Dr. Aswathy G. Nath completed her MBBS from Govt. Medical College Thiruvananthapuram, Kerala. She did her MS in Obstetrics and Gynaecology, from Govt. Medical College, Thiruvananthapuram, Kerala, and completed Fellowship in Gynaecological Oncology from RCC, Thiruvananthapuram, Kerala. She is currently working as Senior Resident in Gynaecological Oncology at Regional Cancer Centre, Thiruvananthapuram, Kerala. Fields of interest are Gynaecological Oncology and Preventive Oncology.
Introduction Accurate surgical staging is an essential component in the management of carcinoma endometrium to assess the stage of disease and to tailor adjuvant treatment. Sentinel node technique was introduced as an alternative for extensive lymphadenectomy in early stages to avoid complications associated with lymphadenectomy.
Aims and Objectives To assess the detection rate and diagnostic accuracy of SLN mapping in patients with early-stage carcinoma endometrium
Materials and Methods Prospective validation study involving 30 patients diagnosed to have early-stage carcinoma endometrium. Sentinel nodes were detected by combined methods of radio colloid dye and isosulphan blue dye injection
Results Sentinel lymph node was detected in 19 patients (63.4%). 11 patients had no sentinel nodes. Total number of sentinel nodes isolated was 68 with a mean of 2.26 per patient (range 0–4). Ten (33.33%) patients had single sentinel node location, while 9 (30%) had more than 1 sentinel lymph nodes. Twelve patients had bilateral sentinel nodes, and the most frequent location of sentinel node was obturator, 19 (63.3%) especially on right hemi-pelvis. One patient had a hot para-aortic node, while none had blue para-aortic sentinel node. Average number of lymph nodes obtained by lymphadenectomy was 13 per patient (range 7–22). All patients with sentinel node had negative frozen report as well as in histopathology. Two patients in whom no sentinel nodes were detected by either techniques had metastatic nodes in histopathology report.
Conclusion Detection rate was maximum with radiocolloid dye, and it is better to utilize the technique for less graded tumours and endometrioid variants.
Keywords : Carcinoma endometrium · Sentinel nodes · Detection rate
Carcinoma endometrium is the commonest genital tract malignancies in females in developed countries. In India, it ranks third most common genital tract malignancy [1]. Accurate surgical staging is an important prognostic factor in the management of carcinoma endometrium. The incidence of metastasis to the pelvic lymph nodes in patients with corpus-confined endometrial cancer varies from 5 to 18% [2]. Retroperitoneal lymph node involvement, including either pelvic or para-aortic lymph nodes, results in a worse prognosis. Patients with lymph node metastasis usually have 5-year survival rate as low as 44% to 52% compared to 95% when the disease is localized [1]. However, the therapeutic role of lymphadenectomy has not been well established with two randomized trials, in fact failing to show a survival benefit. After MRC-ASTEC EN 5 [3] and study by Panici et al. [4], it was proved that there is no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer. Retrospective studies suggested that complete lymphadenectomy may be associated with improved survival outcome [5], and prospective trials evaluating the same are ongoing [6]. Lymphadenectomy as a part of staging in early-stage carcinoma endometrium is still controversial. Lymphatic mapping using various injection techniques is currently being practiced.
Aims and ObjectivesTo assess the detection rate and diagnostic accuracy of SLN mapping in patients with early-stage carcinoma endometrium.
This study was conducted as a validation study in a tertiary care referral hospital in south India to assess the feasibility of sentinel lymph node sampling in early-stage carcinoma endometrium after getting Institution review board and ethics committee approval. It was done as a prospective observational study from January 2018 to January 2019.
Patient SelectionPatients with histological diagnosis of carcinoma endometrium confined to uterus clinically and radiologically were included. Magnetic resonance imaging (MRI) was taken for all patients to assess myometrial invasion and lymph node involvement. MRI showing enlarged lymph nodes (more than 10 mm) were excluded from the study. Representative slides and blocks of referred cases were reviewed by our pathologists to confirm diagnosis as well as grade of lesion. Patients with Endometrioid adenocarcinoma grade 1 with less than 50% myometrial invasion (radiologically), history of prior chemotherapy or radiotherapy, history of other malignancies, and previous surgeries that could change lymphatic drainage of uterus (e.g. myomectomy) were excluded.
Number of patients included was 30. Mean age of patients was 58.7 (range 48–73), and median BMI was 26.44. Twenty-eight were postmenopausal. None of them had previous history of infertility treatment or hormonal exposure. Most frequent co-morbid conditions were Diabetes Mellitus 2 (6.7%), Systemic hypertension 6 (20%) and Hypothyroidism 4 (13.3%). Seven patients (23.3%) had diabetes and hypertension. Clinical and radiological evaluation details are given in Table 1.
All patients underwent laparotomy. None of the patients had allergic reactions to technetium-99 or isosulphan blue dye. Sentinel lymph node was detected in 19 patients (63.4%). Eleven patients had no sentinel nodes in the initial SPECT-CT or intraoperatively. Total number of sentinel nodes isolated was 68 with a mean of 2.26 per patient (range 0–4).Ten (33.33%) patients had a single sentinel node location, while 9 (30%) had more than 1 sentinel lymph node. Twelve patients had bilateral sentinel nodes, and the most frequent location of sentinel node was obturator 19 (63.3%), especially on right hemi-pelvis. One patient had a hot para-aortic node, while none of the patients had blue para-aortic sentinel node. The average number of lymph nodes obtained by lymphadenectomy was 13 per patient (range 7–22) [Table 2].
All patients with sentinel node had a negative frozen report as well as in final histopathology. Two out of eleven patients in whom no sentinel nodes were detected by either techniques had metastatic nodes in final histopathology report. There were no major complications in the intraoperative or postoperative period. While giving isosulphan blue dye injection, there was a transient SPO2 fall which recovered quickly without any interventions. Ninety percentage of patients had a mean hospital stay of 4.5 days, while 2 had post-op stay more than 5 days in view of paralytic ileus.
Use of sentinel lymph node technique was already established
in managing melanoma [7] and carcinoma breast
[8]. Sentinel lymph node technique is based on the hypothesis that sentinel lymph node is the first regional
draining node from the primary tumour. Thus, the histological
status of the sentinel node could accurately predict
the pathological status of the regional lymph node basin.
Detection rate of sentinel node using SPECT-CT was low
(26.6%, 8/30 patients on right hemi-pelvis and 13.3%, 4/30
patients on left hemi-pelvis) in our study compared to other
studies. Based on a study by Hoogendam et al. [9], SPECTCT
is more sensitive in detecting sentinel nodes comparing
planar lymphoscintigraphy. The median detection rate with
SPECT-CT for more than one lymph node in a patient was
98.6% compared with 85.3% for lymphoscintigraphy. Most
common sentinel node detected was obturator node on right
hemi-pelvis.
By combined injection technique using technetium-99
and isosulphan blue dye, detection rate was 63.4% on right
hemi-pelvis and 40% on left hemi-pelvis. In cases where
sentinel nodes were detected, final histopathology report
was also in agreement with frozen report. Two cases where
final histopathology report showed metastatic nodes had
no sentinel nodes intraoperatively by either methods. One
was a case of uterine papillary serous carcinoma, and other
was a poorly differentiated endometrioid adenocarcinoma.
One patient had metastatic deposits at pelvic and para-aortic
areas. Same patient’s histopathology report showed lymphovascular
space invasion and left parametrial tumour deposits.
Second case had metastatic pelvic and para-aortic nodes
with diffuse lymphovascular emboli and dense parametrial
tumour infiltration. The possible reason for non-detection of
sentinel node might be due to occlusion of lymphatic drainage
channels by tumour cells.
Abu-Rustum et al. [10] compared subserosal myometrial injection techniques with cervical injection of tracer to detect sentinel nodes in carcinoma endometrium. With myometrial injection, detection rate varies between zero [11] to ninety-two per cent [12]. In the above-mentioned article, when tracer was given as cervical injection, detection rate was as high as 86%. The author himself gave cervical injection in their institutional study. Similar technique was used in our case also. In order to avoid bias, the same investigator injected technetium-99 as well as blue dye at 3’o clock and 9’o clock positions to all thirty patients and still detection rate was almost similar to average detection rate obtained by myometrial detection technique. But in the study by Fady Khoury-Collado et al. [13] lymph node mapping was performed using blue dye injection to cervix in 71% cases while combined cervical and uterine fundal injection in 29% cases. In their analysis, they found that detection rate increased from 78% (on cervical injection alone) to 94% by combined technique (p = 0.033).
Declarations
Conflict of interest The authors have no conflicts of interest relevant to this article to disclose.
Ethical Statement This study was conducted after Institute review board and Ethical committee clearance—IRB no. 12/2016/09, HEC no. 03/2017.
Informed Consent Informed consent was obtained from all the participants in this study.
1. Cancerindia.org.in › globocan-2018-india-factsheet.
2. Creasman WT, Mutch DE, Herzog TJ. ASTEC lymphadenectomy and radiation therapy studies: are conclusions valid? Gynaecol Oncol. 2010;116(3):293–4.
3. Crosbie EJ, Roberts C, Qian W, et al. Body mass index does not influence post-treatment survival in early stage endometrial cancer: results from the MRC ASTEC trial. Eur J Cancer. 2012;48(6):853–64.
4. Panici PB, Basile S, Maneschi F, et al. Systematic pelvic lymphadenectomy vs no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. JNCI J Natl Cancer Inst. 2008;100(23):1707–16.
5. Chan JK, Wu H, Cheung MK, et al. The outcomes of 27,063 women with unstaged endometrioid uterine cancer. Gynecol Oncol. 2007;106(2):282–8.
6. Mould T, Brand A, Nijman H, et al. STATEC: A randomised trial of non-selective versus selective adjuvant therapy in high risk apparent stage 1 endometrial cancer.
7. Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127(4):392–9.
8. Cody HS III, Hill AD, Tran KN, et al. Credentialing for breast lymphatic mapping: how many cases are enough? Ann Surg. 1999;229(5):723.
9. Hoogendam JP, Veldhuis WB, Hobbelink MG, et al. 99mTc SPECT/CT versus planar lymphoscintigraphy for preoperative sentinel lymph node detection in cervical cancer: a systematic review and metaanalysis. J Nucl Med. 2015;56(5):675–80.
10. Abu-Rustum NR, Khoury-Collado F, Pandit-Taskar N, et al. Sentinel lymph node mapping for grade 1 endometrial cancer: is it the answer to the surgical staging dilemma? Gynecol Oncol. 2009;113(2):163–9.
11. Echt ML, Finan MA, Hoffman MS, et al. Detection of sentinel lymph nodes with lymphazurin in cervical, uterine, and vulvar malignancies. South Med J. 1999;92(2):204–8.
12. Altgassen C, Pagenstecher J, Hornung D, et al. A new approach to label sentinel nodes in endometrial cancer. Gynecol Oncol. 2007;105(2):457–61.
13. Khoury-Collado F, Glaser GE, Zivanovic O, et al. Improving sentinel lymph node detection rates in endometrial cancer: how many cases are needed? Gynecol Oncol. 2009;115(3):453–5.
14. Gien LT, Kwon JS, Carey MS. Sentinel node mapping with isosulfan blue dye in endometrial cancer. J Obstet Gynaecol Can. 2005;27(12):1107–12.
15. Raspagliesi F, Ditto A, Kusamura S, et al. Hysteroscopic injection of tracers in sentinel node detection of endometrial cancer: a feasibility study. Am J Obstet Gynecol. 2004;191(2):435–9.
16. Maccauro M, Lucignani G, Aliberti G, et al. Sentinel lymph node detection following the hysteroscopic peritumoural injection of 99m Tc-labelled albumin nanocolloid in endometrial cancer. Eur J Nucl Med Mol Imaging. 2005;32(5):569–74.
17. Rossi EC, Kowalski LD, Scalici J, et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol. 2017;18(3):384–92.
