ThORAcolaparoscopic disseCtion of Lymph nodes involved in the drainage of the Esophagus: the ORACLE study

Esophageal adenocarcinoma (EAC) is increasing in the West1. EAC arises from
Barrett*s esophagus (BE). In BE, esophageal squamous epithelium progresses to
adenocarcinoma through a multi-step transition consisting of intestinal
metaplasia, low grade dysplasia (LGD), high grade dysplasia (HGD), and finally
invasive cancer. This process can take several years up to decades. Patients
with known BE are offered endoscopic surveillance. Recent developments, such as
the spread of high definition endoscopes though the community, combined with a
higher awareness and improved recognition of early (flat) lesions in Barrett*s
esophagus have led to an increase in detection of early EAC.
Early EAC can be treated with endoscopic resection techniques, such as
endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD)2.
In case of low-risk early EAC (i.e., negative resection margins, histology
showing a tumour confined to the mucosa, not poorly differentiated, and absence
of vascular or lymphatic invasion), an endoscopic resection is considered to be
a curative treatment, since in these lesions spread of tumour cells to the
adjacent lymph nodes is highly exceptional (i.e.<2%)3. In case of submucosal
invasion, poor differentiation grade, or lymphovascular invasion, the risk of
concomitant lymph node metastasis is considered to be too high, and surgical
esophagectomy is recommended in case of acceptable clinical condition4,5. In
case of an irradical endoscopic resection (mainly in case of tumour positive
vertical resection margins), an esophagectomy is needed to excise residual
cancer. In case of a radical endoscopic resection, but a high risk EAC (for
instance deeper submucosal invasion), the additional yield of subsequent
esophagectomy is in the lymph node dissection, since the primary tumour has
been radically resected by endoscopic means. In esophageal squamous cell
carcinoma (ESCC), lymph node metastasis probably occurs even at an earlier
stage than in Barrett*s early cancer. In early ESCC, infiltration into the
muscularis mucosae even without submucosal infiltration carries a significant
risk for lymph node metastasis6,7. Surgical esophagectomy is a major surgical
procedure associated with substantial morbidity, mortality and a temporary
reduced quality of life (QoL). Reported series in the literature mention
surgery-related morbidity rates of 40% and mortality of 2-4.6%, even in expert
centers.2,8 Furthermore, QoL after esophagectomy is significantly affected:
majority of patients experiences complaints related to upper-GI dysfunction,
such as eating problems, gastroesophageal reflux or dumping syndrome. Long-term
follow-up studies showed that it will take six to nine months to regain
pre-operative QoL9,10,11. A retrospective study, which compared QoL between
endoscopically and surgically treated patients, showed that the surgical group
reported significantly more eating problems and gastroesophageal reflux,
whereas the patients who were treated endoscopically showed more worry for
cancer recurrence11.
In early gastric cancer, endoscopic resection of early neoplastic lesions is a
well studied, well accepted and frequently applied therapy, especially in the
Far East. Similar to the esophagus, early gastric lesions can also be divided
into low-risk and high-risk lesions. In high-risk lesions (e.g. in submucosally
invading tumours, or in case of lymphovascular invasion), a surgical
gastrectomy is considered the treatment of choice, even in case of an
endoscopic R0 resection. Recently, the concept of endoscopic R0-resection
followed by laparoscopic lymph node dissection without gastrectomy has gained
interest. In a recent study by Abe et al., data of 21 patients were reviewed
after ESD followed by laparoscopic lymph node dissection with preservation of
the stomach in high risk early gastric cancer12. Of the 21 patients
laparoscopic lymphadenectomy revealed lymph node metastasis in 2 patients.
During a median follow-up of 61 months (including a follow up of 76 and 84
months in the two lymph node positive patients), no recurrent malignant disease
was seen.
We hypothesize that endoscopic radical resection of the tumor in combination
with thoracolaparoscopic lymph node dissection might be of great value in the
treatment of early esophageal carcinoma. This combination may lead to a
tailored treatment and might be associated with less morbidity and mortality
and a less impaired quality of life because of the less invasive character of
the procedure and intact upper-GI functioning. We have studied the feasibility
and safety of the thoracolaparoscopic lymph node dissection in human cadavers
and swine and results are promising. However, to be sure about the feasibility
of this procedure, we have to perform the procedure in humans. Therefore, we
are conducting this study and in the future, a pilot-study will be conducted
which will include patients that will undergo the thoracolaparoscopic lymph
node dissection without concomitant esophagectomy.

To evaluate the feasibility of thoracolaparoscopic lymph node dissection of
lymph nodes involved in the drainage of the esophagus in patients with
esophageal carcinoma

This is a two-center, pilot-study in 6 patients in which a new treatment is
evaluated for early esophageal adenocarcinoma or early esophageal squamous cell
carcinoma.

scopic lymph node dissection of lymph nodes involved in the drainage of the
esophagus, directly followed by esophageal-cardia resection with formation of a
gastric or colonic conduit.

Risk assessment: potential benefits
Included patients will not have any benefit, apart from the fact that they will
contribute developing a new treatment for early esophageal cancer and thus
possible benefit for patients acquiring esophageal cancer in the future.

Risk assessment: potential risks
The risks are minimal, because the patients will receive the standard treatment
right after the thoracolaparoscopic lymph node dissection. Only the procedure
time of the surgery will extend (to a minimum, we think it will take 30 to 60
minutes longer compared to the standard treatment).