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Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment. This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors. Our study highlighted that SNM provides similar long-term oncologic outcomes than LND. • Sentinel node mapping (SNM) allows an accurate detection of nodal involvement. • Low volume disease accounts for about 50% of nodal disease diagnosed with SNM. • Backup lymphadectomy does not improve oncologic outcomes in comparison to SNM alone. [ABSTRACT FROM AUTHOR]

Sentinel node mapping is increasingly being utilized for endometrial cancer staging. However, only limited evidence supporting the adoption of sentinel node mapping instead of conventional lymphadenectomy is still available. Here, we aimed to review the current evidence comparing sentinel node mapping and lymphadenectomy in endometrial cancer staging. This systematic review was registered in the International Prospective Register of Systematic Reviews. Six comparative studies were included. Overall, 3536 patients were included: 1249 (35.3%) and 2287 (64.7%), undergoing sentinel node mapping and lymphadenectomy, respectively. Pooled data suggested that positive pelvic nodes were detected in 184 out of 1249 (14.7%) patients having sentinel node mapping and 228 out of 2287 (9.9%) patients having lymphadenectomy (OR: 2.03; (95%CI: 1.30 to 3.18); p = 0.002). No difference in detection of positive nodes located in the paraaortic was observed (OR: 93 (95%CI: 0.39 to 2.18); p = 0.86). Overall recurrence rate was 4.3% and 7.3% after sentinel node mapping and lymphadenectomy, respectively (OR: 0.90 (95%CI: 0.58 to 1.38); p = 0.63). Similarly, nodal recurrences were statistically similar between groups (1.2% vs. 1.7%; OR: 1.51 (95%CI: 0.70 to 3.29); p = 0.29). In conclusion, our meta-analysis underlines that sentinel node mapping is non-inferior to standard lymphadenectomy in term of detection of paraaortic nodal involvement and recurrence rates (any site and nodal recurrence); while, focusing on the ability to detect positive pelvic nodes, sentinel node mapping could be consider superior to lymphadenectomy. Further randomized studies are needed to asses long term effectiveness of sentinel node mapping. • Sentinel node mapping allows an accurate identification of nodal disease in the pelvic area in comparison to lymphadenectomy. • Sentinel node mapping is non inferior to lymphadenectomy in terms of para-aortic detection rate. • Sentinel node mapping does not increase nodal-specific recurrence. [ABSTRACT FROM AUTHOR]

Nodal assessment represents an integral part of staging procedure for endometrial cancer. The widespread diffusion of sentinel node mapping determinates a phenomenon of migration from stage I to stage III disease, especially for low-risk endometrial cancer patients. The adoption of sentinel node mapping and pathological ultrastaging increase the detection of low volume disease (i.e., micrometastasis and isolated tumor cells), being low volume disease detected in >30% of patients with positive nodes. The prognostic role of low volume disease is discussed as well as the possible adjuvant strategies for patients diagnosed with micrometastasis and isolated tumor cells. The role of further prospective treatments in endometrial cancer, including molecular and genetic profiling, is critically reviewed. • Sentinel node mapping improves detection of stage IIIC endometrial cancer. • Patients at low risk of lymphatic spread are more likely to be diagnosed with low volume disease. • Patients with micrometastasis in sentinel nodes should be receive adjuvant treatment. • Patients with isolated tumor cells in sentinel nodes deserve to be treated on the basis of uterine factors. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to determine the impact of the sentinel lymph node mapping algorithm (SLN-A) on the staging in high-risk endometrial cancer (EC) compared to SLN plus selective lymphadenectomy (S-LND). Methods We retrospectively analyzed the database from a multicenter collaboration that included women with high risk features who underwent primary surgical staging. Results One-hundred and seventy-one women were identified (171), 66 in the SLN-A and 105 in the S-LND group, respectively. Pelvic LD was performed on 115 patients (67.2%) and aortic dissection was performed in 54/105 of the women in the S-LND group (51%). The 5-year comparison did not show a significant difference in the strategy adopted for nodal staging, regarding disease-free survival (DFS) [HR: 0.82; 95% CI 0.53–1.28; p  = 0.390]. Conclusions In this study focusing on women with EC in the HR groups, we did not find a difference in the 5-year DFS when comparing the SLN-A strategy with S-LND. The SLN strategy did not seem to compromise the prognosis of patients with a higher risk of recurrence. [ABSTRACT FROM AUTHOR]

Objective To determine the validity of sentinel lymph node (SLN) biopsy with ICG in endometrial cancer and to evaluate the factors associated with poor mapping or false negative. Methods We reviewed all patients who underwent primary surgery for endometrial carcinoma with SLN mapping using ICG followed by pelvic lymphadenectomy from February 2014 to December 2015. SLNs were ultrastaged on final pathology. Patients' demographics, surgical approach and histopathological factors were prospectively collected. Detection rate, sensitivity and negative predictive value (NPV) were calculated and univariate analysis was performed to evaluate factors associated with failed bilateral detection of SLNs. Results A total of 119 patients were included. The overall and bilateral detection rates were 93% and 74%. Sensitivity and NPV were 100% in patients with bilateral detection; 95% and 99% respectively in cases with at least unilateral detection. Advanced FIGO stage (III or IV) was the only factor related to failed bilateral detection ( p  = 0.01). In 14 hemi-pelvis, the specimen labelled as SLN did not contain nodal tissue on final pathology (only lymphatic channels), which represented 37% of the “failed detection” cases. One false negative occurred in a patient with an ipsilateral clinically suspicious enlarged lymph node. Conclusion ICG is an excellent tracer for SLN mapping in endometrial cancer. Advanced FIGO stage correlated with failed bilateral detection ( p  = 0.01). Suspicious lymph nodes should be removed regardless of the mapping. Care should be taken to ensure that SLN specimen actually contains nodal tissue and not only swollen lymphatic channels, as this represents a significant cause of failed SLN mapping. [ABSTRACT FROM AUTHOR]

Objective While the accuracy of the SLN procedure has been validated in patients with low risk EC, its relevance for high-risk EC remains debated. The aim of this study was to evaluate the accuracy of SLN mapping in patients with high-risk EC. Study Method. We reviewed all patients with high risk EC (grade 3 endometrioid, serous, carcinosarcoma, clear cell and undifferentiated) who underwent primary surgery with SLN mapping followed by pelvic +/− paraaortic lymphadenectomy, between November 2010 and November 2016. Results Among 128 patients who underwent SLN mapping followed by a pelvic lymph node dissection, 41 (32%) had a positive pelvic lymph node. Overall, 48.8% of patients underwent paraaortic node sampling (62/128). Paraaortic lymph node metastasis was identified in 17.7% of patients in whom a para-aortic lymph node dissection was performed (11/62), and all had positive pelvic lymph nodes as well. Successful SLN mapping occurred in 115/128 (89,8%) patients, with a bilateral detection rate at 63.2% (81/128). Positive SLNs were identified in 30.4% of patients (39/128) including 7 isolated tumor cells (ITC), 4 micrometastasis and 28 macrometastasis. When the SLNs were detected bilaterally, only one false negative case occurred, providing a sensitivity and negative predictive value of 95.8% and 98.2% respectively. Conclusion Accurate surgical staging is an important prognostic predictor of survival in patients with endometrial cancer. Given the high sensitivity and high negative predictive value found in our study, we believe that the use of SLN mapping appears to be an appropriate staging procedure in high-risk endometrial cancer. [ABSTRACT FROM AUTHOR]

Objective To determine if a sentinel lymph node (SLN) mapping algorithm will detect metastatic nodal disease in patients with intermediate −/high-risk endometrial carcinoma. Methods Patients were identified and surgically staged at two collaborating institutions. The historical cohort (2004–2008) at one institution included patients undergoing complete pelvic and paraaortic lymphadenectomy to the renal veins (LND cohort). At the second institution an SLN mapping algorithm, including pathologic ultra-staging, was performed (2006–2013) (SLN cohort). Intermediate-risk was defined as endometrioid histology (any grade), ≥ 50% myometrial invasion; high-risk as serous or clear cell histology (any myometrial invasion). Patients with gross peritoneal disease were excluded. Isolated tumor cells, micro-metastases, and macro-metastases were considered node-positive. Results We identified 210 patients in the LND cohort, 202 in the SLN cohort. Nodal assessment was performed for most patients. In the intermediate-risk group, stage IIIC disease was diagnosed in 30/107 (28.0%) (LND), 29/82 (35.4%) (SLN) ( P = 0.28). In the high-risk group, stage IIIC disease was diagnosed in 20/103 (19.4%) (LND), 26 (21.7%) (SLN) ( P = 0.68). Paraaortic lymph node (LN) assessment was performed significantly more often in intermediate −/high-risk groups in the LND cohort ( P < 0.001). In the intermediate-risk group, paraaortic LN metastases were detected in 20/96 (20.8%) (LND) vs. 3/28 (10.7%) (SLN) ( P = 0.23). In the high-risk group, paraaortic LN metastases were detected in 13/82 (15.9%) (LND) and 10/56 (17.9%) (SLN) (%, P = 0.76). Conclusions SLN mapping algorithm provides similar detection rates of stage IIIC endometrial cancer. The SLN algorithm does not compromise overall detection compared to standard LND. [ABSTRACT FROM AUTHOR]

Objective The role of lymphadenectomy in endometrial cancer is still uncertain. We aimed to evaluate the survival outcomes of two different strategies in apparent uterine confined disease by comparing sentinel lymph node (SLN) mapping and selective lymphadenectomy (LD). Methods We retrospectively reviewed women with preoperative stage I endometrial cancer underwent surgical staging with either SLN mapping, or LD in two Italian centers. Results Eight hundred and two women underwent surgical staging for preoperative stage I endometrial cancer were revised (145 Monza; 657 Rome). All patients underwent peritoneal washing, simple hysterectomy with bilateral salpingo-oophorectomy and nodal staging including SLN mapping, or LD. Overall 8229 lymph nodes were removed (1595 in Monza, 6634 in Rome). Pelvic lymphadenectomy was performed in 33.1% and 52.4% in Monza and Rome, respectively (p < 0.001). Patients with positive pelvic LN were 16.7% and 7.3%, in SLN and LD groups, respectively (p = 0.002). Disease-free survival (DFS) curves did not showed a statistically significant difference between centers and strategies adopted (SLN mapping, LD, SLN + LD) with a HR of 0.87 (95% CI 0.63–2.16; p = 0.475). Conclusions Survival outcomes were similar for both strategies. The SLN strategy allowed to identify a higher rate of stage IIIC1 disease even with a lower median number of lymph node removed in SLN group. Applying a SLN algorithm does not impair the prognosis of endometrial cancer patients. The clinical impact and management of low volume metastasis in high-risk patients should be further clarify. [ABSTRACT FROM AUTHOR]

Objective To evaluate the outcome and the role of adjuvant treatment in the management of patients with endometrial cancer and isolated tumor cells (ITCs) identified by SLN mapping. Methods This single center study identified all patients undergoing hysterectomy, salpingo-oophorectomy, lymphadenectomy and SLN mapping for endometrial cancer between November 2010 and December 2015. Data was prospectively collected. Progression-free survival was analyzed according to the Kaplan-Meier method and compared using the log-rank test. Results A total of 519 patients were included. Overall, 85 patients (16.4%) were found to have SLN metastases of which 43 (51%) were macrometastasis, 11 (13%) micrometastasis (MM) and 31 (36%) ITC. Eleven (35%) of patients with ITCs received adjuvant chemotherapy ± whole pelvic radiation therapy (WPRT), 10 (32%) received WPRT, and 10 (32%) received either no adjuvant treatment or vault brachytherapy (VBT) only. ITC patients received significantly less chemotherapy (p = 0.0001) and WPRT (p = 0.007) compared to patients with macrometastasis. Of note, ITC were not considered node positive in our study. With a median follow-up of 29 months (range: 0–67), the progression free survival (PFS) at 3-years for the ITC patients was 95.5%, similar to node negative (87.6%) and micrometastasis patients (85.5%), but statistically better than patients with macrometastasis (58.5%) (p = 0.0012). Only 1/31 patient with ITC recurred (IB, 7 cm carcinosarcoma) despite adjuvant treatments. None of the ITC patients with endometrioid histology recurred (0/28) and none of the ITC patients who did not receive adjuvant treatment or VBT recurred (0/10). Conclusions Patients with endometrial cancer found to have SLN ITCs have an excellent outcome. The use of adjuvant treatment should be tailored to uterine factors and histology and not solely based on the presence of ITCs. Patients with ITCs and otherwise low-risk uterine disease probably derive little benefit from receiving additional treatments. More studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]

Objectives Indocyanine green (ICG) with near-infrared (NIR) fluorescence imaging is a new tracer modality used for lymphatic mapping. We report our initial experience with ICG for SLN mapping in cervical and endometrial cancer using a new endoscopic fluorescence imaging system. Methods We reviewed all patients who underwent primary surgery for early-stage endometrial and cervical carcinoma with SLN mapping using fluorescence imaging followed by pelvic lymphadenectomy from February to July 2014. Intracervical injection of ICG at 3 and 9 o'clock was performed in all cases. SLNs were ultrastaged on final pathology. Sensitivity and specificity values were calculated. Results A total of 50 patients were included in the study (42 endometrial and 8 cervical cancers). The median age was 62 (24-88) and median BMI 29 (19-56). The median SLN count was 3.1 (0-7) and median lymph node count was 15 (2-37). The overall and bilateral detection rate was 96% (48/50) and 88% (44/50). Positive SLNs were identified in 22% of patients (11/50), including 8 isolated tumor cells (ITC), 2 micrometastasis and 1 macrometastasis. There was one side-specific false negative case. Sensitivity, specificity and NPV were 93.3%, 100% and 98.7% respectively per side. Paraaortic node dissection was performed in 22% of cases. Two had paraaortic node metastasis both in patients with positive pelvic SLN. There were no allergic reactions to the ICG. Conclusions Based on our pilot experience, NIR fluorescence imaging with ICG is an excellent and safe tracer modality for SLN mapping with a very high overall (96%) and bilateral (88%) detection rate. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine which patients with near midline lesions may safely undergo unilateral groin dissection based on clinical exam and lymphoscintigraphy (LSG) results. Methods: Patients participating in GOG-173 underwent sentinel lymph node (SLN) localization with blue dye, and radiocolloid with optional LSG before definitive inguinal–femoral lymphadenectomy (LND). This analysis interrogates the reliability of LSG alone relative to primary tumor location in those patients who had an interpretable LSG and at least one SLN identified. Primary tumor location was categorized as lateral (>2cm from midline), midline, or lateral ambiguous (LA) if located within 2cm, but not involving the midline. Results: Two-hundred-thirty-four patients met eligibility criteria. Sixty-four had lateral lesions, and underwent unilateral LND. All patients with LA (N=65) and midline (N=105) tumors underwent bilateral LND. Bilateral drainage by LSG was identified in 14/64 (22%) patients with lateral tumors, 38/65 (58%) with LA tumors and in 73/105 (70%) with midline tumors. At mapping, no SLNs were found in contralateral groins among those patients with LA and midline tumors who had unilateral-only LSGs. However, in these patients groin metastases were found in 4/32 patients with midline tumors undergoing contralateral dissection; none were found in 27 patients with LA tumors. Conclusion: The likelihood of detectable bilateral drainage using preoperative LSG decreases as a function of distance from midline. Patients with LA primaries and unilateral drainage on LSG may safely undergo unilateral SLN. [Copyright &y& Elsevier]

Abstract: Objectives. : Planar lymphoscintigraphy (LSG) is frequently performed for the assessment of the sentinel lymph nodes (SLN) in gynecologic malignancies. Planar imaging helps to localize hot nodes but lacks accuracy of the anatomic location of those nodes. In this study, we compared SPECT-CT to planar LSG in endometrial and cervical cancer to assess its ability to localize SLN. Methods. : We conducted a prospective nonrandomized study of SLN mapping in women with endometrial and cervical cancer. Forty patients with endometrial cancer and 10 with cervical cancer underwent pre-operative LSG with 1 or 4 mCi of 99mTc sulfur colloid administered as injections into the cervix. All patients were scanned immediately with planar LSG obtained in the anterior and lateral views. SPECT-CT imaging was obtained following the planar imaging. Results. : Planar LSG alone localized SLN in 30/40 (75%) endometrial cancer patients while SPECT-CT localized SLN in all 40 patients (100%). In the 10 cases where SLN was not identified with planar imaging, SPECT-CT localized nodes in the external iliac, internal iliac, common iliac and obturator groups. In cervical cancer, planar LSG alone localized sentinel lymph nodes in 8/10 patients (80%) as compared to SPECT-CT, which localized nodes in all 10 patients (100%). SPECT-CT imaging was especially useful in delineating external iliac versus internal iliac or obturator nodes, and the parametrial nodal uptake. Conclusions. : SPECT-CT appears to improve sentinel lymph node detection and anatomic localization as compared to planar imaging in cervical and uterine cancer. [Copyright &y& Elsevier]

Abstract: Objectives: To describe the surgical and pathologic findings of fertility-sparing radical abdominal trachelectomy using a standardized surgical technique, and report the rate of post-trachelectomy adjuvant therapy that results in permanent sterility. Methods: A prospectively maintained database of all patients with FIGO stage IB1 cervical cancer admitted to the operating room for planned fertility-sparing radical abdominal trachelectomy was analyzed. Sentinel node mapping was performed via cervical injection of Technetium and blue dye. Results: Between 6/2005 and 5/2008, 22 consecutive patients with FIGO stage IB1 cervical cancer underwent laparotomy for planned fertility-sparing radical abdominal trachelectomy. Median age was 33 years (range, 23–43). Histology included 13 (59%) with adenocarcinoma and 9 (41%) with squamous carcinoma. Lymph-vascular invasion was seen in 9 (41%) cases. Only 3 (14%) needed immediate completion radical hysterectomy due to intraoperative findings (2 for positive nodes, 1 for positive endocervical margin). Median number of nodes evaluated was 23 (range, 11–44); and 6 (27%) patients had positive pelvic nodes on final pathology — all received postoperative chemoradiation. Sixteen (73%) patients agreed to participate in sentinel node mapping which yielded a detection rate of 100%, sensitivity of 83%, specificity of 100% and false-negative rate of 17%. Eighteen of 19 (95%) patients who completed trachelectomy had a cerclage placed, and 9/22 (41%) patients had no residual cervical carcinoma on final pathology. Median time in the operating room was 298 min (range, 180–425). Median estimated blood loss was 250 ml (range, 50–700), and median hospital stay was 4 days (range, 3–6). No recurrences were noted at the time of this report. Conclusions: Cervical adenocarcinoma and lymph-vascular invasion are common features of patients selected for radical abdominal trachelectomy. The majority of patients can undergo the operation successfully; however, nearly 32% of all selected cases will require hysterectomy or postoperative chemoradiation for oncologic reasons. Sentinel node mapping is useful but until lower false-negative rates are achieved total lymphadenectomy remains the gold standard. Investigating alternative fertility-sparing adjuvant therapy in node positive patients is needed. [Copyright &y& Elsevier]