A randomized controlled study to evaluate autologous platelet rich plasma as an ideal substance for submucosal injection during endoscopic mucosal resection

Endoscopic Mucosal Resection (EMR) is a proven technique for endoscopic removal of sessile gastrointestinal neoplasms. Administration of sub- mucosal injections has become a part and parcel of Endoscopic Mucosal Resection (EMR) to create a sub-mucosal cushion, to separate the sub-mucosa from the muscularis for en-bloc resection and for preventing complications like perforation and hemorrhage secondary to thermal injury. An ideal sub mucosal injection is one which maintains a long lasting mucosal elevation and which gives a hemi spherical shape to the mucosa for easy snaring. Many materials have been proposed for use as sub mucosal injections during EMR. They include saline, hypertonic dextrose water, glycerol, hyaluronic acid, sodium alginate, polymers, hydroxyl ethyl starch, fibrinogen, serum, plasma, and whole blood. Some materials are expensive whereas others can induce allergic reactions. Few others maintain the sub-mucosal elevation for a very short duration.

We hereby propose autologous Platelet Rich Plasma (PRP) as a possible substance that may fit most of the ideal submucosal injection characteristics. Platelets contain a number of proteins,cytokines, and other bioactive factors that initiate and regulate basic aspectsof wound healing. Normal platelet counts in blood range from 150,000/ µ L to 350,000/µ L. Plasma is the fluid portion of blood and contains clotting factors andother proteins and ions. Platelet-rich plasma contains a 3- to 5-fold increasein growth factor concentrations. Platelet concentration of at least 1,000,000platelets/ µ L in 5 mL of plasma, is associated with the enhancement of healing. Platelet Rich Plasma may also contribute to longer duration of sub-mucosal elevation during polypectomy (EMR) which will aid the endoscopist in polypectomy.

This will be a randomized, outcome assessor blinded, active controlled, prospective study.

Patients with sessile gastrointestinal polyps of diameter 1mm to 20mm diagnosed by Upper gastrointestinal endoscopy or colonoscopy will be included for the study. After obtaining written informed consent from the eligible patients, he/ she will be randomized to the type of endoscopic sub-mucosal cushion to be used. For the subjects in Platelet Rich Plasma arm, twenty cc of blood will be drawn through an 18 gauge butterfly needle into two sterile vacutainers, each of ten cc capacity, pre-filled with Ethylene Di-amine Tetra Acetate (EDTA)- an anticoagulant. Acid Citrate Dextrose (ACD) will not be used as it has been proved that mean platelet volume is significantly lower values (6-13%, P< 0.05) in the citrated samples as compared to the same samples in EDTA. The blood will then be subjected to double centrifugation. Evidence advocates the better separation of platelets by double centrifugation.

Blood will not be drawn from the subjects in normal saline arm.

The patient will then be subjected to upper gastrointestinal endoscopy or colonoscopy based on the location of the lesion. After identifying the polyp and noting its approximate size, sub-mucosal cushion material will be injected in the sub-mucosa with a 21 gauge sclerotherapy needle by an assistant who is not a part of the study. Injection upto 5 ml of the material (either Normal Saline or Platelet Rich Plasma) will be permitted.

The following parameters will be noted:

a.Video of the sub-mucosal injection and the sub-mucosal elevation.

b.Time duration for the EMR procedure.

c.Whether the polypectomy was an en-bloc resection or a piece-meal resection.

Note: The duration of sub-mucosal elevation will not be noted. Making this observation will interfere with the EMR procedure as the primary outcome of the study is en-bloc resection rate and not mean duration of sub-mucosal elevation.

 The resected polyp will be placed in 10% formaldehyde solution and will be sent for histo-pathological examination.

Follow-up endoscopy:

Any post- procedural complications like bleeding, perforation etc will be noted immediately after the

EMR and after two weeks during a follow-up endoscopy/ colonoscopy.

Statistical analysis:

En-bloc resection rates will be compared between the two study arms using percentages and proportions. Parametric and non-parametric data will be analyzed with suitable tests of significance.