In this study, we performed the first randomized clinical trial on the effect of fibrin glue on the postoperative lymphatic drainage after gastrectomy and D2 dissection. It was shown that fibrin glue could effectively reduce postoperative lymphatic drainage which leads to reduced length of hospital stay.
The exact incidence of postoperative seroma formation after gastrectomy is not clear, however it has been reported that by increasing the extent of lymph node dissection the incidence of seroma formation after gastrectomy increases . It is reported to be about 0.4% for D2 dissection and reaches to 3.6% for D2 dissection plus pre-aortic lymphadenectomy. Furthermore, dissection of lymph nodes along the common hepatic artery and the celiac artery increases the chance of seroma formation.
Considering the significant morbidity in patients who underwent radical lymphadenectomy in different anatomical sites, different strategies have been applied to reduce the amount of seroma formation which mainly can be divided in to three categories. First, surgical devices for sealing vessels such as argon diathermy, laser scalpel, ultrasonic scalpel, and ultrasonic scissor, second the methods of limiting the dead space[20, 21] and third, hemostatic agents applied directly to surgical site.
Primarily, fibrin glue was used in cardiovascular, liver, lung, gynecological and urological surgery as hemostatic agent. Moreover, upcoming studies showed their role in tissue recovery, regeneration and faster healing. Thus, it became useful in microneurosurgery, and gastrointestinal anastomoses. Generally, the mechanism of action of different types of fibrin-containing-products is to trigger the coagulation process by activating the reaction of fibrinogen and thrombin. Upon contact with a bleeding surface, the fibrinogen-thrombin reaction transforms the active fibrinogen to fibrin and promotes the formation of the fibrin clot. Various types of fibrin-containing-products have been used worldwide and most popular ones are Floseal®, Tachosil® and Tissucol®. These products are different regarding the source of fibrinogen, thrombin and aprotinin which could be of the human or bovine origin. Newer products contain human based compound, in order to lessen potential immunogenic reaction[25, 26] or anaphylaxis caused by bovine aprotinin.
The efficacy of fibrin-containing-products have been assessed through different studies. It has been used in various types of malignancy and various anatomical sites. This divergence has led to different results about the effectiveness of these products. One of the studies in the field of evaluating efficacy of fibrin sealant patches on the incidence of lymphatic morbidity after radial lymphadenectomy has been performed by Gasparri et al. They gathered data on 720 patients from 10 different clinical trials which used fibrin-thrombin sealant in patients whom underwent axillary dissection for breast cancer, extraperitoneal dissection for prostate cancer, inguinal dissection for vulvular cancer or melanoma and pelvic dissection for endometrial cancer. The final conclusion of this study was that application of fibrin-thrombin sealant was effective in reducing postoperative lymphocele formation and reduced the need to percutaneouslly drain the seroma, the median total volume of lymph drained, and the duration of drainage. The underlying rational behind the use of these products is the fact that endothelial cells of blood and lymphatic vessels produces coagulation and fibrinolytic factors in natural hemostatic cascades and cause sealing of lymphatic capillaries, thus the use of such products may have a role in augmentation of the final stage of coagulation when fibrinogen is converted into stable fibrinogen clot[25, 28].
Gerken et al ran a systematic review and meta-analysis to investigate the preventive effect of fibrin–containing tissue sealants on lymphocele formation after radical inguinal lymph node dissection in patients with melanoma. They used six clinical trials including 194 patients. This study failed to show the effect of tissue sealants on the duration of drain placement, total drainage volume, the incidence of postoperative seroma formation, wound infection and skin necrosis. This result might be explained as every study used different setting regarding the surgical radicality, the size of the wound surface, the definition of drain removal criteria, and the rout of application of fibrin-containing product (glue or patch). Thus, this heterogeneity in the study designs had finally caused indefinite results [30–32].
Another systematic review and meta-analysis of randomized controlled trials on application of fibrin sealant for the prevention of lymphocele after lymphadenectomy in patients with gynecological malignancies was performed by Prodromidou et al. Four hundred eighty one patients from six randomized clinical trials were included and it was found that fibrin sealant could significantly decrease total amount of drained fluid and mean duration of drainage. Also, there was no difference in overall incidence of lymphocele[33, 34].
The English literature about the effect of fibrin-containing products on seroma formation after lymphadenectomy is now inconclusive because there are several serous limitations in each study even systematic reviews and meta-analysis ones. The lack of precise definition of seroma formation, diagnostic tools to evaluate and appropriate prophylactic and therapeutic approaches to treat this condition resulted in significant amount of studies without solid statement. Thus to reach safe conclusion studies with high number of included patients, unified planning and design are warranted.
Finally, this study showed possible role of fibrin glue on reducing postoperative seroma formation after gastrectomy and D2 dissection, a result which should be taken cautiously because of limited number of participants.