Efficacy of a Fibrin Sealant (Tissucol Duo®) for the Prevention of Lymphocele After Laparoscopic Pelvic Lymphadenectomy Due to Gynaecological Cancer: a Randomised Controlled Trial

This prospective double blind randomized study was conducted by the Gynaecological Cancer Unit of Donostia University Hospital (San Sebastian, Basque Country, Spain) between February 2012 and June 2016. The study was approved on 24 August 2012 by the clinical research ethics committee of our hospital (study reference number ONC-1111).

All patients diagnosed with gynaecological (cervical, endometrial or ovarian) cancer due to undergo transperitoneal bilateral laparoscopic pelvic lymphadenectomy (LPL) as part of their surgical treatment were invited to participate. Our treatment protocol is based on clinical guidelines of the European Society Gynaecology and Oncology and the Spanish Society of Gynaecology and Obstetrics (SEGO).

The inclusion criteria were that the patient had endometrial, cervical, or ovarian cancer, underwent PL, an expected survival of more than 12 weeks and appropriate bone marrow, kidney and liver function, as well as that they agreed to participate and signed the informed consent form. Patients were excluded if they had previously received radiotherapy or chemotherapy, haematological disorders including coagulation defects, a history of thromboembolic disease or lymphatic system disorders (lymphedema or lymphocele), or allergy to aprotinin, as well as if they declined to participate or did not sign the informed consent form.

After standard preoperative assessment, patients were randomly assigned to having Tissucol Duo® applied to the surgical bed in only the right or only the left hemipelvis after bilateral LPL. The patient, doctors who performed the follow-up and initially the surgeon were blinded to the randomization sequence and site of application. That is, the surgeon was only told to which hemipelvis the sealant was to be applied when he considered that the surgical procedure had been completed. Following the manufacturer´s instructions, 5 ml of sealant was sprayed evenly across the entire surgical bed in only one hemipelvis (the treated hemipelvis). Using this protocol, the investigators sought to minimise intervention bias, in that the surgeon did not know where he was going to spray the sealant until the end of the LPL procedure. The investigators decided to treat only one hemipelvis in each patient, thereby allowing patients to serve as their own controls, in order to compare outcomes with and without the sealant in the same body with the same clinical characteristics and reduce the influence of other factors beyond the treatment.

All the patients received antithrombotic and antibiotic prophylaxis according to our usual protocols and were operated on by the same surgical team, all procedures being carried out using ultrasonic shears (Harmonic®, Ethicon, Cincinnati, OH, USA) In patients with endometrial cancer, we also carried out retroperitoneal aortocaval lymphadenectomy as part of surgical staging (para-aortic lymph node dissection PALND, as described by Querleu) up to the left renal vein, followed by type A radical hysterectomy (Querleu-Morrow 2011/EORT) and opening of the retroperitoneal space after the surgical intervention. In patients with cervical cancer, after LPL and intraoperative lymph node biopsy, the surgeons completed surgery with transperitoneal aortic lymphadenectomy if the biopsy was positive or radical hysterectomy (type B1 or C1) if it was negative.