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Prevalence of lower-extremity lymphedema is lower in patients who underwent sentinel lymph mapping

Endometrial cancer is the most common gynecologic malignancy in the Western world, and it is strongly associated with obesity. Hysterectomy with bilateral salpingo- oophorectomy is the standard initial therapy for patients with newly diagnosed endometrial cancer clinically confined to the uterus and/or cervix, assuming they are medically fit to undergo surgery. The role of pelvic and/or para-aortic lymphadenectomy remains controversial. The risk of nodal metastasis is approximately 30% among the highest-risk cases, such as those with serous histologic profile or deeply invasive FIGO grade 3 endometrioid histologic profiles. Therefore, at least 70% of these patients will undergo an unnecessary lymphadenectomy, as the removal of normal, uninvolved lymph nodes carries no survival advantage and patients who undergo this procedure are at risk of significant morbidity. One potential complication of lymphadenectomy is the development of Lymphedema (LEL), it is a serious and potentially debilitating condition, resulting in the accumulation of protein-rich lymph fluids in subcutaneous tissues. If untreated, lymphedema generally progresses to more-advanced stages, increasing patients’ risk of cellulitic infections, functional decline, and poorly healing wounds. Sentinel lymph node mapping (SLN) mapping has been proposed as an alternative to lymphadenectomy for women with uterine cancer. SLN mapping in patients with endometrial cancer is a relatively novel approach. We have developed and published an SLN mapping algorithm that is now being used internationally. In 2014, the National Comprehensive Cancer Network recognized our SLN mapping algorithm as an acceptable staging approach if performed at experienced centers. SLN mapping for endometrial cancer was initiated at MSK in 2005. Since that time, SLN mapping has been routinely offered and performed. We recently reported that SLN mapping has reduced the number of nodes removed and decreased operative times without compromising our ability to adequately stage these patients . Anecdotally, we have noticed that the rate of LEL is lower in patients who have undergone SLN mapping alone. We assessed the rate of lymphedema in 600 patients approximately who have undergone surgery at our institution for newly diagnosed endometrial cancer. In addition, we assessed the effect of multiple factors on the development of LEL. This is the first study to assess SLN mapping and lymphedema in a large cohort of patients.



Graduated in Medicine at Complutense University of Madrid, Spain. Specialist in the field of Gynecology and Obstetrics from 2015. I was working in public health care hospitals and private clinic in Madrid. Started my PhD program in Cancer and Pregnancy at General University Hospital Gregorio Marañon, Madrid, when I was in my second year of my residency program. Then, I was awarded with a Foundation Grant to finish it in New York City. USA. I was working as a Clinical Research Fellow in Gynecology Oncology Department at Memorial Sloan Kettering Cancer Center, in New York City. Currently, I am working as a fellow in GYNONC at Columbia University in the city of New York. Education: Columbia University of the City of New York. USA.2017 Weill Cornell Medicine. New York. USA. 2016 University of Texas. Houston. USA. 2014. Complutense University of Madrid. Spain. 2010 Hospital Experience: Clínical research fellowship in GYNONC, Memorial Sloan Kettering Cancer Center. New York. USA. Gynecology Oncology training, MD Anderson Cancer center, Houston, Texas. USA Obstetrics Ultrasound, University Hospital Gregorio Marañon. Madrid. Spain. Reproductive Medicine, Fundacion Jimenez Diaz, Madrid. Spain Pelvic pathology, Fuenlabrada Hospital, Madrid. Spain ] Breast Radiology, University Hospital of Mostoles, Madrid. Spain General and Digestive Surgery training, Semmelweis Klinika, Budapest, Hungary. Research Experience: Clinical Research Fellowship in Gynecology Oncology at Columbia University, New York. USA. Clinical Research Fellowship in Gynecology Oncology at Memorial Sloan Kettering Cancer Center, New York. USA. Clinical Research Fellowship in Cancer and Pregnancy at General University Hospital Gregorio Marañon, Madrid. Spain. Other Activities: Reviewer "The journal of minimally invasive Gynecology" JMIG

A comparison of extraperitoneal versus transperitoneal laparoscopic or robotic para-aortic lymphadenectomy for staging of endometrial carcinoma.

Abstract: The optimal surgical approach for complete lymphadenectomy in patients with endometrial cancer is controversial. The objective of our study was to compare the surgical outcomes of extraperitoneal laparoscopic, transperitoneal laparoscopic, and robotic transperitoneal para-aortic lymphadenectomy in endometrial cancer staging.A retrospective review was performed on patients who underwent extraperitoneal or transperitoneal para-aortic lymphadenectomy for endometrial cancer staging from January 2007 to November 2012. Three patient groups were compared: extraperitoneal laparoscopic para-aortic lymphadenectomy, robotic hysterectomy and pelvic lymphadenectomy ("extraperitoneal group"; N = 34); laparoscopic hysterectomy and transperitoneal pelvic and para-aortic lymphadenectomy ("transperitoneal laparoscopic group"; N = 108); and robotic hysterectomy and transperitoneal pelvic and para-aortic lymphadenectomy ("transperitoneal robotic group"; N = 52). Fisher's exact test and Kruskal-Wallis test were used for statistical analysis, and statistical significance was defined as P < 0.05.The median number of para-aortic lymph nodes obtained was higher in the extraperitoneal group than in the transperitoneal laparoscopic and robotic groups (10, 5, and 4.5 nodes, respectively; P < 0.001). BMI was higher in the extraperitoneal group (median, 35.1 kg/m(2)) than in the transperitoneal groups but did not differ between the transperitoneal laparoscopic group (median, 28.4 kg/m(2)) and the transperitoneal robotic group (median, 30.2 kg/m(2)). Among patients with a BMI <35 kg/m(2), the median number of para-aortic nodes harvested was higher in the extraperitoneal group than in the transperitoneal laparoscopic and robotic groups (9, 4, and 5 nodes, respectively; P < 0.01). The same pattern was observed among patients with a BMI ≥35 kg/m(2) (10, 6, and 3 nodes, respectively), but only the extraperitoneal group and the transperitoneal robotic group were significantly different (P = 0.001). There was no significant difference in median estimated blood loss between the extraperitoneal group and either the transperitoneal laparoscopic group (100 vs. 112.5 mL; P = 0.06) or the transperitoneal robotic group (100 vs. 67.5 mL; P = 0.23). The median operative time was longer in the extraperitoneal group (339.5 min; range, 242-453 min) than in the transperitoneal laparoscopic group (286 min; range, 101-480 min) and the transperitoneal robotic group (297.5 min, range 182-633 min) (P < 0.01).Extraperitoneal laparoscopic para-aortic lymphadenectomy resulted in a higher number of para-aortic lymph nodes removed than transperitoneal laparoscopic or robotic lymphadenectomy. The extraperitoneal approach should be considered for endometrial cancer staging.

Pub.: 24 Dec '13, Pinned: 18 Sep '17

Detection of sentinel lymph nodes in minimally invasive surgery using indocyanine green and near-infrared fluorescence imaging for uterine and cervical malignancies.

Abstract: Our primary objective was to assess the detection rate of sentinel lymph nodes (SLNs) using indocyanine green (ICG) and near-infrared (NIR) fluorescence imaging for uterine and cervical malignancies.NIR fluorescence imaging for the robotic platform was obtained at our institution in 12/2011. We identified all cases planned for SLN mapping using fluorescence imaging from 12/2011-4/2013. Intracervical ICG was the fluorophobe in all cases. Four cc (1.25mg/mL) of ICG was injected into the cervix alone divided into the 3- and 9-o'clock positions, with 1 cc deep into the stroma and 1 cc submucosally before initiating laparoscopic entry. Blue dye was concurrently injected in some cases.Two hundred twenty-seven cases were performed. Median age was 60 years (range, 28-90 years). Median BMI was 30.2 kg/m(2) (range, 18-60 kg/m(2)). The median SLN count was 3 (range, 1-23). An SLN was identified in 216 cases (95%), with bilateral pelvic mapping in 179 (79%). An aortic SLN was identified in 21 (10%) of the 216 mapped cases. When ICG alone was used to map cases, 188/197 patients mapped, for a 95% detection rate compared to 93% (28/30) in cases in which both dyes were used (P=NS). Bilateral mapping was seen in 156/197 (79%) ICG-only cases and 23/30 (77%) ICG and blue dye cases (P=NS).NIR fluorescence imaging with intracervical ICG injection using the robotic platform has a high bilateral SLN detection rate and appears favorable to using blue dye alone and/or other modalities. Combined use of ICG and blue dye appears unnecessary.

Pub.: 04 Mar '14, Pinned: 18 Sep '17

A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer.

Abstract: Sentinel lymph node (SLN) mapping continues to evolve in the surgical staging of endometrial cancer (EC). The purpose of this trial was to identify the sensitivity, false negative rate (FNR) and FN predictive value (FNPV) of SLN compared to complete pelvic and para-aortic lymphadenectomy (LAD) in women with high-risk EC.Women with high-risk EC (grade 3, serous, clear cell, carcinosarcoma) were enrolled in this prospective surgical trial. All patients underwent preoperative PET/CT and intraoperative SLN biopsy followed by LAD. Patients with peritoneal disease on imaging or at the time of surgery were excluded. Patients were evaluable if SLN was attempted and complete LAD was performed.123 patients were enrolled between 4/13 and 5/16; 101 were evaluable. At least 1 SLN was identified in 89% (90); bilateral detection 58%, unilateral pelvic 40%, para-aortic only 2%. Indocyanine green was used in 61%, blue dye in 28%, and blue dye and technetium in 11%. Twenty-three pts. (23%) had ≥1 positive node. In 20/23, ≥1 SLN was identified and in 19/20 the SLN was positive. Only 1 patient had bilateral negative SLN and positive non-SLNs on final pathology. Overall, sensitivity of SLN was 95% (19/20), FNR was 5% (1/20) and FNPV was 1.4% (1/71). If side-specific LAD was performed when a SLN was not detected, the FNR decreased to 4.3% (1/23).This prospective trial demonstrated that SLN biopsy plus side-specific LAD, when SLN is not detected, is a reasonable alternative to a complete LAD in high-risk endometrial cancer.

Pub.: 23 May '17, Pinned: 18 Sep '17

Sentinel lymph node mapping in minimally invasive surgery: Role of imaging with color-segmented fluorescence (CSF).

Abstract: Sentinel lymph node mapping, alone or in combination with pelvic lymphadenectomy, is considered a standard approach in staging of patients with cervical or endometrial cancer [1-3]. The goal of this video is to demonstrate the use of indocyanine green (ICG) and color-segmented fluorescence when performing lymphatic mapping in patients with gynecologic malignancies.Injection of ICG is performed in two cervical sites using 1mL (0.5mL superficial and deep, respectively) at the 3 and 9 o'clock position. Sentinel lymph nodes are identified intraoperatively using the Pinpoint near-infrared imaging system (Novadaq, Ontario, CA). Color-segmented fluorescence is used to image different levels of ICG uptake demonstrating higher levels of perfusion. A color key on the side of the monitor shows the colors that coordinate with different levels of ICG uptake. Color-segmented fluorescence may help surgeons identify true sentinel nodes from fatty tissue that, although absorbing fluorescent dye, does not contain true nodal tissue. It is not intended to differentiate the primary sentinel node from secondary sentinel nodes. The key ranges from low levels of ICG uptake (gray) to the highest rate of ICG uptake (red).Bilateral sentinel lymph nodes are identified along the external iliac vessels using both standard and color-segmented fluorescence. No evidence of disease was noted after ultra-staging was performed in each of the sentinel nodes.Use of ICG in sentinel lymph node mapping allows for high bilateral detection rates. Color-segmented fluorescence may increase accuracy of sentinel lymph node identification over standard fluorescent imaging. The following are the supplementary data related to this article.

Pub.: 21 Jun '17, Pinned: 18 Sep '17

Sentinel lymph node mapping for grade 1 endometrial cancer: is it the answer to the surgical staging dilemma?

Abstract: To describe the accuracy of SLN mapping in patients with a preoperative diagnosis of grade 1 endometrial cancer.A prospective, non-randomized study of women with a preoperative diagnosis of endometrial cancer and clinical stage I disease was conducted. A subset analysis of patients with a preoperative diagnosis of grade 1 endometrial endometrioid cancer was performed. All patients had preoperative lymphoscintigraphy with Tc99m on the day of or day before surgery followed by an intraoperative injection of 2 cm(3) of isosulfan or methylene blue dye deep into the cervix or both cervix and fundus. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and regional nodal dissection. Hot and/or blue nodes were labeled as SLNs and sent for histopathological analysis.Forty-two patients with a preoperative diagnosis of grade 1 endometrial carcinoma treated from 3/06 to 8/08 were identified. Twenty-five (60%) had laparoscopic surgery; 17 (40%) were treated by laparotomy. Preoperative lymphoscintigraphy visualized SLNs in 30 patients (71%); intraoperative localization of the SLN was possible in 36 patients (86%). A median of 3 SLNs (range, 1-14) and 14.5 non-SLNs (range, 4-55) were examined. In all, 4/36 (11%) had positive SLNs-3 seen on H&E and 1 as cytokeratin-positive cells on IHC. All node-positive cases were picked up by the SLN; there were no false-negative cases. The sensitivity of the SLN procedure in the 36 patients who had an SLN identified was 100%.Sentinel lymph node mapping using a cervical injection with combined Tc and blue dye is feasible and accurate in patients with grade 1 endometrial cancer and may be a reasonable option for this select group of patients. Regional lymphadenectomy remains the gold standard in many practices, particularly for the approximately 15% of cases with failed SLN mapping.

Pub.: 24 Feb '09, Pinned: 28 Aug '17

The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes.

Abstract: To determine the false-negative rate of a surgical sentinel lymph node (SLN) mapping algorithm that incorporates more than just removing SLNs in detecting metastatic endometrial cancer.A prospective database of all patients who underwent lymphatic mapping for endometrial cancer was reviewed. Cervical injection of blue dye was used in all cases. The surgical algorithm is as follows: 1) peritoneal and serosal evaluation and washings; 2) retroperitoneal evaluation including excision of all mapped SLNs and suspicious nodes regardless of mapping; and 3) if there is no mapping on a hemi-pelvis, a side-specific pelvic, common iliac, and interiliac lymph node dissection (LND) is performed. Paraaortic LND is performed at the attendings' discretion. The algorithm was retrospectively applied.From 9/2005 to 4/2011, 498 patients received a blue dye cervical injection for SLN mapping. At least one LN was removed in 95% of cases (474/498); at least one SLN was identified in 81% (401/498). SLN correctly diagnosed 40/47 patients with nodal metastases who had at least one SLN mapped, resulting in a 15% false-negative rate. After applying the algorithm, the false-negative rate dropped to 2%. Only one patient, whose LN spread would not have been caught by the algorithm, had an isolated positive right paraaortic LN with a negative ipsilateral SLN and pelvic LND.Satisfactory SLN mapping in endometrial cancer requires adherence to a surgical SLN algorithm and goes beyond just the removal of blue SLNs. Removal of any suspicious node along with side-specific lymphadenectomy for failed mapping are an integral part of this algorithm. Further validation of the false-negative rate of this algorithm is necessary.

Pub.: 01 Mar '12, Pinned: 28 Aug '17

Impact of incorporating an algorithm that utilizes sentinel lymph node mapping during minimally invasive procedures on the detection of stage IIIC endometrial cancer.

Abstract: To determine whether the frequency of cases diagnosed with stage IIIC endometrial cancer is affected by the incorporation of a modified surgical lymph node assessment.Since 2008, we have increasingly utilized a modified nodal assessment using an algorithm that incorporates SLN mapping. For this analysis, we identified all cases of newly diagnosed endometrial cancers undergoing a minimally invasive staging procedure not requiring conversion to laparotomy from 1/1/08 to 12/31/10. Procedures were categorized as standard, modified, and hysterectomy only. Differences were based on time period: 2008 (Y1), 2009 (Y2), and 2010 (Y3). Appropriate statistical tests were used.We identified a total of 507 cases. The distribution of cases was 143 (Y1), 190 (Y2), and 174 (Y3). Tumor grade (P=0.05) and high-risk histologies (P=0.8) did not differ during the 3 time periods. A standard staging procedure was performed in the following cases: Y1 (93/143; 65%), Y2 (66/166; 35%), and Y3 (40/164; 23%) (P<0.001). Median operative times were as follows: Y1 (218 min), Y2 (198 min), and Y3 (176.5 min) (P<0.001). The median numbers of total lymph nodes removed among cases with at least 1 node retrieved were: Y1 (20); Y2 (10); Y3 (7) (P<0.001). Cases diagnosed as stage IIIC were as follows: Y1 (10/143; 7%), Y2 (15/166; 7.9%), and Y3 (13/164; 7.5%) (P=1.0).The incorporation of a modified staging approach utilizing the SLN mapping algorithm reduces the need for standard lymphadenectomy and does not appear to adversely affect the rate of stage IIIC detection.

Pub.: 17 Jan '13, Pinned: 28 Aug '17

Sentinel lymph node mapping with pathologic ultrastaging: a valuable tool for assessing nodal metastasis in low-grade endometrial cancer with superficial myoinvasion.

Abstract: To report the incidence of nodal metastases in patients presenting with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node (SLN) mapping protocol including pathologic ultrastaging.All patients from 9/2005 to 12/2011 who underwent endometrial cancer staging surgery with attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with <50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (H&E). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells.Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology-13 cases on routine H&E, 12 cases after ultrastaging. Patients whose tumors had a DMI <50% were more likely to have positive SLNs on routine H&E (p<0.005) or after ultrastaging (p=0.01) compared to those without myoinvasion.Applying a standardized SLN mapping algorithm with ultrastaging allows for the detection of nodal disease in a presumably low-risk group of patients who in some practices may not undergo any nodal evaluation. Ultrastaging of SLNs can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion. The long-term clinical significance of ultrastage-detected nodal disease requires further investigation as recurrences were noted in some of these cases.

Pub.: 09 Oct '13, Pinned: 28 Aug '17

Comparison of a sentinel lymph node and a selective lymphadenectomy algorithm in patients with endometrioid endometrial carcinoma and limited myometrial invasion.

Abstract: To assess clinicopathologic outcomes between two nodal assessment approaches in patients with endometrioid endometrial carcinoma and limited myoinvasion.Patients with endometrial cancer at two institutions were reviewed. At one institution, a complete pelvic and para-aortic lymphadenectomy to the renal veins was performed in select cases deemed at risk for nodal metastasis due to grade 3 cancer and/or primary tumor diameter>2cm (LND cohort). This is a historic approach at this institution. At the other institution, a sentinel lymph node mapping algorithm was used per institutional protocol (SLN cohort). Low risk was defined as endometrioid adenocarcinoma with myometrial invasion <50%. Macrometastasis, micrometastasis, and isolated tumor cells were all considered node-positive.Of 1135 cases identified, 642 (57%) were managed with an SLN approach and 493 (43%) with an LND approach. Pelvic nodes (PLNs) were removed in 93% and 58% of patients, respectively (P<0.001); para-aortic nodes (PANs) were removed in 14.5% and 50% of patients, respectively (P<0.001). Median number of PLNs removed was 6 and 34, respectively; median number of PANs removed was 5 and 16, respectively (both P<0.001). Metastasis to PLNs was detected in 5.1% and 2.6% of patients, respectively (P=0.03), and to PANs in 0.8% and 1.0%, respectively (P=0.75). The 3-year disease-free survival rates were 94.9% (95% CI, 92.4-97.5) and 96.8% (95% CI, 95.2-98.5), respectively.Our findings support the use of either strategy for endometrial cancer staging, with no apparent detriment in adhering to the SLN algorithm. The clinical significance of disease detected on ultrastaging and the role of adjuvant therapy is yet to be determined.

Pub.: 10 Jan '16, Pinned: 28 Aug '17