**10. Controversies**

138 Gastrointestinal Endoscopy

Table 3. Reported complications associated with HGMP/CIP based on literature search to 2010

**Type IV** Dysplasia Low grade Unknown None High Grade Reported Klaase et al., 2001; Mion et al., 1996; Sauvé G et al., 2001 **Type V** Adenocarcinoma Early (pT1 tumor) Reported Abe et al., 2004; Alrawi et al., 2005; Balon et al., 2003; Berkelhammer et al., 1997; Davis et al., 1968; Haruki et al., 2008; Hirayama et al., 2003; Kammori et al., 1996; Noguchi et al., 2001; Pech et al., 2001; Schmidt et al., 1985; Takagi et al., 1995; Yoshida et al., 2009. Advanced Reported Alaani et al., 2007; Carrie, 1950; Chatelain et al., 2002; Christensen & Sternberg, 1987; Clemente, 1974; Danoff et al., 1978; Goëau-Brissonnière et al., 1985; Ishii et al., 1991; Kamiya et al., 1983 ; Klaase et al., 2001; Lauwers et al., 1998; Morson & Belcher, 1952; Pai et al., 1997; Rapheal et al., 1966; Sakamoto et al., 1970; Sperling & Grendell, 1995; von Rahden et al., 2005; Yoshida et al., 1986. **\* Number of cases identified through lite**

 **rature searches up till December 2010 \*\* Not included in the orig**

**inal classification proposed by von Rahden (1)** 

**Clinico-pathological Conditions References classification Type III** Stricture Reported Bosher & Taylor, 1951; Karnak et al., 1999; Powell & Luck, 1988; Steadman et al., 1988; Yarborough et al., 1993. Web Reported Ainsley, 2011; Buse et al., 1993; Waring & Wo, 1997; Weaver, 1979. Bleeding Reported Bataller et al., 1995. Fistula Reported Katsanos et al., 2010 ; Kohler et al., 1988; Garcia et al., 2002 ; Daher et al., 2010. Perforation \*\* Reported Righini et al., 200 ; Sánchez-Pernaute et al., 1999 Polyp \*\* Reported Chatelain et al., 1998; Oguma et al., 2005 ; Rana et al., 2006 ; Schulewitz et al., 2007

Currently, there are several controversies regarding HGMP/CIP. First, there is still dispute with regard to the origin of HGMP/CIP. However, it is widely believed to be congenital origin as result of remnant of columnar epithelium due to failure of complete squamization of the esophagus. There are several factors that favor the congenital origin hypothesis. The embryogenesis of esophagus can explain the profiles of HGMP/CIP; proximal location correlating with the last part of the esophagus, the proximal esophagus to transform to keratinized mucosa. Babies and children do not have sufficient duration of acid exposure to induce changes suggested by the acquired theory. Finally, although the staining pattern based on CK7 and CK20 are similar, staining with MUC protein shows differences between HGMP/CIP and Barrett's (Lauwers et al., 2005).

An earlier study had also shown that the HGMP/CIP had cellular component different from Barrett's esophagus, suggesting embryogenic in origin (Fuerle et al., 1990).

The proposed theory on acquired origin was based on similarities between histological findings of HGMP/CIP and Barrett's esophagus. Mucin protein (MUC) and CK7 and CK20 similarities suggested similar origin. Other study based on MUC also suggested HGMP/CIP being acquired in origin. In the future, other staining methods may be identified and may show clear differences between HGMP/CIP and Barrett's esophagus. Weak evidence come from higher incidence of Barrett's esophagus in patients found to have HGMP/CIP. However, the overall reported incidence rates are still too low to lend strong support for this theory.

The latest theory proposed was based on findings of glandular cystic retentions secondary in the proximal esophagus. The evidence to support this theory are lacking given the very few reports of glandular retention cysts encountered in the clinical practice and reported in the literature. Furthermore, the absence of lesions found in the other part of esophagus makes the second and the third proposed theories less likely. Interestingly, it has also been proposed that the origin may be different, congenital in baby or children and acquired in adult (Lauwers et al., 2005).

Heterotopic Gastric Mucosal Patch of the Proximal Esophagus 141

shown higher pick up rate when the lesions are being looked for. HGMP/CIP can also be found in the other part of the esophagus. On endoscopy, HGMP/CIP appears as a salmoncolored or velvety patch on white light endoscopy that is distinct from the esophageal squamous mucosa. HGMP/CIP may appear different color on other imaging techniques. Use of confocal endoscopy has been reported for the diagnosis of HGMP/CIP (López-Cerón Pinilla M et al., 2011). Majority of HGMP/CIP are solitary but can be multiple and the sizes can range from very small to very large. In patients with multiple patches, they are usually small and are located in close proximity of each other. They are typically found on the right or left lateral esophageal wall but can also be circumferential. They are usually oval, ovoid

> Role of measuring acid output and clinical correlation with symptoms Method of measuring the surface area- Exact size of HGMP/CIP

HGMP/CIP is reported to cause laryngopharyngeal reflux or extra-esophageal symptoms of gastro-esophageal reflux disorder. The reported frequency of laryngopharyngeal reflux symptoms ranged from very low to as high as 75% in patients with HGMP/CIP (Chong & Jalihal, 2010). Fortunately, most laryngopharyngeal reflux symptoms are mild. However, complications such as ulcerations, strictures, perforation and malignant transformation have been reported (von Rahden et al., 2004). Associations with higher frequency of laryngopharyngeal malignancies in patients with laryngopharyngeal reflux have also been

The current clinico-pathological classification proposed by von-Rahden *et al.* provides a useful classification of the various manifestations of HGMP/CIP (von Rahden et al., 2004). It also guides clinical management which largely depends on the presence and severity of symptoms. Management is mainly with pharmacotherapy and instrumentations (endoscopic) and surgery may be required for complicated cases. Ablative therapies with argon plasma coagulation have been reported to provide symptoms relieve or cure in those with globus

Surrogate markers of histological activities of HGMP/CIP Treatment modalities for the various types of HGMP/CIP Role of Helicobacter pylori in histological progression and

or round but can be elongated in shape.

Clinical significance Exact incidence

Best method of detection Magnification endoscopy Narrow band imaging Chromoendoscopy

Role in clinical symptoms

Non acidic secretion

malignant transformation

Table 4. Future areas to address on HGMP/CIP

Origin of HGMP/CIP- Congenital/Acquired

**Current controversies** 

Others

Acid

**Others** 

reported.

Second, the actual incidence of HGMP/CIP is not exactly known. Earlier endoscopic studies have reported rates ranging from 0.35 to 10.0% and a latest study that had used NBI reported a rate of 13.8% (Ohara, 2010). An autopsy studies have reported rate as high as 70%. However, autopsy studies on paediatric population in the mid-twentieth century had only reported rates of less than 10%. With the advent of newer imaging modalities that provide superior endoscopic images, this will provide more accurate incidence. The true incidence rates are likely to be close to the rates reported by NBI studies given the clear distinction of HGMP/CIP observed with NBI. In future studies, it is very important that the endoscopists are aware and to look for this lesions. Several studies have already reported that the pick up rates were higher when endoscopist were aware of the entity (Maconi et al., 2000; Azar et al., 2007).

The third controversy relates the clinical significance of HGMP/CIP in clinical practice. While many have found low prevalence of symptoms in associated with HGMP/CIP, it is no doubt that HGMP/CIP have clinical significance given the reported complications that include malignant transformations.

Other controversies include suggested association with extra-esophageal cancers in the aerodigestive tract. Incidence of laryngeal carcinoma has been shown to be higher in patients with laryngopharyngeal reflux disorder (Copper MP et al., 2000).
