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Oo et al. Mini-invasive Surg 2019;3:13 I http://dx.doi.org/10.20517/2574-1225.2019.02 Page 3 of 9

intestinal metaplasia was only found in 10% of patients with Type II and rare in patients with Type III
tumours which suggests chronic GERD cannot fully explain the surge in Type II and III tumours and that
other factors maybe at play.

Obesity has been consistently implicated as a risk factor for development of GEJ. Apart from the
mechanical pathway resulting in increased reflux, there maybe independent inflammatory and hormonal
mediators. An Australian study, showed that obesity in combination with frequent reflux were risk factors
for development of GEJ tumours than either acting alone suggesting that synergistic as opposed to additive
[16]
effects was most likely .

Infection with H. pylori is associated with increased rates of gastric cancer via mechanisms of chronic
inflammation however there is an inverse association with H. pylori infection and incidence of GEJ
[17]
tumours. A study by Whiteman et al. found that H. pylori was inversely associated with GEJ
adenocarcinoma tumours with odds ratio (OR) 0.41. It is not well understood how the infection confers
a protective benefit but the potential mechanism include decreased acid production and microbiome
[18]
alteration . It is interesting note that the decreasing incidence of H. pylori over time parallels the
increasing incidence of GEJ tumours.

Smoking has been found to have a strong association with GEJ tumours. A pooled analysis of multiple
[19]
primary studies from the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium (BEACON)
found that smoking was positively associated with GEJ adenocarcinoma (OR = 2.18, 95%CI: 1.84-2.58), and
also demonstrated a strong dose-response association.

The other factors found to be associated with GEJ tumours include alcohol intake, intake of highly processed
meat diet while intake of high fibre diet and medications such as non-steroidal anti-inflammatory drugs are
[18]
thought to confer a protective effect . Further studies are required to provide more conclusive evidence.

MANAGEMENT
Management of GEJ tumours is challenging as they involve two contiguous organs and also straddle the
thoracic cavity and abdominal cavity via hiatal opening.

Management of GEJ cancers depends on the stage of the tumour. For early tumours there is a role for
endoscopic submucosal dissection (ESD) but advanced tumours require multimodality treatment including
surgery.

Role of endoscopic treatment in early stage GEJ cancer
With the development of the Insulated-tip diathermic knife (IT-knife) in late 1990 and subsequent
development of the ESD technique in 2003, the endoscopic management of early gastrointestinal tumours
including early gastric cancer and early esophageal cancer became feasible and popular [20-23] . ESD has been
accepted as the minimally invasive curative treatment option for superficial early gastrointestinal cancers
[24]
including those of stomach, esophagus and colonic origins . However, the indication of endoscopic
treatment for early GEJ cancers including Barret’s adenocarcinoma has not been clearly established due to
[25]
unclear pattern of lymph node metastasis . Meta-analysis of 6 retrospective studies have demonstrated
[26]
the safety and feasibility of ESD on early superficial GEJ cancers . Five studies used curative criteria
for gastric cancer and one study used the criteria for esophageal cancer. 269 patients who met the
curative resection criteria did not have any local or distant metastases. Out of 90 patients who underwent
noncurative resection, 3 (3.3%) presented with local recurrence and 2 (2.2%) presented with distant
metastasis. The study was limited by the small number of patients with short duration of follow-up. A
group from Korea compared outcomes of 79 patients with Siewert II adenocarcinoma who underwent ESD