) increased HR when compared with the low-risk group, with an area under the curve of 0.76 (95% CI 0.66 to 0.86). CONCLUSIONS: A prediction model based on age, Barrett's length and the markers p16, MYC and aneusomy determines progression risk in non-dysplastic Barrett's oesophagus.

Cancer risk perception in relation to associated symptoms in Barrett's patients: A cross sectional study on quality of life.

BACKGROUND: Barrett's oesophagus affects patients' quality of life and may be a psychological burden due to the threat of developing an oesophageal adenocarcinoma. OBJECTIVE: Assessing the oesophageal adenocarcinoma risk perceived by non-dysplastic Barrett's oesophagus patients and its association with quality of life, illness perception and reflux symptoms. METHODS: This cross-sectional questionnaire study included 158 Barrett's oesophagus non-dysplastic patients aged 18-75 years. Based on their annual and lifetime oesophageal adenocarcinoma risk estimations measured with the Magnifier Scale, patients were classified as overestimating or underestimating. Associations between the groups where assed on demographics, reflux symptoms and results of the Outcomes Study Short-Form-36 (SF-36) and the Brief Illness Perception Questionnaire (B-IPQ). RESULTS: The annual oesophageal adenocarcinoma risk was overestimated by 41%. Overestimating patients had lower means on the SF-36 domains: bodily pain (annual p = 0.007 and lifetime p = 0.014), general health (annual p = 0.011 and lifetime p = 0.014), vitality (annual p = 0.030), physical functioning (lifetime p = 0.028), worse illness perception (total score p = 0.001) and significantly more reflux symptoms. CONCLUSIONS: Overestimation of the oesophageal adenocarcinoma risk by Barrett's oesophagus patients was associated with decreased quality of life and worse illness perceptions, which is most likely caused by symptoms of dyspepsia and reflux. These symptoms should be adequately treated, and patients may be in need of extra support and specific information about their oesophageal adenocarcinoma risk.

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 Barrett's 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 Barrett's 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.

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.

Cytokeratin and CDX-2 expression in Barrett's esophagus.

OBJECTIVE: Barrett's esophagus (BE) is a premalignant condition of the distal esophagus. For diagnostic purposes it is important to find biomarkers that can specifically identify BE, for instance to differentiate BE epithelial cells from gastric cardia epithelial cells in brush cytology specimens. The objective of this study was to determine the specificity of CDX-2 and a set of cytokeratins (CKs) as specific markers for BE as compared with normal squamous esophageal and gastric cardia tissue. MATERIAL AND METHODS: Immunohistochemistry (IHC) with specific antibodies against CDX-2, and a set of CKs was performed on fresh frozen consecutive tissue sections of normal squamous, gastric cardia and non-dysplastic BE of 80 patients. RESULTS: IHC results showed CK8, CK18 and CK20 expression in both BE and gastric cardia, while CK7 was seen in all BE but also in 26% of gastric cardia biopsies. CK10/13 was only expressed in normal squamous epithelium. CDX-2 nuclear staining was found in 87.5% of the BE biopsies, whereas normal squamous esophagus and cardia biopsies were negative. CONCLUSIONS: CDX-2 in combination with a set of CKs can be used as biomarkers to distinguish between BE and normal squamous esophagus. In order to distinguish BE from cardia tissue, a combination of CDX-2 and CK7 is most informative.

Bone morphogenetic protein 4 expressed in esophagitis induces a columnar phenotype in esophageal squamous cells.

BACKGROUND & AIMS: Barrett's esophagus (BE) is a metaplastic condition in which normal squamous esophageal epithelium is replaced by columnar epithelium. It is proposed that one of the possible mechanisms is dedifferentiation of squamous epithelium into columnar epithelium. The pathophysiology through which this metaplasia occurs is unknown. A recent study by serial analysis of gene expression showed that bone morphogenetic protein 4 (BMP-4) is uniquely expressed in BE. In this study, the role of the BMP pathway in the metaplastic transformation of normal squamous cells into columnar cells was examined. METHODS: Tissues from patients with esophagitis and BE and in an esophagitis-BE rat model were examined for the activation of the BMP pathway. Short-term cultures of primary normal squamous esophageal cells were treated with BMP-4, and cell biological changes were examined by Western blot analysis, immunohistochemistry, and microarrays. RESULTS: In both human and rat tissues, the BMP pathway proved to be activated in esophagitis and BE. Upon incubation of squamous cell cultures with BMP-4, the cytokeratin expression pattern showed a shift that was consistent with columnar epithelium. Involvement of the BMP pathway was suggested by up-regulation of Phosphorylated-Smad 1/5/8 (P-Smad 1/5/8) that was effectively blocked by Noggin, a BMP antagonist. Comparison of the gene expression profiles of squamous cells, BMP-4-treated squamous cells, and BE cells showed a significant shift in the profile of the BMP-4-treated squamous cells toward that of the cultured BE cells. CONCLUSIONS: These results suggest that the BMP pathway could play a role in the transformation of normal esophageal squamous cells into columnar cells.

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.

Efficient automated assessment of genetic abnormalities detected by fluorescence in situ hybridization on brush cytology in a Barrett esophagus surveillance population.

BACKGROUND: Automated assessment of genetic abnormalities detected by fluorescence in situ hybridization (FISH) in brush cytology specimens from patients with Barrett esophagus (BE) may enhance the clinical applicability of this methodology. The objectives of this study were to validate a novel, automated, proprietary system (CytoVison SPOT AX) for the assessment of FISH abnormalities in BE brush cytology and, subsequently, to use this automated method for screening of a BE surveillance cohort. METHODS: FISH with DNA probes for chromosomes 9, 17, and Y, and for the 9p21 (p16), 17q11.2 (Her2/neu), and 17p13.1 (p53) loci was applied on brush cytology specimens from a surveillance cohort of 151 patients with BE. Validation of the automated system was performed by comparison of the automated FISH results with manual scores for the first 60 patients. RESULTS: There was 98% concordance between manual and automated FISH analysis with kappa values from 0.49 to 1 for the different probes. The loss of 17p13.1 (p53) was observed in only 5% of patients with no dysplasia (ND) and in 9% of patients with low-grade dysplasia (LGD) but increased to 46% in patients with high-grade dysplasia (HGD) (P < .005; Fisher exact test). Chromosomes 9 and 17 were observed in 6% of patients with ND, in 21% of patients with LGD, and in 62% of patients with HGD (P < .05). Ten percent of patients with ND had loss of the Y chromosome, which increased to 27% in patients with HGD (P< .05). The amplification of 17q11.2 (Her2/neu) was detected in 62% of patients with HGD (P < .001). CONCLUSIONS: The current investigation indicated that the CytoVison SPOT AX is an objective, efficient system for the analysis of DNA-FISH on BE brush cytology and is applicable for analyzing large populations of BE patients. In the current study cohort, the loss of 17p13.1 (p53), Y chromosome loss, and polysomy of chromosomes 17 and 9 were correlated with increasing grade of dysplasia 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 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.

A comparative analysis by SAGE of gene expression profiles of Barrett's esophagus, normal squamous esophagus, and gastric cardia.

BACKGROUND & AIMS: The metaplastic process in which the normal squamous epithelium of the distal esophagus is replaced by columnar-lined epithelium, known as Barrett's esophagus (BE), is poorly understood. The aim of this study was to define, analyze, and compare transcription profiles of BE, normal cardia epithelium, and squamous epithelium to gain more insight into the process of metaplasia and to identify uniquely expressed genes in these epithelia. METHODS: Serial analysis of gene expression was applied for obtaining transcription libraries of biopsy specimens taken from a BE-affected patient with intestinal type of metaplasia and from normal squamous and gastric cardia epithelia. Validation of results by reverse-transcription polymerase chain reaction and immunoblotting was performed using tissues of 20 patients with BE. RESULTS: More than 120,000 tags were sequenced. Between BE and squamous 776, and between BE and gastric cardia 534 tags were significantly differentially expressed (P < .05, pairwise comparison). In contrast, squamous compared with gastric cardia epithelia showed significant differential expression of 1316 tags. The most up-regulated genes in BE compared with squamous epithelium were trefoil factors, annexin A10, and galectin-4. Each of the epithelia showed a unique cytokeratin expression profile. CONCLUSIONS: This study provides a comparison of the transcriptomes of BE, squamous epithelium, and gastric cardia epithelium. BE proves to be an incompletely differentiated type of epithelium that shows similarities to both normal squamous and gastric cardia epithelia. In addition, several uniquely expressed genes are identified. These results are a major advancement in understanding the process of metaplasia that leads to BE.

A randomized crossover study comparing light-induced fluorescence endoscopy with standard videoendoscopy for the detection of early neoplasia in Barrett's esophagus.

BACKGROUND: Light-induced fluorescence endoscopy (LIFE) may improve the detection of high-grade dysplasia (HGD) and early stage cancer (EC) in Barrett's esophagus (BE). The aim of this study was to compare LIFE with standard endoscopy (SE) in a randomized crossover study. METHODS: Fifty patients with BE underwent SE and LIFE in a randomized sequence (4 to 6-week interval between procedures). The two procedures were performed by two different endoscopists who were blinded to the findings of the other examination. Targeted biopsy specimens were taken from detected lesions, followed by random biopsy specimens with a 2-cm interval, 4-quadrant protocol. Biopsy specimens were routinely evaluated and subsequently reviewed by a single, blinded expert GI pathologist. RESULTS: Targeted biopsy specimens had a sensitivity for the diagnosis of HGD/EC of 62% (8/13) for both techniques. The overall sensitivity (all biopsy specimens) was 85% for SE and 69% for LIFE (p = 0.69). All targeted biopsy specimens had a positive predictive value (PPV) for HGD/EC of 41% for SE and 28% for LIFE (p = 0.40); autofluorescence-targeted biopsy specimens had a PPV of 13%. False-positive lesions had a significantly higher rate of acute inflammation than random biopsy specimens. CONCLUSIONS: In this study, LIFE did not improve the detection of HGD or EC in patients with BE compared with SE.

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 Barrett's esophagus. METHODS: Patients with Barrett's 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 Barrett's esophagus.