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).
