Rationale:
Anastomotic leakage is the most important surgical complication following esophagectomy for
esophageal cancer, leading to increased morbidity and mortality. A major cause of leakage is
impaired healing due to ischemia of the gastric tube that is used for reconstruction of the
gastrointestinal tract. Calcifications of the aorta or stenosis of the celiac trunk on
pre-operative CT scan have been shown to be associated with an increased risk of anastomotic
leakage. So far, no individualized treatment has been initiated for this selected group of
patients. Laparoscopic ischemic conditioning (ISCON) of the gastric tube aims to increase
perfusion at the anastomotic site by redistribution of the gastric blood flow and/or
induction of angiogenesis. This is achieved by occlusion of the supplying gastric arteries
except for the right gastroepiploic artery during a separate intervention prior to
esophagectomy. Of note, these arteries would also be occluded during conventional
esophagectomy, but with laparoscopic ISCON they are occluded at an earlier moment in time
during a separate intervention. Retrospective studies have demonstrated the safety of this
technique. Prospective studies have not yet been performed.
Primary objective:
Assess the safety and feasibility of laparoscopic ISCON 12-18 days prior to esophagectomy for
esophageal cancer in patients with arterial calcifications.
Study design:
Two center phase II prospective single-arm safety and feasibility trial.
Study population:
Patients with resectable esophageal carcinoma (cT1-4a, N0-3, M0) with "major calcifications"
of the thoracic aorta (UCS) and any additional calcification or stenosis of the celiac axis
(modified NASCET score) on preoperative CT scan, who are planned to undergo esophagectomy.
Intervention:
Laparoscopic ISCON followed by esophagectomy after an interval of 12-18 days.
Primary outcome:
all complications grade 2 and higher (Clavien-Dindo classification) occurring during or after
operation 1 (laparoscopic ISCON) and before operation 2 (esophagectomy).
Secondary outcomes:
secondary outcomes with regard to operation 1 (laparoscopic ISCON) are the duration of the
procedure, blood loss, day of discharge postoperatively and grade 1 complications. Secondary
outcomes with regard to operation 2 (esophagectomy) are anastomotic leakage rate, all other
grade 3b or higher complications and 30 day mortality. Further secondary endpoints are the
induction of angiogenesis by biomarkers of microcirculation and redistribution of blood flow
by measurement of indocyanine green (ICG) fluorescence angiography.
Nature and extent of the burden and risks associated with participation, benefit and group
relatedness:
the additional burden for the patient consists of an extra operation of approximately 40
minutes during which laparoscopic ISCON will be performed, prior to the planned
esophagectomy. We would classify the current study as medium risk. Potential benefits in
comparison to current standard treatment are a reduced risk of anastomotic leakage and
severity of anastomotic leakage. Potential risks are complications following operation 1
(laparoscopic ISCON). Mainly, based upon prior experience, we expect gastroparesis to occur
in 25% of patients. Patients with gastroparesis have an increased risk of aspiration and will
require a stomach emptying by nasogastric tube and nasojejunal tube feeding till the
performance of operating 2 (esophagectomy).