Gynecologic Oncology 112 (2009) 405–408
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Gynecologic Oncology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / y g y n o
Transvaginal extraperitoneal lymphadenectomy by Natural Orifices Transluminal Endoscopic Surgery (NOTES) technique in porcine model: Feasibility and survival study Joseph Nassif a,⁎, Chrysoula Zacharopoulou a, Jacques Marescaux b, Arnaud Wattiez a a b
Gynecology department, IRCAD/EITS, Strasbourg University Hospitals, IRCAD / EITS, 1 Place de l'hôpital, 67091, Strasbourg Cedex, France General surgery department, IRCAD/EITS, Strasbourg University Hospitals, IRCAD/EITS, 1 Place de l'hôpital, 67091, Strasbourg Cedex, France
a r t i c l e
i n f o
Article history: Received 27 June 2008 Available online 20 November 2008 Keywords: Extraperitoneal lymphadenectomy Natural Orifices Transluminal Endoscopic Surgery Sentinel lymph node Gynecologic malignancies
a b s t r a c t Objective. Retroperitoneal pelvic and lomboartic lymphadenectomy is widely used as a staging and/or prognostic procedure in gynecologic malignancies. Associated morbidity ranges from 2 to 13% of cases. This study assesses the feasibility of extraperitoneal lymphadenectomy using Natural Orifices Transluminal Endoscopic Surgery (NOTES) in porcine survival model. Methods. Six female pigs weighing 25 to 30 kg were used. Using a transvaginal access to the retroperitoneum, we performed three pelvic lymph node excision and three others in the laterocaval, interaorticocaval and lateroaortic regions. Colpotomy was closed with interrupted absorbable sutures. Results. Retroperitoneal lymphadenectomies were performed successfully in all six pigs. We experienced one accidental peritoneal perforation, one diffuse anterior abdominal wall emphysema, one abdominal wall bleeding secondary to electrical muscle stimulation and two pneumoperitoneums evacuated by Veress needle insertion. All animals thrived until three weeks after the initial intervention. On laparoscopic second look there were no abscess, no infection and no adhesions even with the accidental peritoneal perforation. On laparotomy, no retroperitoneal abscess was found, but there was a small amount of fibrosis at the lymphadenectomy sites. All colpotomies were inspected and showed good healing. Conclusions. This study demonstrated the technical feasibility and safety of extraperitoneal lymphadenectomy by totally NOTES technique and provided the first report on survival porcine model. Cadaver experiments would test its feasibility in humans. Sentinel lymph node could be an application of NOTES lymphadenectomy in humans. NOTES endoscopic instruments are urgently needed for further advances in the technique. Further studies are mandatory to evaluate its future indications. © 2008 Elsevier Inc. All rights reserved.
Introduction Retroperitoneal pelvic and lomboartic lymphadenectomy is widely used as a staging and/or prognostic procedure in gynecologic malignancies. Associated morbidity ranges from 2 to 13% of cases [1]. Keeping in mind, some of those cancer patients will undergo aggressive and morbid post operative treatment. In that respect, one should try to minimize the impact of surgery. Recent advances in minimal invasive surgery offer natural orifices transluminal endoscopic surgery (NOTES) technique. Since Kalloo et al. published their data concerning the feasibility and safety of an oral transgastric endoscopic approach to the peritoneal cavity with long term survival in porcine models, many other intraperitoneal procedures followed in porcine model. Tubal ligation, cholecystectomy, gastrojejunostomy, splenectomy and oophorectomy were performed [2]. Other natural orifices (i.e., transvaginal, transcolonic, transvesical) were used to ⁎ Corresponding author. Fax: +33 388119028. E-mail address:
[email protected] (J. Nassif). 0090-8258/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2008.09.038
access the peritoneal cavity. To the best of our knowledge, the use of NOTES in the retroperitoneal area has never been considered neither in porcine model nor in human, while intra peritoneal procedures are done in humans [2]. We decided to assess the feasibility of extraperitoneal lymphadenectomy for retroperitoneal lymph nodes using NOTES technique in a porcine survival model. Materials and methods Animals Six female pigs weighing 25 to 30 kg were used in this study according to the French laws for animal use and care as well as the directives of the European Community Council (number 86/609/EEC). Preoperative preparation Pigs were deprived of food 24 h before surgery. Premedication consisted of intramuscularly injected ketamine 7 ml and 3 ml of a
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solution containing azaperone, methylene parahydroxybenzoate and propyl parahydroxybenzoate (Stresnil; Janssen-Cilag, Berchem, Belgium). General anesthesia was induced with intravenous propofol 10 ml/30 kg and 2 ml of pancuronium. Endotracheal intubation is performed and anesthesia was maintained with isoflurane 2%. All animals received prophylactic antibiotics (1 g of cephalexin). No bowel preparation is needed. Surgical intervention In the supine position, the animal's introitus was dilated digitally using lubrification (Xylocaine gel). A midline to lateral colpotomy of 1.2 cm was done 1 to 1.5 cm below the uterine cervix. Incision was done with a needleknife (Microknife Boston Scientific, Natick, MA, USA) under direct vision through a double-channel video gastroscope (Karl Storz Endoscopy, Tuttlingen, Germany) (Fig. 1) with monopolar energy. Digital dissection posteriorly aiming the sciatic spine is performed gently. The endoscope is then inserted through the colpotomy. Under direct vision the iliac vessels and surrounding pelvic lymph nodes are easy to locate at about 10 cm from the colpotomy. The psoas muscle is followed along its way, the ureter is identified and followed to reach the kidney at about 20 to 25 cm from the colpotomy. At this point the aorta can be seen and the associated lymph nodes identified. While advancing to the retroperitoneum, CO2 was administered via one of the endoscope's channels to keep good exposure. Care is taken to dissect gently to avoid peritoneal perforation which makes the continuation of the procedure difficult. The pelvic lymph nodes (Fig. 2) are identified near the external iliac vessels and dissected with endoscopic grasper (Karl Storz Endoscopy, Tuttlingen, Germany) and monopolar tip (Fig. 3) (Karl Storz Endoscopy, Tuttlingen, Germany) or with symmetrical polypectomy snare (mtp, Neuhausen, Germany) and extracted with retrograde movement of the scope. Three lymph
Fig. 2. Pelvic lymph node. This is an endoscopic view of the pelvic lymph node next to the external iliac artery.
nodes were removed from each side and an endoclip (EZ-clip, Olympus, Tokyo, Japan) was left to mark the operative field. Two landmarks are useful to follow to access the lomboartic lymph nodes: the ureters or the promontory. Once at the level of the kidney, which is located at 25 to 30 cm from the introitus, we identify three lymph nodes in the laterocaval, interaorticocaval and lateroaortic regions that we excise with the same technique as for the pelvic lymph nodes. Endoclips are also used for marking. Careful hemostasis with monopolar energy is done at the end of the procedure. The lymph nodes were removed without an endoscopic bag through a retrograde movement of the endoscope under direct vision. The insufflated gas was not evacuated because of the dorsal lithotomy position and the low vaginal incision. No other laparoscopic instruments were used during the procedures. The colpotomy is closed with two interrupted absorbable sutures (Vicryl 2.0). Postoperative care All pigs received intravenous flunixine (meglumine) 2 ml/50 kg for analgesia before anesthetic reversal. They were extubated, recovered and kept in individual cages. Oral cephalexin 300 mg/24 h was administered for 5 days. A regular diet was administered on the first operative day. All the animal were monitored daily for signs of distress or change in feeding habits. Second look evaluation Postoperative follow up included second look laparoscopy 3 weeks after the initial procedure to find evidence of intra peritoneal fluid collection, abscess or adhesions. A laparotomy is then performed to evaluate retroperitoneal fibrosis, fluid collection or abscess.
Fig. 1. Transvaginal extraperitoneal lymphadenectomy. This figure shows the position of surgeons during the intervention.
Fig. 3. Lymph node excision. Lymph node excision is performed with endoscopic grasper and monopolar tip.
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Results Retroperitoneal pelvic and lomboartic lymphadenectomies were performed successfully in all six pigs with no major intra operative complication except one accidental peritoneal perforation in the first pig. In all pigs the operative technique was reproducible. The mean operative time was 46 ± 5 min, and decreased with experience. The first procedure took 62 min to perform, and the time needed to fulfil the 6 lymph nodes removal went decreasing until reaching 37 min in the sixth pig. Intra operative complications included: one diffuse anterior abdominal wall emphysema, one abdominal wall bleeding secondary to electrical muscle stimulation and two pneumoperitoneums, one associated to peritoneal perforation and the other not. Both were evacuated by Veress needle insertion. No post operative complications were noted. All animals thrived until three weeks after the initial intervention. On laparoscopic second look there were no abscess, no infection and no adhesions even in the first pig that had the accidental perforation of the peritoneum. On laparotomy, all animals showed no retroperitoneal abscess, but there was little fibrosis in the lymphadenectomy sites marked by the endoclips but not along the dissection without lymphadenectomy. All colpotomies were inspected and showed good healing. No local infection or suture disunion was noted for all six pigs. Discussion Retroperitoneal lymphadenectomy can be performed by laparotomy through xypho-pubic incisions or by laparoscopy through transperitoneal or extratroperitoneal approach [3]. Laparoscopic retroperitoneal lymph node dissection has been shown to be a safe and efficacious procedure with better quality of life compared to open retroperitoneal lymphadenectomy [4]. Extraperitoneal approach is also feasible and safe [5]. Potential benefits of extraperitoneal lymphadenectomy when done by NOTES technique would be: a lesser invasive surgery, no opening in peritoneum, less post operative complications and a good tool for sentinel lymph node (SLN) technique where applicable. In cervical cancer , SLN might be accurate to evaluate lymph node status [6]. The SLN will be found in the external iliac and obturator regions [7]. Hot nodes can be detected by blue dye or Technetium. The association of both techniques increases the detection rate. For endometrial cancer SLN is under development [8] and seems to be reliable [9]. It is difficult to specify a single node as the sentinel in ovarian cancer [10]. In fallopian tube cancer, the extraperitoneal approach was described [11], but no data exist on SLN, but we assume that it will be the same as for ovarian cancer. This could lead us to think that NOTES extraperitoneal lymph nodes exploration is helpful to remove SLN or suspected positive node on imaging. Many issues are to be defined before any clinical application of NOTES lymph node excision: safety of the incision (transvaginally or other), monitoring of gas insufflation in the retroperitoneum, finding human landmarks in retroperitoneum and SLN location and reliability for gynecological malignancies. Though it was a totally NOTES technique in four pigs with no need to use laparoscopic instruments, we evacuated pneumoperitoneum in two pigs by using Veress needle which does not change the definition of NOTES surgery since the umbilicus is regarded as a natural fetal orifice. In these pigs there were no identifiable peritoneal perforation, but we think that due to the thin pigs peritoneum carbon dioxide (CO2) diffusing easily from the retroperitoneum to the peritoneal cavity. We speculate as in human that the peritoneum is thicker and this will protect against intra peritoneal CO2 diffusion. This is important since, at present, we have no other means of exposure than the insufflation of gas in the extraperitoneal approach. When the peritoneal perforation occurred in one pig, the quality of the exposure was worsened and then the
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procedure was more difficult to achieve. The success rate was 100% using the double-channel flexible gastroscope with an excellent operative view. At no stage of the procedures was there a need to use any other surgical device. The excision of lymph nodes was done without disrupting the capsule and with minimal manipulation of the node. No major bleeding or intraoperative incident occurred. We had normal lymph nodes which were easy to dissect but the dissection of metastatic or infiltrated lymph nodes was not evaluated. The size of the surgical specimen is not an issue for NOTES technique. Though the incision for the endoscope's introduction is about 12 mm which is the outer diameter of the double working channels endoscope sheath, one can extend the colpotomy or gastrotomy at the end of the procedure not to lose gas during the intervention, when it comes to larger specimen. Standard endoscopic dissecting, grasping and coagulating tools were attached coaxially and there is no possibility for triangulation with the optical tip (Fig. 4). As flexible endosurgical tools will be developed the NOTES procedures will be easier to perform and less time consuming. To summarize, the main limitations of NOTES technology nowadays are the absence of triangulation, the lack of adequate instrumentation for exposure and hemostasis control and the need for a specialized training. When performed in the retroperitoneum we add the development of the pneumoperitoneum. NOTES as a scarless surgery, is a lesser invasive surgery than laparoscopy which requires at least two abdominal skin incisions. When done retroperitoneally NOTES surgery can be done with no obvious peritoneal opening when Veress needle is not used to drain an accidental pneumoperitoneum as it is the case for extraperitoneal laparoscopy. When done intraperitoneally, NOTES seems to be also less traumatic as it needs only one peritoneal opening to be performed which is not the case for laparoscopy that necessitate at least two peritoneal openings due to trocar insertion. Post operative complications are thought to be lesser than laparoscopy, at least for post operative pain linked to aponeurotic and skin incision, more clinical data are mandatory to demonstrate this fact. When it comes to sentinel node technique, we suggest that the use of NOTES instead of laparoscopy would add to the less invasiveness of sentinel node technique the lesser invasiveness of NOTES compared to laparoscopy as discussed before. If all the above mentioned statements are to be demonstrated, the fact that NOTES surgery is more esthetical than laparoscopy is intuitive since it is a scarless surgery. Follow-up laparoscopy and laparotomy showed no adhesions, no abscess formation, and no injuries to adjacent organs or retroperitoneal fibrosis. The effectiveness and safety of vaginal closure were also demonstrated.
Fig. 4. Grasper and monopolar tip through the endoscope. This figure demonstrates the lack of triangulation between the instruments which are coaxial.
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This study demonstrated the technical feasibility and safety of extraperitoneal lymphadenectomy by NOTES technique and provided the first report on survival porcine model. The 100% success was obtained using a totally NOTES technique. Cadaver experiments would test its feasibility in humans. SLN could be an application of NOTES lymphadenectomy in women. The role of lymphadenectomy in urologic and gynecologic malignancies as well as SLN reliability should be assessed to permit the NOTES technique to be performed in this field. NOTES endoscopic instruments are urgently needed for further advances in the technique. Further studies are mandatory to evaluate this approach. Conflict of interest statement The authors have no conflicts of interest to declare.
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