**4.2 Indirect evidence of progression**

El-Serag and Sonnenberg reported the relationship between the middle forms of erosive oesophagitis, esophageal ulcers, and strictures, in 194,527 hospitalized veterans over a 14-year period, using computerized hospital records [12]. Although patients with esophageal ulcers or strictures were older than those with uncomplicated esophagitis, no particular temporal pattern could be established consistently.

In a large multicenter study including 1253 centers from Germany, Austria, and Switzerland, designed to look at the outcome for patients with GERD. Risk factor analysis was performed for 5289 patients with erosive reflux disease or NERD [28, 31]. Small number of erosive diseases are in the population with a higher level of education and the presence of *Helicobacter pylori*.

The association of a longer duration of symptoms with erosive esophagitis compared to some cases of NERD may complicate erosive disease.

Another study reported results for 51,311 patients over 15 years [32]. In most cases, Barrettt's esophagus peak arrived at the seventh to ninth decades. In 101 patients, there was no change in the length of BE. The authors showed that this happens more often in male patients aged 60, who had a follow-up endoscopy in a follow-up of 7.4 years.

NERD and erosive disease are part of the dilatation of intracellular spaces of esophageal epithelium confirmed on pH monitoring with results as follow: 38 patients with GERD and 22 with NERD. Early pathophysiological marker of esophageal damage is dilatation of intracellular spaces. Therapy with 40 mg omeprazole resulted in 97% complete recovery after 6 months in NERD and GERD [33]. High-grade dysplasia or esophageal adenocarcinoma can be prevented after using PPI therapy in patients with low -grade dysplasia. PPI therapy should be started after stratification by year within 2 years of definitive diagnosis (our results). LGD can be developed in case of delayed therapy with PPI.

This study confirms our observation that fewer patients with BE developed dysplasia after the introduction of PPI therapy in Australia in 1989. We postulated that the incidence of dysplasia was influenced by powerful acid suppression that reduced esophageal acid exposure.

El-Serag and Sonnenberg raported the relationship between the midle forms of erosive oesopahgitis, oesophageal ulcers and strictures, in 194527 hospitalized veterans over a 14-year period, using computerized hospital records [34]. In patients with Barret's oesophagus increased epithelial proliferation is step from dysplasia to adenocarcinoma.

Barrett's esophagus (BE) was found in 11% of our GERD patients [35]. No evidence of completely reverses the length of Barret's osophagus [36, 37].

It is very important to emphasize that anticecretory therapy and using cyclooxygenase 2 (COX-2) inhibitors can prevent development of adenocarcionoma [36]. Overexpression of COX-2 inhibits apoptosis, allowing cancer to grow, and COX-2 inhibitors can help ensure that cancer cells die [38]. At the gene level, COX-2 inhibitors can reduce inflammatory factors [39].

In another study was reported that from 350 patients, only 111 patients developed HGD or adenocarcinoma. It should be noted that study didn't have randomised controlled trial [29, 40]. Low-grade of dysplasia has atipical cells and active inflammation influenced in it [5, 35].

High-grade dysplasia was associated with macroscopic markers: severe esophagitis, nodularity, Barrett's ulcer or stricture [41].

In another study, the time of the start of PPI use in patients with BE was recorded. The degree of acid reduction was not measured. Also, the doses were not reduced, and this therapy was used for a long time, even though the symptoms of the disease were controlled [2]. Cancer risk for a given patient with BE is lower than previously estimated [23]. Risk factors for the progression of BE to EAC include the increasing degree of dysplasia, increasing age, increasing BE segment length, male sex, and smoking, among others [42].

The degree of dysplasia has been directly related to segment length. The greater the length of the BE segment, the more dysplasia we have [25].

However, when the BE develops, its length generally does not change, so the shortsegment BE normally remains short even in the context of continuous exposure of the esophagus to acid. Actually, when we have BE with a short segment, its length does not change much even though it is under the influence of acid [18].

Dysplasia and adenocarcinoma are complications of long and short BE, and are treated similarly [27]. For that more, 20% have an improvement in intestinal metaplasia, but more than 50% had an improvement in patients with low-grade dysplasia. These findings are of great importance in the clinical management of patients with BE, especially given the widespread use of experimental ablative therapies aimed at achieving a similar goal. When we have treated gastroesophageal reflux, we have permission from the EU. Many errors have been minimized through biopsies according to the protocols, the sessions of two biopsies with an output of about 6 months, systematization of regression, so that the biopsy sample was the mucosa of the cardia. It is possible that IM will spontaneously regress to normal tissue without treatment. Additionally, these findings have importance in the clinical management of BE using ablative therapies.

Based on the literature, IM or dysplasia was known after PPI therapy. Intestinal metaplasia was lost in 39% of SSBE patients and 10% of LSBE. Female gender, absence of hiatal hernia, and shorter Barrett'length associated with loss of IM.

But Sampliner and others [43] suggested that follow up every 2 to 3 years in BE if no dysplasia after two endoscopies. If no change endoscopy should be done every year; in patients with LGD, they recommended every 6 months for the first year.

Author Sharma et al. reported in a multicenter study of LGD history; 35% had intermittent LGD; from the total of 1376 patients incidence of dysplasia was 4.3% every year; 7.3% was prevalence at presentation [44].

After medical therapy LGD had a regression. Our advice is that patients with intestinal dysplasia to follow up with proximal endoscopy every year. Patients with dysplasia should have every 3-month gastroscopic examination.

The goals for treating patients with BE are as follows:
