Barrett食管治疗的临床证据

目的针对Barrett食管的治疗方法，进行证据检索和评价，为临床医生和患者提供有关Barrett食管治疗的最新循证医学证据。 方法计算机检索MEDLINE（1978～2006）、CBMdisc（1978～2006）及Cochrane图书馆（2005年第3期），查找与Barrett食管治疗有关的临床随机对照试验、系统评价等，并对所搜集的证据进行评价。 结果Barrett食管的治疗方法包括饮食干预、改变生活方式、药物治疗、内镜下治疗及外科手术治疗等，可依据患者病情选择不同治疗方法。 结论内镜下治疗已取得很大进展，多种治疗方法联用可取得良好效果。     

Controversies in Barrett Esophagus

Barrett esophagus develops when metaplastic columnar epithelium predisposed to develop adenocarcinoma replaces esophageal squamous epithelium damaged by gastroesophageal reflux disease. Although several types of columnar metaplasia have been described in Barrett esophagus, intestinal metaplasia with goblet cells currently is required for a definitive diagnosis in the United States. Studies indicate that the risk of adenocarcinoma for patients with nondysplastic Barrett esophagus is only 0.12% to 0.38% per year, which is substantially lower than previous studies had suggested. Nevertheless, the incidence of esophageal adenocarcinoma continues to rise at an alarming rate. Regular endoscopic surveillance for dysplasia is the currently recommended cancer prevention strategy for Barrett esophagus, but a high-quality study has found no benefit of surveillance in preventing deaths from esophageal cancer. Medical societies currently recommend endoscopic screening for Barrett esophagus in patients with multiple risk factors for esophageal adenocarcinoma, including chronic gastroesophageal reflux disease, age of 50 years or older, male sex, white race, hiatal hernia, and intra-abdominal body fat distribution. However, because the goal of screening is to identify patients with Barrett esophagus who will benefit from endoscopic surveillance and because such surveillance may not be beneficial, the rationale for screening might be made on the basis of faulty assumptions. Endoscopic ablation of dysplastic Barrett metaplasia has been reported to prevent its progression to cancer, but the efficacy of endoscopic eradication of nondysplastic Barrett metaplasia as a cancer preventive procedure is highly questionable. This review discusses some of these controversies that affect the physicians and surgeons who treat patients with Barrett esophagus. Studies relevant to controversial issues in Barrett esophagus were identified using PubMed and relevant search terms, including Barrett esophagus, ablation, dysplasia, radiofrequency ablation, and endoscopic mucosal resection.     

Reflux disease and Barrett's esophagus

Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal disorders. The key feature of GERD is reflux of gastric contents into the esophagus. Medical treatment with proton-pump inhibitors (PPIs) is well established and is considered the standard treatment. Given the high prevalence of the condition and the excellent response to medical therapy, antireflux surgery is an option for patients with volume reflux that is not properly controlled by medical therapy. Adenocarcinoma is a rare but life-threatening complication of GERD. The only known precursor lesion for esophageal adenocarcinoma is Barrett's esophagus. In recent years, a clearer understanding of the development of Barrett's and of its progression toward invasive cancer has developed. Genetic factors almost certainly determine the individual risk. The length of the Barrett's esophagus segment and the size of a hiatal hernia are associated with the risk of developing high-grade dysplasia and esophageal adenocarcinoma.With regard to the clinical management of GERD patients with Barrett's, endoscopic surveillance at 3-year intervals is now considered appropriate in the absence of dysplasia. In patients with high-grade dyspepsia, the situation is more difficult. While a considerable proportion of these patients may already have invasive cancers, there is also the possibility that there is only focal dysplasia. For this reason, it is justifiable to carry out curative endoscopic resection. Mucosal ablation procedures may also be appropriate, but these still need to be properly investigated in clinical trials.     

Reflux disease and Barrett's esophagus

Gastroesophageal reflux disease (GERD) is a common clinical problem. New information suggests that infection with Helicobacter pylori may protect patients from developing GERD and its complications. Endoscopy may be used by clinicians to tailor GERD therapy, but an empirical trial of a proton-pump inhibitor may be an alternative diagnostic approach. Studies continue to show that laparoscopic antireflux surgery is a cost-effective treatment option for patients requiring maintenance therapy with proton-pump inhibitors. However, the minimally invasive nature of the operation should not alter the indications for antireflux surgery, especially for patients with atypical symptoms. It remains unclear why some patients with GERD develop Barrett's esophagus, whereas others do not. Recent guidelines suggest that patients with long-standing GERD symptoms, especially white men over 50 years of age, should undergo endoscopy at least once to screen for Barrett's esophagus. Debate concerning short-segment Barrett's esophagus continues. Intestinal metaplasia at a normal-appearing gastroesophageal junction may be associated with intestinal metaplasia of the stomach and infection with H. pylori, whereas short tongues of intestinal metaplasia in the esophagus are associated with GERD. Cancer surveillance is indicated in short-segment Barrett's esophagus, as dysplasia may develop in these patients. Barrett's esophagus is the only known risk factor for the development of esophageal adenocarcinoma, but the incidence of adenocarcinoma may be lower than previously reported. New clinical guidelines for endoscopic surveillance suggest that the surveillance interval should be lengthened to every two years in patients without dysplasia. Newer treatment options, such as thermal ablation and photodynamic therapy, continue to show promise, but are not yet ready for routine clinical use.     

Biomarkers in Barrett esophagus

Barrett esophagus is a premalignant condition that may progress to adenocarcinoma. The risk of developing cancer has been estimated to be approximately 1 in 250 patient-years of observation; however, there appear to be subsets of patients at much higher risk. Risk stratification has previously been determined by histological identification of dysplasia. Several new biomarkers are being tested to help clinicians better determine the risk of cancer development. Although none of these biomarkers has been proven in a prospective study to predict the onset of cancer, they have been correlated with cancer development. Most of these are factors that have been associated with cancer development in other organs. These include assessment of cell proliferation, expression of cyclooxygenase 2, growth factors and oncogenes, secretory factors, cell cycle proteins, adhesion molecules, and aneuploidy and other genetic abnormalities. In addition to their role as potential cancer biomarkers, these factors have increasingly been reported as surrogate markers to monitor the effectiveness of conservative treatments for Barrett esophagus. In this article, biological markers are reviewed for their relevance in Barrett esophagus. Although most biological markers need to be evaluated further and, for most, prospective follow-up studies are lacking, at present abnormal ploidy status, P16 and P53 gene abnormalities, or allelic losses are the most extensively documented.     

Barrett食管的氩离子凝固术或激光治疗

复习国外氩离子凝固术 (Argonplasmacoagulation ,APC)或激光治疗Barrett食管的有关文献资料结果表明 :APC联合高剂量奥美拉唑或腹腔镜抗反流术治疗BE安全、有效 ;单用激光或联合奥美拉唑治疗Barrett食管 (Barrett’sesopha gus ,BE)患者的肠化上皮消失。因此APC或激光可用于BE的治疗     

The operation of Barrett's esophagus

The purpose of operation in Barrett's esophagus is to protect against esophageal acid exposure. In Western countries antireflux surgery is positive because Barrett's esophagus is recognized as premalignancy. But in Japan many people have SSBE without intestinal metaplasia. Thus if cancer is not detected in Barrett's esophagus, it is difficult to accept surgery. Besides antireflux surgery is not always successful. So the extra-surgical treatment is more recommended than operation in Japan.     

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.     

Photodynamic therapy for dysplastic Barrett esophagus and early esophageal adenocarcinoma

OBJECTIVE: To evaluate our results using photodynamic therapy (PDT) for the treatment of dysplasia or superficial cancer (T1 N0 M0) in patients with Barrett esophagus. PATIENTS AND METHODS: We retrospectively reviewed our clinical experience with 48 patients (34 patients with high-grade dysplasia and 14 patients with superficial cancer in Barrett esophagus) who had been referred for PDT. Initial evaluation included computed tomography and standard and high-frequency catheter endosonography. Follow-up endoscopy was performed 4 to 6 weeks after PDT with ablation of any residual glandular mucosa, using the argon plasma coagulator. Patients were then followed up indefinitely every 3 to 6 months with computed tomography, endosonography, and endoscopic surveillance. RESULTS: The median series follow-up was 18.5 months (range, 1-56 months). Apparent complete photoablation of Barrett mucosa and/or superficial neoplasm was documented in 47 of 48 cases. Complications included symptomatic strictures (11 patients), photosensitivity (7 patients), atrial fibrillation (1 patient) or recurrent congestive heart failure (1 patient), and self-limited esophageal perforation (1 patient). Failure to ablate T1 N0 M0 adenocarcinoma occurred in 1 patient. CONCLUSIONS: Porfimer sodium PDT appears to eradicate dysplastic Barrett mucosa and neoplasia. These results are promising; however, long-term studies are needed to document the efficacy of PDT in reducing the morbidity and mortality in such patients.     

套扎辅助内镜下黏膜切除术治疗Barrett食管的前瞻性研究

目的 研究套扎辅助黏膜切除治疗Barrett食管的有效性、安全性。方法 采用前瞻性研究。套扎辅助黏膜切除治疗57例Barrett食管患者。单环或多环套扎器预先吸引病灶形成假息肉,后再通电切除。切除前不予黏膜下注射。术后1个月复查胃镜。结果 57例患者接受套扎辅助黏膜切除,46例为岛型,11例为舌型。舌型组中特殊肠化、异型增生发生率高于岛型组。活检准确率为94.74%。5例术中出血。无狭窄、穿孔发生。结论 套扎辅助黏膜切除用于Barrett食管诊断治疗安全有效。     

Photodynamic therapy for Barrett's esophagus and high grade dysplasia: results of a patient satisfaction survey.

There are few data available describing the experience of patients who have undergone photodynamic therapy with porfimer sodium for Barrett's esophagus. We describe the results of a satisfaction survey reported by 16 of 18 patients (11 men, 5 women; median age 75 years; median response at 27 months after treatment) treated with photodynamic therapy for Barrett's esophagus with high-grade dysplasia. Treatments were performed on an outpatient basis although two patients required clinic visits for intravenous fluids. Subjects reported their most significant post-treatment problem was odynophagia or dysphagia (75%), which was best treated with a hydrocodone bitartrate and acetaminophen elixir (75%). Cutaneous photosensitivity persisted for a median of six weeks; two patients had phototoxic reactions requiring clinic evaluation and treatment. All but two patients reported swallowing problems lasting a median of four weeks, and weight loss (median 6.8 kg). All patients indicated they would again choose photodynamic therapy if they were faced with a similar choice of endoscopic treatment versus surgery for Barrett's esophagus with high-grade dysplasia. These results indicate a generally high level of satisfaction in patients who have been treated with porfimer sodium photodynamic therapy for Barrett's esophagus with high-grade dysplasia.     

多环黏膜切除术治疗Barrett食管的临床研究

目的研究内镜下应用多环黏膜切除术（multiband mucosectomy,MBM）治疗Barrett食管。方法采用前瞻性研究的方法,在窄波成像（narrow band imaging,NBI）下确认Barrett食管病变范围,用多环黏膜切除器吸引病灶,套扎橡皮圈后用圈套器电切。3个月复查胃镜,评估疗效。结果134例Barrett食管患者共切除病灶206块。急性并发症出血发生率6.7%（9/134）,无一例发生穿孔。术后30d内（迟发性并发症）出血发生率1.5%（2/134）,出现食管狭窄症状39.8%（53/133）;30d后（远期并发症）主要为食管狭窄,发生率2.3%（3/133）。术后3个月复查胃镜,病灶完整切除率98.5%（131/133）。结论内镜下MBM术治疗Barrett食管,简便、安全、有效。     

Antireflux surgery vs medical treatment for gastroesophageal reflux disease: A meta-analysis

AIM: To compare the effect of antireflux surgery with medicine in treating gastroesophageal reflux disease(GERD) patients using meta- analysis.METHODS: MEDLINE, Embase and the Cochrane Library were searched. We only included randomized controlled trials(RCTs) comparing the effect of surgical intervention with medical therapy for GERD. Statistical analyses were performed using Rev Man 5.2 and STATA 12.0 software. Rev Man 5.2 was used to assess the risk of bias and calculate the pooled effect size, while Stata 12.0 was used to evaluate publication bias and for sensitivity analysis. We evaluated the primary outcomes with GERD-/health-related quality of life in short(one to three years) and long(three to twelve years) periods of follow-up. Secondary outcomes evaluated were De Meester scores and the percentage of time that p H 4 to evaluate the degree of acid exposure.RESULTS: This meta-analysis included 7 studies with 1972 patients. It showed a positive effect of antireflux surgery compared with medical treatment in terms of health-related quality of life [standardized mean difference(SMD) = 0.18; 95%CI: 0.01 to 0.34] and GERD-related quality of life(SMD = 0.35; 95%CI: 0.11 to 0.59). We also conducted the subgroup analyses based on follow-up periods and found that surgery remained more effective than medicine over the short to medium follow-up time, but the advantage of antireflux surgery probably not maintained for long time. GERD-related quality of life in the surgical group was significantly higher than medical group for the 3 years follow-up(SMD = 0.45; 95%CI: 0.23 to 0.66); the difference was not statistically significant when the follow-up time was ≥ 3 years(SMD = 0.30; 95%CI:-0.10 to 0.69). Meta-analysis showed a statistically significant difference between thesurgical group and medical group in the percentage of time that p H 4(SMD = 0.38; 95%CI: 0.14 to 0.61). Meta-analysis indicated a positive effect of antireflux surgery compared with medical treatment concerning De Meester scores(SMD = 0.32; 95%CI: 0.00 to 0.65).CONCLUSION: Although both were effective, in some respects surgical intervention was more effective than medical therapy to treat GERD when follow-up time was up to three years.     

Gastroesophageal reflux disease and Barrett's esophagus

Gastroesophageal reflux disease (GERD) is a very common disorder, mainly occurring in Western countries. The nonerosive form of GERD, which occurs in more than half of the patients affected, deserves particular attention. Administering symptomatic therapy without a prior endoscopic examination has become an attractive option, since it also provides diagnostic information. Proton-pump inhibitors (PPIs) have become established as the standard therapy, but new insights into the pathophysiology of the condition may lead to new treatment options using gamma-aminobutyric acid (GABA) agonists. Endoscopic therapy is still at the experimental stage and has yet to prove its value as an alternative to PPI and surgery. However, it is questionable whether antireflux surgery is more cost-effective in the longer term.[nl]Gastroenterologists are now much more aware of Barrett's esophagus than was the case a few years ago. Barrett's esophagus is a frequent finding in patients with reflux symptoms, but is a rare cause of death in affected patients. For several reasons, there is a large gap between recommendations regarding surveillance, on the one hand, and everyday practice on the other. New diagnostic procedures such as chromoendoscopy may allow better detection of premalignant and malignant alterations in metaplastic mucosa, but the safety of such techniques has been questioned. Prophylactic ablation is a debatable approach, whereas endoscopic interventions in patients with high-grade dysplasia and early adenocarcinoma are continuing to develop as attractive alternatives to esophagectomy in selected patients. It remains to be seen whether chemoprevention using cyclooxygenase-2 (COX-2) inhibitors should be carried out in high-risk patients with Barrett's esophagus, in order to prevent malignant transformation to esophageal cancer.     

Esophageal dysmotility in patients undergoing photodynamic therapy

OBJECTIVE: To study the esophageal motility of patients with esophageal adenocarcinoma or Barrett esophagus with high-grade dysplasia before and after photodynamic therapy. PATIENTS AND METHODS: In this prospective study conducted between January 1998 and October 1999, esophageal motility testing of the lower esophageal sphincter and esophageal body was performed with a water-perfused catheter, 2 days before and at least 3 weeks after patients underwent photodynamic therapy for esophageal adenocarcinoma or Barrett esophagus. Results were classified as normal motility, ineffective esophageal motility, or aperistalsis. RESULTS: Twenty-three patients were studied, 13 with carcinoma and 10 with Barrett esophagus. Overall, 11 patients (48%) had normal motility, 6 (26%) had ineffective esophageal motility, and 6 (26%) had aperistalsis. Five patients with aperistalsis had carcinoma. Follow-up tracings after photodynamic therapy found that 6 patients (26%) had normal motility, 7 (30%) had ineffective esophageal motility, and 10 (43%) had aperistalsis. CONCLUSIONS: Esophageal dysmotility is common in patients with esophageal adenocarcinoma or Barrett esophagus. Photodynamic therapy may worsen esophageal motility in some patients. Dysphagia after photodynamic therapy therefore may be related to underlying esophageal dysmotility and may not always be caused by stricture or underlying carcinoma.     

Gastroesophageal reflux patients' defective antioxidative capacity in the proximal esophageal mucosa before antireflux surgery and also after 4-year follow-up

BACKGROUND: Oxidative stress has a role in the pathogenesis of gastroesophageal reflux disease (GERD). AIM: To investigate the redox balance in proximal esophagus before and 6 and 48 months after antireflux surgery. METHODS: In 20 GERD patients and 9 controls oxidative stress by myeloperoxidase activity (MPO activity) and antioxidative capacity of esophageal mucosa by superoxide dismutase activity (SOD), and glutathione content (GSH) was measured from proximal esophageal samples. RESULTS: In proximal esophagus of GERD patients compared to controls', antioxidative capacity appearing as GSH level was significantly decreased (P < 0.001) at all time points and as SOD levels preoperatively (P < 0.001) and 4 years postoperatively (P = 0.01). MPO activity of patients was significantly lower than controls' preoperatively, and 6 months and 4 years postoperatively (P < 0.05). MPO activity remained lower than that of the distal esophagus at 6 months and 4 years (P < 0.01 for both). CONCLUSIONS: In GERD patients, proximal esophageal mucosal antioxidative defense is defective before and after antireflux surgery. Antireflux surgery seems not to change the level of oxidative stress in proximal esophagus, suggesting that defective mucosal antioxidative capacity plays a role in development of oxidative damage to the esophageal mucosa in GERD.     

Gastroesophageal reflux disease: natural history and long-term medical and surgical outcomes

Gastroesophageal reflux disease (GERD) is a chronic condition that affects a large proportion of the adult population. Persistent untreated GERD can lead to esophageal strictures, premalignant Barrett's esophagus, and an increased risk of adenocarcinoma of the esophagus. Currently, the most effective medical treatment targets gastric acid suppression, allowing healing of erosive/peptic lesions and controlling symptoms. Most patients take over-the-counter medication or are successfully treated by their primary care physician. Gastroenterologists and gastrointestinal surgeons see patients with complications, refractory symptoms despite acid-suppressive therapy, or atypical symptoms. For the medical management of GERD, proton pump inhibitors are potent acid suppressants with favorable side-effect profiles and long-term efficacy and safety. Medical therapy can heal 80% to 100% of patients with erosive esophagitis with 30% to 60% of patients reporting sustained resolution of heartburn. Surgery may be offered to patients with GERD as an alternative to long-term antireflux medication. Careful selection of appropriate surgical candidates is important, and the risk of developing new or recurrent symptoms requiring medication should be disclosed to patients contemplating the surgical alternative.     

Frequency of Barrett's neoplasia after initial negative endoscopy with biopsy: a long-term histopathological follow-up study

BACKGROUND: Barrett's adenocarcinoma is being diagnosed increasingly. We examine possible differences between long segment and short-segment Barrett esophagus (LSBE and SSBE) in long-term follow-up on the basis of our histopathology registry. METHODS AND PATIENTS: All Barrett's esophagus patients diagnosed histologically between 1990 and 1995 (n = 1071) were selected. Long-term follow-up data from endoscopy with biopsy were sought on all patients without neoplasia on initial endoscopic biopsy (n = 1003). A total of 255 individuals (25.4 %) were regarded as drop-outs (201 lost and 54 without further endoscopy). Of the remaining 748 patients with follow up for more than 5 years, 315 had documented LSBE, 246 had SSBE, and 187 had no length of Barrett esophagus recorded (NLBE). RESULTS: In the study cases (male : female ratio 2.1 : 1, mean age +/- SD 60.9 +/- 14.2 years), the biopsy procedure was fully compliant with guidelines in only 32.5 %. Only 5 cases (0.6 %) had visible lesions reported on endoscopy, but all were negative for neoplasia. Over a mean follow-up of 78.2 +/- 35.6 months (range 0-240), 7 new cases of low grade intraepithelial neoplasia (LGIN) and 15 cancer cases developed, accounting for a yearly incidence of 0.2 % (LGIN) or 0.4 % (cancer) after an initial negative endoscopy. When the cases with initial diagnosis of neoplasia were included, this yearly incidence rose to 0.5 % (LGIN), 0.3 % (high grade intraepithelial neoplasia [HGIN]) or 1.7 % (cancer). Differences between SSBE and LSBE were only encountered for cancer incidence. CONCLUSION: The yearly incidence of Barrett esophagus cancer varies between 0.4 % and 1.7 %. Despite the limitations of this retrospective and pathology-based study, the observed risk of developing cancer in Barrett esophagus without neoplasia is comparable to that found in other studies, mainly from the US and the UK, and varies between 0.7 % and 1.0 % of yearly incidence.     

Barrett Esophagus

Barrett esophagus is a metaplastic change in the lining of the distal esophageal epithelium, characterized by replacement of the normal squamous epithelium by specialized intestinal metaplasia. The presence of Barrett esophagus increases the risk of esophageal adenocarcinoma several-fold. Esophageal adenocarcinoma is a malignancy with rapidly rising incidence and persistently poor outcomes when diagnosed after the onset of symptoms. Risk factors for Barrett esophagus include chronic gastroesophageal reflux, central obesity, white race, male gender, older age, smoking, and a family history of Barrett esophagus or esophageal adenocarcinoma. Screening for Barrett esophagus in those with several risk factors followed by endoscopic surveillance to detect dysplasia or adenocarcinoma is currently recommended by society guidelines. Minimally invasive nonendoscopic tools for the early detection of Barrett esophagus are currently being developed. Multimodality endoscopic therapy—using a combination of endoscopic resection and ablation techniques—for the treatment of dysplasia and early adenocarcinoma is successful in eliminating intestinal metaplasia and preventing progression to adenocarcinoma, with outcomes comparable to those after esophagectomy. Risk stratification of those diagnosed with Barrett esophagus is a challenge at present, with active research focused on identifying clinical and biomarker panels to identify those with low and high risk of progression. This narrative review highlights some of the challenges and recent progress in this field.     

Gastroesophageal reflux disease. Identification and management of the surgical patient

Antireflux surgery remains the most reliable and expedient means of treating patients with a mechanically defective lower esophageal sphincter who are experiencing pathologic gastroesophageal reflux. Identifying these patients, who are known to have a poor response to medical therapy, permits control of the reflux process before serious complications develop. Well-planned and precisely performed antireflux surgery by an experienced medical team will enhance reflux control and reduce postoperative complications.