A Collagen-Fibrin Patch (Tachosil®) for the Prevention of Symptomatic Lymphoceles After Pelvic Lymphadenectomy in Women With Gynecologic Malignancies: a Randomized Clinical Trial

1. Background Women with gynecologic malignancies such as cervical and endometrial cancer routinely undergo pelvic lymphadenectomy based on tumor characteristics assessed prior to or during surgery. Pelvic lymphadenectomy may be performed by open surgery or laparoscopy (1-4). Postoperative complications during and after pelvic lymphadenectomy include local abscess, bleeding, lymphocele, and chronic lymphedema of the lower extremities, which has an incidence of 1 to 2% (2,3). In the present trial, we will focus on pelvic lymphoceles, one of the most common complications of pelvic lymphadenectomy. Simonato et al. described a rate of 19/30 (63%) of sonographically detected lymphoceles in men undergoing pelvic extraperitoneal lymphadenectomy for prostate cancer (4). In this trial, 4/19 men with lymphoceles were symptomatic and required medical interventions. In women with cervical cancer, asymptomatic lymphoceles detected by ultrasound have been noted in up to 11% of women after pelvic lymphadenectomy (1,3,5). In 2% of women, clinical symptoms will require a therapeutic intervention (5).

Tachosil® is a fibrin-collagen coated patch and heas been licensed in 2004 and 2007 in Europe for surgical use in humans to support surgical hemostatic interventions. The efficacy and safety of Tachosil® has been demonstrated in liver resection, pulmonary lobectomy, and kidney tumor resection trials (6-8). In men, but not in women, it has been demonstrated that the application of a collagen-fibrin patch to the lymphadenectomy surgery site may prevent a significant proportion of lymphoceles. In a randomized trial, Simonato et al. found that the pelvic application of two Tachosil® patches to the obturator fossa and the femoral canal was sufficient to significantly reduce the rate of sonographically detected lymphoceles within 4 weeks after surgery from 19/30 to 5/30 cases (p=0.001) as well as the mean drainage volume from 190 to 64 ml. Percutaneous puncture of a symptomatic lymphocele was necessary in 1/30 individuals in the intervention group compared to 4/30 individuals in the control group. (4). In women with gynecologic malignancies a single center randomized controlled trial has found, that Tachosil® seems effective to reduce the rate of lymphoceles after pelvic lymphadenectomy (5). 7/30 (23.3%) women in the treatment group compared to 9/28 (57.7%) women in the control group developed asymptomatic lymphoceles (p<0.05) (5). No significant differences between the two groups were observed in the development of symptomatic lymphoceles or the rate of interventions (5). This may be attributable to the small sample size of this study. As symptomatic lymphoceles are more relevant for the patient, it seems clinically more important to the evaluate the impact of Tachosil® on the rate of symptomatic lymphoceles after pelvic lymphadenectomy.

Symptomatic lymphoceles are defined by the CTCA 4.03 grading system as lymphoceles grade >2. This includes all lymphoceles needing medical intervention. Thus this definition comprises, lymphoceles with the presence of localized pelvic pain, pelvic abscess, fever, and/or leg edema in the presence of a sonographically verified pelvic lymphocele.

In summary, the data available in the literature demonstrate that pelvic lymphocles occur in 11 to 63% of individuals undergoing pelvic lymphadenectomy. Symptomatic lymphoceles seem to occur in about 32% of patients undergoing pelvic lymphadenectomy. Intraoperative application of a collagen-fibrin patch may reduce the number of lymphoceles, mean drainage volume, and the necessity of medical interventions such as percutaneous puncture.

Therefore, we intend to perform a multi center randomized clinical trial assessing the efficacy of a collagen-fibrin patch for preventing symptomatic lymphoceles in women undergoing pelvic lymphadenectomy for gynecologic malignancies, ie cervical and endometrial cancer. We hypothesize that, based on the data of Simonato et al. and Tinelli et al., the application of a collagen-fibrin patch (Tachosil®) will reduce the number of symptomatic pelvic lymphoceles by at least 66%.