Japanese Journal of Clinical Oncology Advance Access originally published online on July 26, 2006
Japanese Journal of Clinical Oncology 2006 36(9):578-581; doi:10.1093/jjco/hyl066
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2006 Foundation for Promotion of Cancer Research
Can We Omit Para-Aorta Lymph Node Dissection in Endometrial Cancer?
Department of Obstetrics and Gynecology, Akita University School of Medicine, Akita, Japan
For reprints and all correspondence: Hidenori Tanaka, Department of Obstetrics and Gynecology, Akita University School of Medicine, 1-1-1 Hondo, Akita-City, Akita-Ken, 010-8543, Japan. E-mail: tanakah{at}obgyn.med.akita-u.ac.jp
Received December 6, 2005; accepted May 11, 2006
 |
Abstract |
|---|
 TOP Abstract INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
|---|
Background: Patients with endometrial cancer can present with various complicating illnesses, including obesity, diabetes mellitus, hypertension and advanced aging. These patients are at high risk of severe post-operative complications. Thus, the question of whether or not to perform systemic pelvic and para-aortic lymphadenectomy remains controversial for all patients. It is reported that external iliac lymph nodes are the most commonly involved lymph nodes in endometrial cancer, and para-aortic lymph node (PAN) metastases spread via a route shared by the common iliac lymph nodes. The aim of this study was to evaluate the potential efficacy of omitting PAN dissection when metastasis of the common iliac and external iliac lymph nodes is negative.
Methods: Between January 1994 and June 2004, a total of 101 patients at Akita University Hospital who had undergone total hysterectomy and bilateral salpingo-oophorectomy, total pelvic lymphadenectomy and para-aortic lymphadenectomy to the level of the renal vein for endometrial cancer were enrolled in this study.
Results: Eleven patients in all were found to have metastasis for PANs. Among 13 patients with common and/or external iliac positive lymph nodes, 10 showed PAN metastasis. Of the 88 patients with negative lymph nodes, 87 showed no PAN metastasis. Based on these data, common and/or external iliac lymph nodes had 90.9% sensitivity (10/11) and 96.7% specificity (87/90) for detecting PAN metastasis.
Conclusion: Para-aortic lymphadenectomy might be avoided by the negativity of such lymph nodes, thereby minimizing post-operative complications.
Key Words: endometrial cancer • systemic pelvic and para-aortic lymphadenectomy
|
INTRODUCTION |
|---|
|
TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
|---|
The prevalence of endometrial cancer is increasing rapidly in Japan, mirroring the change among Japanese women from a Japanese lifestyle to a Western lifestyle (1). In 1988, FIGO recommended as the primary surgical procedure total hysterectomy and bilateral salpingo-oophorectomy with pelvic and para-aortic lymph node (PAN) dissection (2). However, patients with endometrial cancer can present with various complicating illnesses, including obesity, diabetes mellitus, hypertension and advanced aging. These patients are at high risk of severe post-operative complications, such as severe lymph edema and pulmonary embolism. Thus, the question of whether or not to perform systemic pelvic and para-aortic lymphadenectomy remains controversial for all patients in Japan and many countries. According to National Comprehensive Cancer Network guidelines (3), patients with stage Ia (patients with no superficial myometrial invasion) and grade 1 endometrial cancer may undergo only total hysterectomy and bilateral salpingo-oophorectomy. Also, it is well known that patients with endometrial cancer have a good prognosis because over half are negative for lymph node metastasis, and 10–20% of all endometrial cancer patients have stage Ia disease. However, operative or intraoperative detection of lymph node metastasis is difficult (4).
Previous studies have estimated different patterns of lymphatic spread to the pelvic lymph nodes and PANs in endometrial cancer (5,6). Mariani et al. reported that external iliac lymph nodes are the most commonly involved lymph nodes in endometrial cancer, and PAN metastases spread via a route shared by the common iliac lymph nodes when tumor involves the cervix (7). Following a retrospective examination of lymph node metastasis data for endometrial cancer patients who underwent complete systematic lymphadenectomy at our hospital, we hypothesized that the common iliac and external iliac lymph nodes were the key lymph nodes in metastasis and that their involvement could indicate either involvement of other lymph nodes or the need for complete systematic lymphadenectomy. The aim of this study was to evaluate the potential efficacy of omitting PAN dissection when metastasis of the common iliac and external iliac lymph nodes is negative.
|
PATIENTS AND METHODS |
|---|
|
TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
|---|
PATIENTS AND LYMPH NODE SAMPLES
Between January 1994 and June 2004, a total of 101 patients at the Akita University Hospital who had undergone total hysterectomy and bilateral salpingo-oophorectomy, total pelvic lymphadenectomy and para-aortic lymphadenectomy to the level of the renal vein for endometrial cancer were enrolled in this study. In the course of carrying out this operation, we incised the bilateral peritoneum along the ascending and descending colon, mobilized the ascending and descending colon along with the small intestine, displacing them to the right or left upper side. Thirty patients who had undergone incomplete systematic lymphadenectomy were excluded from the study. The characteristics of the 101 patients (age range, 30–76 years; mean age, 57.0 ± 8.6 year) are summarized in Table 1. Patient cases were categorized according to the FIGO surgical staging system (2): stage I, 69 patients; stage II, 4 patients; stage III, 27 patients; stage IV, 1 patient.
|
All resected lymph nodes were examined by hematoxylin and eosin (H&E) staining. The primary uterine tumors were histologically diagnosed according to World Health Organization (WHO) classification: endometrial adenocarcinoma (G1 or G2), 73 patients; endometrial adenocarcinoma (G3), 19 patients; clear cell carcinoma, six patients; and other types of carcinomas, three patients.
The pathologists at our hospital made the histopathological diagnosis independently. And, they could perform intraoperative decision with the lymph node frozen section (FS) in the case of the gastric cancer, colon cancer or breast cancer.
|
RESULTS |
|---|
|
TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
|---|
The locations of lymph node metastasis are summarized in Fig. 1. Of 101 patients, 16 patients (15.8%) were found to have lymph node metastasis for pelvic lymph nodes and PANs (Table 2); external iliac nodes, eight patients; common iliac nodes, seven patients; obturator nodes, 10 patients; internal iliac nodes, seven patients; and PANs, 11 patients. The obturator lymph nodes were the most commonly involved pelvic lymph node site. However, the combination of external iliac nodes and/or common iliac nodes was a more frequent site for metastasis than the obturator lymph nodes. And, there was no skipping of these lymph nodes (i.e. pelvic positive/PAN positive but external iliac nodes and/or common iliac nodes negative). Of note, only one patient had PAN direct metastasis without pelvic lymph node metastasis.
|
|
SENSITIVITY AND SPECIFICITY OF COMMON ILIAC AND/OR EXTERNAL ILIAC LYMPH NODE METASTASIS FOR PAN METASTASIS
Eleven patients in all patients were found to have metastasis for PANs. Among 13 patients with common and/or external iliac positive lymph nodes, 10 had PAN metastasis (Table 3). Of the 88 patients with negative lymph nodes, 87 showed no PAN metastasis. Based on these data, common and/or external iliac lymph nodes had 90.9% sensitivity (10/11) and 96.7% specificity (87/90) for detecting PAN metastasis. However, among the 10 patients with positive obturator lymph nodes, seven had PAN metastasis (Table 3). Obturator lymph nodes had 63.6% sensitivity (7/11) and 96.7% specificity (87/90) for detecting PAN metastasis. The sensitivity was much lower than that for the common and/or external iliac lymph nodes.
|
|
DISCUSSION |
|---|
|
TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
|---|
Many previous studies have dealt with total pelvic lymphadenectomy and para-aortic lymphadenectomy in endometrial cancer, since patients with lymphadenectomy had a significantly better prognosis than those without lymphadenectomy (8,9). These reports, however, focused only on whether lymphadenectomy should include PAN as well as pelvic lymphadenectomy. Some reports stated that PAN lymphadenectomy did not improve prognosis, because the presence of PAN metastasis indicates systemic metastasis (10). Furthermore, complete lymphadenectomy resulted in ileus, massive bleeding, vascular injury and severe post-operative pulmonary embolism. In fact, there was one pulmonary embolism case after the complete systematic lymphadenectomy. The omission of lymphadenectomy is, therefore, desirable when no metastasis is detected in the lymph node.
In the present study, the common lymph node for metastasis is the obturator node (Table 2). However, the combination lymph nodes (external and/or common lymph nodes) were a more frequent site for metastasis than the obturator lymph nodes. Furthermore, Table 3 shows that the sensitivity rate of the combination lymph nodes (90.9%) was higher than the obturator lymph nodes (63.6%). These data indicate the reason why we selected the common and external lymph nodes as the pelvic nodes. We think that the metastasis of these lymph nodes was strongly associated with para-aortic node metastasis. Mariani et al. reported that external iliac lymph nodes were the most commonly involved lymph nodes in endometrial cancer and that PAN metastasis spread via a route shared by the common iliac lymph nodes when tumor involves the cervix (7). In addition, Matsumoto et al. (11) reported that PAN metastasis was significantly associated with common iliac.
Given these findings, we believe that metastasis most commonly tends to develop first in the combination site of common iliac and external lymph nodes and that these nodes are, therefore, key lymph nodes associated with PAN metastasis. Consequently, during surgery, we routinely perform lymphadenectomy of the external lymph nodes first. Also lymphadenectomy of the common external lymph nodes at the side of the external lymph nodes is easy to perform.
We also found that metastasis of the common and/or external iliac lymph nodes had 90.9% sensitivity (10/11) and 96.7% specificity (87/90) for detecting PAN metastasis. These data suggest that PAN dissection can be omitted when metastasis of the common iliac and external iliac lymph nodes is expected to be absent intraoperatively. We have already established the system of the intraoperative FS diagnosis. The key lymph nodes in this study were examined with H&E staining, immediately. FS was routinely performed in a large series of many organs and lymph nodes. Overall, FS diagnoses were accurate in 551 of 564 cases (97.6%) in our hospital and the false negative rate was 0.2% (1/564) (data not shown). Therefore, we believe that intraoperative FS diagnosis of this study is reliable.
However, one patient had PAN metastasis without pelvic wall lymph node metastasis. It is reported that endometrial cancer can directly metastasize to both pelvic and para-aortic lymph nodes with pelvic lymph nodes metastases being dominant, a distinct lymphatic spread pattern better viewed as being somewhere between cervical cancer and ovarian cancer (11). The histological diagnosis of this case was clear cell carcinoma. Clinically, prognosis is less favorable with clear cell carcinoma than with endometrioid carcinoma (12). We believe that this is due to the higher potential of clear cell carcinoma for metastasis than that of endometrioid adenocarcinoma and that clear cell carcinoma may take another route of metastasis to PAN metastasis. Therefore, it might be necessary to perform PAN lymphadenectomy in patients with clear cell carcinoma who do not have pelvic lymph node metastasis.
In conclusion, the present study revealed that presence or absence of metastasis in the common iliac and external iliac lymph nodes is closely associated with PAN metastasis. We now propose that PAN lymphadenectomy may be avoided on the basis of negativity of such lymph nodes, thereby, minimizing post-operative complications associated with systemic pelvic and para-aortic lymphadenectomy, which are of high medical risk.
|
References |
|---|
|
TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
|---|
1 Japanese Ministry of Health, Labour and Welfare database 2003.
2 Announcements: FIGO (the International Federation of Obstetricians and Gynecologists) stages: 1988 revision. Gynecol Oncol 1989; 35: 125–6.[CrossRef]
3 NCCN guideline version 1.2003.
4 Quinlivan JA, Petersen RW, Nicklin JL. Accuracy of frozen section for the operative management of endometrial cancer. BJOG 2001;108:798–803.[CrossRef][Medline]
5 Larson DM, Johnson KK. Pelvic and para-aortic lymphadenectomy for surgical staging of high-risk endometrioid adenocarcinoma of the endometrium. Gynecol Oncol 1993;51:345–8.[CrossRef][Web of Science][Medline]
6 Ayhan A, Yarali H, Urman B, Gunalp S, Yuce K, Ayhan A, Havlioglu S. Lymph node metastasis in early endometrium cancer. Aust N Z J Obstet Gynaecol 1989;29:332–5.[Web of Science][Medline]
7 Miriani A, Webb MJ, Keeney GL, Podratz KC. Routes of lymphatic spread: a study of 112 consecutive patients with endometrial cancer. Gynecol Oncol 2001;81:100–4.[CrossRef][Web of Science][Medline]
8 Hirahatake K, Hareyama H, Sakuragi N, Nishiya M, Makinoda S, Fujimoto S. A clinical and pathologic study on para-aortic lymph node metastasis in endometrial carcinoma. J Surg Oncol 1997;65:82–7.[CrossRef][Web of Science][Medline]
9 Yokoyama Y, Maruyama H, Sato S, Saito Y. Indispensability of pelvic and paraaortic lymphadenectomy in endometrial cancers. Gynecol Oncol 1997;64:411–7.[CrossRef][Web of Science][Medline]
10 Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer 1987;60(8 Suppl):2035–41.[CrossRef][Web of Science][Medline]
11 Matsumoto K, Yoshikawa H, Yasugi T, Onda T, Nakagawa S, Yamada M, et al. Distinct lymphatic spread of endometrial carcinoma in comparison with cervical and ovarian carcinomas. Cancer Lett 2002;180:83–9.[CrossRef][Web of Science][Medline]
12 Abeler VM, Kjorstad KE. Clear cell carcinoma of the endonetrium: a histopathological and clinical study of 97 cases. Gynecol Oncol 1991;40:207–17.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||