Clinical trial NCT02507414: Mesenteric Traction Syndrome During Upper Gastrointestinal Surgery
Official title: Characterization of the Mesenteric Traction Syndrome During Upper Gastrointestinal Surgery for Malignant Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastrointestinal Neoplasms
Mesenteric Traction Syndrome
Keywords: Mesenteric Traction Syndrome
Upper gastrointestinal cancer surgery
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Danish Cancer Society
First posted: 2015-07-24
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: It is the hypothesis of this project that the Mesenteric Traction Syndrome (MTS) is a common event during upper gastrointestinal cancer surgery (UGC surgery) and that the induction of the syndrome is an important factor in provoking further peri- and postoperative complications and in worsening the surgical stress response (SSR). The characteristics of MTS is hypotension, tachycardia, and flushing.

In order to uncover the role of MTS in cancer surgery and the effects on the oncological patients, the aim of the project is:

1. To characterize MTS in patients undergoing three common forms of UGC surgery using a new objective methodology and by recording biomarkers suspected of playing a role in the pathophysiology of MTS and postoperative complication development.

Three different interventions will be examined during this prospective trial:

1. Continuous measurement of microcirculation on the forehead using Laser Speckle Contrast Imaging during surgery.
2. Analyses of plasma samples obtained pre-, intra-, and one day postoperatively.
3. Continuous measurements of haemodynamic variables during surgery.

Detailed description: Background

Surgical procedures for upper gastrointestinal cancer (UGC) induce a considerable risk of morbidity and mortality, and more than half of all UGC patients die within one year of diagnosis. Radical surgery is crucial to survival, but is associated with a high risk of complications which contributes to a poor long-term prognosis. Despite advances in surgical techniques and perioperative management, postoperative complications frequently occur.

An essential part of gastrointestinal cancer surgery is the reconstruction of the digestive tract by forming a gut-to-gut reconnection, an anastomosis. Especially during UGC surgery this reconstructive anastomosis is at high risk of insufficient healing and can thus leak intestinal contents into the surrounding tissues, causing life-threatening infections. Development of measures that can reduce the perioperative complications in these vulnerable patients is therefore of vital importance

Patients undergoing surgery for UGC are subjected to a substantial trauma reaction termed the surgical stress response (SSR). SSR is characterized by activation of the sympathetic nervous system, the endocrine system, as well as by immunological and hematological responses leading to hypotension, systemic and local inflammation. In addition, surgical stress can cause immunosuppression in response to the complex interaction of various hormones, cytokines and acute phase reactants. Furthermore, it has recently been reported that perioperative immunosuppression increases the incidence of cancer recurrence, growth of metastases and reduces survival.

A contributing factor to SSR, and possibly most importantly, to the rate of postoperative complications, may be the mesenteric traction syndrome (MTS). MTS arises when the organs of the abdomen are manipulated during surgery. One of the main symptoms is substantial circulatory changes (hypotension, tachycardia and subsequent flushing), which can potentially lead to surgical complications.

Hypothesis and aim

It is the hypothesis of this project that the Mesenteric Traction Syndrome (MTS) is a common event during UGC-surgery and that the induction of the syndrome is an important factor in provoking further peri- and postoperative complications and in worsening the SSR. In order to uncover the role of MTS in cancer surgery and the effects on the oncological patients, the aim of the project is:

To characterize MTS in patients undergoing three common forms of UGC surgery using a new objective methodology and by recording biomarkers suspected of playing a role in the pathophysiology of MTS and postoperative development of complications.

Methods

75 patients undergoing UGC surgery (25 each of the three most common cancer types of UGC) will be included. This study will use a novel skin flushing measuring method called laser speckle contrast imaging (LSCI) to measure skin blood flow of the forehead. LSCI is a real-time and non-touch measuring device capable of measuring blood flow on a large field surface (15 cm x 20 cm). In parallel, inflammatory and hormonal stress biomarkers considered to be associated with SSR, will be measured. In this study, it is hypothesized, that by correlating a new method of quantifiable flushing measurement and known biomarkers, it is possible to relate the extent of flushing to the severity of hypotension and MTS and by proxy the extent of complications.

Furthermore, the participants will be exposed to head down tilt at three pre defined time points with subsequent monitoring of haemodynamics and SSR. This intervention is done to assess the patients' fluid status in the end of surgery as well as postoperatively, as hypovolemia is associated with postoperative complications.

Statistics

The incidence of MTS in UGC patients was previously unknown and power calculations was performed based on previous reported cases of MTS during abdominal surgery (incidence of 30% and 85%). 15 patients are required in each group in order to obtain a statistical power greater than 0.90 with an α-level of \< 0.05,. Groups of 25 patients are therefore chosen to ensure statistical significance.

Eligibility criteria: Inclusion Criteria:

- patients under going either whipple's procedure, liver resection, or gastric resection.

Exclusion Criteria:

* Robotic assisted procedures
* Lack of informed consent

Primary outcomes:
measure: Relative changes in plasma-hormone concentrations (pro-ANP, PGF2, GLP-1, ACTH, cortisone, adrenaline, IL-1, IL-6, TNF-alfa and CRP (stress hormones)) from baseline.
timeFrame: 15 blood samples obtained pre-, intra-, and 18 hours postoperatively
Secondary outcomes:
measure: Postoperative complications
timeFrame: Participants will be followed during the hospital stay, with an expected average of ten days
measure: Relative changes in heart rate from baseline measured in beats per minute
timeFrame: Continuous measurements intra- and postoperatively.
measure: Relative changes in microcirculation from baseline during surgery measured in flux-units
timeFrame: A continuous measurement starting one minute prior to the surgical procedure and terminates after 60 minutes.
measure: 30-days and 90-days mortality
timeFrame: 30-days and 90-days mortality
measure: Length of stay
timeFrame: Expected time frame of 10 days in average.
measure: Relative changes in median arterial pressure from baseline measured in mmHg
timeFrame: Continuous measurements intra- and postoperatively.
measure: Relative changes in cardiac output from baseline measured in litres per minute
timeFrame: Continuous measurements intra- and postoperatively.
measure: Relative changes in systemic vascular resistance from baseline measured in dyn.s/cm5
timeFrame: Continuous measurements intra- and postoperatively.
Other outcomes:
Locations:
Study officials:
References:
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