The results of the pilot study demonstrated that postoperative CSDs had a major negative impact on patients' daily activities, comfort, and time. In a theoretical scenario, the majority of patients in the pilot study were willing to pay $100–$200 out-of-pocket to reduce the time to drain removal by at least 4 days. Given these findings, a randomized controlled trial was performed using fibrin sealant at the time of ILND to potentially decrease seroma formation and the time to CSD removal. The randomization process was successful with a similar distribution of clinicopathologic factors among the fibrin sealant group and the control group. Our findings, however, do not support the use of a fibrin sealant for this purpose, as it did not affect the time to drain removal for melanoma patients undergoing ILND.
The pathophysiology of seroma formation has not fully been delineated. The majority of literature pertains to breast cancer patients undergoing mastectomy with or without axillary lymph node dissection. In these patients, it has been suggested that a number of anatomical factors play a role in seroma formation including the creation of a large potential dead space, irregularity of the chest wall, and movement of the chest wall secondary to respiration and shoulder movement all of which may prevent flap adherence . Leakage from transected lymphatics is believed to be an important factor in seroma formation although this is supported by only scant evidence. Other studies have suggested that seroma formation may result from an inflammatory exudate [19, 20].
Kuroi et al., have identified several risk factors for seroma formation in breast cancer patients including obesity, extended radical mastectomy, and large output drain volume in the early postoperative period . Others have found that thermal trauma from electrocautery dissection may increase the incidence of seroma formation, however, alternative techniques such as sharp dissection or ultrasonic scissors may increase operative blood loss . Another surgical technique that may decrease seroma formation is obliteration of the dead space by suture flap fixation although this technique is not widely used [23, 24].
Fibrin tissue adhesives, which first became commercially available in Europe in 1978, have been used in numerous surgical procedures [9–11]. To our knowledge, this is the first published prospective trial to assess the benefit of fibrin sealant as a means of decreasing lymphatic drainage in melanoma patients undergoing ILND. The basis for the current study included several studies that used fibrin tissue adhesives in axillary lymph node dissection or modified radical mastectomy for breast cancer [25–30]. Given the technical similarities between these procedures and ILND–all of which include the creation of large skin flaps, transaction of multiple small blood vessels and lymphatics, and an anatomical area at risk for shearing forces–we postulated that the proposed benefits of using fibrin tissue adhesives following axillary surgery would translate to ILND.
Although a number of studies have used fibrin tissue adhesive following breast and axillary surgery, the results have been inconsistent. Several randomized trials have reported a benefit of using fibrin tissue adhesives in axillary lymph node dissection or modified radical mastectomy for breast cancer [26, 31–34]. However, a similar number of prospective randomized trials have reported that fibrin sealants are ineffective at preventing seroma formation, decreasing the time to drain removal, or reducing costs in patients undergoing breast procedures [27–30]. Recently, Carless et al. performed a meta-analysis of 11 trials that had used fibrin sealant to prevent seroma formation after breast cancer surgery and found that fibrin sealant did not reduce the rate of postoperative seroma, drainage volume, or length of hospital stay . These findings are similar to ours.
There are several limitations to the current study. First, the study was small, including a total of only 30 patients, which was 80 percent powered to detect a 7 day difference in time-to-drain removal. Second, it is possible that the amount of fibrin sealant applied or the concentration used in this study was not optimal for lymphatic sealing.
Several factors, including safety issues and cost, must be considered when using fibrin sealants. The fibrinogen and thrombin components of TISSEEL are obtained from pooled human plasma from screened donors  and thus carries a risk of viral transmission. To avert this risk, a double-vapor heat deactivation procedure is used to eliminate viruses, and polymerase chain reaction testing for viral deoxyribonucleic acid is performed [8, 13]. Another safety concern in TISSEEL is that aprotinin, the antifibrinolytic component used to prevent sealant degradation, is from a bovine source, and thus the product is contraindicated in patients who are sensitive to bovine products . Newer, synthetic fibrin sealants have been developed to avoid the risk of allergic reactions. Another promising application of fibrin sealant matrices is the addition of products such as antibiotics or antineoplastics that would allow the fibrin sealant to act as a medium for local delivery of these agents [13, 34].