Moritz Koch, Peter Kienle, Dalibor Antolovic, Markus W. Büchler, Jürgen Weitz
M. Koch (u)
Department of Surgery, University of Heidelberg, 69120 Heidelberg, Germany e-mail: moritz_koch@med.uni-heidelberg.de
Abstract
Lateral pelvic lymphadenectomy is routinely performed in advanced lower rectal cancers by Japanese surgeons, whereas in the western world it has not progressed to a frequently performed technique. Claimed benefit for this extensive surgery is an improved locoregional control; on the other hand, low positive lateral lymph node yields, questionable prognostic significance, and high morbidity (urinary and sexual dysfunction) are main reasons against this procedure. Clinical results published on lateral lymphadenectomy in the literature are conflicting. Due to major improvements in local control and survival of rectal cancer patients mainly based on preoperative radiotherapy and total mesorectal excision (TME), only a few patients may profit from lateral lymph node dissection. This article gives an overview of the current status and the clinical relevance of the lateral lymph node compartment in rectal cancer surgery.
Introduction
The clinical and prognostic significance of the lateral pelvic lymph node com- partment remains a controversial issue in rectal cancer surgery. Lateral pelvic lymphadenectomy is usually performed in urologic and gynecologic operations [1, 2]. This procedure was first described in rectal cancer surgery in the early fifties, but until now it has not progressed to a frequently performed operative technique in western countries. On the other hand, lateral lymph node dissection is used as a standard procedure for lower rectal cancers in Japan.
A postulated benefit of lateral pelvic lymphadenectomy is an improved locore- gional control by excision of both the mesenteric and extramesenteric lymphatic drainage, resulting in an increased overall survival of rectal cancer patients. Op- ponents of the method name low positive lateral lymph node yields, questionable prognostic significance, and high morbidity (urinary and sexual dysfunction) as main reasons for not performing this procedure. Clinical results published on Recent Results in Cancer Research, Vol. 165
Springer-Verlag Berlin Heidelberg 2005c
lateral lymphadenectomy in the literature are conflicting. Furthermore there is significant disagreement on aspects of surgical anatomy and definitions.
This article gives an overview of the current status and of the clinical relevance of the lateral lymph node compartment in rectal cancer surgery.
Anatomy and Definition of the Lateral Lymph Node Compartment
Takahashi et al. distinguish between three planes located around the rectum [3].
The inner space is surrounded by the visceral pelvic fascia on the posterior side and Denonvilliers fascia on the anterior side; the autonomic pelvic nerve plexuses are located below these fascias laterally on both sides. The intermediate space is bordered by the parietal pelvic fascia on the posterior side and the internal iliac arteries and their branches on the anterior and lateral sides. The outer space finally is located outside the internal iliac arteries and their branches. These anatomic structures act as a barrier to lymphatic drainage, whereas the lateral ligaments on both sides of the mesorectum are an exception to this rule. Although the lateral ligament is not a clear anatomic entity, it is clinically an important pathway for lymphatic and blood vessels and for parasympathetic and sympathetic nerve fibers forming visceral branches from the pelvic plexuses.
Two main pathways are important for lymphatic drainage of the middle and lower rectum: the superior lymphatic drainage along the inferior mesenteric artery and the lateral lymphatic drainage along the internal iliac artery [3–5]. Lymphatic flow from the rectum mainly goes upwards within the inner space along the infe- rior mesenteric artery. As total mesorectal excision usually incorporates complete removal of the inner space, all lymphatic spread of rectal cancer within this com- partment is removed. Some lymphatic vessels, mostly from the lower rectum, penetrate into the intermediate and outer space via the lateral ligaments and as- cend along the internal iliac arteries. This region is called the lateral lymph node compartment.
According to the Japanese Classification of Colorectal Carcinoma, Ueno et al.
classified the lateral pelvic lymph node compartment into five regions: the middle rectal root region (along the middle rectal artery), the internal iliac region (along the internal iliac artery), the obturator region (along the obturator nerve and vessels), the common iliac region (along the common iliac artery), and the external iliac region (along the external iliac region) [5]. Canessa et al., on the other hand, subdivided the lateral pelvic lymph nodes into three surgical groups (presacral, obturator, and hypogastric) [6]. In that study using cadaveric dissection of the lateral pelvic lymph node compartment, they found the highest number of lymph nodes in the obturator group [6]. A major problem of the published studies is that several different classifications and definitions of the lateral pelvic lymph node compartment were used, which makes comparisons of the results difficult.
Incidence and Prognostic Significance of Lateral Lymphatic Spread in Rectal Cancer
The incidence of lateral lymph node metastasis in rectal cancer reported in the literature ranges from 4% to 30%, depending mainly on tumor height and tumor stage [3, 5, 7–12]. The highest rate of metastatic lateral lymph nodes is detected in patients with lower rectal cancer (below peritoneal reflection) and with advanced tumor stage [7, 8, 11]. Comparison and interpretation of the data of the published studies is difficult because of variation in patient selection, definitions, and statis- tical analysis. Lateral nodal involvement in rectal cancer is often associated with a positive lymph node status in the routinely dissected lymph nodes (e.g., perirec- tal lymph nodes). This makes the analysis of the prognostic significance of lateral lymphatic spread itself somewhat more difficult.
In a large retrospective series of 448 rectal cancer patients, Moriya et al. found that patients with Dukes’ C tumor at or below the peritoneal reflection showed perirectal spread alone in 69% and perirectal spread plus lateral spread in 23%;
lateral spread alone was found in 4% [13]. Although lateral node metastasis is considered an important prognostic factor among Japanese surgeons, there was no significant difference in disease-free survival of patients with only upward lymph node metastasis compared to those with lateral node metastasis and upward lymph node metastasis reported by Moriya et al. [13]. These observations were confirmed by Takahashi et al. who, in a retrospective series of 764 rectal cancer patients, could demonstrate that lateral lymph node metastasis alone (without perirectal or upward lymph node involvement) occurred in only 16 patients (2%). As all of those patients underwent lateral lymph node dissection, resulting in a five-year survival rate of 75%, the authors concluded that patients with lateral lymph node metastasis could be cured by this procedure.
Several retrospective clinical studies revealed a prognostic significance of lat- eral lymphatic spread in rectal cancer and an improved survival of rectal cancer patients after resection with extended lateral lymph node dissection compared to conventional resection without lateral lymph node dissection [5, 9, 11, 14]. In order to prevent urinary and sexual dysfunction after extended lateral lymph node dis- section, Mori et al. combined autonomic nerve-preserving (ANP) resection with lateral lymph node dissection in patients with lower rectal cancer, stage UICC III [8]. They also observed a significantly improved 5-year survival rate in the ANP resection group compared to the patient group with extended lateral lymph node dissection [8].
Ueno et al. examined lateral (iliac) lymph nodes from 70 consecutive patients with low rectal cancer for occult microscopic metastasis using serial sectioning [5].
They detected occult microscopic foci in 5 patients (7%), whereas the overall inci- dence of lateral spread was 24% (17/70 patients), and the highest incidence of posi- tive lymph nodes was found in the middle rectal root region along the middle rectal artery [5]. With the use of immunohistochemistry Shimoyama et al. examined lat- eral lymph nodes of 57 patients with low rectal cancer classified histopathologically as tumor-free, and detected lateral lymph node micrometastases in 11 (19.3%) pa-
tients [15]. These 11 patients with lateral lymph node micrometastases showed a significantly higher recurrence rate and had a worse overall survival compared to the 46 patients without lateral lymph node metastases [15].
Since there are no data from prospective randomized controlled trials available in the literature, the prognostic and clinical significance of lateral lymph node metastasis remains unclear.
Therapeutic and Clinical Consequences
The above cited studies were mainly performed by surgeons in Japan, where lateral lymph node dissection is widely used for advanced lower rectal cancer with the aim to decrease the local recurrence rate [3]. Hojo et al. compared conventional excision with extended excision (plus lateral lymph node dissection) of middle and lower rectal cancers and showed a significantly lower local recurrence rate for the lateral dissection group in Dukes’ C patients (23.6% vs. 32.8%). However, a major drawback of this study is that the overall local recurrence rate was rather high compared to results of recent studies without lateral lymphadenectomy [14]. The extended resection performed in Japan resulted in a high rate of genitourinary dys- function, as the pelvic autonomic nervous system (hypogastric nerves and pelvic plexus) was often sacrificed during lateral lymph node dissection [16]. As a con- sequence of this, nerve-sparing surgery with wide pelvic lymphadenectomy was introduced from 1984 onwards [7]. Several reports from Japanese surgeons have demonstrated various types of pelvic autonomic nerve preservation procedures (depending on the extent of the local tumor) which resulted in improved urinary and sexual function compared to previous results [7, 10, 16]. Uyama et al. demon- strated that lateral lymph node dissection with autonomic nerve preservation for lower rectal cancer can also be performed laparoscopically [17]. However, it is still unclear which patients benefit from extended lateral lymph node dissection and which patients do not need such extensive surgery [7]. Therefore Ueno et al.
examined prognostic variables in rectal cancer patients with lateral lymph node metastasis and showed that the most important factors for poor prognosis and outcome are: distant metastases, the total number of involved lymph nodes, cir- cumferential resection margin, and age [12]. The search for prognostic parameters defining patient subgroups who truly profit from this aggressive surgical approach remains ongoing.
In contrast, surgeons in western countries advocate total mesorectal excision (TME), proposed by Heald in 1982, as the standard surgical method to achieve good local control and to preserve autonomic nerve function in rectal cancer [18, 19]. Another argument against performing lateral lymph node dissection is that lateral lymph node metastases primarily reflect systemic spread rather than regional disease [20]. Combined treatment modalities, e.g., TME together with preoperative radiotherapy, have led to a very effective therapeutic concept in rec- tal cancer in recent years, resulting in a low local recurrence rate and improved survival [21, 22]. Accordingly Watanabe et al. suggested that preoperative radio- therapy may be an alternative to extended lateral lymphadenectomy [23]. In his
retrospective study, 115 patients with low rectal cancer were divided into different therapy groups, and there was no difference between the group with radiotherapy (without lateral lymph node dissection) and the group with lateral lymph node dissection (without radiotherapy) in terms of overall survival, disease-free sur- vival, and recurrence rate [23]. These results were later confirmed in a study by Koda et al. [24]. However, until now, no prospective randomized controlled trial had been conducted comparing lateral lymphadenectomy with TME and radio- therapy. One randomized controlled trial compared lateral node dissection versus nerve-preserving resection (without lateral node dissection) in patients with rectal cancer after preoperative radiotherapy [25]. In that study, no difference in survival and local recurrence rate was observed between the two treatment groups, and the authors concluded that lateral node dissection is not necessary in terms of curability for patients with advanced lower rectal cancer who undergo preopera- tive radiotherapy [25]. However, lateral node dissection still remains the standard treatment for advanced lower rectal cancer in Japan, as the results are similar to TME with prior radiotherapy. Havenga et al. demonstrated that standardized surgery is probably the most important prognostic factor in rectal cancer treat- ment [26]. They analyzed 691 patients with rectal cancer from three international centers in the United States, Europe, and Japan and could demonstrate similar survival and local recurrence rates in all three centers [26].
New intraoperative staging procedures such as sentinel lymph node mapping in rectal cancer are currently under examination in order to evaluate their prognostic and therapeutic significance [27].
In conclusion, due to major improvements in local control and survival of rectal cancer patients on the basis of preoperative radiotherapy and total mesorectal excision, only a certain subgroup of rectal cancer patients may profit from more aggressive surgical approaches such as lateral lymph node dissection. In the future, sentinel lymph node mapping may facilitate a further individualization of therapy allowing the selection of patients who would gain prognostic and therapeutic benefit from lateral lymph node dissection.
References
1. DiSaia PJ, Creasman WT (1999) Clinical gynecologic oncology. Chicago: Mosby-Year Book 2. Heidenreich A, Varga Z, von Knobloch R (2002) Extended pelvic lymphadenectomy in pa-
tients undergoing radical prostatectomy: high incidence of lymph node metastasis. J Urol 167:1681–1686
3. Takahashi T, Ueno M, Azekura K, Ohta H (2000) Lateral node dissection and total mesorectal excision for rectal cancer. Dis Colon Rectum 43(Suppl):S59–S68
4. Morikawa E, Yasutomi M, Shindou K, Matsuda T, Mori N, Hida J, et al (1994) Distribution of metastatic lymph nodes in colorectal cancer by the modified clearing method. Dis Colon Rectum 37:219–223
5. Ueno H, Yamauchi, Hase K, Ichikura T, Mochizuki H (1999) Clinicopathological study of intrapelvic cancer spread to the iliac area in lower rectal adenocarcinoma by serial sectioning.
Br J Surg 86:1532–1537
6. Canessa CE, Miegge LM, Bado J, Silveri C, Labandera D (2004) Anatomic study of lateral pelvic lymph nodes: implications in the treatment of rectal cancer. Dis Colon Rectum 47:297–303
7. Morita T, Murata A, Koyama M, Totsuka E, Sasaki M (2003) Current status of autonomic nerve- preserving surgery for mid and lower rectal cancers. Dis Colon Rectum 46(Suppl):S78–S88 8. Mori T, Takahashi K, Yasuno M (1998) Radical resection with autonomic nerve presentation
and lymph node dissection techniques in lower rectal cancer surgery and its results: the impact of lateral lymph node dissection. Langenbeck’s Arch Surg 383:409–415
9. Dong XS, Xu HT, Yu ZW, Liu M, Cui BB, Zhao P, et al (2003) Effect of extended radical resection for rectal cancer. World J Gastroenterol 9:970–973
10. Hida J, Yasutomi M, Tokoro T, Kubo R (1999) Examination of nodal metastases by a clearing method supports pelvic plexus preservation in rectal cancer surgery. Dis Colon Rectum 42:510–514
11. Fujita S, Yamamoto S, Akasu T, Moriya Y (2003) Lateral pelvic lymph node dissection for advanced lower rectal cancer. Br J Surg 90:1580–1585
12. Ueno H, Mochizuki H, Hashiguchi Y, Hase K (2001) Prognostic determinants of patients with lateral nodal involvement by rectal cancer. Ann Surg 234:190–197
13. Moriya Y, Sugihara K, Akasu T, Fujita S (1997) Importance of extended lymphadenectomy with lateral node dissection for advanced lower rectal cancer. World J Surg 21:728–732 14. Hojo K, Sawada T, Moriya Y (1989) An analysis of survival and voiding, sexual function after
wide iliopelvic lymphadenectomy in patients with carcinoma of the rectum, compared with conventional lymphadenectomy. Dis Colon Rectum 32:128–133
15. Shimoyama M, Yamazaki T, Suda T, Hatakeyama K (2003) Prognostic significance of lateral lymph node micrometastases in lower rectal cancer. Dis Colon Rectum 46:333–339 16. Saito N, Koda K, Takiguchi N, Oda K, Soda H, Nunomura M et al (1999) Nerve-sparing
surgery for advanced rectal cancer patients: special reference to Dukes C patients. World J Surg 23:1062–1068.
17. Uyama I, Sugioka A, Matsui H, Fujita J, Komori Y, Hanai T et al (2001) Laparoscopic lateral node dissection with autonomic nerve preservation for advanced lower rectal cancer. J Am Coll Surg 193:579–584
18. Heald RJ, Husband EM, Ryall RD (1982) The mesorectum in rectal cancer surgery: the clue to pelvic recurrence? Br J Surg 69:613–616
19. Heald RJ, Ryall RD (1986) Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 28:1479–1482
20. Enker WE, Thaler HT, Cranor ML, Polyak T (1995) Total mesorectal excision in the operative treatment of carcinoma of the rectum. J Am Coll Surg 181:335–346
21. Swedish Rectal Cancer Trial (1997) Improved survival with preoperative radiotherapy in resectable rectal cancer. . N Engl J Med 336:980–987
22. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, et al (2001) Preop- erative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345:638–646
23. Watanabe T, Tsurita G, Muto T, Sawada T, Sunouchi K, Higuchi Y, et al (2002) Extended lymphadenectomy and preoperative radiotherapy for lower rectal cancers. Surgery 132:27–
33
24. Koda K, Saito N, Oda K, Takiguchi N, Sarashina H, Miyazaki M (2004) Evaluation of lateral lymph node dissection with preoperative chemo-radiotherapy for the treatment of advanced middle to lower rectal cancers. Int J Colorectal Dis 19:188–94
25. Nagawa H, Muto T, Sunouchi K, Higuchi Y, Tsurita G, Watanabe T, et al (2001) Randomized, controlled trial of lateral node dissection vs. nerve-preserving resection in patients with rectal cancer after preoperative radiotherapy. Dis Colon Rectum 44:1274–1280
26. Havenga K, Enker WE, Norstein J, Moriya Y, Heald RJ, van Houwelingen HC, et al (1999) Improved survival and local control after total mesorectal excision or D3 lymphadenectomy in the treatment of primary rectal cancer: an international analysis of 1411 patients. Eur J Surg Oncol 25:368–374
27. Mulsow J, Winter DC, O’Keane JC, O’Connell PR (2003) Sentinel lymph node mapping in colorectal cancer. Br J Surg 2003; 90:659–667
