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Scientific background

The Leipzig School of Radical Pelvic Surgery was established in 2005 with the objective to provide insights concerning locoregional tumor spread deduced from embryonic development and to demonstrate their translation into a new principle of surgical radicality for the treatment of lower female genital tract cancer.

 

Principles of conventional cancer surgery

​Principles of conventional cancer surgery: Wide tumor excision and staging lymph node dissection

Traditional surgery for local cancer control is based on functional topographic anatomy confounded by empirical dissection artefacts and on the model of isotropic tumor progression. The clinical practice translated from these principles is wide tumor excision, i.e. the resection of the tumor with a metrically defined circumferential tissue margin free of neo- or dysplastic lesions. However, that treatment may cause considerable morbidity. Moreover, despite R0 resection, local recurrences, often indicating a poor prognosis, occur in up to 50 percent with high risk cases. Although fundamental for the concept of surgical tumor treatment, the prognostic robustness of margin width could never be demonstrated.

Regional lymph node dissection is performed for nodal staging. In case of proven metastases surgical treatment alone is regarded insufficient for tumor control and adjuvant (chemo)radiation is recommended. Postoperative radiation therapy may reduce locoregional relapses of gynecologic malignancies but overall survival is not improved. Instead, treatment morbidity is significantly increased and a great proportion of patients is overtreated.​

Embryonic development and malignant progression

The ontogenetic cancer field model of locoregional tumor spread

The development of organisms from the fertilized oocyte (ontogenesis) proceeds with trajectories of successive bifurcations making up the pathways for the different cell types (cell lineage specification, cell fate progression). Complex epigenetic processes generate temporarily stable global chromatin structures that determine form and function of the corresponding cell type at the intermediate and terminal stages.

Each step in fate progression increases the morphological and functional complexity of the cell type at the cost of its plasticity concomitant with reduced positional potential. The tissue domains permissive for a distinct cell type become more and more specified.

Before determination, cells comprise the expanding habitats of multiple cell types whose stem cells can transdifferentiate into each other. Populations of determined cell types are confined to topographically defined compartments further segregating into subcompartments and finally zones of the mature organism.
The cancer field model considers cancer progression as pathological fate regression of transformed stem cells in the mature organism with a competent adaptive immune system. The tissues for potential local tumor progression, the cancer fields, represent the mature derivatives of the founder tissue domains in reverse sequence. Thus, an order of cancer is established. The topologic relationship between the local tumor extent and the mature tissues of sequential developmental steps determines the ontogenetic tumor stage (oT). 

The regional lymph nodes executing peripheral immune tolerance for their tributary tissues provide additional permissive sites for discontinuous tumor spread, especially for epithelial neoplasms.

The ontogenetic cancer field model for regional progression of carcinomas assumes that memory Treg cells and memory Breg cells against peripheral antigens of the normal tributary tissue in the draining lymph node provide a proliferation matrix for tumor cells with similar antigens. Since the lymph nodes are invariably connected to their tributary regions through afferent lymphatics and exhibit common tissue antigens, the potential regional propagation field can be identified for each local cancer field of the individual neoplasm.

Considering the ontogenesis of the lymphatic system and secondary lymphoid tissue / lymph nodes allows the topographic identification of first-, second- and third-line lymph nodes with corresponding potential for metastases formation for any local cancer field and thus to establish an ontogenetic nodal staging system as well.​

Redefining cancer surgery

​Cancer field resection and therapeutic lymph node dissection

Clinical translation of these insights resulted in cancer field resection and therapeutic lymph node dissection based on ontogenetic anatomy mapping the body with regard to development. Cancer field resection preserves tissue of adjacent compartments of different embryonic origin despite close proximity to the neoplasm. Based on the model of ontogenetic cancer fields, total mesometrial resection (TMMR), extended mesometrial resection (EMMR), vulvar field resection (VFR) and laterally extended endopelvic resection (LEER) with therapeutic lymph node dissection (tLND) have been developed for the therapy of cervical, vulvar and vaginal cancer. These new surgical procedures achieve excellent locoregional tumor control without adjuvant radiotherapy at minimized treatment - related morbidity.

The favorable clinical results with TMMR obtained at the University of Leipzig have been reproduced by a multicentric prospective observational study as published recently.​

TMMR Video

TMMR VIDEO

Participants of the course receive the latest version of the TMMR video.

 

 

 

 

 

 

 

 

 

 

Höckel M, Horn LC, Fritsch H. Association between the mesenchymal compartment of uterovaginal organogenesis and local tumor spread in stage IB-IIB cervical carcinoma: a prospective study. Lancet Oncol. 2005;6:751–756.​

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