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Background: A complex relationship between adipose tissue and malignancy, involving an inflammatory response, has been reported. The goal of this work was to assess the prevalence of white adipose tissue (WAT) inflammation in patients with endometrial cancer (EC), and the association with circulating inflammation markers. Furthermore, the aim was to characterize the pathways activated in and the cell type composition of adipose tissue in patients with EC.Methods: Adipose tissue and blood samples were prospectively collected from 101 patients with EC at initial surgery. WAT inflammation was determined based on adipocytes surrounded by macrophages forming crown-like structures. Circulating levels of metabolic syndrome-associated and inflammatory markers were quantified. RNA-sequencing was performed on adipose samples (n = 55); differential gene expression, pathway, and cellular decomposition analyses were performed using state-of-the-art bioinformatics methods.Results: WAT inflammation was identified in 46 (45.5%) of 101 EC patients. Dyslipidemia, hypertension, and diabetes mellitus were significantly associated with WAT inflammation (p < .05). WAT inflammation was associated with greater body mass index (p < .001) and higher circulating levels of leptin, high-sensitivity C-reactive protein, and interleukin-6, as well as lower levels of adiponectin and sex hormone-binding globulin (p < .05). Transcriptomic analysis demonstrated increased levels of proinflammatory and pro-neoplastic-related gene expression in inflamed omental adipose tissue.Conclusions: WAT inflammation is associated with metabolic syndrome, obesity, and inflammatory markers, as well as increased expression of proinflammatory and proneoplastic genes. [ABSTRACT FROM AUTHOR]

To describe the incidence of adverse reactions to indocyanine green (ICG) administered during sentinel lymph node (SLN) biopsy for endometrial cancer, and to propose an ICG management algorithm for these patients. All patients who underwent surgery for endometrial cancer with SLN biopsy using ICG from 1/2017 to 8/2020 were identified using a single-institution prospective database. Surgical adverse events (SAEs) related to the procedure were identified. A review of the literature was performed. In all, 1414 patients met inclusion criteria and were evaluated. Sixty-seven (4.7%) patients had a history of either an iodine or contrast allergy. No patients had a history of documented ICG allergy. Among patients with an iodine or contrast allergy, 65 (97%) received a corticosteroid with or without diphenhydramine prior to ICG administration. One hundred five patients (7.4%) experienced 116 SAEs. Among these patients, 3 experienced potentially allergic SAEs possibly related to ICG administration. After thorough chart review, however, the likelihood these SAEs were due to ICG appeared low. No patients experienced an anaphylactic response after ICG admission. There were no anaphylactic reactions to ICG intracervical administration during 1414 consecutive SLN biopsies, including in patients with a documented iodine or contrast allergy. Intracervical injection of ICG is safe, and premedication using corticosteroids with or without diphenhydramine prior to SLN biopsy is a reasonable strategy in patients with iodinated contrast allergy. • Indocyanine green (ICG) can cause adverse reactions • There is a paucity of data regarding adverse reactions to intracervical ICG administration • Premedication prior to intracervical ICG injection is reasonable in select patients [ABSTRACT FROM AUTHOR]

To compare long-term oncologic outcomes in patients with clinically uterine-confined endometrioid endometrial cancer who underwent surgical staging with robot-assisted (RA) versus conventional laparoscopy. We performed a retrospective chart review of patients with newly diagnosed, uterine-confined endometrioid endometrial cancer who were treated and had primary surgery at our institution between 1/1/2009–1/1/2018. Clinicopathologic, surgical, and survival data were collected. Appropriate statistical methods were applied. Of 1728 patients identified, 1389 (80.4%) underwent RA and 339 (19.6%) conventional laparoscopy. At diagnosis, median age was 60 years (range, 24–92) and median BMI was 30.2 kg/m2 (range, 15.1–71.5). In the RA group, patients had longer operative time (170 vs 152 min, P <.001), lower conversion rate to laparotomy (0.6% vs 4.7%, P <.001), and a higher proportion had a BMI > 40 kg/m2 (17.2% vs 11.5%, P =.01) and same-day discharge (19.2% vs 5.3%, P <.001). Overall, 93% (RA) and 90% (conventional) of patients underwent lymph node assessment (P =.1). Comparing the RA versus conventional groups, final surgical stage on pathology (P =.6), median follow-up (55.7 vs 52.9 months, P =.4), and rates of perioperative complications (9.9% vs 7.7%, P =.6), recurrence (9.5% vs 7.4%, P =.3), 5-year PFS (88.5% vs 91.0%, P =.3), and 5-year OS (92.5% vs 92.4%, P =.7) were not significantly different. No significant increase in risk of recurrence (HR = 1.2, 95% CI: 0.8–1.9, P =.3) or poorer OS outcomes (HR = 0.9, 95% CI: 0.6–1.4, P =.7) were observed in the RA group. In uterine-confined endometrioid endometrial cancers, surgical staging using RA laparoscopy was not associated with adverse survival outcomes compared to conventional laparoscopy. • Robot-assisted laparoscopy was not associated with adverse survival outcomes compared to conventional laparoscopy. • Complication rates were similar between robot-assisted and conventional laparoscopy in early-stage endometrial cancer. • Lower rate of conversion to laparotomy and higher rate of same-day discharge were observed with robot-assisted laparoscopy. [ABSTRACT FROM AUTHOR]

To compare outcomes of patients with premalignant endometrial pathology undergoing hysterectomy with or without sentinel lymph node (SLN) removal. Outcomes of interest included surgical adverse events (AEs), cancer status on final pathology, postoperative treatment, and The Cancer Genome Atlas (TCGA) molecular risk profiles. We retrospectively identified patients with premalignant pathology on preoperative endometrial biopsy who underwent hysterectomy with or without SLN mapping/excision at our institution from 01/01/2017–12/31/2021. Clinical, pathologic, surgical, and TCGA profiling data were abstracted. Appropriate statistical tests were used. Of 221 patients identified, 161 (73%) underwent hysterectomy with SLN excision and 60 (27%) underwent hysterectomy without SLN excision. Median age and body mass index were similar between groups. Median operative time was 130 min for those who underwent SLN mapping/excision versus 136 min for those who did not (p = 0.6). Thirty-day postoperative AE rates were 9% (n = 15/161) and 13% (n = 8/60), respectively (p = 0.9). Ninety-eight (44%) of 221 patients had grade 1–2 endometrioid endometrial cancer on final pathology (4 [4%] were stage IB or higher). Ten (10%) of 98 patients, all within the SLN group, received adjuvant treatment. Among all patients, of 33 (15%) with TCGA molecular classification data, 27 (82%) had copy number-low, 3 (9%) microsatellite instability-high, 2 (6%) POLE -ultramutated, and 1 (3%) copy number-high disease. SLN assessment appears safe, detects a small number of occult nodal metastases for those upstaged, and provides additional staging information that can guide adjuvant treatment. SLN mapping should be discussed in preoperative counseling and offered using a shared decision-making approach. • Premalignant endometrial pathology is often upstaged to cancer on final pathology after hysterectomy • In this setting, sentinel lymph node (SLN) mapping detects a small number of occult lymph node metastases • SLN mapping did not increase surgical morbidity in those with premalignant endometrial pathology undergoing hysterectomy • SLN mapping in this setting can provide pertinent information if pathologic or molecular risk factors are later identified • Shared decision making can help patients understand the risks and benefits of SLN mapping in this setting [ABSTRACT FROM AUTHOR]

To compare the prevalence of patient-reported lower-extremity lymphedema (LEL) with sentinel lymph node (SLN) mapping versus comprehensive lymph node dissection (LND) for the surgical management of newly diagnosed endometrial carcinoma. Patients who underwent primary surgery for endometrial cancer from 01/2006-12/2012 were mailed a survey that included a validated 13-item LEL screening questionnaire in 08/2016. Patients diagnosed with LEL prior to surgery and those who answered ≤6 survey items were excluded. Of 1275 potential participants, 623 (49%) responded to the survey and 599 were evaluable (180 SLN, 352 LND, 67 hysterectomy alone). Median BMI was similar among cohorts (P = 0.99). External-beam radiation therapy (EBRT) was used in 10/180 (5.5%) SLN and 35/352 (10%) LND patients (P = 0.1). Self-reported LEL prevalence was 27% (49/180) and 41% (144/352), respectively (OR, 1.85; 95% CI, 1.25–2.74; P = 0.002). LEL prevalence was 51% (23/45) in patients who received EBRT and 35% (170/487) in those who did not (OR, 1.95; 95% CI, 1.06–3.6; P = 0.03). High BMI was associated with increased prevalence of LEL (OR, 1.04; 95% CI, 1.02–1.06; P = 0.001). After controlling for EBRT and BMI, LND retained independent association with an increased prevalence of LEL over SLN (OR, 1.8; 95% CI, 1.22–2.69; P = 0.003). Patients with self-reported LEL had significantly worse QOL compared to those without self-reported LEL. This is the first study to assess patient-reported LEL after SLN mapping for endometrial cancer. SLN mapping was independently associated with a significantly lower prevalence of patient-reported LEL. High BMI and adjuvant EBRT were associated with an increased prevalence of patient-reported LEL. • SLN mapping was independently associated with significantly lower rate of patient-reported lower extremity lymphedema (LEL). • Increasing BMI and use of adjuvant EBRT were associated with an increased prevalence of patient-reported LEL. • SLN mapping in the surgical management of newly diagnosed endometrial cancer may spare these patients from LEL. • Survival outcomes were similar between SLN mapping and comprehensive lymphadenectomy after endometrial cancer surgery. [ABSTRACT FROM AUTHOR]

The objective of our study was to assess survival among patients with uterine serous carcinoma (USC) undergoing sentinel lymph node (SLN) mapping alone versus patients undergoing systematic lymphadenectomy (LND). We retrospectively reviewed patients undergoing primary surgical treatment for newly diagnosed USC at our institution from 1/1/1996-12/31/2017. Patients were assigned to either SLN mapping alone (SLN cohort) or systematic LND without SLN mapping (LND cohort). Progression-free (PFS) and overall survival (OS) were estimated using Kaplan-Meier method, compared using Logrank test. 245 patients were available for analysis: 79 (32.2%) underwent SLN, 166 (67.7%) LND. 132 (79.5%) in the LND cohort had paraaortic LND (PALND) versus none in the SLN cohort. Median age: 66 and 68 years in the SLN and LND cohorts, respectively (p>0.05). Proportion of stage I/II disease: 67.1% (n = 53) and 64.5% (n = 107) in the SLN and LND cohorts, respectively (p>0.05). Median follow-up: 23 (range, 1–96) and 66 months (range, 4–265) in the SLN and LND cohorts, respectively (p < 0.001). Two-year OS in stage I/II disease (n = 160, 60.1%): 96.6% (SE ± 3.4) and 89.6% (SE ± 2.2) in the SLN and LND cohorts, respectively (p = 0.8). Two-year OS in stage III disease (n = 77): 73.6% (SE ± 10.2) and 77.3% (SE ± 5.8) in the SLN and LND cohorts, respectively (p = 0.8). SLN mapping alone and systematic LND yielded similar survival outcomes in stage I-III USC. In our practice, the SLN algorithm has replaced systematic LND as the primary staging modality in this setting. • Systematic LND showed no survival benefit vs SLN mapping alone in patients with USC. • Detection of nodal metastasis is the same in SLN mapping alone vs systematic LND. • Advanced disease and LVSI were the most significant factors in oncologic outcomes. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess outcomes in a cohort of patients (pts) with a preoperative diagnosis of atypical endometrial hyperplasia undergoing hysterectomy with and without sentinel node evaluation and to assess molecular classification in this cohort. Methods: We included all patients in our prospective database (between 2017 and 2021) diagnosed with premalignant pathology on preoperative endometrial biopsy (including endometrial intraepithelial neoplasia, complex atypical hyperplasia, and hyperplasia bordering on carcinoma) who underwent hysterectomy (HYST) and hysterectomy with sentinel lymph node (SLN) mapping. All biopsies were reviewed by gynecologic pathologists. Clinical, pathologic, surgical, and treatment data and TCGA molecular classification were abstracted, and appropriate statistical tests were utilized. Results: We identified 221 pts; 161 (73%) SLN and 60 (27%) HYST. Median age (56 vs 57 years, p=0.1) and BMI (33 vs 34 kg/m2, p=0.4) were similar. Bilateral SLN mapping was documented for 158 (98%) SLN pts. Of 221 pts, 98 (45%) had FIGO grade 1-2 endometrioid endometrial cancer (EC) on final hysterectomy pathology: 17 (28%) HYST and 81 (50%) SLN pts (p=0.003). Myoinvasion was identified in 15/221 (7%) pts, with 2/15 (13%) being the outer half myoinvasion. Among 98 pts with EC, four (4%) were stage IB or higher, including one pt with stage IIIC and one with stage IIIA. Among 161 patients in the SLN group, one (0.6%) was node-positive and three (2%) pts had isolated tumor cells in an SLN. Ten of 98 (10%) pts received adjuvant treatment, and all were within the SLN group (chemotherapy [ n =1], IVRT [ n =8], or combination chemotherapy and radiation [ n =1]). No pt has recurred in either group, with a median follow-up of 13.8 mos (range: 0.4-52). Eight of 60 HYST (13%) and 15/161 SLN (9%) pts had a postoperative 30-day adverse event (p=0.9). TCGA molecular classification was available for 38 pts: 32 (87%) CN-L, three (8%) MSI-H, two (5%) POLE , and no CN-H pts. Conclusions: Among pts with a preoperative biopsy of premalignant endometrial pathology, 45% were upgraded to endometrial cancer, including 7% with myoinvasion and variable TCGA molecular subtype. SLN mapping did not increase postoperative morbidity and showed a low incidence of occult disease but can help avoid reoperation with full lymphadenectomy for staging. Referral of pts with endometrial hyperplasia to gynecologic oncologists provides an opportunity for shared decision-making to balance the risks and benefits of SLN biopsy. [ABSTRACT FROM AUTHOR]