Definition of compartment-based radical surgery in uterine cancer: radical hysterectomy in cervical cancer as ‘total mesometrial resection (TMMR)’ by M Höckel translated to robotic surgery (rTMMR)
© Kimmig et al.; licensee BioMed Central Ltd. 2013
Received: 8 March 2013
Accepted: 7 August 2013
Published: 26 August 2013
Radical hysterectomy has been developed as a standard treatment in Stage I and II cervical cancers with and without adjuvant therapy. However, there have been several attempts to standardize the technique of radical hysterectomy required for different tumor extension with variable success. Total mesometrial resection as ontogenetic compartment-based oncologic surgery - developed by open surgery - can be standardized identically for all patients with locally defined tumors. It appears to be promising for patients in terms of radicalness as well as complication rates. Robotic surgery may additionally reduce morbidity compared to open surgery. We describe robotically assisted total mesometrial resection (rTMMR) step by step in cervical cancer and present feasibility data from 26 patients.
Patients (n = 26) with the diagnosis of cervical cancer were included. Patients were treated by robotic total mesometrial resection (rTMMR) and pelvic or pelvic/periaortic robotic therapeutic lymphadenectomy (rtLNE) for FIGO stage IA-IIB cervical cancer.
No transition to open surgery was necessary. No intraoperative complications were noted. The postoperative complication rate was 23%. Within follow-up time (mean: 18 months) we noted one distant but no locoregional recurrence of cervical cancer. There were no deaths from cervical cancer during the observation period.
We conclude that rTMMR and rtLNE is a feasible and safe technique for the treatment of compartment-defined cervical cancer.
The ontogenetic compartment theory states that malignant tumor growth is confined to permissive compartments derived from a common primordium in embryonic development. Tumor permeation may be facilitated in the permissive ontogenetic compartment but suppressed at the compartment borders . The existence of developmental compartments was shown first in Drosophila  and reviewed by Dahmann et al.. A clinical implementation was described first for total mesorectal excision (TME) in the treatment of rectal cancer [4, 5]. Höckel and Fritsch investigated embryonic development of the female reproductive tract with respect to embryological different compartments [6–8] and were able to define three different primordial tissue complexes from cranial to caudal: the paramesonephric-mesonephric-Müllerian tubercle complex, >the deep urogenital sinus (UGS) vaginal plate complex and the superficial UGS-genital folds and tubercle process . First evidence for the functionality of this theory concerning the paramesonephric-mesonephric-Müllerian tubercle complex in cervical cancer has been shown for cervical cancer with respect to local tumor control following total mesometrial resection (TMMR) without any adjuvant radiotherapy [9, 10] but also with respect to the pattern analysis of local tumor spread in advanced and recurrent disease . It has to be questioned whether the confirmation of these findings could fundamentally change the classification of radical hysterectomy and the indication for adjuvant radiotherapy .
With respect to regional spread data and pelvic therapeutic lymphadenectomy (tLNE), they were also systematically analyzed and also assigned to ontogenetic lymphatic compartments, which may be classified as external iliac nodes, paravisceral nodes, common iliac nodes and presacral nodes .
The original technique has been developed and described in open surgery. At present, increasing numbers of minimally invasive approaches to radical surgery in cervical cancer are being reported. However, it is difficult to compare the results while lacking a systematic description of the different techniques used. The TMMR and tLNE may be perfectly standardized, but the technique of robotically assisted minimally invasive preparation may differ markedly to the open approach. We recently reported on the technique of therapeutic pelvic and paraaortic lymphadenectomy transferred to robotic surgery in genital cancer with special respect to uterine cancer. Therapeutic lymphadenectomy is performed for control of regional tumor spread; dependent on the original site of the primary tumor, however, it has mandatorily to be combined with complete removal of the appropriate local compartment at risk. In the case of cervical cancer, the removal of the local compartment can be performed as a total mesometrial resection as already outlined. This technique has been translated to robotically assisted laparoscopic surgery (rTMMR) with the support of Michael Höckel. To define this procedure reproducibly with respect to anatomical landmarks, we describe the technique step by step and present feasibility data from the first 26 patients. We present this concept of rTMMR internationally (the technical principles without feasibility data were reported up to now in German only and, therefore, are not accessible to the majority of international oncological surgeons ) intending to provoke scientific discussion within the community of surgical oncologists. This discussion should primarily take place with respect to the impact of robotically assisted compartment-adapted radical hysterectomy in cervical cancer; however, it also demonstrates the impact of exact visual definition of crucial surgical steps for future research in surgical oncology and comparison of clinical data.
The first author has been trained in the surgical technique of TMMR and tLNE, attending in the Leipzig School of Surgery in 2006. All radical hysterectomies were consequently performed using the ontogenetically derived, nerve-sparing technique of TMMR and tLNE, if adequate. In 2010, robotically assisted laparoscopic surgery was implemented using a da Vinci™ Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA). The principles of the surgical steps were systematically translated to robotic surgery and optimized to guarantee the same radicalness compared to open surgery but preserving the advantages of an endoscopic approach. The different steps were discussed with M. Höckel by video sequences. Finally, M. Höckel participated in the surgery in Essen and confirmed the equality of the robotic approach with respect to his operation technique defined by open surgery. The resulting rTMMR technique will be described in detail.
Patients and specimens
As a first proof of feasibility, 26 patients with cervical cancer FIGO stage IA-IIB were treated by robotic total mesometrial resection (rTMMR) +/− robotic therapeutic lymphadenectomy (rtLNE). All patients gave their informed consent to the procedure. Therapeutic lymphadenectomy was performed by robotic surgery in analogy to the procedure described by M. Höckel [6, 9]. The complete clearance of the lymph node basins of the lymphatic drainage system - including the intercalated mesometrial nodes and the lymph basins - downstream to the Müllerian compartment was defined to be a superior quality parameter compared to the number of removed lymph nodes as described previously by the authors . The lymph node basins for cervical cancer include: paravisceral nodes (internal iliac nodes including gluteal and rectal nodes, (pv)), external iliac nodes (ei) first line, and common iliac nodes (ci) and presacral/subaortic nodes (ps) on both sides, second line. Periaortic nodes including inframesenteric (im) and, if indicated, supramesenteric/infrarenal (sm/ir) nodes were removed in case of pelvic nodal disease, since these basins have to be considered tertiary and quaternary with respect to the cervix. Perioperative morbidity and early postoperative morbidity were analyzed. In addition, we noted perioperative blood loss by hemoglobin levels and frequency of perioperative blood transfusions. The tumor-related outcome was recorded.
Analysis of clinical and histopathological data was performed using SPSS version 17.0 for Macintosh™ (SPSS, Chicago, IL, USA). We conducted a descriptive analysis only, considering the limited number of patients and the explorative character of this analysis.
Technique and results
rTMMR with tLNE were performed in a steep Trendelenburg position, trocar positioning is depicted in Figure 1. Prior to rTMMR, therapeutic lymphadenectomy starting at the aortic bifurcation has been performed as specified previously . Accordingly, all regional nodes of lymph node basins at risk are removed, except for intercalated mesometrial nodes located predominantly in the vascular mesometrium.
The removal of the uterus, the fallopian tubes, the vascular and ligamentous mesometria and the part of vagina starts dorsally.
Step 4. To detach the vesicouterine attachment, the anterior surface of the uterus has to be exposed and put under tension to facilitate incision of the peritoneum at the vesicouterine fold. The peritoneum has to be incised in the direction of the lateral part of the round ligaments to divide these at the entrance to the inguinal channel. The loose connective tissue is dissected until the ureters are identified entering the vesical wall (Figure 9). The preparation is extended laterally and the border of the vesical and Müllerian compartments is identified.
In contrast to M. Höckel, we do not readapt the natural sigma adhesions, representing the sole difference to the original method described for open surgery. However, this may be easily implemented if desired.
In total, 26 patients with the diagnosis of cervical cancer underwent surgery. All patients received a total mesometrial resection of the uterus. Therapeutic pelvic and, if necessary, periaortic lymphadenectomy was added when indicated.
Three patients had been treated by radiochemotherapy first due to positive periaortic nodes and/or local inoperability. In these patients, TMMR was performed as ‘adjuvant’ treatment after completion of radiochemotherapy. In all other patients, surgery was the primary treatment. The mean age of the patients was 49.5 years (31 to 75 years). The mean body mass index (BMI) of the patients was 24.3 kg/m2 (range 18 to 33 kg/m2), 42% had preoperative comorbidity and prior intraabdominal surgery was noted in 54%.
Correlation of tumor stage, preoperative treatment, lymph node count and complication rate with type of surgical procedure
Mean lymph node count
TMMR and pelvic LNE
TMMR, pelvic and pa LNE
All interventions were performed as intended without modifications and no transition to open surgery was necessary due to complications or technical problems. Tumor resection was microscopically confirmed being complete (R0) in all cases. Mean lymph node count was 32.4 for pelvic and 42.2 for pelvic and periaortic lymphadenectomy, respectively. Periaortic lymphadenectomy was performed inframesenterically only in the case of proven negative periaortic nodes. In any case, it was not the number of nodes, but video-documented, complete clearance of lymph node basins that was taken as criterion for sufficient therapeutic lymphadenectomy as outlined in .
There were no intraoperative complications, in total postoperative complications occurred in six patients (23%). Two had minor local wound infection, two infected lymph cysts requiring revision, one had a postoperative laparoscopic revision for bleeding and one patient had a vaginal cuff dehiscence.
With respect to blood loss, hemoglobin levels were determined pre- and postoperatively (on the first day). Mean decrease of hemoglobin concentration was determined to be 2.1 g/dl in TMMR (0.5 to 3 g/dl), 3.3 g/dl in TMMR and pelvic lymphadenectomy (1.1 to 4.9 g/dl) and 3.3 g/dl in TMMR and pelvic/periaortic lymphadenectomy (2.4 to 4.6 g/dl). Blood transfusion was applied in four patients (15%) showing postoperative hemoglobin levels of 7.8, 8.3, 8.6 and 10.3 g/dl. Mean follow-up of the patients was 18 months (range 2 to 27 months). One patient who had received primary radiochemotherapy was lost to follow-up. There was one distant recurrence (1/25 corresponding to 4%). One intercurrent death occurred at 18 months postoperatively without evidence of tumor recurrence or association to cancer therapy. No patient has died of tumor or sequelae of the tumor-associated therapy during the observation period.
The patient with recurrence presented with stage pT2b, pN1, G2 and had a rupture of the anterior cervical fascia during surgery with exposure of the tumor to the surgical field. She refused radiation therapy and developed trocar site recurrence after 9 months, treated by radiation therapy and surgical excision, respectively. There was no additional locoregional recurrence. At evaluation, 20 months after diagnosis of recurrence, she was doing well without evidence of disease.
We were able to show that the principle of compartment-based surgery performed as total mesometrial resection (TMMR) combined with therapeutic lymphadenectomy (tLNE) as described by M. Höckel [9, 10] can systematically be translated to minimally invasive, robotically assisted procedures (rTMMR and rtLNE). Robotic surgery enables us to develop and dissect structures with high ‘optical’ accuracy, thus allowing us to prepare and remove compartment-associated tissue completely without injuring adjacent structures by respecting the filmy septa at the compartment borders; thus, excellent visual documentation by HD video recording is dramatically facilitated.
The method appears to be feasible and safe. It has to be considered that the presented data were collected consecutively during the first attempts in this surgical procedure. However, the mean follow-up time of 18 months is limited and the number of patients (with respect to the fact that six patients at FIGO stage IA and three patients who had prior radiotherapy were included) is admittedly small, it should be noticed, nevertheless that there has been no locoregional tumor recurrence during this observation period. Thus, it may be assumed that laparoscopic, robotically assisted TMMR and tLNE (rTMMR and rtLNE) may be safe with respect to local tumor control. This would be in accordance with the impression that due to the excellent 3D vision, along with the magnification of the surgical field and the high precision and control of movements, the accuracy of this technique may be considered at least equivalent to open surgery. Therefore it may be assumed that a comparable radicalness may be achieved.
As a consequence, further development of minimally invasive surgical techniques for treatment for cervical cancer confined to the Müllerian compartment should focus on evaluation of rTMMR and rtLNE. First, compartment-based surgery appears to exert excellent locoregional control in cervical cancer combined with a low complication rate as shown for open surgery [10, 13]. Second, the translation to a minimally invasive method by robotic assistance adds the advantages of minimally invasive surgery regarding blood loss, mobilization, length of hospitalization and short-term complications as it has previously been shown for robotic surgery [16, 17]. With respect to the port-site recurrence in our report, we stress that exposure of the tumor to the surgical field must strictly be avoided. Although port-site metastases are a well-known phenomenon, they seem to be a rare event [18, 19]. In robotic surgery, it is reported that the rate of port-site metastases is low and similar to conventional laparoscopy [20, 21]. Nevertheless, we recommend ensuring that no direct contact of the tumor with the operative field takes place. In this regard, we consider the closure of the cervical channel or the vagina prior to the opening of the vagina abdominally an important procedure in uterine cancers.
In conclusion, we suggest that the minimally invasive approach of compartment-based oncologic surgery for uterine cancers by robotic assistance is feasible, safe and may be beneficial for patients with cervical cancer confined to the Müllerian compartment. In order to evaluate whether the excellent monocentric data with outstanding locoregional tumor control and low morbidity of M. Höckel in cervical cancer [6, 9, 10] holds true in a multicentric setting, an observational study has been initiated. Starting recruitment in 2013, results of TMMR and tLNE with respect to morbidity and survival will be analyzed. Participation will be independent of surgical access - open or laparoscopic or laparoscopic robotically assisted - but requires verifiable standardization with an accordant training of TMMR, tLNE and pathological workup. For robotically assisted total mesometrial resection (rTMMR) the technique described in this publication will be the reference basis. Interested experienced surgeons who are willing to fulfill the requirements are invited by the first author to apply for participation.
In future, from our point of view, this kind of preparation and auditing of surgical studies could contribute to a better comparability between different sites and surgeons, which is not only mandatory in scientific studies, but may also beneficial in education and clinical practice. The clear definition of a surgical procedure, supported by educational illustrations and videos may serve as a pioneer of a new generation of surgical studies and - not least - surgical education.
We thank Michael Höckel, Head of the Department of Gynecology and Obstetrics and Head of the Leipzig School of Radical Pelvic Surgery, University of Leipzig, Germany, for his intensive and steady support in understanding ontogenetically derived compartment-based radical surgery in uterine cancer; moreover, we thank him especially for helping us translating his method from open to robotically assisted laparoscopic surgery and, last but not least, for the numerous fruitful discussions.
- Höckel M: Cancer permeates locally within ontogenetic compartments: clinical evidence and implications for cancer surgery. Future Oncol. 2012, 8: 29-36. 10.2217/fon.11.128.View ArticlePubMedGoogle Scholar
- Garcia-Bellido A, Ripoli P, Morata G: Developmental compartmentalization on the wing disk of Drosophila. Nat New Biol. 1973, 245: 251-253.View ArticlePubMedGoogle Scholar
- Dahmann C, Oates AC, Brand M: Boundary formation and maintenance in tissue development. Nature Reviews. 2011, 12: 43-55.View ArticlePubMedGoogle Scholar
- Heald RJ, Rayan DRH: Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986, 327: 1479-1482. 10.1016/S0140-6736(86)91510-2.View ArticleGoogle Scholar
- Quirke P, Dixon MF, Durdey P, Williams NS: Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Lancet. 1986, 2: 996-998.View ArticlePubMedGoogle Scholar
- Höckel M, Horn LC, Fritsch H: Association between the mesenchymal compartment of uterovaginal organogenesis and local tumour spread in state 1B-2B cervical carcinoma: a prospective study. Lancet Oncol. 2005, 6: 751-756. 10.1016/S1470-2045(05)70324-7.View ArticlePubMedGoogle Scholar
- Höckel M, Schmidt K, Bornmann K, Horm LC, Dornhöfer N: Vulvar field resection: novel approach to the surgical treatment of vulvar cancer based on ontogenetic anatomy. Gynecol Oncol. 2010, 119: 106-113. 10.1016/j.ygyno.2010.06.019.View ArticlePubMedGoogle Scholar
- Höckel M, Horn LC, Illig R, Dornhöfer N, Fritsch H: Ontogenetic anatomy of the distal vagina: relevance for local tumor spread and implications for cancer surgery. Gynecol Oncol. 2011, 122: 313-318. 10.1016/j.ygyno.2011.04.040.View ArticlePubMedGoogle Scholar
- Höckel M, Horn LC, Hentschel B, Höckel S, Naumann G: Total mesometrial resection: high resolution nerve-sparing radical hysterectomy based on developmentally defined surgical anatomy. Int J Gynecol Cancer. 2003, 13: 791-803.View ArticlePubMedGoogle Scholar
- Höckel M, Horn LC, Manthey N, Braumann UD, Wolf U, Teichmann G, Frauenschläger K, Dornhöfer N, Einenkel J: Resection of the embryologically defined uterovaginal (Müllerian) compartment and pelvic control in patients with cervical cancer: a prospective analysis. Lancet Oncol. 2009, 10: 683-692. 10.1016/S1470-2045(09)70100-7.View ArticlePubMedGoogle Scholar
- Höckel M, Kahn T, Einenkel J, Manthey N, Braumann U-D, Hildebrandt G, Leo C, Hentschel B, Vaupel P, Horn L-C: Local spread of cervical cancer revisited: a clinical and pathological pattern analysis. Gynecol Oncol. 2010, 117: 401-408. 10.1016/j.ygyno.2010.02.014.View ArticlePubMedGoogle Scholar
- Höckel M: Do we need a new classification for radical hysterectomy? Insights in surgical anatomy and local tumor spread from human embryology. Gynecol Oncol. 2007, 1: 106-112.View ArticleGoogle Scholar
- Höckel M, Horn L-C, Tetsch E, Einenkel J: Pattern analysis of regional spread and therapeutic lymph node dissection in cervical cancer based on ontogenetic anatomy. Gynecol Oncol. 2012, 125: 168-174. 10.1016/j.ygyno.2011.12.419. Epub 2011 Dec 8View ArticlePubMedGoogle Scholar
- Kimmig R: Robotic surgery for cervical cancer. Endoscopic total mesometrial resection and therapeutic lymphonodectomy [Robotic Surgery beim Zervixkarzinom. Endoskopische total emesometriale Resektion und therapeutische Lymphonodektomie]. Gynakologe. 2012, 45: 707-711. 10.1007/s00129-012-3045-2.View ArticleGoogle Scholar
- Kimmig R, Iannaccone A, Buderath P, Aktas B, Wimberger P, Heubner M: Definition of compartment-based radical surgery in uterine cancer - part I. Therapeutic pelvic and periaortic lymphadenectomy by Michael Höckel translated to robotic surgery (rtLNE). ISRN Obstet Gynecol. 2013, 2013: 297921-10.1155/2013/297921.PubMed CentralView ArticlePubMedGoogle Scholar
- Reza M, Maeso S, Blasco JA, Andradas E: Meta-analysis of observational studies on the safety and effectiveness of robotic gynaecological surgery. Br J Surg. 2010, 97: 1772-1783. 10.1002/bjs.7269.View ArticlePubMedGoogle Scholar
- Paley PJ, Veljovich DS, Shah CA, Everett EN, Bondurant AE, Drescher CW, Peters WA: Surgical outcomes in gynecologic oncology in the era of robotics: analysis of first 1000 cases. Am J Obstet Gynecol. 2011, 204: e1-e9.View ArticlePubMedGoogle Scholar
- Zivanovic O, Sonoda Y, Diaz JP, Levine DA, Brown CL, Chi DS, Barakat RR, Abu-Rustum NR: The rate of port-site metastases after 2251 laparoscopic procedures in women with underlying malignant disease. Gynecol Oncol. 2008, 111: 431-437. Epub 2008 Oct 16View ArticlePubMedGoogle Scholar
- Palomba S, Falbo A, Russo T, La Sala GBJ: Port-site metastasis after laparoscopic surgical staging of endometrial cancer: a systematic review of the published and unpublished data. Minim Invasive Gynecol. 2012, 19: 531-537. 10.1016/j.jmig.2012.03.023.View ArticleGoogle Scholar
- Iavazzo C, Gkegkes ID: Port-site metastases after robot-assisted surgery: a systematic review. Int J Med Robot. 2013, 10.1002/rcs.1512.Google Scholar
- Ndofor BT, Soliman PT, Schmeler KM, Nick AM, Frumovitz M, Ramirez PT: Rate of port-site metastasis is uncommon in patients undergoing robotic surgery for gynecological malignancies. Int J Gynecol Cancer. 2011, 21: 936-940. 10.1097/IGC.0b013e3182174609.PubMed CentralView ArticlePubMedGoogle Scholar
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