Circumferential endoscopic mucosal resection in Barrett's esophagus with high-grade intraepithelial neoplasia or mucosal cancer. Preliminary results in 21 patients

BACKGROUND AND STUDY AIMS: Treatment by endoscopic mucosal resection (EMR) has been established for early lesions in Barrett's esophagus. However, the remaining Barrett's esophagus epithelium remains at risk of developing further lesions. The aim of this study was to evaluate the efficacy of circumferential endoscopic mucosectomy (circumferential EMR)s in removing not only the index lesion (high-grade intraepithelial neoplasia (HGIN) or mucosal cancer), but also the remaining Barrett's esophagus epithelium. PATIENTS AND METHODS: A total of 21 patients were included in the study (11 men, 10 women), who had Barrett's esophagus and either HGIN (n = 12) or mucosal cancer (n = 9). Of the patients, 17/21 were at high surgical risk and five had refused surgery. On the basis of preprocedure endosonography their lesions were classified as T1N0 (n = 19) or T0N0 (n = 2). The lesions and the Barrett's esophagus epithelium were removed by polypectomy after submucosal injection of 10-15 ml of saline; a double-channel endoscope was used in 15/21 cases. Circumferential EMR was performed in two sessions, the lesion and the surrounding half of the circumferential Barrett's esophagus mucosa being removed in the first session. In order to prevent the formation of esophageal stenosis, the second half of the Barrett's esophagus mucosa was resected 1 month later. RESULTS: Complications occurred in 4/21 patients (19 %), consisting of bleeding which was successfully managed by endoscopic hemostasis in all cases. No strictures were observed during follow-up (mean duration 18 months) and endoscopic resection was considered complete in 18/21 patients (86 %). For three patients, histological examination showed incomplete removal of tumor: one of these underwent surgery; two received chemoradiotherapy, and showed no evidence of residual tumor at 18 months' and 24 months' follow-up, respectively. Two patients in whom resection was initially classified as complete later presented with local recurrence and were treated again by EMR. Barrett's esophagus mucosa was completely replaced by squamous cell epithelium in 15/20 patients (75 %). CONCLUSIONS: Circumferential EMR is a noninvasive treatment of Barrett's esophagus with HGIN or mucosal cancer, with a low complication rate and good short-term clinical efficacy. Further studies should focus on long-term results and on technical improvements.     

Photodynamic therapy and endoscopic mucosal resection for Barrett's dysplasia and early esophageal adenocarcinoma

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic ablation with porfimer sodium photodynamic therapy (PDT) have recently been combined to improve the accuracy of histologic staging and remove superficial carcinomas. MATERIALS AND METHODS: All patients with Barrett's esophagus and high-grade dysplasia were evaluated with computed tomography and endosonography. Patients with nodular or irregular folds underwent EMR followed by PDT. RESULTS: In three patients, endoscopic mucosal resection upstaged the diagnosis to mucosal adenocarcinoma (T1N0M0). PDT successfully ablated the remaining glandular mucosa. Complications were limited to transient chest discomfort and odynophagia. CONCLUSIONS: The use of EMR resection in Barrett's high-grade dysplasia patients with mucosal irregularities resulted in histologic upstaging to mucosal adenocarcinoma, requiring higher laser light doses for PDT. PDT after EMR appears to be safe and effective for the complete elimination of Barrett's mucosal adenocarcinoma. EMR should be strongly considered for Barrett's dysplasia patients being evaluated for endoscopic ablation therapy.     

Intraepithelial high-grade neoplasia and early adenocarcinoma in short-segment Barrett's esophagus (SSBE): curative treatment using local endoscopic treatment techniques

BACKGROUND AND STUDY AIMS: In recent years, short-segment Barrett's esophagus (SSBE) has attracted increasing attention in the context of reflux disease. However, there is continuing controversy regarding its potential for malignant transformation. PATIENTS AND METHODS: Between October 1996 and September 1999, 50/115 patients (43 %) with intraepithelial high-grade neoplasia or early Barrett's adenocarcinoma, who underwent local endoscopic treatment, had developed a malignant lesion in an (SSBE). In the framework of a prospective observational study, 28 patients were treated with endoscopic mucosal resection (EMR), 13 with photodynamic therapy, and three with argon plasma coagulation; six patients received combinations of these treatments. RESULTS: Complete local remission was achieved in 48/49 patients (98 %). One patient switched to surgery after the first EMR, because there was submucosal tumor infiltration, and in one patient out of 50 local endoscopic treatment failed. A mean of 1.7 +/- 1.4 treatment sessions was required for local endoscopic treatment. The method-associated mortality was 0 %. The rate of relevant complications (stenosis, bleeding) was 6 % (3/50 patients). No cases of severe hemorrhage (Hb fall >2 g/dl) or perforation occurred. During a mean follow-up period of 34 +/- 10 months, metachronous intraepithelial high-grade neoplasms or early adenocarcinomas were seen in 11/48 patients (23 %), who received further successful endoscopic treatment. Four patients died during the follow-up period, but in only one patient was this due to his Barrett's adenocarcinoma (this was the patient who underwent esophageal resection). CONCLUSIONS: The malignant potential of short-segment Barrett's esophagus must not be underestimated. Organ-preserving local endoscopic treatment shows good acute-phase and long-term results. Local endoscopic treatment represents an alternative to esophageal resection in the case of intraepithelial high-grade neoplasia and selected early adenocarcinomas in Barrett's esophagus.     

Curative endoscopic therapy in patients with early esophageal squamous-cell carcinoma or high-grade intraepithelial neoplasia

BACKGROUND AND STUDY AIMS: Endoscopic resection of esophageal squamous-cell neoplasia with curative intent is considered to be a safe and effective alternative treatment to radical surgery in cases where the neoplasia is intraepithelial or limited to the mucosal layer. These patients are at risk for recurrent malignancy in the preserved esophagus, however. We conducted a prospective study to evaluate the efficacy and safety of endoscopic resection and to analyze variables associated with recurrence in patients with mucosal or intraepithelial squamous-cell neoplasia. PATIENTS AND METHODS: Between December 1997 and September 2005, 65 patients (mean age +/- standard deviation [SD] 62.9 +/- 9.5 years), 12 with high-grade intraepithelial neoplasia (HGIN) and 53 with mucosal squamous-cell cancer, were included in our study and were treated using endoscopic resection. Details of patient and tumor characteristics were documented prospectively. All patients were included in a staging protocol including high-resolution endoscopy with Lugol staining, endoscopic ultrasound, computed tomography, and abdominal ultrasound. Endoscopic resection was performed using a ligation technique. The data acquired were subjected to univariate and multivariate analysis. RESULTS: A total of 179 resections were performed (mean number of resections +/- SD per patient, 2.8 +/- 1.8): 11/12 patients with HGIN (91.7%), and 51/53 patients with mucosal cancer (96.2%) achieved a complete response during a mean follow-up period of 39.3 +/- 22.8 months; three patients were still under therapy at the end of the study period. Recurrence of malignancy after achieving a complete response was observed in 16 patients (26%), but these patients all achieved another complete response after further endoscopic treatment. Independent risk factors for recurrence was multifocal carcinoma (RR 4.1, P = 0.018). Tumor-related deaths occurred in two patients (3%), and eight patients died as a result of co-morbidity. Complications were seen in 15/65 patients (23%, all esophageal stenoses). The 7 year survival rate calculated for all groups was 77%. CONCLUSIONS: According to the results of long-term follow-up in this study, endosocopic resection appears to be an effective and safe method of curative treatment in patients with HGIN and mucosal squamous-cell carcinomas of the esophagus. Multifocal carcinoma and T1m1 tumors seem to be highly associated with recurrence.     

Is topical delta-aminolevulinic acid adequate for photodynamic therapy in Barrett's esophagus? A pilot study

BACKGROUND AND STUDY AIMS: The methods of endoscopic ablation of metaplastic and dysplastic areas in Barrett's esophagus so far described, are not satisfactory with respect to efficacy and safety. Therefore we investigated whether photodynamic therapy (PDT) with topical delta-aminolevulinic acid (delta-ALA) leads to ablation of specialized columnar epithelium and eradication of low-grade dysplasia while not producing phototoxicity and systemic side effects. PATIENTS AND METHODS: 14 patients with histologically proven Barrett's esophagus, seven of whom had evidence of low-grade dysplasia, underwent endoscopic treatment with topical delta-ALA. Photoactivation (wavelength, 632 nm) was performed at 1.5 - 2 hours after drug administration using an argon dye laser. Patients received omeprazole 80 mg daily for 2 months; thereafter; maintenance therapy depended on reflux symptoms. Patients were endoscopically re-evaluated after 7 days, and subsequently at 3, 6, 12 and up to 48 months (mean follow up 33 months). Re-treatment with high-dose topical delta-ALA was offered to the 11 patients with remaining metaplasia and was carried out in five of them. RESULTS: Low-grade dysplasia was eradicated in all patients. One patient with no dysplasia before PDT developed a high-grade dysplasia after PDT. Complete ablation of Barrett's metaplasia was observed in 21 % of the patients after the first treatment session and in 20 % after the second treatment session. The mean reduction in the length of Barrett's metaplasia was 1.54 +/- 1.29 cm after the first PDT session and 1.02 +/- 0.80 cm after the second PDT session. Post-endoscopic pain and photosensitivity reactions were less frequent with low-dose delta-ALA PDT than with high-dose PDT (pain 15 %, 100 %, respectively; P = 0.001 by Fisher's exact test; phototoxicity, 0 %, 50 %, respectively; P = 0.021 by Fisher's exact test). CONCLUSION: Low-dose topical administration of delta-ALA provides ablation of low-grade dysplasia in the range obtained with oral delta-ALA. In addition, it is safe and well tolerated. Since, however, topical administration of delta-ALA is not able to consistently eradicate Barrett's esophagus, alternative methods will have to be developed.     

Radiofrequency ablation is effective for the treatment of high-grade dysplasia in Barrett's esophagus after failed photodynamic therapy

Endoscopic radiofrequency ablation (RFA) is an effective treatment for high-grade dysplasia in Barrett's esophagus in ablation-na?ve patients, but no studies have evaluated its use in patients in whom ablative therapy has previously failed. We describe 14 patients with residual high-grade dysplasia following aminolevulinic acid or Photofrin (porfimer sodium) photodynamic therapy (PDT). An overall complete reversal of dysplasia was achieved in 86?% with a combination of RFA and rescue endoscopic mucosal resection. The median total follow-up is 19 months. The rate of strictures was 7?% (1/14) and there was a low rate of buried glands (0.5?% follow-up biopsies). These data suggest RFA is both safe and effective for eradication of high-grade dysplasia in patients in whom PDT has failed.     

Barrett's esophagus: endoscopic resection

In experienced hands, ER is a safe method of resecting dysplastic lesions and early carcinomas of the GI tract, and it has decisive advantages compared with other local endoscopic treatment procedures (such as thermal destruction and PDT). The opportunity for histological processing of the resected specimen provides information regarding the depth of invasion of the individual layers of the GI tract wall. Additionally, it has advantages regarding excision with healthy margins. This means that even when there is infiltration of the submucosa that has not been detected before treatment--in which case local endoscopic therapy is no longer appropriate--a patient with early Barrett's cancer still is able to undergo surgical resection. As was shown recently, the morbidity and mortality of ER are significantly dependent on the frequency with which esophagectomy is performed in each center. When there were more than 20 procedures of this type per year, the surgical mortality was 8%, whereas in centers conducting fewer than 10 procedures per year the rate was 21%. In view of the consequent claim that ER should only be performed at high-volume centers, curative endoscopic treatment of early esophageal carcinomas also should be performed only in centers with a similar frequency to that of the surgical high-volume centers. It is only in these conditions that the conclusion is defensible that patients with HGIN or mucosal Barrett's carcinoma should undergo ER with curative intent instead of radical ER. Randomized and controlled studies comparing radical esophagectomy with endoscopic therapy are desirable, but they are difficult to conduct, not least because valid 5-year survival data show no significant difference between patients who have undergone endoscopic treatment for early Barrett's cancers and the average German population of the same age and sex.     

Poor results of 5-aminolevulinic acid-photodynamic therapy for residual high-grade dysplasia and early cancer in barrett esophagus after endoscopic resection

BACKGROUND AND STUDY AIMS: The aim of the study was to evaluate the efficacy of photodynamic therapy (PDT) in the treatment of residual high-grade dysplasia or early cancer (HGD/EC) after endoscopic resection in Barrett esophagus. PATIENTS AND METHODS: Study patients were separated into group A, with proven residual HGD/EC, and group B with possible HGD/EC (positive lateral margins in the endoscopic resection specimen, without HGD/EC in the remaining Barrett esophagus). PDT treatment consisted of 5-aminolevulinic (5-ALA) photosensitization (40 mg/kg) followed by illumination of the Barrett esophagus with a total light dose of 100 J/cm (2). Complete remission was defined as the absence of HGD/EC in biopsies taken in two consecutive follow-up endoscopies. The percentage regression of Barrett esophagus, as well as the recurrence rate of HGD/EC, was calculated. RESULTS: 20 patients underwent PDT (group A, 11; group B, 9). Mild complications were seen in 4/26 procedures. The overall success rate was 15/20 (75 %). There was a significant difference in success rate between group A (55 %) and group B (100 %); P = 0.03. All patients had residual Barrett esophagus after PDT; the median regression percentage was 50 % (IQR 25 - 70 %). Recurrence of HGD/EC occurred in four patients (two each in groups A and B) after a median follow up of 30 months. CONCLUSIONS: In this selected group of patients, the addition of 5-ALA-PDT after endoscopic resection for HGD/EC had a disappointing success rate in patients who had residual HGD/EC after endoscopic resection. Most patients undergoing 5-ALA-PDT have residual Barrett mucosa after PDT and 5-ALA-PDT does not seem to prevent recurrences during follow-up.     

Clinical impact of conventional endosonography and endoscopic ultrasound-guided fine-needle aspiration in the assessment of patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma who have been referred for endoscopic ablation therapy

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection and photodynamic therapy are exciting, minimally invasive curative techniques that represent an alternative to surgery in patients with Barrett's esophagus and high-grade dysplasia or intramucosal adenocarcinoma. However, there is lack of uniformity regarding which staging method should be used prior to therapy, and some investigators even question whether staging is required prior to ablation. We report our experience with a protocol of conventional endoscopic ultrasound staging prior to endoscopic therapy. PATIENTS AND METHODS: A total of 25 consecutive patients with a diagnosis of high-grade dysplasia or intramucosal adenocarcinoma in Barrett's esophagus who had been referred to the University of Chicago for staging in preparation for endoscopic therapy between March 2002 and November 2004 were included in the study. All 25 patients underwent repeat diagnostic endoscopy and conventional endosonography with a radial echo endoscope. Any suspicious lymph nodes that were detected were sampled using endoscopic ultrasound-guided fine-needle aspiration. RESULTS: Baseline pathology in the 25 patients (mean age 70, range 49-85) revealed high-grade dysplasia in 12 patients and intramucosal carcinoma in 13 patients. Five patients were found to have submucosal invasion on conventional endosonography. Seven patients had suspicious adenopathy, six regional (N1) and one metastatic to the celiac axis (M1a). Fine-needle aspiration confirmed malignancy in five of these seven patients. Based on these results, five patients (20%) were deemed to be unsuitable candidates for endoscopic therapy. CONCLUSIONS: By detecting unsuspected malignant lymphadenopathy, conventional endosonography and endoscopic ultrasound with fine-needle aspiration dramatically changed the course of management in 20% of patients referred for endoscopic therapy of Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma. Based on our results, we believe that conventional endosonography and endoscopic ultrasound with fine-needle aspiration when nodal disease is present should be performed routinely in all patients referred for endoscopic therapy in this setting.     

Argon plasma coagulation in the treatment of Barrett's high-grade dysplasia and in situ adenocarcinoma

BACKGROUND AND STUDY AIMS: Endoscopic therapy of high-grade dysplasia (HGD) and superficial adenocarcinoma associated with Barrett's esophagus (BE), using Nd:YAG laser, KTP laser, or photodynamic therapy (PDT), has been reported to be effective in a curative role. Argon plasma coagulation (APC) appears to be effective in the eradication of nondysplastic Barrett's mucosa, but no results are available in the management of early neoplasms complicating BE. We report our initial experience in the application of APC in this indication. PATIENTS AND METHODS: Ten patients (mean age 74.2) with histologically proven HGD (n = 7) or in situ adenocarcinoma (n = 3) associated with BE (mean length 6 cm) and unfit for surgery were treated using APC and high-dose omeprazole (40 mg daily) until squamous re-epithelialization or complete eradication of the initially apparent lesions. Endoscopic follow-up was maintained at every 3 months. RESULTS: Complete eradication of HGD and in situ adenocarcinoma was achieved after a mean number of 3.3+/-1.5 APC sessions in 8/10 patients (80%). The eight patients with complete clearance of the neoplastic areas did not show any evidence of local recurrence during a median follow-up of 24 months (range 12-36 months). One patient with initial HGD had persistence of HGD 30 months after initial diagnosis, and one patient progressed to invasive adenocarcinoma after failure of APC and PDT. CONCLUSIONS: APC is safe and effective in the management of HGD and in situ adenocarcinoma associated with BE, and might represent an interesting alternative in selected patients who are not candidates for surgery.     

Endoscopic therapy for Barrett's esophagus

There are many foreign reports about the endoscopic ablation therapy for Barrett's esophagus. Endoscopic ablation therapy include thermal therapy (electrocoagulation, laser etc.), photodynamic therapy or endoscopic resection and so on. Ablation of Barrett's esophagus by these therapy in combination with adequate acid suppression lead to mucosal replacement by squamous epithelium. But the true value of these endoscopic therapy has not been fully investigated. Further studies are required.     

Endoscopic fluorescence detection of intraepithelial neoplasia in Barrett's esophagus after oral administration of aminolevulinic acid

BACKGROUND AND STUDY AIMS: Barrett's esophagus is strongly associated with adenocarcinoma. Early malignant transformation of the Barrett's mucosa is often not visible endoscopically and may remain undetected until the invasive adenocarcinoma stage. Endoscopic surveillance is currently carried out on random four-quadrant biopsies at 1-2 cm intervals. Endoscopic fluorescence detection of protoporphyrin IX induced by 5-aminolevulinic acid can identify premalignant lesions. This study evaluates endoscopic fluorescence detection in patients having Barrett's esophagus and compares the results to those of standard endoscopy with random four-quadrant biopsies. PATIENTS AND METHODS: The study included 30 examinations in 28 patients (22 men, 6 women; age range 37-78 years, mean age 60 years,), with five patients having known intraepithelial neoplasia. A dose of 20 mg/kg of 5-aminolevulinic acid was given orally 5 hours before examination. Random four-quadrant biopsies were performed 4-6 weeks before endoscopic fluorescence detection. RESULTS: Of the biopsies taken during the endoscopic fluorescence detection procedure, 28 % (23/81) were true positives. More than one-third of the false-positive results were due to inflammation. None of the 97 control biopsies taken on nonfluorescing areas during endoscopic fluorescence detection were dysplastic. Endoscopic fluorescence detection showed low-grade intraepithelial neoplasia in five patients which was not diagnosed with random four-quadrant biopsies, while random four-quadrant biopsies alone showed three low-grade intraepithelial neoplasias that were invisible during endoscopic fluorescence detection. All high-grade intraepithelial neoplasias or adenocarcinomas (2/2) were detected with both methods. CONCLUSIONS: Fluorescence detection achieved a similar performance when compared with four-quadrant random biopsy, but resulted in fewer biopsies (81 for endoscopic fluorescence detection vs 531 for random four-quadrant biopsies).     

Histological analysis of endoscopic resection specimens from 326 patients with Barrett's esophagus and early neoplasia

BACKGROUND AND STUDY AIMS: Endoscopic resection has been recommended as a local curative approach for Barrett's neoplasia, but large series are still rare. In the present study we analyzed the histological characteristics of endoscopic resection specimens of Barrett's neoplasia. PATIENTS AND METHODS: 742 endoscopic resection specimens obtained from 326 patients were assessed. The following histological characteristics were evaluated: type of neoplasia, grade of differentiation, depth of infiltration, invasion into lymphatic and blood vessels, and resection status (tumor-free margins were regarded as indicating R0 status). RESULTS: 31 patients had no neoplasia and were excluded from the analysis. Among the remaining 295 patients (711 resection specimens), histological findings were: low-grade intraepithelial neoplasia, 1.0 %; high-grade intraepithelial neoplasia, 2.7 %; and mucosal carcinoma 80.3 %. Carcinomas infiltrating the submucosal layer were rare (sm1 7.5 %; sm2 3.7 %; sm3 4.8 %), as were those invading lymph vessels (3.5 %), and there were none with venous invasion. Most of the carcinomas were well-differentiated (72.2 %), and many of these (92.7 %) were limited to the mucosa, in contrast to moderately and poorly differentiated carcinomas (73.7 % and 22.7 %, respectively). R0 status was achieved in 74.5 % of patients; in 47.8 % this was after repeated endoscopic resection. In 26.8 % of patients, R0 resection was achieved at the first attempt. CONCLUSIONS: Our study demonstrates that early Barrett's neoplasms removed by endoscopic resection are mostly limited to the mucosa, are well to moderately differentiated, and very rarely show invasion of the lymph or blood vessels. Although these lesions seem to be low risk with regard to metastatic spread and therefore treatable endoscopically, improved endoscopic resection methods for achieving one-piece (en bloc) R0 resection should be developed.     

Long-Segment early squamous cell carcinoma of the proximal esophagus: curative treatment and long-term follow-up after 5-aminolevulinic acid (5-ALA)-photodynamic therapy

Photodynamic therapy (PDT) is an established treatment for the ablation of dysplastic Barrett's epithelium and early esophageal carcinoma, but no data have been published on curative 5-aminolevulinic acid (5-ALA)-PDT for long-segment early esophageal cancer with infiltration of the upper sphincter. We describe successful curative treatment of an unusual early long-segment squamous cell carcinoma (uT1a,N0) of the proximal esophagus (18 - 28 cm aborally), with three sessions of 5-ALA-PDT. Endoscopic and endosonographic follow-up macroscopically showed a complete remission of the tumor, proven by biopsy showing total histological ablation. After a follow-up period of 23 months, there has been no indication of tumor recurrence. Early superficial (< 3 mm) squamous cell carcinomas of the esophagus can be ablated completely by 5-ALA-PDT. However, long-term follow-up is required in order to prove the effectiveness of endoscopic ablation therapy for early esophageal cancer.     

The clinical strategy for the Barrett's esophagus

The treatment of Barrett's esophagus is controversial. Current treatments include endoscopic therapy, surgical procedures, gastric acid-suppressive therapy with proton pump inhibitors (PPIs), and cancer chemoprevention such as nonsteroidal anti-inflammatory drugs. Endoscopic therapy combined with gastric acid suppressive therapy can result in squamous reepithelialization of the Barrett's mucosa. Antireflux surgery and PPIs therapy are potential options for the treatment of gastroesophageal reflux symptoms in patients with Barrett's esophagus. But there are no prospective studies that support any alternative approach to treatment. Although chemoprevention therapy may reduce cancer risk in Barrett's esophagus, no randomized controlled trials that prove its efficacy have been reported.     

A new long-range through-the-scope balloon applicator for photodynamic therapy in the esophagus and cardia.

BACKGROUND AND STUDY AIMS: Photodynamic therapy (PDT) is a new local, endoscopically controlled therapeutic technique based on the sensitization of malignant and precancerous lesions prior to light-induced tissue destruction. PDT of Barrett's esophagus with severe dysplasia, or of mucosal carcinomas and superficial squamous-cell cancer of the esophagus, requires light application devices allowing homogeneous illumination of the tissue surface in spite of esophageal motility and respiratory movement. On the basis of a commercially available through-the-scope balloon system, we developed a long-range light applicator for homogeneous and circumferential irradiation during PDT, and describe here the initial clinical experience with the device. PATIENTS AND METHODS: The new balloon applicator consists of a flexible cylindrical diffuser fiber with a length of up to 10 cm, depending on the lesion to be illuminated, and an inflatable balloon based on the type of balloon used for esophageal dilation. The balloon is made of a transparent polyurethane membrane with negligible absorption (<5%) at lambda = 600-700 nm, and it can be positioned through the biopsy channel of a conventional endoscope, with direct endoscopic visualization of the targeted lesion. The light intensity distribution perpendicular to the optical axes of the diffuser was measured for red laser light (lambda = 632.8 nm) and for green laser light (lambda = 542 nm). The study of photodynamic treatment included two women and four men (aged 48-79 years) with histologically proved high-grade dysplasia (n = 2) or mucosal cancer in Barrett's esophagus (n = 2) and superficial squamous-cell cancer (SCC) (n = 2), who had undergone EUS staging showing uT0 or uT1N0. Laser light irradiation was conducted after oral ingestion of 5-aminolevulinic acid (5-ALA) or intravenous administration of meta-(tetrahydroxyphenyl)chlorin (mTHPC). RESULTS: Both in vitro and in vivo, precise positioning of the new application system at the targeted tissue and homogeneous illumination were feasible, safe and effective. The total efficiency of transmitted light at wavelengths of lambda = 632.8 nm and lambda = 542 nm was 85-90%. A high degree of homogeneity was measured with applicator lengths of between 15 mm and 95 mm, and the maximum deviation from the mean intensity extended over a range of 40% over the total length of 80 mm. High-grade dysplasia was eradicated in all patients, and in addition mucosal cancer was successfully destroyed in three-quarters of them, requiring an average of 1.3 treatment sessions, with a mean follow-up of 12 months (range 10-15 months). CONCLUSIONS: This centering balloon system may in the future be capable of improving light application techniques during esophageal photodynamic therapy, making PDT a more reliable alternative modality for minimally invasive treatment of high-grade dysplasia and early Barrett's esophagus or squamous-cell carcinoma, as compared with esophagectomy.     

Optical coherence tomography: advanced technology for the endoscopic imaging of Barrett's esophagus

BACKGROUND AND STUDY AIMS: Endoscopic optical coherence tomography (OCT) is an emerging medical technology capable of generating high-resolution cross-sectional imaging of tissue microstructure in situ and in real time. We assess the use and feasibility of OCT for real-time screening and diagnosis of Barrett's esophagus, and also review state-of-the-art OCT technology for endoscopic imaging. MATERIALS AND METHODS: OCT imaging was performed as an adjunct to endoscopic imaging of the human esophagus. Real-time OCT (13-microm resolution) was used to perform image-guided evaluation of normal esophagus and Barrett's esophagus. Beam delivery was accomplished with a 1-mm diameter OCT catheter-probe that can be introduced into the accessory channel of a standard endoscope. Different catheter-probe imaging designs which performed linear and radial scanning were assessed. Novel ultrahigh-resolution (1.1-microm resolution) and spectroscopic OCT techniques were used to image in vitro specimens of Barrett's esophagus. RESULTS: Endoscopic OCT images revealed distinct layers of normal human esophagus extending from the epithelium to the muscularis propria. In contrast, the presence of gland- and crypt-like morphologies and the absence of layered structures were observed in Barrett's esophagus. All OCT images showed strong correlations with architectural morphology in histological findings. Ultrahigh-resolution OCT techniques achieved 1.1-microm image resolution in in vitro specimens and showed enhanced resolution of architectural features. Spectroscopic OCT identified localized regions of wavelength-dependent optical scattering, enhancing the differentiation of Barrett's esophagus. CONCLUSIONS: OCT technology with compact fiberoptic imaging probes can be used as an adjunct to endoscopy for real-time image-guided evaluation of Barrett's esophagus. Linear and radial scan patterns have different advantages and limitations depending upon the application. Ultrahigh-resolution and spectroscopic OCT techniques improve structural tissue recognition and suggest future potential for resolution and contrast enhancements in clinical studies. A new balloon catheter-probe delivery device is proposed for systematic imaging and screening of the esophagus.     

Endoscopic mucosal resection for squamous premalignant and early malignant lesions of the esophagus

BACK AND STUDY AIMS: Endoscopic mucosal resection (EMR) is used to treat premalignant and malignant digestive tract lesions. This report presents the efficacy and safety of EMR for squamous superficial neoplastic esophageal lesions. PATIENTS AND METHODS: A retrospective cohort study presented data from 51 patients with 54 lesions over an 8-year period, between November 1997 and September 2005. Dysplasas or mucosal (m) T1 carcinomas were treated with repeated EMR until there was a complete local remission. Patients with submucosal (sm) T1 carcinomas were treated with repeated EMR until there was a complete local remission. Patients with submucosal (sm) T1 carcinomas or more advanced stage were offered surgery or chemoradiotherapy. RESULTS: There was no mortality, perforation, or major hemorrhage, and there were three easily dilated stenoses. Of the patients, 16 had lesions graded as T1sm or more advanced and one patient was found to have normal tissue post EMR. Complete local remission was achieved in 31 of the 34 patients with dysplasia or T1 m cancers (91%). There was no distant relapse and there was local disease recurrence in eight of the 31 patients (26%). The 5-year survival rate was 95%. CONCLUSIONS: EMR for squamous superficial neoplastic lesions of the esophagus is safe and provides satisfactory survival results.     

Optimization of the diameter of a radial irradiation device for photodynamic therapy in the esophagus

BACKGROUND AND STUDY AIMS: Photodynamic therapy (PDT) is a local therapeutic technique based on the photosensitization of lesions using a dye prior to light-induced tissue destruction. PDT of intraepithelial neoplasia in Barrett's esophagus, or of early squamous-cell carcinoma of the esophagus, requires light application devices that allow homogeneous and well-defined illumination of the tissue surface. Such devices must be large enough to induce complete unfolding of the esophagus in spite of esophageal motility and elasticity. The aim of this study was therefore to determine the optimal diameter of a cylindrical illumination device for PDT in this organ. PATIENTS AND METHODS: The study included nine patients (aged 49-72 years) who underwent panendoscopy. Flexible transparent hollow tubes with diameters ranging from 13 to 19 mm were successively introduced into the esophagus, and the esophageal wall was viewed from the inside through the tube using a flexible small-diameter endoscope. The number of folds was counted. Observations of the upper, middle, and lower thirds of the esophagus were recorded. The radial location of the folds was also recorded, and defined as follows: anterior wall (up), posterior wall (down), side walls (right, left). RESULTS: No significant difference in the number of folds between the lower and middle parts of the esophagus was noticed. However, the upper third had significantly fewer folds (about 30 %) than the other two parts. For diameters above 17 mm, this difference was less dramatic. The number of such folds was shown to decrease with the increasing diameter of the device. CONCLUSIONS: It appears that 18 mm or more is the optimal diameter for a fixed-geometry cylindrical photodynamic therapy irradiating device for the patient category considered in this study. It was also observed that most folds were located on the side walls of the esophagus.     

Squamous reepithelialization after circumferential endoscopic mucosal resection of superficial carcinoma arising in Barrett's esophagus

Recent reports on the results of endoscopic ablation of Barrett's mucosa have been promising, particularly when total mucosal ablation is coupled with aggressive acid-suppression treatment using high-dose proton-pump inhibitor therapy. There is also a considerable literature on reepithelialization after ablative treatments in Barrett's esophagus. This report describes a case of multifocal superficial adenocarcinoma arising in Barrett's mucosa that was successfully treated with total circumferential endoscopic mucosal resection, with a subsequent follow-up of more than 2 years. This is the first report describing the process of squamous reepithelialization after endoscopic mucosal resection in Barrett's esophagus.