Is sentinel lymph node assessment useful in patients with a preoperative diagnosis of endometrial intraepithelial neoplasia?

OBJECTIVE: To determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy. METHODS: Retrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021. RESULTS: One hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2-3 EC including 8 with >50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading >50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy. CONCLUSIONS: Information from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging.

Scalp cooling for reducing alopecia in gynecology oncology patients treated with dose-dense chemotherapy: A pilot project.

OBJECTIVE: Determine the efficacy of scalp cooling for the prevention of chemotherapy-induced alopecia in gynecology oncology patients. METHODS: This prospective pilot study included patients diagnosed with a gynecological malignancy that received DigniCap™ scalp cooling. Patients were divided into two groups based on chemotherapy regimen: Carboplatin with area under the curve (AUC) 5-6 every three weeks and (1) conventional Paclitaxel 175 mg/m2 every three weeks or (2) Paclitaxel 80 mg/m2 weekly. A 1-10 visual analogue scale (1 no hair loss, 10 - complete hair loss) was used to assess degree of hair loss by patients themselves and by a certified dermatologist using photographs. Changes in quality of life and body image were measured using the European Organization for Research and Treatment of Cancer quality of life questionnaire version 3 (EORTC QLQ-C30) and the Body Image Scale (BIS) for cancer patients. RESULTS: Hair preservation occurred with use of a scalp cooling device for patients receiving weekly Paclitaxel (n = 20), but not conventional every three weeks Paclitaxel (n = 8). Ten of 15 patients (66.7%) in the dose-dense group lost less than 50% of their hair based on self-assessment and 14 of 16 (87.5%) based on dermatologist assessment. No patient in this group acquired a cranial prosthesis (wig). There was no difference between groups in terms of quality of life (QoL) and BIS scores. CONCLUSION: Scalp cooling may allow for hair preservation in gynecology oncology patients receiving Carboplatin AUC 5-6 and weekly Paclitaxel 80 mg/m2 combination chemotherapy.

Sentinel Lymph Node Sampling as an Alternative to Lymphadenectomy in Patients With Endometrial Cancer and Obesity.

OBJECTIVE: Although its use in endometrial cancer staging is relatively new, sentinel lymph node (SLN) sampling has been shown to be highly accurate and is associated with few complications. However, some studies report lower rates of detection with SLN sampling among patients with obesity. The aim of the current study is to evaluate the feasibility of SLN sampling in endometrial cancer for patients with obesity, and to determine whether omitting lymph node dissection (LND) in surgical staging using SLN sampling impacts oncologic outcomes. METHODS: we conducted a retrospective study of patients with obesity (BMI ≥35 kg/m2), diagnosed with endometrial carcinoma between 2007 and 2017, that compared surgical and oncologic outcomes of 2 cohorts: patients who underwent LND and patients who underwent SLN without lymphadenectomy. The primary outcome was operative time. Secondary outcomes included intraoperative bleeding; lymph node assessment information; intraoperative and postoperative adverse events; and oncologic outcomes including progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS). PFS was defined as the time from surgery to the recurrence or death from any cause. OS was defined as time from diagnosis to death or the last date the patient was known to be alive, and DSS was defined as the time from the surgery to death from the disease. RESULTS: Out of 223 patients with a median BMI of 40.6 kg/m2, 140 underwent LND and 83 underwent SLN alone. The median operative time for patients in the SLN group was shorter than that of patients in the LND group (190.5 [range 108-393] vs. 238 [131-440] min; P < 0.001), and the SLN group had lower median estimated blood loss than the LND group (30 [range 0-300] vs. 40 [range 0-800] mL; P = 0.03). At the 24-month follow-up cut-off, 98% of patients were alive and 95.5% were disease free, with no significant differences in OS, DSS, and PFS between the 2 groups (P = 0.7, P = 0.8, and P = 0.4, respectively). CONCLUSIONS: In patients with obesity, omitting LND from surgical staging with SLN sampling was associated with shorter operative times and less bleeding and did not affect survival at 2 years.

Immunoglobin G/total antibody testing for SARS-CoV-2: A prospective cohort study of ambulatory patients and health care workers in two Belgian oncology units comparing three commercial tests.

BACKGROUND: Coronavirus disease (COVID-19) is interfering heavily with the screening, diagnosis and treatment of cancer patients. Better knowledge of the seroprevalence and immune response after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in this population is important to manage them safely during the pandemic. METHODS: 922 cancer patients, 100 non-cancer patients and 94 health care workers (HCW) attending the Multidisciplinary Oncology Unit of Antwerp University Hospital from 24th of March 2020 till 31st of May 2020, and the Oncology Unit of AZ Maria Middelares Hospital, Ghent, from 13th of April 2020 till 31st of May 2020 participated in the study. The Alinity® (A; Abbott) and Liaison® (D; DiaSorin) commercially available assays were used to measure SARS-CoV-2 IgG, while total SARS-CoV-2 Ig was measured by Elecsys® (R; Roche). RESULTS: In the overall study population IgG/total SARS-CoV-2 antibodies were found in respectively 32/998 (3.2%), 68/1020 (6.7%), 37/1010 (3.7%) and of individuals using the A, D or R test. Forty-six out of 618 (7.4%) persons had a positive SARS-CoV-2 polymerase chain reaction (RT-PCR) test. Seroprevalence in cancer patients (A:2.2%, D:6.2%, R:3.0%), did not significantly differ from that in non-cancer patients (A:1.1%, D:5.6%, R:0.0%), but was lower than the HCW (A:13%, D:12%, R:12%; respectively Fisher's exact test p = 0.00001, p = 0.046, p = 0.0004). A positive SARS-CoV-2 RT-PCR was found in 6.8% of the cancer patients, 2.3% of the non-cancer patients and 28.1% of the HCW (Fisher's exact test p = 0.0004). Correlation between absolute values of the different Ig tests was poor in the cancer population. Dichotomising a positive versus negative test result, the A and R test correlated well (kappa 0.82 p McNemar test = 0.344), while A and D and R and D did not (respectively kappa 0.49 and 0.57; result significantly different p McNemar test = <0.0001 for both). The rate of seroconversion (>75%) and median absolute antibody levels (A: 7.0 versus 4.7; D 74.0 versus 26.6, R: 16.34 versus 7.32; all >P Mann Whitney U test = 0.28) in cancer patients and HCW with a positive RT-PCR at least 7 days earlier did not show any differences. However, none (N = 0/4) of the patients with hematological tumours had seroconversion and absolute antibody levels remained much lower compared to patients with solid tumours (R: 0.1 versus 37.6, p 0.003; D 4.1 versus 158, p 0.008) or HCW (all p < 0.0001). CONCLUSION: HCW were at high risk of being infected by SARS-CoV-2 during the first wave of the pandemic. Seroprevalence in cancer patients was low in the study period. Although Ig immune response in cancer patients with solid tumours does not differ from healthy volunteers, patients with hematological tumours have a very poor humoral immune response. This has to be taken into account in future vaccination programmes in this population. SARS-CoV-2 antibody tests have divergent results and seem to have little added value in the management of cancer patients.

The added value of sentinel node mapping in endometrial cancer.

OBJECTIVE: To evaluate long-term oncological outcomes and the added value of sentinel lymph node sampling (SLN) compared to pelvic lymph node dissection (LND) in patients with endometrial cancer (EC). METHODS: During the evaluation phase of SLN for EC, we performed LND and SLN and retrospectively compared the oncologic outcome with the immediate non-overlapping historical era during which patients underwent LND. RESULTS: From 2007 to 2010, 193 patients underwent LND and from December 2010 to 2014, 250 patients had SLN mapping with completion LND. Both groups had similar clinical characteristics. During a median follow-up period of 6.9 years, addition of SLN was associated with more favorable oncological outcomes compared to LND with 6-year overall survival (OS) of 90% compared to 81% (p = 0.009), and progression free survival (PFS) of 85% compared to 75% (p = 0.01) respectively. SLN was associated with improved OS (HR 0.5, 95% CI 0.3-0.8, p = 0.004), and PFS (HR 0.6, 95% CI 0.4-0.9, p = 0.03) in a multivariable analysis, adjusted for age, ASA score, stage, grade, non-endometrioid histology, and LVSI. Patients who were staged with SLN were less likely to have a recurrence in the pelvis or lymph node basins compared to patients who underwent LND only (6-year recurrence-free survival 95% vs 90%, p = 0.04). CONCLUSION: Addition of SLN to LND was ultimately associated with improved clinical outcomes compared to LND alone in patients with endometrial cancer undergoing surgical staging, suggesting that the data provided by the analysis of the SLN added relevant clinical information, and improved the decision on adjuvant therapy.

The impact of wait times on oncological outcome in high-risk patients with endometrial cancer.

OBJECTIVE: To evaluate the impact of surgical wait times on outcome of patients with grade 3 endometrial cancer. METHODS: All consecutive patients surgically treated for grade 3 endometrial cancer between 2007 and 2015 were included. Patients were divided into two groups based on the time interval between endometrial biopsy and surgery: wait time from biopsy to surgery ≤12 weeks (84 days) vs more than 12 weeks. Survival analyses were conducted using log-rank tests and Cox proportional hazards models. RESULTS: A total of 136 patients with grade 3 endometrial cancer were followed for a median of 5.6 years. Fifty-one women (37.5%) waited more than 12 weeks for surgery. Prolonged surgical wait times were not associated with advanced stage at surgery, positive lymph nodes, increased lymphovascular space invasion, and tumor size (P = .8, P = 1.0, P = .2, P = .9, respectively). In multivariable analysis adjusted for clinical and pathological factors, wait times did not significantly affect disease-specific survival (adjusted hazard ratio [HR]: 1.2, 95% confidence interval [CI], 0.6-2.5, P = .6), overall survival (HR: 1.1, 95% CI, 0.6-2.1, P = .7), or progression-free survival (HR: 0.9, 95% CI, 0.5-1.7, P = .8). CONCLUSION: Prolonged surgical wait time for poorly differentiated endometrial cancer seemed to have a limited impact on clinical outcomes compared to biological factors.

Targeted sequencing of histologically defined serous endometrial cancer reflects prognosis and correlates with preoperative biopsy.

The aim of this study was to evaluate the impact of discordant endometrial sampling on the prognosis of patients finally diagnosed with uterine papillary serous carcinoma (UPSC) and to analyze UPSC mutational profile. Retrospective cohort study comparing outcomes of patients post-operatively diagnosed with UPSC and preoperatively diagnosed with endometrioid endometrial cancer (EEC) or UPSC. Genes commonly implicated in carcinogenesis were analyzed in a subgroup of 40 patients post-operatively diagnosed with UPSC, using next generation sequencing. 61 patients with UPSC on post-surgical, final pathology were included in the study. Prior to surgery, 15 were diagnosed with EEC (discordant) and 46 were correctly diagnosed with UPSC (concordant). After a median follow-up of 41.6 months [5.4-106.7], a preoperative diagnosis of EEC was associated with better 3-year progression-free survival (100% vs. 60.9%, P = 0.003) and longer disease free interval (63.5 versus 15 months, P = 0.026) compared to patients with an initial diagnosis of UPSC. Patients with a concordant diagnosis of UPSC were 5 times more likely to progress or die compared to those with a discordant EEC diagnosis (P = 0.02, P = 0.03, respectively), and their tumors were associated with higher rates of TP53 (88.9% vs. 61.5%, P = 0.04), and a lower rate of PTEN (14.8% vs. 38.5%, P = 0.09) and ARID1A (3.7% vs. 23.1%, P = 0.05) mutations. A pre-surgical diagnosis of EEC is associated with improved prognosis in patients with UPSC. Some histologically defined UPSC tumors contain endometrioid-like molecular characteristics that may confer a survival advantage, suggesting a possible need for molecular approaches to better stratify patients into risk groups.

Risk factors for lymph nodes involvement in obese women with endometrial carcinomas.

OBJECTIVE: To assess risk factors for lymph node involvement in patients with endometrial cancer and a body-mass index (BMI) ≥30 kg/m2. MATERIALS AND METHODS: A retrospective analysis was performed of obese patients diagnosed with endometrial carcinoma between 2007 and 2015, treated in a single center in Montreal. Preoperative variables evaluated were age, BMI, parity, and preoperative ASA score, grade, CA-125 and histology. Odds ratios (OR) and hazard ratios (HR) and their respective 95% confidence intervals (95%CI) were calculated using multivariable logistic regression and Cox proportional hazard models. RESULTS: The study included 230 women with BMI ≥30, 223 (97.0%) had complete staging. Pelvic lymph node involvement was detected in 26 patients (11.3%). Sentinel node detection and pelvic lymph node dissection decreased with increasing BMI (adjusted OR 0.86, 95%CI 0.76-0.97 and 0.76, 95%CI 0.59-0.96, respectively, per 1 kg/m2 increment). Pelvic lymph node involvement was inversely correlated with BMI (adjusted OR 0.88, 95%CI 0.79-0.99) and present in 16/85 (18.8%), 6/56 (10.7%), and 4/82 (4.9%) of patients with a BMI of 30.0-34.9, 35.0-39.9, and ≥40.0 kg/m2, respectively. Preoperative CA-125 was associated with lymph node involvement (adjusted OR 2.77, 95%CI 1.62-4.73, per quartile increment). CONCLUSION: Pelvic lymph node dissection might be omitted in selected cases of morbidly obese patients with failed sentinel nodes mapping and a low CA-125.

Impact of lower uterine segment involvement in type II endometrial cancer and the unique mutational profile of serous tumors.

OBJECTIVE: Evaluation of the impact of lower uterine segment involvement (LUSI) in type II endometrial cancer, and mutational profile of uterine papillary serous carcinomas (UPSC). METHODS: Retrospective cohort study comparing patients with type II endometrial cancer with LUSI to patients without LUSI. Genes commonly implicated in carcinogenesis were analyzed in a subgroup of 42 patients with UPSC using next generation sequencing. RESULTS: 83 patients with type II endometrial cancer were included in the study, of these, LUSI was diagnosed in 31.3%. During a median follow-up of 45.5 months, patients with LUSI developed more local and distant recurrences (local: 19.2% vs. 3.5%, P = .03; distant: 50% vs. 17.5%, P = .004) and progression events (73.1% vs. 26.3%, P < .001), with shorter mean progression-free survival (16 months compared to 26.5 months, P < .01). In a multivariate analysis, LUSI was the only significant pathological factor, associated with a 2.9-fold increase in the risk of progression (P = .007), and a 2.6-fold increase in the risk of death (P = .02). In the subgroup of patients with UPSC, mutations were identified in 54 genes, including TP53 (80%), PPP2R1A (40%), and PTEN (22.5%). Frequent mutations in the PTEN-PI3K-AKT signaling pathway were found in patients with tumor in the upper uterine segment only (P = .04), with PTEN being mutated in 29% of the samples (P = .07). CONCLUSION: Type II endometrial cancers presenting in the LUS have a significantly worse prognosis and this might be associated with a unique mutational profile.

Sentinel lymph node mapping in endometrial cancer: a systematic review and meta-analysis.

INTRODUCTION: Appropriate extent of lymphadenectomy in clinically, early stage endometrial cancer remains controversial but sentinel lymph node (SLN) mapping has emerged as an alternative staging strategy, until the advent of molecular prognostic markers. We sought to perform a systematic review of the literature to determine pooled estimates for SLN detection rate and diagnostic accuracy, while exploring impact of the SLN on adjuvant therapy and oncologic outcomes. EVIDENCE ACQUISITION: We performed a systematic search utilizing Medline, EMBASE, and Web of Science electronic databases for all studies published in the English language until October 31, 2017. Studies were included for review and potential aggregate analyses if they contained at least 30 endometrial cancer patients with undergoing SLN mapping and reported on detection rates (overall, bilateral or para-aortic) or diagnostic accuracy (sensitivity and negative predictive value [NPV]). Pooled estimates were calculated via meta-analyses utilizing a random-effects model. Studies reporting on the impact of SLN on adjuvant therapy, as well as studies comparing SLN mapping to completion lymphadenectomy were qualitatively reviewed and analyzed as well. EVIDENCE SYNTHESIS: We identified 48 eligible studies, which included 5348 patients for review and inclusion in the meta-analysis for SLN detection or diagnostic accuracy. The pooled SLN detection rates were were 87% (95% CI: 84-89%, 44 studies) for overall detection, 61% (95% CI: 56-66%, 36 studies) for bilateral detection, and 6% (95% CI: 3-9%, 31 studies) for para-aortic detection. Indocyanine green use improved overall (94%, 95% CI: 92-96%, 19 studies) SLN detection rates compared to blue tracer (86%, 95% CI: 83-89%, 31 studies) or technetium-99 (86%, 95% CI: 83-89%, 25 studies). This trend was similarly seen in terms of bilateral detection rates (74% vs. 59% vs. 57%, respectively). There was no difference in para-aortic SLN detection rate between each tracer. The pooled estimates for diagnostic accuracy for 34 studies were 94% (95% CI: 91-96%) for sensitivity and 100% (95% CI: 99 - 100%) for NPV. Diagnostic accuracy of SLN mapping was not negatively affected in patients with high-grade endometrial histology. Patients with SLN mapping are more likely to receive adjuvant therapy and do not have inferior survival or recurrence outcomes compared to those undergoing completion lymphadenectomy. CONCLUSIONS: SLN mapping is a feasible and accurate alternative to stage patients with endometrial cancer. Utilizing indocyanine green results in the highest SLN detection rates. Future studies should prospectively examine the impact of SLN mapping on progression-free and overall survival.

Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer.

OBJECTIVE: Pilot study to assess the value of weekly paclitaxel plus carboplatin every 3weeks (dose dense regimen, DD) compared to the standard 3-weekly protocol in the adjuvant setting for endometrial cancer. METHODS: Retrospective cohort study comparing consecutive patients with high and intermediate-high risk endometrial cancer, undergoing DD protocol (from 2011 to 2015) to a non-overlapping historical cohort with similar characteristics who received treatment every three weeks (2008-2011). RESULTS: 122 patients with endometrial cancer were included in the study, of these, 61 patients received the dose dense protocol and 61 were treated with the standard 3-weekly protocol. After a median follow-up of 61.6months in the 3-weekly cohort, compared with 41.6months in the DD cohort, 40 progressions were recorded. 29 progressions were observed in women treated in the standard protocol, with a three years progression free survival (PFS) of 57.4%, compared to 11 progressions observed in patients in the DD schedule, with a three years PFS of 79.5% (P=0.03). Patients who were treated with the DD protocol were less likely to have progression events compared to the standard cohort with a hazard ratio of 0.4 on multivariate analysis (CI 95%, 0.2-0.8, P=0.01), had significantly less distant metastases (P=0.01), and had improved overall survival when diagnosed with advanced stage disease (P=0.02). Complaints of musculoskeletal pain were more frequent in the standard cohort (n=17, 27.9%) compared to the dose dense cohort (n=4, 6.6%), P=0.005. CONCLUSION: Preliminary data suggests that dose dense chemotherapy might be a reasonable and superior option for adjuvant treatment of endometrial cancer, compared to standard chemotherapy.

Unexpected locations of sentinel lymph nodes in endometrial cancer.

INTRODUCTION: To evaluate the anatomical location of sentinel lymph nodes (SLN) following intra-operative cervical injection in endometrial cancer. METHODS: All consecutive patients with endometrial cancer undergoing sentinel lymph node mapping were included in this prospective study following intra-operative cervical injection of tracers. Areas of SLN detection distribution were mapped. RESULTS: Among 436 patients undergoing SLN mapping, there were 1095 SLNs removed, and 7.9% of these SLNs found in 13.1% of patients, were detected in areas not routinely harvested during a standard lymph node dissection. These included the internal iliac vein, parametrial, and pre-sacral areas. The SLN was the only positive node in 46.1% (15/36) of cases with successful mapping and completion lymphadenectomy, including 3 cases where the sentinel node in the atypical location was the only node with metastatic disease. CONCLUSION: SLN mapping using intra-operative cervical injection is capable to map out areas not typically included in a standard lymphadenectomy. The sentinel node is the most relevant lymph node to analyze and may enable to discover metastatic disease in unusual areas.

Laparoscopic arcuate line hernia repair.

Arcuate line hernia is considered a surgical rarity. This type of hernia is characterized by protrusion of intraperitoneal structures in a concave parietal fold in the abdominal wall. In this report, we aim to describe the diagnostic images of 2 cases of arcuate line hernia. Laparoscopic repair using a polypropylene mesh with a preattached inflatable balloon has been illustrated as well.