**5. Clinical manifestations**

The majority of patients found to have HGMP/CIP are asymptomatic and the HGMP/CIP are usually detected incidentally while being evaluated with endoscopy for other gastrointestinal complaints. The clinical importance of HGMP/CIP remains controversial with some authors believe that they are benign and of no clinical relevance. Others have shown HGMP/CIP to be clinically important especially for a subset of patients with HGMP/CIP. For those who have symptoms attributable to the HGMP/CIP, most are mild and are detected only on direct inquiries. For a small proportion of patients, the symptoms can be prominent and patients may have many consultations before a diagnosis is made. The prevalence of any symptoms, typically those considered extra-esophageal symptoms complex of gastroesophageal reflux such as chronic cough, throat irritation or sore throat, regurgitation, globus pharyngeus, dysphagia or hoarseness ranges from very low to as high as 75% (Chong & Jalihal, 2010; Maconi et al., 2000).

HGMP/CIP like other ectopic gastric mucosal have been proven to be able to secrete acid in sufficient quantity to induce inflammatory changes and acid related symptoms (Baudet et al., 2006; Galan et al., 1998; Hamilton et al., 1986; Korkut et al., 2010; Nakalima et al., 1993; Yüksel et al., 2008). Acid is the main cause of symptoms in patients with HGMP/CIP. Given the proximity of the HGMP/CIP to the laryngopharyngeal area, it is not surprising that

Heterotopic Gastric Mucosal Patch of the Proximal Esophagus 133

symptoms and these include; a) missed patches, b) the mucosal types of HGMP/CIP and c) the underlying degree of inflammatory changes that can affect acid output. Patients with predominant antral mucosal type HGMP/CIP may not have or minimal acid related symptoms. Patients with severe inflammatory changes approaching atrophy may have reduce acid output, hence minimal symptoms. Interestingly, more patients with HGMP/CIP also experienced heartburn compared to those with HGMP/CIP. This patients either had non erosive gastroesophageal reflux or symptoms induced by acid secreted by the patch flowing down. One study showed that greater acid production was found in those with

On endoscopy, HGMP/CIP appears as salmon or velvety colored patch that is clearly distinct to the slatey white esophageal squamous cell mucosa (Figure 7). A majority of HGMP/CIP is round or ovoid. Some can be elongated with the maximal dimension in the longitudinal direction. Rarely, HGMP/CIP can be so big that they cover almost or the entire circumference of the esophagus. Smaller patches tend to be round or oval, are usually elevated or flat with smooth texture and white edges. Larger patches tend to be depressed on maximal insufflations during endoscopic examination and are ovoid or elongated with jagged edges and nodular surface textures. Occasionally, inflammatory changes similar to those observed in reflux esophagitis can be seen at the edges. Most are single patch and

Overall, 9.1% (p=ns)

Overall, 5.5% (p=ns) Overall, 22.2%

0% (p<0.05)

Overall, 73.1% (p<0.05) 29.2 vs. 10.6% (p<0.01) 54.2 vs. 11.7% (p<0.01) 23.1 vs. 7.1% (p<0.01) 42.3 vs. 13.1% (p<0.01) 50.0 vs. 22.5% (p<0.01)

(milder symptoms included)

Overall, 45% vs. 21.5% (p=0.07)

**Authors [Ref] Symptoms Prevalence** 

dysphagia to liquid/solid

Upper esophageal and

Globus, burning sensation in throat,

Dysphagia, throat discomfort and

Dysphagia 21 vs. 4.0, p<0.001

Symptoms (not defined) Dysphagia Overall not defined 39.4% vs.

laryngopharyngeal symptoms Individual symptoms not defined

Symptoms Chronic cough Sore throat/hoarseness

Table 2. Prevalence of symptoms reported to be associated with HGMP/CIP

Symptoms inquired Pharyngeal discomfort,

odynophagia &

Symptoms

heartburn

Globus Regurgitation Heartburn

larger HGMP/CIP patch (Baudet et al., 2006).

**6. Diagnosis** 

Jacob et al [1997]

Maconi et al [2000]

Akbayir et al [2004]

Baudet et al [2006]

[2007]

[2010]

Poyrazoglu et al

Chong & Jalihal

**6.1 Endoscopic features** 

Fig. 6. Schematic illustration of cytokeratin (CK) 7 and 20 expression in the normal esophagus, Barrett's metaplasia, squamocolumnar junction, and proximal stomach. LATCHFORD A et al. Gut 2001; 49:746-747 (*Reprinted with permission from GUT BMJJournal*) (Latchford et al., 2001).

even weakly acidic secretion can cause symptoms. Others have proposed that mucin secretion can also cause symptoms (Bajbouj et al., 2009). Proximal esophagus dysmotility has also been shown to be associated with HGMP/CIP (Korkut et al., 2010).

Studies that had looked at specific groups of patients, such as those with laryngopharyngeal complaints, have found mixed results. The overall prevalence of HGMP/CIP was in the similar range compared to studies that had been carried out on patients coming for routine endoscopy. One study that had looked specifically at patients with laryngopharyngeal reflux found significantly more HGMP/CIP in patients than controls, those without LPR symptoms (11.4% vs. 1.6%, *p*<0.05). These patients also had significantly more laryngeal acid reflux documented on pH study (Akbayir N. et al., 2004). Similarly, other studies have found more laryngopharyngeal reflux symptoms in patients with HGMP/CIP (Akbayir et al, 2004; Baudet et al., 2006; Borhan-Manesh & Franum, 1993; Tang et al., 2004). Another study looking at patients who had undergone fundoplications for gastroesophageal reflux with laryngeal reflux only found one patient (3.4%) to have HGMP/CIP (Salminen & Ovaska, 2009). This patient had a small HGMP/CIP and the authors concluded that HGMP/CIP does not have a significant role in laryngopharyngeal reflux in patients with gastroesophageal reflux disease.

Unfortunately, all these studies have not inquired on the same symptoms complex and hence make comparison difficult.

Interestingly, only one study had assessed the size of HGMP/CIP on clinical symptoms and did not find significant differences (Chong & Jalihal, 2010). This study categorized HGMP/CIP to small/moderate (<15mm) and large (>15mm). Only cough was significantly more (50% vs. 8.3%, p=0.022) common in patients with larger patch. Interestingly, patients with smaller HGMP/CIP were found to have more globus and regurgitation. Several explanations were given for the lack of correlations between size of HGMP/CIP and symptoms and these include; a) missed patches, b) the mucosal types of HGMP/CIP and c) the underlying degree of inflammatory changes that can affect acid output. Patients with predominant antral mucosal type HGMP/CIP may not have or minimal acid related symptoms. Patients with severe inflammatory changes approaching atrophy may have reduce acid output, hence minimal symptoms. Interestingly, more patients with HGMP/CIP also experienced heartburn compared to those with HGMP/CIP. This patients either had non erosive gastroesophageal reflux or symptoms induced by acid secreted by the patch flowing down. One study showed that greater acid production was found in those with larger HGMP/CIP patch (Baudet et al., 2006).
