A Multi-center, Double Blinded Randomized Controlled Trial Evaluating Closure of the Dead Space After Mastectomy Using Sutures or Tissue Glue Versus Conventional Closure. Protocol for the Seroma Reduction After Mastectomy (SAM) Trial

1. INTRODUCTION AND RATIONALE

Seroma formation is a common side effect after surgery for breast cancer, with an incidence of 3% to 85%. Seroma is a collection of serous fluid that contains blood plasma and/ or lymph fluid. Some surgeons regard seroma formation as a necessary evil after breast cancer surgery. Seroma formation and its sequelae form the mainstay of complications in breast cancer surgery. Complications vary from delayed wound healing, infection, skin flap necrosis, patient discomfort and repeated visits to the out patient clinic to deal with seroma and its sequelae.

The key to reducing seroma formations seems to partly lie in the obliteration of dead space. However, the techniques used to achieve this goal are subjects of much controversy and debate. In a randomized controlled study it was difficult to elucidate whether reducing the dead space or ligation of lymphatics or a combination of both were responsible of reduction of seroma formation.

The use of electrocautery has been demonstrated to increase seroma formation following mastectomy, however no other surgical devices (laser scalpel, argon diathermy and ultrasonic scalpel) or substances have proven to be superior in seroma reduction. Seroma formation after axillary dissection for breast cancer cannot be avoided but hopefully it can be minimized by mechanical dead space closure. This systematic review highlights the fact that seroma formation is multifactorial and prevention of seroma is difficult at present. Certain prospective trials have been performed that demonstrate that flap anchoring and therefore dead space reduction could be very beneficial. The trial performed by Laurence et al analysed flap fixation and closed suction drainage. In this study there was no difference in seroma rates, but patients without drains were discharged earlier. In the trial performed by Sakkary et al the amount of fluid drained was significantly less in the flap fixation group however patient discomfort (seroma aspirations and out patient visits) were not assessed.

A Cochrane review was published in 2013 regarding Fibrin Glue (Tissuecol), Fibrin Glue did not influence the incidence of postoperative seroma, the mean volume of seroma, wound infections, complications and the length of hospital stays in people undergoing breast cancer surgery. Due to significant methodological and clinical diversity among the included studies this conclusion may be considered weak and biased. Therefore, a major multicentre and high-quality RCT is required to validate these findings. ARTISS tissue glue is a two-component fibrin sealant matrix of human fibrinogen and human thrombin wich has the advantage of setting in 60 seconds. This means that the surgeon has 60 seconds to correctly position the skin flaps before the tissue sealant sets,