Inflammatory Response
Conditions
Brief summary
Esophagectomy is the cornerstone for treatment of esophageal cancer. However, it is associated with substantial morbidity and mortality. Studies suggest that systemic inflammation after surgery has a negative impact on surgical outcomes. Attenuation of an excessive inflammatory response within the perioperative period for high-risk surgical procedures may reduce morbidity and mortality. The inflammatory response may be important in the development of these complications and reduction of inflammatory cytokine may be associated with an improved outcome. The current study will evaluate the feasibility and safety of neuromodulation during minimally invasive surgery for esophageal cancer (esophagectomy) to assess impact on the inflammatory response. During the esophagectomy, a stimulation lead will be placed on the exposed nerves, and energy applied to the lead to test whether the nerves can be activated. The study will also measure potential physiological responses to nerve activation.
Detailed description
Active dampening of the inflammatory response may be an important therapeutic target to decrease complications and improve recovery following esophagectomy. The current study is intended to evaluate the feasibility and safety of stimulating the exposed nerves in esophagectomy patients. During minimally invasive esophagectomy, a neurovascular bundle (NVB) is exposed or partially exposed as part of the obligatory lymph node dissection. At the point in the esophagectomy when the NVB is being isolated, a lead will be applied laparoscopically to 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. The NVB will be stimulated while physiologic responses are observed. 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 esophagectomy 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 (or day of discharge if earlier).
Interventions
DEVICEStimulator device
The stimulator device will be used to electrically stimulate the NVB
Sponsors
NAMSA
Galvani Bioelectronics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DEVICE_FEASIBILITY
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female of non-reproductive potential or male * Undergoing minimally invasive esophagectomy * Confirmed presence of splenic NVB loop via imaging prior to surgery * Age equal or above 21 years at the screening visit * Capable of giving signed informed consent (IC) * Normal blood pressure, or hypertensive managed with medication such that they are deemed fit for surgery
Exclusion criteria
* Previous splenectomy * Existing implantable device * Active pancreatitis or history of severe pancreatitis with complications, hepatic or splenic disease * Use of oral steroids 4 weeks prior to inclusion * Current use immunosuppressive agents or biologicals. Previous use of biologicals is allowed, if a washout period of 2 months is applied * Use of anticoagulants within 1 week of surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility applying and removing the stimulation lead: Proportion of participants in whom the lead was successfully applied and removed | 1 day | Proportion of participants in whom the lead was successfully applied and removed |
| Safety of placement, stimulation and removal of the lead: Incidence of adverse events | 7 days | Incidence of adverse events |
Secondary
| Measure | Time frame |
|---|---|
| Peak Systolic Velocity (PSV) blood flow change measured by doppler ultrasound | Before stimulation and during stimulation |
| End Diastolic Velocity (EDV) blood flow change measured by doppler ultrasound | Before stimulation and during stimulation |
| Velocity Time Integral (VTI) blood flow change measured by doppler ultrasound | Before stimulation and during stimulation |
Other
| Measure | Time frame |
|---|---|
| Cytokine IL-6 | Before stimulation to Day 1 post stimulation |
| Cytokine IL-8 | Before stimulation to Day 1 post stimulation |
| Heart Rate (HR) change | Before stimulation and during stimulation |
| Cytokine TNF | Before stimulation to Day 1 post stimulation |
| C-Reactive Protein level | At days 2 and 3 post stimulation |
| Cytokine IL-10 | Before stimulation to Day 1 post stimulation |
| Systolic Blood Pressure (SBP) change | Before stimulation and during stimulation |
| Diastolic Blood Pressure (DBP) change | Before stimulation and during stimulation |
| Mean Arterial Blood Pressure (MAP) change | Before stimulation and during stimulation |
| Hematology (white blood cell (WBC) counts) | Before stimulation to Day 1 post stimulation |
Countries
Netherlands
Outcome results
None listed