- Email: [email protected]
Laparoscopic Sentinel Lymph Node Dissection – A Novel Technique for the Staging of Prostate Cancer
european urology 49 (2006) 280–285
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Prostate Cancer
Laparoscopic Sentinel Lymph Node Dissection – A Novel Technique for the Staging of Prostate Cancer Stefan Corvin a,*, David Schilling a, Kai Eichhorn b, Ilse Hundt b, Joerg Hennenlotter a, Aristotelis G. Anastasiadis a, Markus Kuczyk a, Roland Bares b, Arnulf Stenzl a a b
Department of Urology, Eberhard-Karls-University, Tuebingen, Germany Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen, Germany
Article info
Abstract
Article history: Accepted August 1, 2005 Published online ahead of print on December 9, 2005
Objectives: Pelvic lymph node metastases indicate a poor prognosis for prostate cancer patients. The aim of this study was to evaluate the suitability of laparoscopic radioisotope guided sentinel lymph node (SLN) dissection in staging of prostate carcinoma. Methods: 28 patients with prostate cancer and intermediate or high risk for lymph node metastases considered for external beam radiotherapy underwent laparoscopic pelvic lymphadenectomy at our institution. For visualization of individual SLN distribution, an image fusion system consisting of a gamma-camera with integrated X-ray tube was used. During laparoscopic lymphadenectomy, SLN were identified using a laparoscopic gamma probe. Results: Preoperative imaging and laparoscopic gamma probe allowed an excellent delineation of SLN. 57% (preoperative imaging) as well as 48% (intraoperative measurements) of SLN were found outside the obturator fossa. All SLN were removed successfully without intra- or postoperative complications. Despite extended lymphadenectomy, no significant lymphocele appeared. 10 lymph node metastases were found in 7 out of the 31 patients (23%) with 3 of the 10 metastases lying outside the obturator fossa representing the standard lymphadenectomy area. Conclusions: The present data demonstrate that laparoscopic SLN dissection is an excellent minimally invasive and technically feasible tool for staging of intermediate and high risk prostate cancer. # 2005 Elsevier B.V. All rights reserved.
Keywords: Laparoscopy Sentinel lymph node Prostate cancer
* Corresponding author. Department of Urology, Eberhard-Karls-University, Hoppe-SeylerStrasse 3, D-72076 Tuebingen. Tel. +49 7071 2986000; Fax: +49 7071 295092. E-mail address: [email protected] (S. Corvin).
0302-2838/$ – see front matter # 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2005.08.021
281
european urology 49 (2006) 280–285
1.
Introduction
Prevalence of lymph node metastasis in prostate cancer is associated with poor prognosis. Therefore, an exact staging diagnosis of lymph node status is essential before chosing the optimal therapy for the individual patient. Despite improvement in imaging techniques, pelvic lymph node dissection is still the most precise and reliable evaluation method for lymph node staging. The anatomical boundaries of pelvic lymph node dissection for the staging of prostate cancer are still controversially discussed. Although the obturator region is often considered the primary landing site for metastases, recent data demonstrate a more variable lymphatic drainage of the prostate. Therefore, some authors suggest a more extended dissection field to identify metastases that would be missed by a limited dissection [1,2]. Recent data demonstrate incidences of 35% [3] and 19% [4] of metastases in areas outside the standard field, including the external iliac and obturator regions. However, an extended dissection has been shown to be associated with an increased risk of complications like lymphocele, deep venous thrombosis, ureteral injury or lower extremity edema [5]. Therefore, the sentinel lymph node (SLN) concept has been applied to lymph node
staging in prostate cancer [6]. This concept implies that lymph node metastases are first identified in the SLN and that negative SLN exclude metastatic disease. The suitability of the SLN concept for prostate cancer staging has been shown by various authors [7,8]. It was the aim of this study to evaluate whether SLN dissection can also be performed by means of the laparoscopic approach. 2.
Patients and methods
A total of 28 patients with prostate cancer and intermediate or high risk for lymph node metastases considered for external beam radiotherapy underwent laparoscopic pelvic lymphadenectomy at our institution (Table 1). All patients were investigated with abdominal/pelvic CT and bone scans preoperatively. Mean PSA was 42 28 ng/ml (10 to 289 ng/ ml) with a mean Gleason Score of 6.3 1.1 (3 to 9). Mean patient age was 65.6 5.1 years There was no evidence of distant metastases as shown by bone scan and computerized tomography. 99mTechnetium labeled nanocolloid was used as radioactive tracer for SLN identification. 250 MBq of the tracer were injected into both prostatic lobes under transrectal ultrasonographic guidance 17 to 24 hours before surgery. Own experiences demonstrate that this dosage provides optimum results concerning preoperative imaging and intraoperative measurements. A total volume of 0.6 ml was injected at 6 different locations of the transitional as well as the peripheral
Table 1 – Patient characteristics with individual distribution of SLN and metastases (obt = obturator fossa, ci = common iliac artery, ii = internal iliac artery, ei = external iliac artery, ps = presacral) Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
Gleason score 7 5 5 6 6 9 7 5 7 6 7 8 9 3 7 5 7 4 7 6 6 5 6 7 7 5 8 6
Lymph nodes removed 29 34 11 19 15 14 12 18 37 6 21 29 26 16 20 13 16 17 10 7 23 25 19 24 20 19 20 19
PSA (ng/ml) 25 21 36 41 49 38 27 41 10 33 21 10 73 36 10 139 50 10 10 30 43 20 25 289 17 27 18 33
SLN (imaging)
SLN (intraoperative)
obt,ci,ii, obt,ii obt,ps obt,ei,ii obt,ci,ii,ps obt,ei obt ei,ci,ii obt,ci obt,ii obt ii,ps obt,ei
obt,ci,ii obt,ii obt,ps obt,ei,ii obt,ci,ii,ps obt,ei obt,ei ci,ii obt,ci obt,ii obt ci obt
obt obt,ci,ii obt ps obt,ei obt,ei obt obt obt obt obt,ci obt,ci,ii obt
obt,ei,ci,ii obt,ci
Metastases
ei
obt obt
obt,ii
obt,ei obt,ei obt
obt
obt obt
obt,ei
obt,ci obt,ci,ii obt
obt
282
european urology 49 (2006) 280–285
Fig. 1 – Three-dimensional delineation of sentinel lymph nodes by means of the image fusion system.
zone using a 21 gauge needle. 60 min prior to injection, patients received a dose of broad-spectrum antibiotic, which was continued until postoperative day 2. For visualization of individual SLN distribution, an image fusion system consisting of a double-headed gamma-camera (SPECT) with integrated Xray tube was used (Millenium VG & Hawkeye1, GE Medical Systems Europe, Buc Cedex, France). This system allows an exact delineation of the lymph nodes within an abdominal/ pelvic CT (Fig. 1). Imaging was performed 1 to 3 hours after injection. After insertion of a bladder catheter, the patient is placed in a supine position. A 458 Trendelenburg position is mandatory to mobilize the bowel cranially providing a better exposure of pelvic structures. We prefer a transperitoneal laparoscopic access for pelvic lymph node dissection. A pneumoperitoneum is established using a Veress needle or by performing a minilaparotomy and placing a Hasson trocar under direct visual control. An 11 mm trocar is placed at the umbilicus (camera), a 5 mm trocar in the midclavicular line on the right side of the abdomen and a 12 mm trocar (gamma probe) about
2 cm above the symphysis. During laparoscopic lymphadenectomy, SLN are identified using a laparoscopic gamma probe. This probe indicates radioactivity levels with an acoustic signal. Simultaneously, the levels are indicated quantitavely on a display. Repetitive measurements were conducted to confirm reproducibility of SLN detection. Lymph nodes of the common iliac, external iliac, obturator, internal iliac and presacral regions were measured. SLN were removed depending on preoperative imaging and intraoperative measurements followed by a standardized bilateral resection of the obturator lymph nodes.
3.
Results
No allergic or septic complications occured after radioisotope injection. Transrectal ultrasound allowed an exact bilateral centrally placed intraprostatic injection of the tracer substance. By means of preoperative lymphoscintigraphy combined with a
european urology 49 (2006) 280–285
CT scan, a mean of 2.1 1.1 lymph node stations per patient were identified as SLN. The image fusion system allowed an exact three-dimensional delineation of SLN. 43% of the lymph nodes were found in the obturator fossa, 12% in the presacral area, 12% in the external, 13% in the common and 20% in the internal iliac region (Table 1). Laparoscopic SLN dissection could be performed successfully without significant complications or conversion to open surgery. SLN could be identified intraoperatively using the laparoscopic gamma probe. Despite extended dissection, no lymphocele appeared. A mean of 19.3 5.5 (6 to 37) lymph nodes per patient were removed during pelvic lymphadenectomy. Intraoperatively, 52% of SLN were found outside the obturator fossa in the region of the internal (19%), external (14%) and common iliac artery (17%), as well as presacrally (2%). 10 Lymph node metastases were found in 7 out of the 31 patients (23%). 3 metastases were outside the obturator fossa, 2 being localized at the external and 1 at the internal iliac artery. In one patient a metastasis was found in the obturator fossa despite negative pre- and intraoperative SLN-imaging.
4.
Discussion
Despite negative CT scan, 25% of our patients presented with lymph node metastases. These findings confirm that modern imaging techniques have only limited sensitivity for lymph node involvement. Preliminary data indicate that innovative methods like 11C-choline PET [9] or highresolution magnetic resonance imaging with magnetic nanoparticles [10] might become sensitive tools for an accurate preoperative lymph node staging, however further clinical research is needed. With the introduction of prostate specific antigen (PSA) for prostate cancer screening, the incidence of lymph node metastases has decreased [11]. Therefore the need for pelvic lymph node dissection has been questioned. Algorithms based on preoperative parameters like PSA, T stage and tumor grade have been defined to predict lymph node status and to identify those patients in whom lymphadenectomy can be omitted [12,13]. These algorithms, however, are based on histological findings after limited but not extensive lymph node dissection, therefore reducing their reliability. Therefore, pelvic lymph node dissection remain the only reliable methode detecting lymph node metastases in prostate cancer patients, although the definitive dissection range has not yet been determined. Many authors prefer a minimal dissection area including only the lympha-
283
tic tissue between the external iliac vein and the obturator nerve. Although the obturator node package is often considered the primary landing site for metastatic cancer, lymphatic drainage of the prostate is variable [14]. Therefore extended fields including the lymphatic tissue along the external iliac vein, in the obturator fossa, lateral and medial of the internal iliac artery, along the common iliac artery and even in the presacral field have been described [1]. Bader could demonstrate that lymph node metastases along the internal iliac vessels were found in more than half of his patients with 19% located in this region exclusively [4]. Also, there is no consensus about the consequences of microscopic lymph node involvement in patients with clinically organ confined disease. There is some evidence that radical prostatectomy can be curative in patients with micrometastatic lymph node involvement [15]. This supports the importance of a meticulous lymph node dissection. In the present study, a mean of 19.3 5.5 lymph nodes per patient were removed. This observation is mentioned, because Weinga¨rtner could show that approximately 20 lymph nodes are required for a reliable lymph node staging [16]. In recent years, the SLN technique has been established for various malignant tumors like breast cancer, malignant melanoma and penile carcinoma [17]. This procedure has been shown to facilitate detection of occult metastases in clinically node negative regions and to decrease morbidity by preventing unnecessary lymph node dissections. Encouraging results also exist about the suitability of the SLN concept for prostate cancer staging [6,7,18,19]. In a study including 350 patients, Wawroschek et al. could demonstrate a great variability of lymphatic drainage of the prostate. 335 individuals showed at least 1 SLN in lymphoscintigraphy and 24.7% had lymph node metastases. In 2 patients metastases were found in non-SLN [8]. A limited pelvic lymph node dissection of the obturator fossa nodes would have detected only 46.7% of node-positive cases. Own results demonstrate a SLN distribution comparable to literature data [7] with about 40% of SLN lying in the obturator fossa and the others in the external, common and internal iliac region as well as in the presacral area. However, it must been taken into consideration that there is no generally accepted classification of the anatomical regions of the pelvis making comparison of different studies with different surgeons and radiologists difficult. In our study, differences in SLN distribution were found between preoperative imaging and intraoperative gamma probe measurements. It may be speculated that these differences
284
european urology 49 (2006) 280–285
are caused by dynamics in lymphatic transport or a fading of the tracer. 25% of the patients presented with lymph node metastases. This is less than expected using established nomograms predicting the risk of pelvic lymph node metastases [20], however may be caused by the limited number of patients in our small series. 30% of metastatic lymph nodes were found outside the obturator fossa and would have been missed during standard lymphadenectomy. SLN dissection minimizes the extent of surgery compared to extended pelvic lymphadenectomy. Limiting the number of resected lymph nodes helps to reduce the morbidity of surgery. In a randomized study comparing extended and limited lymph node dissection, Clark et al. found an increased risk of complications associated with the extended procedure [5]. With the introduction of innovative instruments like the laparoscopic gamma probe, sentinel lymphadenectomy can be performed laparoscopically. The general benefits of laparoscopy compared to open surgical procedures have been demonstrated in numerous studies. Patients in the laparoscopic group have less postoperative pain, shorter hospital stays and resume sooner to normal activities [21,22]. Furthermore the elevated intraabdominal pressure due to the pneumoperitoneum with consecutive compression of smaller vessels reduces the risk of bleeding. In conclusion, laparoscopy seems to be the optimum approach for sentinel pelvic lymphadenectomy. At present, only limited data are available on the influence of technical details, e.g. optimal injection technique, on reproducibility of sentinel lymph node identification. In breast and penis cancer as well as in melanoma the tracer is injected peritumorally. In prostate cancer however, the origin of metastases within the prostate is not known. In an experimental study with adult foxhounds, Wawroschek et al. could demonstrate that with the combination of central and peripheral injection, even with a reduced injection volume, an optimized SLN delineation can be achieved [23]. Further studies in humans are necessary to establish an effective strategy for laparoscopic SLN dissection.
References [1] Golimbu M, Morales P, Al-Askari S, Brown J. Extended pelvic lymphadenectomy for prostatic cancer. J Urol 1979;121:617–20. [2] Stone NN, Stock RG, Unger P. Laparoscopic pelvic lymph node dissection for prostate cancer: comparison of the extended and modified techniques. J Urol 1997;158:1891–4.
[3] Heidenreich A, Varga Z, von Knobloch R. Extended pelvic lymphadenectomy in patients undergoing radical prostatectomy: high incidence of lymph node metastasis. J Urol 2002;167:1681–6. [4] Bader P, Burkhard FC, Markwalder R, Studer UE. Is a limited lymph node dissection an adequate staging procedure for prostate cancer? J Urol 2002;168:514–8. [5] Clark T, Parekh DJ, Cookson MS, Chang SS, Smith ER, Wells N, et al. Randomized prospective evaluation of extended versus limited lymph node dissection in patients with clinically localized prostate cancer. J Urol 2003;169:145–8. [6] Wawroschek F, Vogt H, Weckermann D, Wagner T, Harzmann R. The sentinel lymph node concept in prostate cancer – first results of gamma probe-guided sentinel lymph node identification. Eur Urol 1999;36:595–600. [7] Takashima H, Egawa M, Imao T, Fukuda M, Yokoyama K, Namiki M. Validity of sentinel lymph node concept for patients with prostate cancer. J Urol 2004;171:2268–71. [8] Wawroschek F, Vogt H, Wengenmair H, Weckermann D, Hamm M, Keil M, et al. Prostate lymphoscintigraphy and radio-guided surgery for sentinel lymph node identification in prostate cancer. Technique and results of the first 350 cases. Urol Int 2003;70:303–10. [9] De Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJ. Preoperative staging of pelvic lymph nodes in prostate cancer by 11C-Choline PET. J Nucl Med 2003;44:331–5. [10] Harisinghani MG, Gervais DA, Maher MM, Cho CH, Hahn PF, Varghese J, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003;348:2491–9. [11] Danella JF, de Kernion JB, Smith RB, Steckel J. The contemporary incidence of lymph node metastases in prostate cancer: implications for laparoscopic lymph node dissection. J Urol 1993;149:1488–91. [12] Partin AW, Kattan MW, Subong EN, Walsh PC, Wojno KJ, Oesterling JE, et al. Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage on localized prostate cancer. A multiinstitutional update. JAMA 1997;277:1445–51. [13] Bluestein DL, Bostwick DG, Bergstrahl EJ, Oesterling JE. Eliminating the need for bilateral pelvic lymphadenectomy in select patients with prostate cancer. J Urol 1994; 151:1315–20. [14] McLaughlin AP, Saltzstein SL, McCullough DL, Gittes RF. Prostatic carcinoma: incidence and location of unsuspected lymphatic metastases. J Urol 1976;115:89–94. [15] Frazier HA, Robertson JE, Paulson DF. Does radical prostatectomy in the presence of positive pelvic lymph nodes enhance survival? World J Urol 1994;12:308–12. [16] Weingartner K, Ramaswamy A, Bittinger A, Gerharz EW, Voge D, Riedmiller H. Anatomical basis for pelvic lymphadenectomy in prostate cancer: results of an autopsy study and implications for the clinic. J Urol 1996;156:1969–71. [17] Horenblas S, Jansen L, Meinhardt W, Hoefnagel CA, de Jong D, Nieweg OE. Detection of occult metastasis in squamous cell carcinoma of the penis using a dynamic sentinel node procedure. J Urol 2000;163:100–4. [18] Wawroschek F, Wagner T, Hamm M, Weckermann D, Vogt H, Ma¨rkl B, et al. The influence of serial sections,
european urology 49 (2006) 280–285
immunohistochemistry, and extension of pelvic lymph node dissection on the lymph node status in clinically localized prostate cancer. Eur Urol 2003;43:132–7. [19] Brenot-Rossi I, Bastide C, Garcia S, Dumas S, Esterni B, Pasquier J, et al. Limited pelvic lymphadenectomy using the sentinel lymph node procedure in patients with localised prostate carcinoma: a pilot study. Eur J Nucl Med Mol Imaging 2005;32:635–40. [20] Gagiannos I, Karakiewicz P, Eastham JA, Ohori M, Rabbani F, Gerigk C, et al. A preoperative nomogram identifying decreased risk of positive pelvic lymph nodes in patients with prostate cancer. J Urol 2003;170:1798–803.
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[21] McDougall EM, Clayman RV, Elashry OM. Laparoscopic radical nephrectomy for renal tumour: the Washington University experience. J Urol 1996;155:1180–5. [22] Winfield HN, Donovan JF, Lund GO, Kreder KJ, Stanley KE, Brown BP, et al. Laparoscopic partial nephrectomy: initial experience and comparison to the open surgical approach. J Urol 1995;153:1409–14. [23] Wawroschek F, Wengenmair H, Senekowitsch-Schmidtke R, Hamm M, Henke J, Schonberger T, et al. Prostate lymphoscintigraohy for sentinel lymph node identification in canines: reproducibility, update, and biokinetics depending on different injection strategies. Urol Res 2003;31:152–8.
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Prostate Cancer
Laparoscopic Sentinel Lymph Node Dissection – A Novel Technique for the Staging of Prostate Cancer Stefan Corvin a,*, David Schilling a, Kai Eichhorn b, Ilse Hundt b, Joerg Hennenlotter a, Aristotelis G. Anastasiadis a, Markus Kuczyk a, Roland Bares b, Arnulf Stenzl a a b
Department of Urology, Eberhard-Karls-University, Tuebingen, Germany Department of Nuclear Medicine, Eberhard-Karls-University, Tuebingen, Germany
Article info
Abstract
Article history: Accepted August 1, 2005 Published online ahead of print on December 9, 2005
Objectives: Pelvic lymph node metastases indicate a poor prognosis for prostate cancer patients. The aim of this study was to evaluate the suitability of laparoscopic radioisotope guided sentinel lymph node (SLN) dissection in staging of prostate carcinoma. Methods: 28 patients with prostate cancer and intermediate or high risk for lymph node metastases considered for external beam radiotherapy underwent laparoscopic pelvic lymphadenectomy at our institution. For visualization of individual SLN distribution, an image fusion system consisting of a gamma-camera with integrated X-ray tube was used. During laparoscopic lymphadenectomy, SLN were identified using a laparoscopic gamma probe. Results: Preoperative imaging and laparoscopic gamma probe allowed an excellent delineation of SLN. 57% (preoperative imaging) as well as 48% (intraoperative measurements) of SLN were found outside the obturator fossa. All SLN were removed successfully without intra- or postoperative complications. Despite extended lymphadenectomy, no significant lymphocele appeared. 10 lymph node metastases were found in 7 out of the 31 patients (23%) with 3 of the 10 metastases lying outside the obturator fossa representing the standard lymphadenectomy area. Conclusions: The present data demonstrate that laparoscopic SLN dissection is an excellent minimally invasive and technically feasible tool for staging of intermediate and high risk prostate cancer. # 2005 Elsevier B.V. All rights reserved.
Keywords: Laparoscopy Sentinel lymph node Prostate cancer
* Corresponding author. Department of Urology, Eberhard-Karls-University, Hoppe-SeylerStrasse 3, D-72076 Tuebingen. Tel. +49 7071 2986000; Fax: +49 7071 295092. E-mail address: [email protected] (S. Corvin).
0302-2838/$ – see front matter # 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2005.08.021
281
european urology 49 (2006) 280–285
1.
Introduction
Prevalence of lymph node metastasis in prostate cancer is associated with poor prognosis. Therefore, an exact staging diagnosis of lymph node status is essential before chosing the optimal therapy for the individual patient. Despite improvement in imaging techniques, pelvic lymph node dissection is still the most precise and reliable evaluation method for lymph node staging. The anatomical boundaries of pelvic lymph node dissection for the staging of prostate cancer are still controversially discussed. Although the obturator region is often considered the primary landing site for metastases, recent data demonstrate a more variable lymphatic drainage of the prostate. Therefore, some authors suggest a more extended dissection field to identify metastases that would be missed by a limited dissection [1,2]. Recent data demonstrate incidences of 35% [3] and 19% [4] of metastases in areas outside the standard field, including the external iliac and obturator regions. However, an extended dissection has been shown to be associated with an increased risk of complications like lymphocele, deep venous thrombosis, ureteral injury or lower extremity edema [5]. Therefore, the sentinel lymph node (SLN) concept has been applied to lymph node
staging in prostate cancer [6]. This concept implies that lymph node metastases are first identified in the SLN and that negative SLN exclude metastatic disease. The suitability of the SLN concept for prostate cancer staging has been shown by various authors [7,8]. It was the aim of this study to evaluate whether SLN dissection can also be performed by means of the laparoscopic approach. 2.
Patients and methods
A total of 28 patients with prostate cancer and intermediate or high risk for lymph node metastases considered for external beam radiotherapy underwent laparoscopic pelvic lymphadenectomy at our institution (Table 1). All patients were investigated with abdominal/pelvic CT and bone scans preoperatively. Mean PSA was 42 28 ng/ml (10 to 289 ng/ ml) with a mean Gleason Score of 6.3 1.1 (3 to 9). Mean patient age was 65.6 5.1 years There was no evidence of distant metastases as shown by bone scan and computerized tomography. 99mTechnetium labeled nanocolloid was used as radioactive tracer for SLN identification. 250 MBq of the tracer were injected into both prostatic lobes under transrectal ultrasonographic guidance 17 to 24 hours before surgery. Own experiences demonstrate that this dosage provides optimum results concerning preoperative imaging and intraoperative measurements. A total volume of 0.6 ml was injected at 6 different locations of the transitional as well as the peripheral
Table 1 – Patient characteristics with individual distribution of SLN and metastases (obt = obturator fossa, ci = common iliac artery, ii = internal iliac artery, ei = external iliac artery, ps = presacral) Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
Gleason score 7 5 5 6 6 9 7 5 7 6 7 8 9 3 7 5 7 4 7 6 6 5 6 7 7 5 8 6
Lymph nodes removed 29 34 11 19 15 14 12 18 37 6 21 29 26 16 20 13 16 17 10 7 23 25 19 24 20 19 20 19
PSA (ng/ml) 25 21 36 41 49 38 27 41 10 33 21 10 73 36 10 139 50 10 10 30 43 20 25 289 17 27 18 33
SLN (imaging)
SLN (intraoperative)
obt,ci,ii, obt,ii obt,ps obt,ei,ii obt,ci,ii,ps obt,ei obt ei,ci,ii obt,ci obt,ii obt ii,ps obt,ei
obt,ci,ii obt,ii obt,ps obt,ei,ii obt,ci,ii,ps obt,ei obt,ei ci,ii obt,ci obt,ii obt ci obt
obt obt,ci,ii obt ps obt,ei obt,ei obt obt obt obt obt,ci obt,ci,ii obt
obt,ei,ci,ii obt,ci
Metastases
ei
obt obt
obt,ii
obt,ei obt,ei obt
obt
obt obt
obt,ei
obt,ci obt,ci,ii obt
obt
282
european urology 49 (2006) 280–285
Fig. 1 – Three-dimensional delineation of sentinel lymph nodes by means of the image fusion system.
zone using a 21 gauge needle. 60 min prior to injection, patients received a dose of broad-spectrum antibiotic, which was continued until postoperative day 2. For visualization of individual SLN distribution, an image fusion system consisting of a double-headed gamma-camera (SPECT) with integrated Xray tube was used (Millenium VG & Hawkeye1, GE Medical Systems Europe, Buc Cedex, France). This system allows an exact delineation of the lymph nodes within an abdominal/ pelvic CT (Fig. 1). Imaging was performed 1 to 3 hours after injection. After insertion of a bladder catheter, the patient is placed in a supine position. A 458 Trendelenburg position is mandatory to mobilize the bowel cranially providing a better exposure of pelvic structures. We prefer a transperitoneal laparoscopic access for pelvic lymph node dissection. A pneumoperitoneum is established using a Veress needle or by performing a minilaparotomy and placing a Hasson trocar under direct visual control. An 11 mm trocar is placed at the umbilicus (camera), a 5 mm trocar in the midclavicular line on the right side of the abdomen and a 12 mm trocar (gamma probe) about
2 cm above the symphysis. During laparoscopic lymphadenectomy, SLN are identified using a laparoscopic gamma probe. This probe indicates radioactivity levels with an acoustic signal. Simultaneously, the levels are indicated quantitavely on a display. Repetitive measurements were conducted to confirm reproducibility of SLN detection. Lymph nodes of the common iliac, external iliac, obturator, internal iliac and presacral regions were measured. SLN were removed depending on preoperative imaging and intraoperative measurements followed by a standardized bilateral resection of the obturator lymph nodes.
3.
Results
No allergic or septic complications occured after radioisotope injection. Transrectal ultrasound allowed an exact bilateral centrally placed intraprostatic injection of the tracer substance. By means of preoperative lymphoscintigraphy combined with a
european urology 49 (2006) 280–285
CT scan, a mean of 2.1 1.1 lymph node stations per patient were identified as SLN. The image fusion system allowed an exact three-dimensional delineation of SLN. 43% of the lymph nodes were found in the obturator fossa, 12% in the presacral area, 12% in the external, 13% in the common and 20% in the internal iliac region (Table 1). Laparoscopic SLN dissection could be performed successfully without significant complications or conversion to open surgery. SLN could be identified intraoperatively using the laparoscopic gamma probe. Despite extended dissection, no lymphocele appeared. A mean of 19.3 5.5 (6 to 37) lymph nodes per patient were removed during pelvic lymphadenectomy. Intraoperatively, 52% of SLN were found outside the obturator fossa in the region of the internal (19%), external (14%) and common iliac artery (17%), as well as presacrally (2%). 10 Lymph node metastases were found in 7 out of the 31 patients (23%). 3 metastases were outside the obturator fossa, 2 being localized at the external and 1 at the internal iliac artery. In one patient a metastasis was found in the obturator fossa despite negative pre- and intraoperative SLN-imaging.
4.
Discussion
Despite negative CT scan, 25% of our patients presented with lymph node metastases. These findings confirm that modern imaging techniques have only limited sensitivity for lymph node involvement. Preliminary data indicate that innovative methods like 11C-choline PET [9] or highresolution magnetic resonance imaging with magnetic nanoparticles [10] might become sensitive tools for an accurate preoperative lymph node staging, however further clinical research is needed. With the introduction of prostate specific antigen (PSA) for prostate cancer screening, the incidence of lymph node metastases has decreased [11]. Therefore the need for pelvic lymph node dissection has been questioned. Algorithms based on preoperative parameters like PSA, T stage and tumor grade have been defined to predict lymph node status and to identify those patients in whom lymphadenectomy can be omitted [12,13]. These algorithms, however, are based on histological findings after limited but not extensive lymph node dissection, therefore reducing their reliability. Therefore, pelvic lymph node dissection remain the only reliable methode detecting lymph node metastases in prostate cancer patients, although the definitive dissection range has not yet been determined. Many authors prefer a minimal dissection area including only the lympha-
283
tic tissue between the external iliac vein and the obturator nerve. Although the obturator node package is often considered the primary landing site for metastatic cancer, lymphatic drainage of the prostate is variable [14]. Therefore extended fields including the lymphatic tissue along the external iliac vein, in the obturator fossa, lateral and medial of the internal iliac artery, along the common iliac artery and even in the presacral field have been described [1]. Bader could demonstrate that lymph node metastases along the internal iliac vessels were found in more than half of his patients with 19% located in this region exclusively [4]. Also, there is no consensus about the consequences of microscopic lymph node involvement in patients with clinically organ confined disease. There is some evidence that radical prostatectomy can be curative in patients with micrometastatic lymph node involvement [15]. This supports the importance of a meticulous lymph node dissection. In the present study, a mean of 19.3 5.5 lymph nodes per patient were removed. This observation is mentioned, because Weinga¨rtner could show that approximately 20 lymph nodes are required for a reliable lymph node staging [16]. In recent years, the SLN technique has been established for various malignant tumors like breast cancer, malignant melanoma and penile carcinoma [17]. This procedure has been shown to facilitate detection of occult metastases in clinically node negative regions and to decrease morbidity by preventing unnecessary lymph node dissections. Encouraging results also exist about the suitability of the SLN concept for prostate cancer staging [6,7,18,19]. In a study including 350 patients, Wawroschek et al. could demonstrate a great variability of lymphatic drainage of the prostate. 335 individuals showed at least 1 SLN in lymphoscintigraphy and 24.7% had lymph node metastases. In 2 patients metastases were found in non-SLN [8]. A limited pelvic lymph node dissection of the obturator fossa nodes would have detected only 46.7% of node-positive cases. Own results demonstrate a SLN distribution comparable to literature data [7] with about 40% of SLN lying in the obturator fossa and the others in the external, common and internal iliac region as well as in the presacral area. However, it must been taken into consideration that there is no generally accepted classification of the anatomical regions of the pelvis making comparison of different studies with different surgeons and radiologists difficult. In our study, differences in SLN distribution were found between preoperative imaging and intraoperative gamma probe measurements. It may be speculated that these differences
284
european urology 49 (2006) 280–285
are caused by dynamics in lymphatic transport or a fading of the tracer. 25% of the patients presented with lymph node metastases. This is less than expected using established nomograms predicting the risk of pelvic lymph node metastases [20], however may be caused by the limited number of patients in our small series. 30% of metastatic lymph nodes were found outside the obturator fossa and would have been missed during standard lymphadenectomy. SLN dissection minimizes the extent of surgery compared to extended pelvic lymphadenectomy. Limiting the number of resected lymph nodes helps to reduce the morbidity of surgery. In a randomized study comparing extended and limited lymph node dissection, Clark et al. found an increased risk of complications associated with the extended procedure [5]. With the introduction of innovative instruments like the laparoscopic gamma probe, sentinel lymphadenectomy can be performed laparoscopically. The general benefits of laparoscopy compared to open surgical procedures have been demonstrated in numerous studies. Patients in the laparoscopic group have less postoperative pain, shorter hospital stays and resume sooner to normal activities [21,22]. Furthermore the elevated intraabdominal pressure due to the pneumoperitoneum with consecutive compression of smaller vessels reduces the risk of bleeding. In conclusion, laparoscopy seems to be the optimum approach for sentinel pelvic lymphadenectomy. At present, only limited data are available on the influence of technical details, e.g. optimal injection technique, on reproducibility of sentinel lymph node identification. In breast and penis cancer as well as in melanoma the tracer is injected peritumorally. In prostate cancer however, the origin of metastases within the prostate is not known. In an experimental study with adult foxhounds, Wawroschek et al. could demonstrate that with the combination of central and peripheral injection, even with a reduced injection volume, an optimized SLN delineation can be achieved [23]. Further studies in humans are necessary to establish an effective strategy for laparoscopic SLN dissection.
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