MANAGEMENT OF BARRETT ESOPHAGUS Medical management GERD is the basic pathophysiology underlying BE

MANAGEMENT OF BARRETT ESOPHAGUS

Medical management
GERD is the basic pathophysiology underlying BE. Whether symptomatic or asymptomatic acid refluxate is known factor leading to intestinal metaplasia, hence all patients should be treated with PPI (1). Whether PPIs decreases the risk of BE progression is still being evaluated . In a meta-analysis of seven studies that included 2813 patients with Barrett’s esophagus and 317 patients with high-grade dysplasia or esophageal adenocarcinoma, the use of PPIs was associated with a decreased risk of high-grade dysplasia and/or esophageal adenocarcinoma (adjusted odds ratio 0.29; 95% CI 0.12-0.79) (2) In another meta-analysis (including a total of 5712 patients with BE), PPIs were found to have no association with the risk of EAC and/or HGD in patients with BE (unadjusted OR 0.43, 95% CI 0.17-1.08). Analysis for duration response relationship revealed no significant trend toward protection against EAC or HGD with PPIs usage (3). Thus PPI improves quality of life by controlling symptoms , but its role in preventing desease progression is debatable.
Role of Antireflux surgery
Both acid and bile refluxate are implicated in the pathogenesis of EAC . PPIs reduces the acid production and thus reduces injury to the epithelial cells however they donot prevent reflux. Fundoplication partial or complete decreases both acid or bile refluxate and hence should prevent EAC in patients of BE . After antireflux surgery, most patients with Barrett’s enjoy long-lasting relief of reflux symptoms, and nearly all patients consider themselves cured or improved. one study concluded that dysplasia and intestinal metaplasia may regress after surgery . (4)
Although earlier retrospective studies concluded that Antireflux surgery may prevent EAC better than medical therapy in patients with Barrett’s esophagus. Where as other studies and very recent meta-analysis failed to show significant oncological benefits of antireflux surgery (5,6 ,7) Antireflux surgery in the setting of BE should not be recommended as an antineoplastic measure.

SURVEILLANCE
The goal of surveillance is to improve outcomes by detecting dysplasia or esophageal adenocarcinoma early enough to provide effective treatment. Current guidelines suggest surveillance for most patients with Barrett’s esophagus, but whether surveillance is beneficial is unclear . Available observational studies have not consistently shown that surveillance is beneficial. The efficacy of surveillance has been questioned
Corley et al did not demonstrate an association between surveillance and a decreased risk of death in a case-control study of 70 patients with esophageal adeno-carcinoma. The study was criticized for excessively long interval between surveillance and an inadequate number of biopsies (8) .
In a Retrospective review of 224 patients, Grant et al found that those who underwent surveillance had significantly lower stage tumors at the time of diagnosis. (9) Verbeek et al demonstrated decreased esophageal adenocarcinoma mortality at 2 and 5 years for those adhering to a surveillance program (hazard ratio HR, 0.79 (10)
Since the guidelines for surveillance are based on weak evidence , patient may choose not to undergo any surveillance programme. But given the risk and anxiety associated with possibility of progression to EAC most of the gastroenterologist recommend surveillance . ACG guidelines endorse the surveillance strategy of endoscopy with biopsy every 3-5 years if there is no dysplasia in patient with BE. Endoscopy and biopsy every 6-12 months for low grade dysplasia and every 3 months for High-grade dysplasia in the absence of eradication therapy. (11)
Patients diagnosed with BE undergo 4 quadrants biopsy every 2 cm from the GE junction , if biopsy is reported equivocal ,biopsy is repeated from all 4 quadrants every 1 cm after adequate PPI therapy for preferably 3 months. Any dysplasia is confirmed by expert pathologist and treatment options should be discussed with the patient. (11)

LOW GRADE DYSPLASIA (LGD)
In the patients of BE with the diagnosis of Low grade dysplasia in surveillance confirmation is needed by one additional expert pathologist. When there is doubt repeat EGD and bipsy is performed after optimizing PPI therapy, with in 6 months. In such cases if LGD is confirmed then patients may undergo some form of endoscopic therapy for eradication of abnormal mucosa followed by continued surveillance. Alternatively patient may choose to undergo surveillance without undergoing any form of endoscopic therapy. Although there is enough evidence now that treatment of BE with LGD by eradication of abnormal mucosa decreases further progression compared to surveillance alone, still surveillance alone is reasonable alternate to the therapy in such patients in view of slow progression of LGD to EAC (12,13,14)

HIGH-GRADE DYSPLASIA (HGD)
Diagnosis of HGD (previously termed as carcinoma in situ) is confirmed by an expert pathologist. Patients of BE with HGD should undergo endoscopic treatment in order to prolong there survival . such patients have very high risk of malignancy. Management depends not only on pathological findings but general condition of patient , their life expectancy and availability of resources. If such patient have some gross lesion like mucosal nodularity or an ulcer it should be subjected to endoscopic resection or biopsy first and then some form of mucosal ablation therapy (15, 16,17). It is true that all EAC arises in the background of BE , where as not all BE progresses to EAC. Risk of progreesion of IM to EAC is very low , although risk is very low but it is real and significant, recent studies suggesting rates closer to 0.1 to 0.4 percent per year .(18) Although the risk of developing esophageal cancer is increased at least 40 fold above that of the general population, the absolute risk of developing cancer for an individual patient with nondysplastic Barrett’s esophagus is low.
A systematic review and meta-analysis of studies that reported the incidence of esophageal adenocarcinoma (EAC) and/or high-grade dysplasia (HGD) among patients with BE with LGD, identified 24 studies reporting on 2694 patients of BE with LGD, with 119 cases of EAC. Pooled annual incidence rates of EAC alone and EAC and/or HGD in patients with BE-LGD were 0.54% (95% CI, 0.32-0.76; 24 studies) and 1.73% (95% CI, 0.99-2.47; 17 studies). (19)

INDEFINITE FOR DYSPLASIA” (IND)

If diagnosis of dysplasia is equivocal in histopathology examination, pathologist report such findings as IND. In a large cohort study Patients with a first diagnosis of IND in Barrett’s esophagus between 2002 and 2011 were selected from a nationwide registry of histopathology diagnoses in The Netherlands. Patients were followed up until treatment for HGD or detection of EAC. In total, 1258 patients met the inclusion criteria, of whom 842 (66.9?%) underwent endoscopic follow-up.?Patients were followed for a total of 2585 person-years . The progression rate from IND to the combined end point of HGD or EAC was 2.0 and progression to EAC was 1.2 . (20)

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Population with BE Rate of progression to EAC( percent)
No dysplasis 0.25
LGD 0.54
IND 0.2 to 1.2
HGD 4 to 8

MODALITIES OF TREATMENT
Endoscopic ablative therapies — various modalities are described (21,22,23)
Radio frequency ablation (RFA)
Photodyanamic therapy (PDT)
Cryoablation
Argon plasma coagulation (APC)

There is strong evidence now that endoscopic ablation is better than continued surveillance in patients with LGD and HGD in terms of oncological outcome as well as cost. And has better acceptability , quality of life, adverse effect and mortality compared to esophagectomy

RADIOFREQUENCY ABLATION
RFA uses radiofrequency energy delivered by a balloon or paddle-shaped device that has a series of closely spaced electrodes to ablate the Barrett’s mucosa . RFA rapidly generates a uniform circumferential thermal injury with limited depth. For patients with visible mucosal irregularities associated with dysplasia, endoscopic resection should be performed prior to RFA. A number of well-designed studies, including a randomized, sham-controlled trial, suggest that RFA is highly effective at removing all Barrett’s epithelium at both the endoscopic and histologic level with a favorable safety profile. Studies also suggest that RFA reduces the risk of malignant progression. In one randomized trial, patients with low- or high-grade dysplasia who underwent RFA were less likely to progress to higher grades of dysplasia or cancer than patients who underwent sham-therapy (4 versus 16 percent) . (24)
In a meta-analysis of 18 studies of 3802 patients
Complete eradication of Intestinal metaplasia (IM)was achieved in 78% of patients (95% confidence interval CI, 70%-86%) and Complete eradication of dysplasia was achieved in 91% (95% CI, 87%-95%). After treatment IM recurred in 13% (95% CI, 9%-18%).
Progression to cancer occurred in 0.2% of patients during treatment and in 0.7% of those after CE-IM. (25)
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CRYOTHERAPY
It is no contact therapy .Cryotherapy system uses spray catheter through working channel standard endoscope which delivers low pressure (