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.

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.

The Feasibility of Laparoscopic Surgery in Gynecologic Oncology for Obese and Morbidly Obese Patients.

BACKGROUND: Surgical interventions are the mainstay of treatment for many gynecological cancers. Although minimally invasive surgery offers many potential advantages, performing laparoscopic pelvic surgery in obese patients remains challenging. To overcome this, many centers have shifted their practice to robotic surgery; however, the high costs associated with robotic surgery are concerning and limit its use. OBJECTIVE: This study aimed to examine the feasibility of performing laparoscopic gynecologic oncology procedures in obese and morbidly obese patients. MATERIALS AND METHODS: This retrospective study evaluated patients who underwent laparoscopic surgeries by a gynecologic oncologist from January 2012 to June 2016 at a designated gynecologic oncology center. Patients were categorized as nonobese (body mass index [BMI] < 30 kg/m), obese (BMI 30-39.9 kg/m), and morbidly obese (BMI ≥ 40 kg/m). Intra and postoperative complications and outcomes were recorded. Group differences were computed with Kruskal-Wallis nonparametric test (continuous) or Fisher exact test (categorical). RESULTS: Of 497 patients, 288 were nonobese (58%), 162 obese (33%), and 47 morbidly obese (9%). Complex surgical procedures were performed in 57.4% of obese patients and 55.3% of morbidly obese patients. Although morbidly obese and obese patients had longer operative times (mean of 181 and 166 minutes vs 144 minutes, P = 0.014), conversion from laparoscopy to laparotomy occurred in 9.05% of all patients, with no group differences. Low intraoperative (9%-11%) and severe postoperative (2.41%) complication rates were observed overall, with no group differences. There was no statistically significant difference in the rate of emergency room visits 30 days postoperation between the 3 BMI groups (P = 0.6108). Average length of postoperative stay was statistically significant (P = 0.0003) but was low overall (1-2 days). Hospital readmission rates were low, with the lowest rate among morbidly obese patients (2.13%). CONCLUSIONS: Our data suggest that laparoscopic gynecologic-oncology procedures for obese patients are feasible and safe.

Feasibility and safety of same-day discharge after laparoscopic radical hysterectomy for cervix cancer.

OBJECTIVE: To evaluate the safety and feasibility of same day-discharge (SDD) after laparoscopic radical hysterectomy for cervix cancer by determining complication rates and factors associated with post-operative admission. METHODS: In this retrospective cohort study, patients undergoing laparoscopic radical hysterectomy for cervix cancer at a single institution from January 2006 to November 2015 were identified. Admitted patients were compared to same-day discharge patients. Rates of post-operative complications and readmission were analyzed and regression analysis used to determine factors associated with admission. RESULTS: 119 patients were identified. 75 (63%) were SDD patients (mean stay 156.7±50.2min) and 44 (37%) were admitted patients (mean stay 1.2±0.6days). Ten (13%) SDD patients sought medical attention within 30days post-operatively vs. nine (20%) admitted patients (p=0.17). Reasons SDD patients sought attention included pain (n=1), wound concerns (n=2), vaginal bleeding (n=2), DVT/VTE (n=1), fever (n=2) and fistula (n=2). All patients developed symptoms and presented between 5 and 13days post-operatively thus no complications could have been detected or prevented through initial admission. Four SDD patients were readmitted within 30days of surgery (p=0.25), two required re-operation (p=0.16). Admitted patients were older (p=0.049), had longer operations (p=0.02), increased blood loss (p=0.0004), increased intra-operative complications (p=0.001), surgery later in the day (p=0.004) and before April 2010 (p=0.001). On multivariate analysis, older age (OR1.05, p=0.03), surgery later in the day (OR 7.22, p=0.002) and presence of an intra-operative complication (OR 10.25, p=0.02) were significantly associated with admission. CONCLUSION: Same-day discharge after laparoscopic radical hysterectomy for cervix cancer is safe, with a low risk of post-operative morbidity and hospital readmission.

Comparison of three surgical approaches for staging lymphadenectomy in high-risk endometrial cancer.

OBJECTIVE: To compare laparotomy, laparoscopy, and robotic surgical approaches to lymphadenectomy for high-risk endometrial cancer staging. METHODS: A retrospective cohort study enrolled patients who underwent surgery for pathologic high-risk endometrial carcinoma at the University Health Network, Toronto, Canada, between January 1, 2005 and December 31, 2013. The primary outcome, the median number of nodes retrieved, was compared based on surgical technique. The secondary outcome was the detection of metastatic nodes. RESULTS: A total of 176 patients who underwent surgery for high-risk endometrial cancer were included, of whom 147 (83.5%) had pelvic and 78 (44.3%) had para-aortic lymphadenectomy. Laparotomy, laparoscopy, and robotic approaches were applied for 69 (39.2%), 44 (25.0%), and 63 (35.8%) patients, respectively. Minimally-invasive staging was associated with an increased proportion of patients undergoing pelvic lymphadenectomy compared with laparotomy (P=0.005). The median number of nodes removed in the pelvis and para-aortic regions did not differ between surgical approaches. The detection of metastatic nodes was also similar between the groups. Increased blood loss (P<0.001) and longer hospital admission (P<0.001) were observed with laparotomy procedures. CONCLUSION: All three techniques demonstrated adequate staging of high-risk endometrial carcinoma. Based on improved peri-operative outcomes, the use of minimally-invasive techniques is advocated where appropriate.

A comparison of the toxicity and tolerability of two intraperitoneal chemotherapy regimens for advanced-stage epithelial ovarian cancer.

OBJECTIVES: Randomized controlled trials (RCTs) in optimally cytoreduced epithelial ovarian cancer (EOC) patients have demonstrated an impressive survival benefit of intraperitoneal (IP) platinum over intravenous (IV), but its use has been limited by significant toxicity from cisplatin. The aim of this study was to compare the toxicity and tolerability of IP cisplatin to IP carboplatin in women with optimally cytoreduced EOC. METHODS: Retrospective analysis of 141 women with EOC who underwent optimal surgical cytoreduction followed by IV paclitaxel and IP cisplatin or IP carboplatin was performed. Toxicities of the two treatment regimens were compared. As a secondary outcome, overall survival (OS) and progression-free survival (PFS) probabilities were obtained using the Kaplan-Meier estimate; the log-rank test was used to compare survival curves. RESULTS: Of the 141 patients, 77 (54.6%) received IP cisplatin and 64 (45.4%) received IP carboplatin. Eighty-six percent received at least 4 cycles of IP chemotherapy. IP cisplatin was associated with significantly more grade 3 nausea and vomiting (10.4% vs. 1.6%, p=0.033), grade 3 neuropathy (7.8% vs. 0%, p=0.013) and grade 2-3 neutropenia (22.1% vs. 9.4%, p=0.042). No difference in PFS (p=0.602) or OS (p=0.107) was found between the groups. CONCLUSION: IP chemotherapy had a high completion rate in both groups of patients. IP carboplatin required a less resource intense protocol and was tolerated better than IP cisplatin with less gastrointestinal, neurologic and hematologic toxicities.

Emergency Caesarean Section in Obese Parturients: Is a 30-Minute Decision-to-Incision Interval Feasible?

OBJECTIVE: To determine the effect of obesity on decision-to-incision and decision-to-delivery time intervals in emergency Caesarean section. METHODS: We performed a retrospective study of emergency Caesarean sections performed between 2005 and 2009. Indications for emergency Caesarean section were defined as those posing an immediate threat to the life of the mother or fetus. The primary outcomes were the time intervals from decision for emergency delivery to skin incision, and decision to delivery of the infant. The secondary outcome was a composite of poor neonatal outcomes comprising umbilical cord artery pH lt; 7.20, Apgar score lt; 7 at five minutes, admission to NICU, or neonatal death. RESULTS: A total of 232 women underwent emergency Caesarean section, and 140 of these met the inclusion criteria. At the time of delivery, 78/140 (55.7%) patients were categorized as obese (BMI ≥ 30kg/m2). The median decision-to-incision and decision-to-delivery intervals were significantly longer in the obese group, with a median delay of 4.5 minutes in both time intervals. Time-to-event analysis demonstrated prolongation of the decision-to-incision interval in the obese group (hazard ratio 0.71, P lt; 0.05). There was no difference in the neonatal composite outcome, but there was a significant reduction in median five-minute Apgar score in the obese group (P = 0.02). CONCLUSION: Obesity is associated with prolonged decision-to-incision and decision-to-delivery intervals, without associated neonatal morbidity, in a tertiary hospital setting. Further studies are required to assess the specific factors limiting expedient delivery in this population.

Objective : Déterminer l'effet de l'obésité sur les intervalles décision-incision et décision-accouchement en ce qui concerne la tenue d'une césarienne d'urgence. Méthodes : Nous avons mené une étude rétrospective portant sur les césariennes d'urgence menées entre 2005 et 2009. Les indications menant à la tenue d'une césarienne d'urgence ont été définies comme étant celles qui constituaient une menace immédiate pour la vie de la mère ou celle du fœtus. Les critères d'évaluation principaux ont été l'intervalle entre la décision de procéder à un accouchement d'urgence et l'exécution de l'incision cutanée, et l'intervalle entre cette décision et la naissance de l'enfant. Le critère d'évaluation secondaire était un composite de diverses mauvaises issues néonatales, dont un pH artériel (cordon ombilical) lt; 7,20, un indice d'Apgar lt; 7 à cinq minutes, l'admission à l'UNSI et le décès néonatal. Résultats : Au total, 232 femmes ont subi une césarienne d'urgence et 140 d'entre elles répondaient aux critères d'inclusion. Au moment de l'accouchement, 78/140 (55,7 %) patientes ont été catégorisées comme étant obèses (IMC ≥ 30kg/m2). Les intervalles décision-incision et décision-accouchement médians étaient considérablement plus longs dans le groupe des femmes obèses (délai médian de 4,5 minutes pour ce qui est de ces deux intervalles). L'analyse du délai avant la survenue de l'événement a démontré la prolongation de l'intervalle décision-incision au sein du groupe des femmes obèses (rapport de risque, 0,71; P lt; 0,05). Bien qu'aucune différence n'ait été constatée en ce qui concerne l'issue composite néonatale, une baisse significative de l'indice d'Apgar médian à cinq minutes a été observée au sein du groupe des femmes obèses (P = 0,02). Conclusion : L'obésité est associée à une prolongation des intervalles décision-incision et décision-accouchement, sans répercussions connexes sur la morbidité néonatale, en milieu hospitalier tertiaire. La tenue d'autres études s'avère requise pour l'évaluation des facteurs particuliers qui limitent la tenue d'un accouchement en temps opportun au sein de cette population.

The subfornical organ: a central target for circulating feeding signals.

The mechanisms through which circulating ghrelin relays hunger signals to the CNS are not yet fully understood. In this study, we have examined the potential role of the subfornical organ (SFO), a circumventricular structure that lacks the normal blood-brain barrier, as a CNS site in which ghrelin acts to influence the hypothalamic centers controlling food intake. We report that ghrelin increased intracellular calcium concentrations in 28% (12 of 43) of dissociated SFO neurons and that the SFO expresses mRNA for the growth hormone secretagogue receptor. Whole-cell patch recordings from SFO neurons demonstrated that in 29% (9 of 31) of neurons tested ghrelin induced a mean depolarization of 7.4 +/- 0.69 mV, accompanied by an increase in action potential frequency. Voltage-clamp recordings revealed that ghrelin activates a putative nonselective cationic conductance. Previous reports that the satiety signal amylin exerts similar excitatory effects on SFO neurons led us to examine whether these two peptides influence different subpopulations of SFO neurons. Concentration-dependent depolarizing effects of amylin were observed in 59% (28 of 47) of SFO neurons (mean depolarization, 8.32 +/- 0.60 mV). In contrast to ghrelin, voltage-clamp recordings suggest that amylin influences a voltage-dependent current activated at depolarized potentials. We tested single SFO neurons with both peptides and identified cells responsive only to ghrelin (n = 9) and only to amylin (n = 7) but no cells that responded to both peptides. These data support a role for the SFO as a center at which ghrelin and amylin may influence separate subpopulations of neurons to influence the hypothalamic regulation of feeding.