Ligation of the gastrosplenic ligament during upper gastrointestinal surgery; Effect on splenic and gastric perfusion: pilot study

With the increasing incidence of therapy resistant gastro-esophageal reflux and
increasingly frequent unwillingness of patients to be burdened by a lifelong
PPI subscription, an increasing amount of patients undergo antireflux surgery.
Many surgeons deem division of the gastrosplenic ligament necessary in
antireflux surgery to facilitate the creation of an adequate fundoplication;
ligating the ligament enables additional mobilization of the stomach. The need
for this, however, is still subject of debate in recent literature. The
gastrosplenic ligament connects the greater curvature of the stomach with the
hilum of the spleen and contains the short gastric and left gastro-epiploic
vessels. The short gastric vessels are part of the blood supply to both the
superior pole of the spleen and the gastric fundus. Peripheral splenic arterial
branches have little collateral circulation, thus ligating the short gastric
vessels could result in an infarct. While partial infarction of the spleen in
patients with chronic pain after antireflux surgery has a reported incidence of
around 1%, the true incidence of infarction of either the gastric fundus or
spleen is unknown. Since a splenic infarction has a large overlap in symptoms
with the normal postoperative course of antireflux surgery, we suspect that
infarction is underreported. Additionally, it is unclear if - and to what
extent - postoperative pain is associated with the altered vascularization of
the spleen or stomach.

Minimally invasive surgery has improved the postoperative recovery period to
the point where postoperative pain is the main barrier for outpatient
treatment. If postoperative pain can be linked to splenic or gastric
infarction, this could be an argument to leave the gastrosplenic ligament
intact if possible. To be able to sufficiently judge the effects of ligating
the short gastric vessels, surgeons need adequate information on the incidence
of the iatrogenic splenic infarction after fundoplication and its association
with postoperative pain. This pilot feasibility study could provide the basis
for a future larger cohort study.

This pilot study aims to report on the diagnostic value of indocyanine green
and fluorescence laparoscopy on vascularization defects of the stomach and
spleen during antireflux surgery.

It is our hypothesis that many splenic and gastric infarctions occur without
the surgeon noticing, and there may be a connection between postoperative pain
and this infarction.

Primary Objective:
- Determining the effect of ligating the short gastric vessels on the
vascularization of the spleen and gastric fundus.

This monocenter prospective observational study aims to objectify the effect of
ligating the short gastric vessels on arterial blood supply to the superior
pole of the spleen and gastric fundus using fluorescence laparoscopic imaging.

This observational study will be conducted at the Jeroen Bosch Ziekenhuis in
's-Hertogenbosch, the Netherlands. Patients will be included during a six-month
period and will be followed for 1 week to ascertain the absence of adverse
events. No adverse events are expected to occur outside of the 24-hour
postoperative window, since indocyanine green administration is the only
intervention.

When a patient is referred to a participating surgeon for antireflux surgery,
the surgeon will ensure that the indication for surgery is valid through
detailed medical history, physical examination, upper endoscopy results, pH
measurements, manometry, CT imaging or gastric scintigraphy. After receiving
informed consent for surgical treatment, the surgeon will discuss inclusion in
the study with the patient. The patient will receive study information from the
researcher and receive sufficient time for consideration of participating in
the study. Before surgery, the researcher ascertains that the patient is
suitable for the trial. This means the patient meets all the inclusion criteria
and does not meet any of the exclusion criteria. After informed consent is
obtained by the researcher, the patient will be enrolled in the study.

After inclusion in the study, patients will undergo standard treatment
including laparoscopic antireflux surgery. During surgery, the patient will be
administered indocyanine green intravenously once before and once after
ligating the short gastric vessels. With the use of the near-infrared
fluorescence mode of the laparoscopic equipment tissue perfusion defects will
be visually inspected.

Patients participating in this study will receive standard care and outpatient
clinic follow-up. Daily practice in our clinic includes routine ligation of the
gastrosplenic ligament during antireflux surgery, therefore the surgical
procedure and follow-up protocol for study patients will be identical to the
regular treatment, with the addition of the injection of indocyanine green. The
additional risk for the patient is limited to the administration of indocyanine
green through a peripheral IV. Indocyanine green is a diagnostic tool, approved
for use in cardiac, liver and ocular perfusion imaging. Indocyanine green is
best known for its use in assessing the hepatic function and measuring hepatic
blood flow. In the last decade, the use of indocyanine green in
gastro-intestinal surgery has greatly increased worldwide for a great variety
of applications; its use in assessing the micro- and macrocirculation in
contemporary experimental surgery is well established. Published use cases in
gastro-intestinal surgery include assessing the level of anastomosis in
gastro-intestinal surgery, identifying deviations from the normal vascular
anatomy in laparoscopic gastrectomy, determining the viability of the
anastomosis after bowel resection and bile duct identification. Nausea,
anaphylactoid or anaphylactic reactions have been described in very rare cases
(less than 1 in 10.000, see SPC Verdye). The anaphylaxis-related mortality is
estimated at 1 in 330.000, see SPC Verdye). Patients with an allergy to
ingredients of indocyanine green will not be included in the study. The dose
used in clinical practice (0.1-0.5mg/ml/kg) is well below the toxicity level
reported in the SPC (see SPC Verdye). Indocyanine green is cleared quickly and
exclusively by the liver after intravenous administration. Due to its serum
half-life of only three minutes, no background fluorescence is detectable after
approximately 15 minutes, which allows a second injection within the same
procedure. Proving the feasibility of assessing perfusion of the gastric fundus
and superior pole of the spleen in antireflux surgery will ultimately be of
value in future research, determining the true incidence and clinical
implications of infarctions after antireflux surgery. Additionally, these
findings could provide new information for optimizing the surgical approach in
the future and provide a basis for research on post-operative complaints.