Value of endoscopic surveillance in the detection of neoplastic change in Barrett's oesophagus

Fifty-six patients with Barrett's oesophagus diagnosed between 1977 and 1986 were prospectively studied by 6-monthly endoscopic surveillance and biopsy. During follow-up to-date, four patients have developed high-grade dysplasia and three have adenocarcinoma of the oesophagus. Two of the adenocarcinomas were preceded by progressively severe dysplastic changes but in the third no dysplasia had been previously detected. The incidence of adenocarcinoma was 1 per 56 patient-years of follow-up. Changes in symptomatology or gross endoscopic appearances were usually absent, even after adenocarcinoma had developed, indicating that biopsy is essential for early diagnosis. The high risk of malignant change makes endoscopic surveillance advisable in all patients with Barrett's oesophagus.     

Advanced endoscopic imaging in Barrett's oesophagus

Barrett's oesophagus is a metaplastic condition with an inherent risk of progression to adenocarcinoma. It is essential to identify dysplastic changes within Barrett's oesophagus in order to individualise surveillance strategies and establish which patients warrant endoscopic treatment. There is a trend towards endoscopic resection of focal high-grade dysplasia followed by whole segment ablation. However, endoscopic identification of dysplastic lesions is unreliable and subjective making targeted therapy extremely difficult. In addition, the current practice of taking random quadrantic biopsies may miss dysplastic disease and intramucosal adenocarcinoma. Several advanced endoscopic imaging techniques have been described and tested in clinical trials in an effort to improve the detection of early lesions, although none are routinely used in clinical practice. In this article we will review these techniques and discuss their potential for clinical implementation. We will also discuss the potential benefits of multimodal imaging and highlight several newer techniques which have shown early promise for in?vivo diagnosis.     

Barrett's oesophagus: endoscopic diagnosis and follow-up

Barrett's oesophagus (BO), or replacement of the squamous mucosa by a specialized intestinal metaplasia due to gastro-oesophageal reflux disease (GORD), predisposes to adenocarcinoma. It is estimated that 6 to 12% of patients undergoing GI endoscopy have short BO (< 3 cm), and 1% have a long BO. Macroscopic diagnosis of BO is sometimes difficult and, in case of doubt, endoscopy should be redone after a period of efficient anti-secretory treatment. Diagnosis of BO is histological and should be confirmed by biopsies. The incidence of adenocarcinoma is globally estimated at 0.5% patient by year of follow-up, and exists for both short and long BO. Due to this low incidence, screening for BO is only justified in patients at high risk for adenocarcinoma (male gender, age > 50 ans, old GORD in a young patient). Low-grade dysplasia (LGD) then high-grade dysplasia (HGD) precedes adenocarcinoma. Histological diagnosis of LGD is difficult: the main cause of confusion is inflammation so diagnosis of LGD must be confirmed after a 3-month high-dose anti-secretory treatment. Diagnosis of HGD is easier but multiple biopsies are needed to determine the focal or multifocal disposition of HGD. The benefit of follow-up of BO is debated. Aged patients should be followed only if dysplasia is present. When dysplasia is absent, an endoscopic control with biopsies is desirable within 3 to 5 years. In case of dysplasia, the latter must be confirmed by another examination of biopsies, particularly in case of suspicion of HGD and after antisecretory treatment. In case of LGD, endoscopy with biopsies should be redone 6 months later to screen for HGD, then every year if LGD is confirmed. In case of HGD, the 5-year risk of cancer is 60% so surgical or endoscopic treatment is usually proposed. If HGD follow-up is decided, it should be performed on a 3- to 6-month basis.     

Endoscopic ablation of Barrett's esophagus using argon plasma coagulation (APC) following surgical laparoscopic fundoplication

BACKGROUND: Barrett's esopagus (BE) is considered a risk factor for the development of esophageal carcinoma. Recently, partial restoration of squamous mucosa after ablation of BE with endoscopic techniques has been described. METHODS: From November 1996 to November 1999, 23 patients with histologically proven BE have been treated by endoscopic argon plasma coagulation (APC) following suppression of gastro-esophageal reflux by laparoscopic fundoplication. Histological follow-up after completed ablation ranged from 16 to 45 months (mean, 31.9 months). RESULTS: Histologically, complete squamous reepithelialization was observed in 20/23 patients, whereas a regrowth of a mixed squamous and gastric type mucosa was observed in 1 patient. Small islands of intestinal metaplasia were observed under the neosquamous epithelium in two patients (9%) during follow-up. CONCLUSION: The success rate of APC ablation following laparoscopic antireflux surgery in our series may be as high as 91%. Nevertheless, small islands of intestinal metaplasia under the new squamous epithelium may persist in some patients. In these circumstances, the authors recommend that endoscopic ablation of BE should be confined to controlled clinical trials.     

Invasive carcinoma after endoscopic ablative therapy for high-grade dysplasia in Barrett's oesophagus

BACKGROUND: Patients with high-grade dysplasia (HGD) in Barrett's oesophagus carry a significant risk of developing adenocarcinoma. Endoscopic mucosal resection (EMR) and photodynamic therapy (PDT) aim at the radical ablation of the dysplastic area. METHODS: We used EMR to resect the macroscopic area of dysplastic mucosa followed by PDT to eliminate residual disease. PDT was performed after oral administration of 5-aminolevulinic acid (ALA, 40 mg/kg), using fractionated illumination 3 and 6 h later with 630 nm light at 100 J/cm(2) through an endoscopic balloon diffuser. RESULTS: We report 2 patients who developed adenocarcinoma shortly after incomplete endoscopic ablation of Barrett's epithelium. In a 61-year-old man with HGD in 8-cm Barrett's segment, HGD persisted 3 months after treatment. The oesophagectomy specimen showed a 2.3-cm pT2N0M0 adenocarcinoma in Barrett's. In a 69-year-old woman with extensive HGD in 5-cm Barrett's, HGD persisted after 3 PDT sessions in 1 year. Adenocarcinoma occurred 6 months after treatment. The oesophagectomy showed a pT1bN0M0 adenocarcinoma and extensive multifocal HGD in Barrett's. CONCLUSIONS: The combination of EMR and PDT may be a promising option for local treatment of patients with HGD in Barrett's oesophagus, provided all dysplastic tissue can be removed. Currently it should be offered only to patients who are willing to participate in a clinical trial with an intensive endoscopic follow-up programme.     

Fifty-eight years of Barrett's oesophagus

Summary  BACKGROUND: The history of Barrett's oesophagus has taken nearly six decades to evolve, and is still in the process of understanding. METHODS: Review of the history of Barrett's oesophagus. RESULTS: The vigour with which both surgeons and gastroenterologists have pursued this condition is unparalleled. At the outset the presentations of stricture, ulceration and bleeding were of interest mainly to surgeons. The columnar-lining was first thought to be congenital in origin, and only later was the association with gastroesophageal reflux accepted. Histological appraisal made great strides towards the understanding of the disease and in recent years has again played a major role in this regard. Tests of oesophageal function in the columnar-lined oesophagus showed severe deterioration, and led to measures to treat and protect the oesophagus from acid reflux. The realization that this was a pre-malignant lesion added enormously to the interest and efforts to prevent malignant deterioration. Molecular biological studies have opened new vistas to the pathogenesis of the changes taking place in the epithelium, and have introduced advances in treatment. CONCLUSIONS: Earlier diagnosis has prompted less radical surgical treatment methods and better overall results. The condition has now become more prevalent in far Eastern countries, expanding the interest to causative dietary factors. This full cycle of research now focuses on prevention of the disease and its complications.      

Endoscopic treatment of Barrett's oesophagus

Aims of the treatment of Barrett's oesophagus (BO) are disappearance of symptoms and inflammatory complications of gastro-oesophageal reflux disease (GORD), prevention of occurrence of dysplasia and adenocarcinoma, and early treatment of high-grade dysplasia (HGD) and adenocarcinoma. Anti-secretory treatment with proton-pump inhibitors (PPI) must result in disappearance of both symptoms and oesophagitis. The only correction of symptoms, as well as normalization of pHmetry, are not considered as adequate criteria for efficiency of treatment. It has not been demonstrated that treatment with PPI prevented occurrence of dysplasia and adenocarcinoma so the only BO is not an indication for treatment with PPI, which results in only partial regression of height and/or surface of BO. Endoscopic ablation of BO, combined with PPI, allows complete regression of intestinal metaplasia in about 50% of cases. Photodynamic therapy (PDT) seems the best technique for treatment of HGD and mucosal adenocarcinoma. This treatment is not indicated in case of low-grade dysplasia, since its benefit on survival is less clear than for HGD. Endoscopic treatment does not suppress the need for prolonged endoscopic follow-up since BO recurs in approximately one third of patients. For HGD isolated or associated with mucosal adenocarcinoma (proven by endoscopic ultrasound), endoscopic treatment can consist in mucosectomy or ablation with PDT or plasma argon coagulation (PAC) of these lesions if localized, possibly followed by complete ablation of BO by PAC, and always associated with an efficient treatment of GORD by PPI or anti-reflux surgery. Submucosal adenocarcinomas must be treated by oesophagectomy if allowed by the general condition of the patient.     

Treatment of duodenal adenomas with endoscopic argon plasma coagulation

BACKGROUND: Surgical resection has been the standard treatment for duodenal adenomas. It has a high associated morbidity rate and a significant recurrence rate. The aim of this study was to evaluate endoscopic treatment of these lesions with argon plasma coagulation. METHODS: We retrospectively identified patients with non-ampullary duodenal adenomas without a polyposis syndrome and who were treated endoscopically between 1st January 1999 and 31st December 2003. Their management, follow up and outcomes were reviewed. RESULTS: Fifteen patients were included, with mean age 72 years (range 46-85 years). All were treated with at least one session of argon plasma coagulation. Initially, 13 adenomas were macroscopically cleared. Of these, eight (61%) had no recurrence during mean follow up of 40 months (26-68 months). The mean time to recurrence was 14 months (6-30 months). Eradication was possible a second time in four of five recurrent adenomas. There was one complication, of haemorrhage, from 37 sessions of argon plasma coagulation. No patient developed duodenal adenocarcinoma during the study period. CONCLUSION: Argon plasma coagulation may be safe and effective for the treatment of duodenal adenomas, but further research is required. Progression of adenomas is slow and perhaps no treatment is required.     

Surveillance for Barrett's oesophagus in the UK

BACKGROUND: Endoscopic screening for Barrett's oesophagus is being offered without evidence of efficacy Barrett's oesophagus is not an ideal candidate for a screening programme, as the natural history is unclear, uncertainties surround the indication for intervention and the treatment is associated with high morbidity and mortality rates. METHODS: To determine the practices that clinicians employ in the management of Barrett's oesophagus in the UK, postal questionnaires were sent in May 1997 to 297 randomly selected members of the British Society of Gastroenterology asking for details of their current practice. RESULTS: Of 152 respondents, 106 (70 per cent) performed surveillance for Barrett's oesophagus; 46 (30 per cent) did not carry out screening. There was no difference in the practices carried out by physicians or surgeons, teaching or acute general hospital clinicians, or those with an upper gastrointestinal interest. There was a wide disparity in screening interval: just over half (52 per cent) screen at yearly intervals. Only nine (8 per cent) took four quadrant biopsies per 2 cm of Barrett's oesophagus. Nearly half (49 per cent) manage mild dysplasia by increasing the frequency of endoscopy; only seven (7 per cent) prescribed patients a proton pump inhibiting agent. Faced with severe dysplasia, 33 (31 per cent) offered surgery immediately; 22 (21 per cent) simply followed the patient by endoscopy. Those not choosing to perform screening most frequently cited lack of evidence of efficacy as the reason behind their decision. CONCLUSION: There is wide variation in surveillance practices for Barrett's oesophagus. Some methods are ineffectual. The recommendations made by the Barrett's Oesophagus Working Party in 1991 are not followed, possibly because they are not practical. New workable guidelines based on available evidence and a consensus of expert opinion should be established; this was suggested by 38 per cent of respondents who performed screening.     

Prevention of pleural effusion following hepatectomy using argon beam coagulation

BACKGROUND: Postoperative pleural effusion occurs frequently after hepatectomy. The value of the argon beam coagulator (ABC) for the prevention of pleural effusion after hepatectomy in patients with hepatocellular carcinoma was studied. METHODS: Sixty patients were divided randomly into two groups: an ABC group (n = 28), in which the cut surface of the hepatic ligaments and bare area of the retroperitoneum were cauterized using an ABC, and a control group (n = 32) in which the ABC was not applied. Patient characteristics, preoperative and postoperative liver function, and postoperative pleural effusion were compared between the two groups. RESULTS: There were no significant differences between the two groups with respect to histological findings, clinical stage, type of resection, operative data, and preoperative and postoperative laboratory data. One of 28 patients in the ABC group and nine of 32 patients in the control group had pleural effusion. The incidence was significantly lower in the ABC group than in the control group (P = 0.01). Pleurocentesis was needed in two of the ten patients and thoracic drainage in four patients. CONCLUSION: Application of an ABC to the cut surface of the hepatic ligaments and bare area of retroperitoneum after liver mobilization may prevent postoperative pleural effusion.     

Barrett's oesophagus: the rationale for surgical resection

Surgical resection has a limited place in the management of Barrett's oesophagus with high-grade dysplasia, except when failure of endoscopic mucosectomy is likely (extended Barrett's oesophagus, nodular or ulcerated lesions at endoscopy). For superficial carcinoma, it is often difficult to differentiate mucosal carcinoma (carrying a risk of nodal metastasis less than 7%) from submucosal carcinoma (carrying a risk of nodal metastasis ranging from 16 to 47%), oesophagectomy is routinely indicated if operative risk is low. When operative risk is not minimal, endoscopic mucosectomy is indicated for lesions limited to the mucosa and the proximal third of submucosa; for lesions extending beyond, an oesophagectomy must be discussed. These indications must take into account both age and general condition of the patient, as well as the expertise in oesophageal surgery of the group.     

Barrett's oesophagus: place of antireflux surgery

The aim of this study was to review the literature about the effect of antireflux surgery on the metaplasia-dysplasia-adenocarcinoma sequence in patients with Barrett's oesophagus. Antireflux operations (by laparotomy or laparoscopy) can alter the natural history of Barrett's oesophagus, allowing disease stabilization in a substantial proportion of patients without high grade dysplasia at time of surgery. It also may induce complete or partial regression of Barrett's epithelium, especially for short segment of Barrett's oesophagus, but in unpredictable manner. While regression of low-grade dysplasia is commonly observed, histologic progression is rarely observed after effective antireflux surgery. However, ineffective antireflux surgery expose to histologic progression to high-grade dysplasia or adenocarcinoma. These data support the need for a long-term clinical, endoscopic, and histologic follow-up program after antireflux surgery in patients with Barrett's oesophagus.     

Outcome of endoscopy surveillance for Barrett's oesophagus

Background: Endoscopic surveillance of individuals with Barrett's oesophagus is undertaken to detect early stage oesophageal malignancy. The impact of a surveillance programme on endoscopy resources and disease detection is uncertain. Methods: In 2004, we commenced a structured Barrett's oesophagus surveillance programme. The surveillance protocol specifies surveillance interval and number of oesophageal biopsies required according to previous endoscopy and biopsy findings. The first 3 years of surveillance were reviewed to assess programme adherence, impact on endoscopy resources and the incidence of high‐grade dysplasia and adenocarcinoma in patients undergoing surveillance. Results: Four hundred five patients were enrolled in the surveillance programme, and 776 patient years of endoscopy follow‐up were analysed. Four‐quadrant biopsies every 2 cm throughout the Barrett's oesophagus were performed in 89.8% of endoscopies. A total of 93.7% of patients had surveillance endoscopy performed at the appropriate time interval. Formalizing surveillance was followed by a decrease in the mean time interval for endoscopy surveillance from 16 months to 15 months, although the mode endoscopy surveillance interval lengthened from 1 year to 2 years. The mean number of biopsies per endoscopy increased from 5.9 to 7. In four patients, T1 stage oesophageal adenocarcinoma was identified, and in six patients, high‐grade dysplasia was identified (combined incidence of adenocarcinoma/high‐grade dysplasia 1 per 77.6 endoscopy years of follow‐up). Conclusions: Structured Barrett's surveillance detects malignant progression at an early stage, which provides opportunities for curative surgical or endoscopic intervention. Formalizing surveillance resulted in a high rate of adherence to agreed guidelines and rationalized the use of endoscopy resources without significantly increasing workload.     

Endoscopic resection in neoplastic lesions of the oesophagus

Background Endoscopic resection has gained more and more importance in the treatment of early oesophageal neoplasia over the past 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.Methods The suck-and-cut technique with ligation device or cap should be favoured over normal strip biopsy in the oesophagus because of the size of the resected specimen and the technical feasibility.Results Endoscopic resection (ER) of high-grade intra-epithelial neoplasia and mucosal adenocarcinoma in Barretts oesophagus should be considered as the treatment of choice, due to excellent long-term results. First mid-term results of endoscopic therapy of early squamous cell neoplasia in the oesophagus show promising results; however, long-term results are awaited.Conclusion ER of oesophageal neoplastic lesions is a safe and effective method but should be performed only by experienced endoscopists.     

Safety of argon plasma coagulation for hemostasis during endoscopic mucosal resection

Showing the safety of argon plasma coagulation (APC) over mucosal defects during/after endoscopic mucosal resection (EMR), 2 studies using resected pig (ex vivo) and living minipig (in vivo) stomachs were performed. As an ex vivo study, APC was applied over mucosal defects in 2 groups; with prior submucosal saline injection and without injection. Only subtle tissue damage was observed in the injection group, whereas apparent damage was observed in the noninjection group. The damaged distances in depth significantly increased as the pulse duration increased and those at the pulse duration of 4 seconds, which might be maximal in clinical practice, were approximately 1 mm. As an in vivo study, APC was applied over mucosal defects immediately after EMR. Only subtle tissue damage was observed even at the pulse duration of 20 seconds as shown in the ex vivo study. APC can be performed safely over the mucosal defects during/after EMR.