Pirkanmaa Hospital District, M building, Small auditorium, address: Teiskontie 35.
Doctoral defence of Lic.Med. Reita Nyberg
The field of science of the dissertation is Obstetrics and Gynaecology.
The opponent is professor Ulla Puistola (University of Oulu). Professor Johanna Mäenpää acts as the custos.
The language of the dissertation defence is Finnish.
Sentinel lymph node method in vulvar and ovarian cancer
Lymphatic spread if one of the most important prognostic factors in gynecological cancers. Therefore, nodal staging is an essential part of cancer diagnosis and treatment planning. The sentinel lymph node (SLN) is the first lymph node to receive lymphatic fluid from the tumor and is at greatest risk of metastasis. By locating and retrieving the SLN for pathological analysis it is possible to predict the stage of the regional lymph nodes in relation to cancer metastasis without extensive surgical procedures, saving the patient from complications associated with the surgery. This study was conducted in order to find out the usability of the SLN concept in vulvar and ovarian cancer.
In the first study, the reliability of SLN method in vulvar cancer was evaluated. In patients operated in Tampere University Hospital during 2001-2004, the SLNs were located with blue dye and radiocolloid injections and dissected separately for analysis before completing a groin lymph node dissection. In early stage vulvar cancer, the SLNs were detected in all cases, there were no false-negative SLNs and the SLN method accurately predicted the nodal stage. SLN method seemed reliable and has since been implemented to clinical practice.
The tissue samples from the same patients were used in the second study for evaluating associations between a lymphangiogenesis marker VEGF-C, SLN metastasis, surgical stage and clinical course of the disease. 67 % of the malignant vulvar tumors expressed VEGF-C in their invasive edges. This expression was also seen in 76 % of SLN metastases. Positive tumoral VEGF-C expression did not significantly associate with higher surgical stage, presence of SLN metastasis, higher recurrence rate or poorer prognosis. Negative VEGF-C expression in SLN metastasis might serve as an indicator of metastasis-free non-SLN, but that should be verified in a larger study.
The other objective of the thesis was to establish a SLN technique for intraoperative use in ovarian cancer surgery, where it previously has been considered unfeasible. The feasibility of the method was first tested in patients operated for high risk endometrial cancer. Blue dye and radiocolloid were injected into a healthy ovary at the beginning of laparotomy, and the blue and hot SLNs were located during lymph node dissections. In 94 % of patients, 1-3 SLNs per patient were detected and they all located in the para-aortic area. SLNs related to the left ovary were mostly (64 %) detected above inferior mesenteric artery (IMA), whereas almost all right-ovary-related SLNs (94 %) were located under the IMA level (p=0.001). This pilot study led to a feasibility study conducted in an authentic patient population with ovarian tumors.
During the last study, blue dye and radiocolloid were injected next to the ovarian mass into the mesovarium at the beginning of each operation. If the mass was benign and radical surgery was not required, the SLNs were mapped transperitonally. When a lymphadenectomy was performed, all SLNs were mapped and removed separately for analysis after opening of the retroperitoneum. The final histopathology of the SLNs and non-SLNs were compared. In all patients, 1-3 SLNs per patient were detected. In 60 % of the cases, the SLNs were located in the para-aortic area. In 30 % of patients, there were SLN both in pelvis and in the para-aortic area. Isolated pelvic SLNs were rare (10 %). SLNs related to the left ovary were located more cranially than right-ovary-related SLNs. Three patients underwent complete lymph node dissections due to early-stage ovarian cancer, and one patient had nodal metastasis. A positive SLN predicted correctly her nodal stage. This study increased the knowledge of essential routes of lymphatic spread in ovarian cancer. SLN concept deserves further investigation in relation to the surgical treatment of early ovarian cancer.
The dissertation is published in the publication series of Acta Universitatis Tamperensis; 2314, Tampere University Press, Tampere 2017. The dissertation is also published in the e-series Acta Electronica Universitatis Tamperensis; 1818, Tampere University Press 2017.