Sentinel lymph node mapping in endometrial cancer: Current evidence and practice.

Surgical staging with total hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment is the standard of care for patients with clinical early-stage endometrial cancer. Traditionally, complete pelvic and para-aortic lymphadenectomy (LND) was performed to assess for nodal metastases; however, numerous prospective studies have demonstrated that sentinel lymph node biopsy has similar diagnostic accuracy, and is an acceptable alternative to complete LND. This has led to a paradigm shift in endometrial cancer staging.

Diagnostic accuracy of frozen section and patterns of nodal spread in high grade endometrial cancer: A secondary outcome of the SENTOR prospective cohort study.

OBJECTIVES: The study aimed to define the accuracy of intraoperative frozen section (FS) for the detection of metastases in sentinel lymph node biopsy (SLNB) and describe the pattern of lymph node (LN) spread and relation to molecular classifiers in patients with high-grade endometrial cancer (EC). METHODS: We performed a secondary outcome of clinicopathologic data from the Sentinel Lymph Node Biopsy versus Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging (SENTOR) prospective cohort study evaluating SLNB in patients with clinical stage I high-grade EC (ClinicalTrials.gov ID: NCT01886066). The primary outcome was the sensitivity of FS of the sentinel lymph node (SLN) specimen, compared to a standardized ultrastaging protocol. Secondary outcomes included the pattern and characteristics of LN spread. RESULTS: There were 126 patients with high-grade EC with a median age of 66 years (range:44-86) and a median Body Mass Index (BMI) of 26.9 kg/m2 (range:17.6-49.3). FS was performed on surgical specimens from 212 hemipelves; SLNs were identified in 202 specimens (95.7%) and fatty tissue alone was identified in 10 specimens (4.7%). Of the 202 hemipelves in which SLNs were identified, 24 were positive for metastatic disease on final pathology. Initial FS correctly identified only 12, yielding a sensitivity of 50% (12/24, 95% CI 29.6-70.4) and a negative predictive value of 94% (178/190, 95% CI 89-96.5). A total of 24 patients (19%) had LN metastases: 16 (13%) had isolated pelvic metastases, 7 (6%) had both pelvic and para-aortic metastases and 1 (0.8%) had an isolated para-aortic metastasis. CONCLUSIONS: Intraoperative FS of SLNs in high-grade EC patients has poor sensitivity. Since isolated para-aortic metastases are rare, para-aortic lymphadenectomy may be omitted in patients in which SLNs were successfully mapped to the pelvis.

Adverse Fetal Outcomes and Maternal Mortality Following Nonobstetric Abdominopelvic Surgery in Pregnancy: A Systematic Review and Meta-analysis.

OBJECTIVE: To quantify the absolute risks of adverse fetal outcomes and maternal mortality following nonobstetric abdominopelvic surgery in pregnancy. SUMMARY BACKGROUND DATA: Surgery is often necessary in pregnancy, but absolute measures of risk required to guide perioperative management are lacking. METHODS: We systematically searched MEDLINE, EMBASE, and EvidenceBased Medicine Reviews from January 1, 2000, to December 9, 2020, for observational studies and randomized trials of pregnant patients undergoing nonobstetric abdominopelvic surgery. We determined the pooled proportions of fetal loss, preterm birth, and maternal mortality using a generalized linear random/mixed effects model with a logit link. RESULTS: We identified 114 observational studies (52 [46%] appendectomy, 34 [30%] adnexal, 8 [7%] cholecystectomy, 20 [17%] mixed types) reporting on 67,111 pregnant patients. Overall pooled proportions of fetal loss, preterm birth, and maternal mortality were 2.8% (95% CI 2.2-3.6), 9.7% (95% CI 8.3-11.4), and 0.04% (95% CI 0.02-0.09; 4/10,000), respectively. Rates of fetal loss and preterm birth were higher for pelvic inflammatory conditions (eg, appendectomy, adnexal torsion) than for abdominal or nonurgent conditions (eg, cholecystectomy, adnexal mass). Surgery in the second and third trimesters was associated with lower rates of fetal loss (0.1%) and higher rates of preterm birth (13.5%) than surgery in the first and second trimesters (fetal loss 2.9%, preterm birth 5.6%). CONCLUSIONS: Absolute risks of adverse fetal outcomes after nonobstetric abdom- inopelvic surgery vary with gestational age, indication, and acuity. Pooled estimates derived here identify high-risk clinical scenarios, and can inform implementation of mitigation strategies and improve preoperative counselling.

Evaluation of Adverse Pregnancy Outcomes in Physicians Compared With Nonphysicians.

Importance: Physicians may be at risk of pregnancy complications due to prolonged work hours, overnight shifts, occupational hazards, and older maternal age at first birth compared with nonphysicians. Observational studies of physicians, including comparisons across physician specialties, are needed. Objective: To compare adverse maternal and perinatal outcomes between pregnant physicians and nonphysicians and between physicians of different specialties. Design, Setting, and Participants: A population-based retrospective cohort study was conducted in Ontario, Canada. Participants included physicians and nonphysician comparators residing in high-income areas who experienced a birth at 20 or more weeks' gestation from April 1, 2002, to November 26, 2018. Data analysis was performed from December 2020 to March 2022. Exposures: Physician occupation and physician specialty. Main Outcomes and Measures: Severe maternal morbidity (in pregnancy and up to 42 days' post partum) and severe neonatal morbidity (up to hospital discharge among live-born infants) were the primary outcomes. Logistic regression under a generalized estimating equations approach was used to compare outcomes between physicians and nonphysicians, accounting for potentially more than 1 pregnancy per woman. Odds ratios were adjusted (aOR) for maternal age, parity, previous preterm birth, calendar year, immigration status, comorbidities, multiple gestation, and mode of delivery. Results: A total of 10 489 births occurred among 6161 licensed physicians, and 298 683 births occurred among 211 191 nonphysician counterparts. Physicians were older (median [IQR] age, 34 [31-36] vs 32 [29-35] years) and more likely to be nulliparous (5049 [48.1%] vs 128 961 [43.2%]) compared with nonphysicians. Severe maternal morbidity was more likely to occur among physicians than nonphysicians (unadjusted OR, 1.21; 95% CI, 1.04-1.41) but not after adjusting for study covariates (aOR, 1.13; 95% CI, 0.97-1.32). Severe neonatal morbidity was less likely to occur among infants of physicians than infants of nonphysicians (aOR, 0.79; 95% CI, 0.72-0.87). Compared with family physicians, neither nonsurgical specialists (aOR, 1.12; 95% CI, 0.82-1.53) nor surgical specialists (aOR, 1.43; 95% CI, 0.74-2.76) were at increased risk of severe maternal morbidity. Similar findings were observed for severe neonatal morbidity (nonsurgical specialists: aOR, 0.98; 95% CI, 0.80-1.19; surgical specialists: aOR, 1.08; 95% CI, 0.68-1.71). Conclusions and Relevance: The findings of this study suggest that female physicians may be at slightly higher risk of severe maternal morbidity. This association appeared to be mediated by their tendency to delay childbearing compared with nonphysicians. Newborns of physicians appear to experience less morbidity. Such differences were not observed between physician specialty groups.

Sentinel Lymph Node Mapping in High-Grade Endometrial Cancer.

Sentinel lymph node (SLN) mapping is becoming an acceptable alternative to full lymphadenectomy for evaluating lymphatic spread in clinical stage I endometrial cancer (EC). While the assessment of pelvic and para-aortic lymph nodes is part of the surgical staging of EC, there is a long-standing debate over the therapeutic value of full lymphadenectomy in this setting. Although lymphadenectomy offers critical information on lymphatic spread and prognosis, most patients will not derive oncologic benefit from this procedure as the majority of patients do not have lymph node involvement. SLN mapping offers prognostic information while simultaneously avoiding the morbidity associated with an extensive and often unnecessary lymphadenectomy. A key factor in the decision making when planning for EC surgery is the histologic subtype. Since the risk of lymphatic spread is less than 5% in low-grade EC, these patients might not benefit from lymph node assessment. Nonetheless, in high-grade EC, the risk for lymph node metastases is much higher (20-30%); therefore, it is crucial to determine the spread of disease both for determining prognosis and for tailoring the appropriate adjuvant treatment. Studies on the accuracy of SLN mapping in high-grade EC have shown a detection rate of over 90%. The available evidence supports adopting the SLN approach as an accurate method for surgical staging. However, there is a paucity of prospective data on the long-term oncologic outcome for patients undergoing SLN mapping in high-grade EC, and more trials are warranted to answer this question.

Ovarian cancer incidence and death in average-risk women undergoing bilateral salpingo-oophorectomy at benign hysterectomy.

BACKGROUND: Opportunistic bilateral salpingo-oophorectomy is often offered to patients undergoing benign hysterectomy to prevent ovarian cancer, but the magnitude of risk reduction obtained with bilateral salpingo-oophorectomy in this population remains unclear and must be weighed against potential risks of ovarian hormone deficiency. OBJECTIVE: This study aimed to quantify the relative and absolute risk reduction in ovarian cancer incidence and death associated with bilateral salpingo-oophorectomy at the time of benign hysterectomy. STUDY DESIGN: We performed a population-based cohort study of all adult women (≥20 years) undergoing benign hysterectomy from 1996 to 2010 in Ontario, Canada. Patients with ovarian pathology, previous breast or gynecologic cancer, or evidence of genetic susceptibility to malignancy were excluded. Inverse probability of treatment-weighted Fine-Gray subdistribution hazard models were used to quantify the effect of bilateral salpingo-oophorectomy on ovarian cancer incidence and death while accounting for competing risks and adjusting for demographic characteristics, gynecologic conditions, and comorbidities. Analyses were performed in all women and specifically in women of postmenopausal age (≥50 years) at the time of hysterectomy. RESULTS: We identified 195,282 patients (bilateral salpingo-oophorectomy, 24%; ovarian conservation, 76%) with a median age of 45 years (interquartile range, 40-51 years). Over a median follow-up of 16 years (interquartile range, 12-20 years), 548 patients developed ovarian cancer (0.3%), and 16,170 patients (8.3%) died from any cause. Bilateral salpingo-oophorectomy was associated with decreased ovarian cancer incidence (hazard ratio, 0.23; 95% confidence interval, 0.14-0.38; P<.001) and decreased ovarian cancer death (hazard ratio, 0.30; 95% confidence interval, 0.16-0.57; P<.001). At 20 years follow-up, the weighted cumulative incidences of ovarian cancer were 0.08% and 0.46% with bilateral salpingo-oophorectomy and ovarian conservation, respectively, yielding an absolute risk reduction of 0.38% (95% confidence interval, 0.32-0.45; number needed to treat, 260). After restricting to women aged ≥50 years at hysterectomy, the absolute risk reduction was 0.62% (95% confidence interval, 0.47-0.77; number needed to treat, 161). CONCLUSION: Bilateral salpingo-oophorectomy resulted in a significant absolute reduction in ovarian cancer among women undergoing benign hysterectomy. Population-average risk estimates derived in this study should be balanced against other potential implications of bilateral salpingo-oophorectomy to inform practice guidelines, patient decision-making, and surgical management.

Association of bilateral salpingo-oophorectomy with all cause and cause specific mortality: population based cohort study.

OBJECTIVES: To determine if bilateral salpingo-oophorectomy, compared with ovarian conservation, is associated with all cause or cause specific death in women undergoing hysterectomy for non-malignant disease, and to determine how this association varies with age at surgery. DESIGN: Population based cohort study. SETTING: Ontario, Canada from 1 January 1996 to 31 December 2015, and follow-up to 31 December 2017. PARTICIPANTS: 200 549 women (aged 30-70 years) undergoing non-malignant hysterectomy, stratified into premenopausal (<45 years), menopausal transition (45-49 years), early menopausal (50-54 years), and late menopausal (≥55 years) groups according to age at surgery; median follow-up was 12 years (interquartile range 7-17). EXPOSURES: Bilateral salpingo-oophorectomy versus ovarian conservation. MAIN OUTCOMES MEASURES: The primary outcome was all cause death. Secondary outcomes were non-cancer and cancer death. Within each age group, overlap propensity score weighted survival models were used to examine the association between bilateral salpingo-oophorectomy and mortality outcomes, while adjusting for demographic characteristics, gynaecological conditions, and comorbidities. To account for comparisons in four age groups, P<0.0125 was considered statistically significant. RESULTS: Bilateral salpingo-oophorectomy was performed in 19%, 41%, 69%, and 81% of women aged <45, 45-49, 50-54, and ≥55 years, respectively. The procedure was associated with increased rates of all cause death in women aged <45 years (hazard ratio 1.31, 95% confidence interval 1.18 to 1.45, P<0.001; number needed to harm 71 at 20 years) and 45-49 years (1.16, 1.04 to 1.30, P=0.007; 152 at 20 years), but not in women aged 50-54 years (0.83, 0.72 to 0.97, P=0.018) or ≥55 years (0.92, 0.82 to 1.03, P=0.16). Findings in women aged <50 years were driven largely by increased non-cancer death. In secondary analyses identifying a possible change in the association between bilateral salpingo-oophorectomy and all cause death with advancing age at surgery, the hazard ratio gradually decreased during the menopausal transition and remained around 1 at all ages thereafter. CONCLUSION: In this observational study, bilateral salpingo-oophorectomy at non-malignant hysterectomy appeared to be associated with increased all cause mortality in women aged <50 years, but not in those aged ≥50 years. While caution is warranted when considering bilateral salpingo-oophorectomy in premenopausal women without indication, this strategy for ovarian cancer risk reduction does not appear to be detrimental to survival in postmenopausal women.

Sentinel lymph node biopsy in high-grade endometrial cancer: a systematic review and meta-analysis of performance characteristics.

OBJECTIVE: A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280). DATA SOURCES: We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. ClinicalTrials.gov was searched to identify ongoing registered clinical trials. STUDY ELIGIBILITY CRITERIA: We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data. METHODS: We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44-82.5 years) and the study-level median body mass index was 28.6 kg/m2 (range, 19.4-43.7 kg/m2). The pooled detection rates were 91% per patient (95% confidence interval, 85%-95%; I2=59%) and 64% bilaterally (95% confidence interval, 53%-73%; I2=69%). The overall node positivity rate was 26% (95% confidence interval, 19%-34%; I2=44%). Of the 87 patients with positive node results, a sentinel lymph node biopsy correctly identified 80, yielding a pooled sensitivity of 92% per patient (95% confidence interval, 84%-96%; I2=0%), a false negative rate of 8% (95% confidence interval, 4%-16%; I2=0%), and a negative predictive value of 97% (95% confidence interval, 95%-99%; I2=0%). CONCLUSION: Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer.

Delay of Pregnancy Among Physicians vs Nonphysicians.

Importance: Women physicians may delay childbearing and experience childlessness more often than nonphysicians, but existing knowledge is based largely on self-reported survey data. Objective: To compare patterns of childbirth between physicians and nonphysicians. Design, Setting, and Participants: Population-based retrospective cohort study of reproductive-aged women (15-50 years) in Ontario, Canada, accrued from January 1, 1995, to November 28, 2018, and observed to March 31, 2019. Outcomes of 5238 licensed physicians of the College of Physicians and Surgeons of Ontario were compared with those of 26 640 nonphysicians (sampled in a 1:5 ratio). Physicians and nonphysicians were observed from age 15 years onward. Exposures: Physicians vs nonphysicians. Main Outcomes and Measures: The primary outcome was childbirth at gestational age of 20 weeks or greater. Cox proportional hazards models were used to examine the association between physician status and childbirth, overall and across career stage (postgraduate training vs independent practice) and specialty (family physicians vs specialists). Results: All physicians (n = 5238) and nonphysicians (n = 26 640) were aged 15 years at baseline, and 28 486 (89.1%) were Canadian-born. Median follow-up was 15.2 (interquartile range, 12.2-18.2) years after age 15 years. Physicians were less likely to experience childbirth at younger ages (hazard ratio [HR] for childbirth at 15-28 years, 0.15; 95% CI, 0.14-0.18; P < .001) and initiated childbearing significantly later than nonphysicians; the cumulative incidence of childbirth was 5% at 28.6 years in physicians and 19.4 years in nonphysicians. However, physicians were more likely to experience childbirth at older ages (HR for 29-36 years, 1.35; 95% CI, 1.28-1.43; P < .001; HR for ≥37 years, 2.62; 95% CI, 2.00-3.43; P < .001), and ultimately achieved a similar cumulative probability of childbirth as nonphysicians overall. Median age at first childbirth was 32 years in physicians and 27 years in nonphysicians (P < .001). After stratifying by specialty, the cumulative incidence of childbirth was higher in family physicians than in both surgical and nonsurgical specialists at all observed ages. Conclusions and Relevance: The findings of this cohort study suggest that women physicians appear to delay childbearing compared with nonphysicians, and this phenomenon is most pronounced among specialists. Physicians ultimately appear to catch up to nonphysicians by initiating reproduction at older ages and may be at increased risk of resulting adverse reproductive outcomes. System-level interventions should be considered to support women physicians who wish to have children at all career stages.

Acceptability and Feasibility of Early Palliative Care Among Women with Advanced Epithelial Ovarian Cancer: A Randomized Controlled Pilot Study.

OBJECTIVE: To evaluate the acceptability of early palliative care (EPC) among patients with advanced ovarian cancer and to determine the feasibility of larger-scale phase III trials. METHODS: We performed a randomized controlled pilot study of adult women (>18 years) with pathologically confirmed epithelial ovarian cancer that had recurred or progressed on first-line therapy and had no immediate need for palliative care. We randomly assigned patients to either EPC or standard oncologic care (SOC), and collected patient-reported outcomes (PRO) at baseline, 3 months, and 6 months; end-of-life care quality indicators were collected at study completion. Study endpoints were rates of enrollment, EPC adherence, and PRO completion. RESULTS: Of 32 eligible patients approached, 23 enrolled (72%; 95% CI 53-86) and were randomly assigned to either EPC (n = 12) or SOC (n = 11). At baseline, participants had poor physical and emotional wellbeing, high rates of depression (65%), and understood that their disease was not curable (87%). Eleven patients (92%; 95% CI 62-100) attended their EPC consultation, and all visits took place within 4 weeks of enrollment. However, PRO completion was low due to deaths by 3 (5/23) and 6 months (9/23). CONCLUSION: Patients had accurate perceptions of their disease status, were willing to be randomly assigned to EPC, and attended scheduled appointments. However, a definitive trial in this group is not feasible without major adjustments to eligibility criteria and a multicentre, international effort. We propose that EPC be considered routinely at progression or recurrence given patients' symptom burden and clear acceptance of the intervention, as well as evidence of benefit from adequately powered trials in other malignancies.

1,2,4-Oxadiazole topsentin analogs as staphylococcal biofilm inhibitors targeting the bacterial transpeptidase sortase A.

The inhibition or prevention of biofilm formation represents an emerging strategy in the war against antibiotic resistance, interfering with key players in bacterial virulence. This approach includes the inhibition of the catalytic activity of transpeptidase sortase A (Srt A), a membrane enzyme responsible for covalently attaching a wide variety of adhesive matrix molecules to the peptidoglycan cell wall in Gram-positive strains. A new series of seventeen 1,2,4-oxadiazole derivatives was efficiently synthesized and screened as potential new anti-virulence agents. The ability of inhibiting biofilm formation was evaluated against both Gram-positive and Gram-negative pathogens. Remarkably, all these compounds inhibited S. aureus and/or P. aeruginosa biofilm formation in a dose dependent manner, with 50% biofilm inhibitory concentrations (BIC50s) below 10 µM for the most active compounds. Inhibition of SrtA was validated as one of the possible mechanisms of action of these new 1,2,4-oxadiazole derivatives, in the tested Gram-positive pathogen, using a specific enzymatic assay for a recombinant S. aureus SrtA. The three most active compounds, eliciting BIC50 values for S. aureus ATCC 25923 between 0.7 and 9.7 µM, showed a good activity toward the enzyme eliciting IC50 values ranging from 2.2 to 10.4 µM.

Practice variation in bilateral salpingo-oophorectomy at benign abdominal hysterectomy: a population-based study.

BACKGROUND: Bilateral salpingo-oophorectomy at benign hysterectomy is not recommended in premenopausal women who are in the premenopausal stage because of its potential associations with increased all-cause mortality and cardiovascular disease; however, contemporary practice patterns are unknown. OBJECTIVE: This study aimed to quantify between-surgeon variation in bilateral salpingo-oophorectomy and identify surgeon and patient characteristics associated with bilateral salpingo-oophorectomy to evaluate current quality of care and identify targets for knowledge translation and future research. STUDY DESIGN: We conducted a population-based retrospective cross-sectional study of adult women (≥20 years) undergoing benign abdominal hysterectomy from 2014 to 2018 in Ontario, Canada. Hierarchical multivariable logistic regression models, stratified by age group (<45, 45-54, ≥55 years), were used to model between-surgeon variation after multivariable adjustment for patient and surgeon characteristics. Cases of bilateral salpingo-oophorectomy were classified as potentially appropriate or potentially avoidable based on the presence or absence of diagnostic indications. RESULTS: Of 44,549 eligible women, 17,797 (39.9%) underwent concurrent bilateral salpingo-oophorectomy, and 26,752 (60.1%) did not. In all three age strata, the individual surgeon providing care was one of the strongest factors influencing whether patients received bilateral salpingo-oophorectomy (median odds ratio, 2.00-2.53). Surgeons accounted for more than 22% of the residual observed variation in bilateral salpingo-oophorectomy in women aged 45-54 years compared with 16% and 14% of the residual observed variation in bilateral salpingo-oophorectomy in women aged <45 and ≥55 years, respectively. Non-gynecologic patient factors, such as obesity (odds ratio, 1.33; 95% confidence interval, 1.17-1.52; P<.001) and residing in low-income regions (odds ratio, 1.34; 95% confidence interval, 1.16-1.55; P<.001), were also associated with bilateral salpingo-oophorectomy. Approximately 40% of patients who underwent bilateral salpingo-oophorectomy had no indication for the procedure in their discharge records. CONCLUSION: Marked between-surgeon variation in bilateral salpingo-oophorectomy rates, even after adjusting for patient case mix, suggests ongoing uncertainty in practice. Stronger evidence-based guidelines on the risks and benefits of salpingo-oophorectomy as women age are needed, particularly focusing on perimenopausal women.

Assessment of Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging.

Importance: Whether sentinel lymph node biopsy (SLNB) can replace lymphadenectomy for surgical staging in patients with high-grade endometrial cancer (EC) is unclear. Objective: To examine the diagnostic accuracy of, performance characteristics of, and morbidity associated with SLNB using indocyanine green in patients with intermediate- and high-grade EC. Design, Setting, and Participants: In this prospective, multicenter cohort study (Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging [SENTOR] study), accrual occurred from July 1, 2015, to June 30, 2019, with early stoppage because of prespecified accuracy criteria. The study included patients with clinical stage I grade 2 endometrioid or high-grade EC scheduled to undergo laparoscopic or robotic hysterectomy with an intent to complete staging at 3 designated cancer centers in Toronto, Ontario, Canada. Exposures: All patients underwent SLNB followed by lymphadenectomy as the reference standard. Patients with grade 2 endometrioid EC underwent pelvic lymphadenectomy (PLND) alone, and patients with high-grade EC underwent PLND and para-aortic lymphadenectomy (PALND). Main Outcomes and Measures: The primary outcome was sensitivity of the SLNB algorithm. Secondary outcomes were additional measures of diagnostic accuracy, sentinel lymph node detection rates, and adverse events. Results: The study enrolled 156 patients (median age, 65.5 years; range, 40-86 years; median body mass index [calculated as weight in kilograms divided by height in meters squared], 27.5; range, 17.6-49.3), including 126 with high-grade EC. All patients underwent SLNB and PLND, and 101 patients (80%) with high-grade EC also underwent PALND. Sentinel lymph node detection rates were 97.4% per patient (95% CI, 93.6%-99.3%), 87.5% per hemipelvis (95% CI, 83.3%-91.0%), and 77.6% bilaterally (95% CI, 70.2%-83.8%). Of 27 patients (17%) with nodal metastases, 26 patients were correctly identified by the SLNB algorithm, yielding a sensitivity of 96% (95% CI, 81%-100%), a false-negative rate of 4% (95% CI, 0%-19%), and a negative predictive value of 99% (95% CI, 96%-100%). Only 1 patient (0.6%) was misclassified by the SLNB algorithm. Seven of 27 patients with node-positive cancer (26%) were identified outside traditional PLND boundaries or required immunohistochemistry for diagnosis. Conclusions and Relevance: In this prospective cohort study, SLNB had acceptable diagnostic accuracy for patients with high-grade EC at increased risk of nodal metastases and improved the detection of node-positive cases compared with lymphadenectomy. The findings suggest that SLNB is a viable option for the surgical staging of EC.

Thiazole Analogues of the Marine Alkaloid Nortopsentin as Inhibitors of Bacterial Biofilm Formation.

Anti-virulence strategy is currently considered a promising approach to overcome the global threat of the antibiotic resistance. Among different bacterial virulence factors, the biofilm formation is recognized as one of the most relevant. Considering the high and growing percentage of multi-drug resistant infections that are biofilm-mediated, new therapeutic agents capable of counteracting the formation of biofilms are urgently required. In this scenario, a new series of 18 thiazole derivatives was efficiently synthesized and evaluated for its ability to inhibit biofilm formation against the Gram-positive bacterial reference strains Staphylococcus aureus ATCC 25923 and S. aureus ATCC 6538 and the Gram-negative strain Pseudomonas aeruginosa ATCC 15442. Most of the new compounds showed a marked selectivity against the Gram-positive strains. Remarkably, five compounds exhibited BIC50 values against S. aureus ATCC 25923 ranging from 1.0 to 9.1 µM. The new compounds, affecting the biofilm formation without any interference on microbial growth, can be considered promising lead compounds for the development of a new class of anti-virulence agents.