Feasibility of Splenic Nerve Stimulation During Esophagectomy

The current study is designed to evaluate the feasibility and safety of
placing, stimulating, and removing a lead with cuff electrode (lead) on the
splenic neurovascular bundle (NVB) during thoracolaparoscopic esophagectomy.
Electrostimulation of the NVB may affect the inflammatory response to
esophagectomy, though the ability to apply and remove a lead cuff, and to
activate splenic nerves, has not been demonstrated in human studies. During
minimally invasive esophagectomy, the splenic NVB is exposed as part of the
lymph node dissection and is therefore easily accessible, thus creating an
opportunity to test electrostimulation of the splenic NVB with minimal
additional risk to the participants. In the first 3-5 patients the techniques
will be optimized, therefore, their might be a change that they benefit less
from the treatment compared to the next 10 patients in the study.

Evaluate the feasibility of an investigational lead to be temporarily applied
to and removed from the splenic neurovascular bunble (NVB)

A pliot safety study. At the point in the standard esophagectomy when the
lymphadenectomy is performed, the splenic NVB is being isolated and an
investigational lead will be implanted laparoscopically around the NVB and
connected to an external pulse generator. An ultrasound transducer will be
introduced to the abdomen and placed on the NVB to visualize splenic arterial
blood flow during stimulation. The NVB will be stimulated three times (with
intervening pauses to observe post-stimulation recovery from physiological
changes) using parameters selected to cause a change in splenic arterial blood
flow (a biomarker of NVB activation). Stimulation parameters may be adjusted
over the course of the study based on experience with prior study participants.
Blood samples will be taken before, and at certain pre-defined time points
after, stimulation and recovery. The lead and ultrasound transducer will be
removed after completion of stimulation, and the surgery will continue. Surgeon
experience applying and removing the cuff electrode will be documented, in
addition to the responses to NVB stimulation. Post-operative safety will be
followed through 7-days post-surgery (or day of discharge if earlier).

Placement of a lead with a cuff electrode on the splenic NVB and stimulation of
these bundles

The risk of bleeding because the splenic artery is damaged is very small (<5%).
It is possible that local sympathetic nerves going to the spleen can be
damaged while placing or removing the instrument. However to date we do not
have evidence that there are any clinical consequences related to this damage.
There is a risk of damaging the pancreas, however this is risk is also present
during a 'normal' esophagectomy (<5%).
Temporarily induced hemodynamic changes that are triggered by stimulation are
constantly monitored by an anesthesiogist, who can use pharmacological agents
if necessary.

There is limited burden for participants. The screening visit will take 15-30
minutes, but will be done following a regular outpatient clinic visit. All
interventions take place during the esophagectomy and only one blood draw is
performed when the patient is conscious.