Management of inguinal lymph nodes in locally advanced, surgically unresectable, squamous cell carcinoma of the vulva.

OBJECTIVE: To assess clinical outcomes of inguinal lymph node surgical resection compared to primary groin radiotherapy for locally advanced, surgically unresectable vulvar cancer. METHODS: All patients treated with radiation for vulvar cancer were identified between Jan 1, 2000 - Dec 31, 2020 at 2 academic centres. Inclusion criteria were those treated with curative intent primary radiotherapy +/- chemotherapy, tumors >4 cm, and surgically unresectable squamous cell vulvar carcinoma. Groin recurrence-free survival (RFS) was compared for groin surgery and primary groin radiotherapy using the Kaplan Meier method and log rank test. Groin failures are described by treatment modality, radiation dose and lymph node size. RESULTS: Of 476 patients treated with radiation for vulvar cancer, 112 patients (23.5%) met inclusion and exclusion criteria. The median (95% CI) follow up was 1.9 (1.4-2.5) years. Complete clinical response was significantly higher (80.0%) in patients with surgical groin resection compared to patients treated with primary groin radiotherapy (58.2%) (p = 0.04). On multivariable analysis, after adjusting for clinical and/or radiologically abnormal lymph nodes (p = 0.67), surgical groin resection was significantly associated with lower groin recurrence (HR 0.2 (95%CI 0.05-0.92), p = 0.04). The 3-year groin recurrence-free survival (RFS) was significantly higher at 94.4% (87.1-100) in patients with surgical groin resection compared to 79.2% (69.1-90.9) in patients treated with primary radiation (p = 0.02). CONCLUSIONS: In locally advanced squamous cell vulvar cancer, surgical groin management improves groin RFS compared to radiotherapy alone.

Predictors and outcomes of same day discharge after minimally invasive hysterectomy in gynecologic oncology within the National Surgical Quality Improvement Program database.

OBJECTIVE: To assess trends over time of same day discharge after minimally invasive hysterectomy in oncology, identify perioperative factors influencing same day discharge, and evaluate 30 day postoperative morbidity. METHODS: A retrospective cohort of elective minimally invasive hysterectomies performed for gynecologic oncologic indications between January 2013 and December 2021 was identified using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Clinical and surgical characteristics, length of stay, and 30 day postoperative complications were captured. Clinical and surgical factors affecting same day discharge rate and impact of same day discharge on postoperative outcomes were evaluated using χ2 tests and logistic regression. RESULTS: Patients undergoing minimally invasive hysterectomy (n=32 823) had a same day discharge rate of 34.5% over the 9 year period, increasing from 15.5% in 2013 to 55.1% in 2021. The rate of patients discharged on postoperative day 1 decreased from 76.4% to 41.4% over this period. On multivariable analysis, same day discharge decreased with: age 70-79 years (odds ratio (OR) 0.80) and ≥80 years (OR 0.42); body mass index 40-49.9 kg/m2 (OR 0.89) and ≥50 kg/m2 (OR 0.67); patient comorbidities, including hypertension (OR 0.85), chronic steroid use (OR 0.74), bleeding disorder (OR 0.54), anemia (OR 0.89), and hypoalbuminemia (OR 0.76); and surgical time >90th percentile (OR 0.40) (all p<0.05). Lymphadenectomy did not impact the same day discharge rate (unadjusted OR 1.03, p=0.22). Same day discharge had no effect on 30 day postoperative composite morbidity (OR 0.91, p=0.20), and was associated with fewer readmissions (OR 0.75, p=0.005). Age 70-79 years (OR 1.07, p=0.435) and age ≥80 years (OR 1.11, p=0.504) did not increase postoperative morbidity. However, body mass index categories 40-49.9 kg/m2 (OR 1.28, 95% CI 1.08 to 1.51) and ≥50 kg/m2 (OR 1.60, 95% CI 1.27 to 2.01) were associated with greater 30 day composite morbidity. CONCLUSION: In this study, same day discharge following minimally invasive hysterectomy for oncologic indications was safe, and rates are rising among all age and body mass index categories. Quality improvement initiatives are needed at oncology centers to promote early discharge after minimally invasive gynecologic oncology surgery.

Access to Surgery for Endometrial Cancer Patients During the COVID-19 Pandemic in Ontario, Canada: A Population-Based Study.

OBJECTIVES: To assess the impact of the COVID-19 pandemic on endometrial cancer stage and surgical treatment in Ontario, Canada. METHODS: This descriptive study identified cases from January 1, 2017 to December 31, 2021 from endometrial cancer hysterectomy specimens in the Ontario Health-Cancer Care Ontario, ePath system. Endometrial biopsy records from January 1, 2016 to December 31, 2021 were matched to surgical specimens by provincial health card number. Time to surgery and surgical stage were compared before (2017-2019) and during (2020-2021) the COVID-19 pandemic. RESULTS: There were 10 446 women treated with hysterectomy for endometrial cancer in Ontario from 2017-2021. In April and May 2020, corresponding with the provincial state of emergency, there was a 56% relative reduction in endometrial biopsies. Despite this 2-month reduction in endometrial biopsy volume, there was no change in surgical volume for endometrial cancer treatment. The median time from endometrial biopsy to surgery was 56 days (IQR 40, 80) during the pandemic (2020-2021) compared to 58 days (IQR 43, 82) prior to the pandemic (2017-2019) (P < 0.001). There was no upstaging of endometrial cancer during the COVID-19 pandemic. CONCLUSIONS: The Ontario healthcare system continued to prioritize service delivery to endometrial cancer patients during the COVID-19 pandemic, despite the increase in virtual care and decrease in operating room time. There were no significant surgical delays or upstaging of endometrial cancer.

Adverse postoperative outcomes associated with perioperative blood transfusion in gynecologic oncology surgery.

OBJECTIVE: To examine the incidence of perioperative blood transfusion and association with 30 day postoperative outcomes in gynecologic cancer surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify all gynecologic oncology cases from 2013 to 2019. Clinical and surgical characteristics and 30 day postoperative complications were retrieved. The primary outcome was 30 day composite morbidity, based on the occurrence of one or more of the 18 adverse events. Secondary outcomes were 30 day mortality, length of stay in hospital, and composite surgical site infection, defined as superficial, deep, or organ space surgical site infection. The χ2 test and logistic regression analyses were performed to compare the outcomes of patients with and without perioperative blood transfusion. RESULTS: There were 62 531 surgical gynecologic oncology cases with an overall transfusion incidence of 9.4%. The transfusion incidence was significantly higher at 22.4% with laparotomy compared with 1.7% with minimally invasive surgery (p<0.0001). On multivariable analysis for laparotomy patients, blood transfusion was predictive of composite morbidity (adjusted odds ratio (OR) 1.65, 95% confidence interval (CI) 1.48 to 1.85) and length of stay in hospital ≥5 days (adjusted OR 9.02, 95% CI 8.21 to 9.92). In advanced ovarian cancer patients (n=3890), the incidence of perioperative blood transfusion was 40.8%. On multivariable analysis, perioperative blood transfusion was the most predictive factor for composite morbidity (adjusted OR 1.67, 95% CI 1.35 to 2.07) and length of stay in hospital ≥7 days (adjusted OR 9.75, 95% CI 7.79 to 12.21). CONCLUSION: Perioperative blood transfusion is associated with increased composite morbidity and prolonged length of stay in hospital. Preoperative patient optimization and institutional practices should be reviewed to improve the use of blood bank resources and adherence to restrictive blood transfusion protocols.

Low incidence of venous thromboembolism after gynecologic oncology surgery: Who is at greatest risk?

OBJECTIVE: To determine the 30-day incidence of venous thromboembolism (VTE) after gynecologic oncologic surgery and identify perioperative factors associated with postoperative VTE. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to identify all gynecologic oncology cases from 2013 to 2019. Clinical and surgical characteristics, VTE events and 30-day postoperative complications were retrieved. Chi-square analysis and logistic regression models were performed to compare characteristics and postoperative outcomes of patients with and without VTE. RESULTS: A total of 63,198 gynecologic oncology patients were included. The incidence of 30-day postoperative VTE was 1.2% (n = 781). On multivariable analysis, postoperative VTE was significantly associated with ascites (odds ratio (OR) 1.8), disseminated cancer (OR 1.7), pre-operative albumin <30 g/L (OR 1.9), laparotomy (OR 2.8), operative time > 180 min (OR 2.0), and increased surgical complexity (OR 2.2) (all p < 0.001). The incidence of VTE was higher after laparotomy compared to minimally invasive surgery (MIS) (2.3% v. 0.6%, p < 0.001). When stratified by type of gynecologic malignancy undergoing laparotomy, incidence of VTE was higher in patients with ovarian (2.4%) and uterine (2.4%) malignancies, compared to cervical cancer (1.1%) (p < 0.001). The 30-day incidence of VTE was 1.7% in 2013 compared to 0.9% in 2019 (laparotomy: 2.6% in 2013 to 1.6% in 2019 and MIS: 0.8% in 2013 to 0.4% in 2019). CONCLUSION: Postoperative VTE is a potentially preventable complication of gynecologic oncology surgery. Our findings indicate that laparotomy, ascites, disseminated cancer, longer operative time, and low pre-operative albumin are risk factors for VTE.

The accuracy of intraoperative frozen section examination of sentinel lymph nodes in squamous cell cancer of the vulva.

OBJECTIVE: To assess the diagnostic accuracy of intraoperative pathologic examination of sentinel lymph nodes (SLNs) and patient outcomes in vulva cancer. METHODS: This retrospective study included patients with unifocal, <4 cm, invasive vulvar squamous cell carcinoma and clinically negative groin nodes treated with SLN biopsy from January 2008-March 2020. Intraoperative SLN frozen section and final pathology were compared. If the SLN was negative, inguinal femoral lymphadenectomy (IFLD) was omitted. Recurrence location and groin recurrence free survival (RFS) were assessed. RESULTS: The SLN cohort included 173 patients, with 258 groins. On frozen section, there were 36/258 positive and 222 negative groins. On final pathology, there were 39/258 positive: 31 macrometastases, 6 micrometastases, 2 isolated tumor cells (ITCs) and 219 negative groins. The sensitivity, specificity, PPV and NPV for intraoperative detection of metastatic disease, was 89.7% and 99.5%, 97.2% and 98.2%, respectively. There was 1 false positive and 4 false negative frozen section results where final pathology revealed 2 ITCs, 1 micrometastasis and 1 macrometastasis. Based on intraoperative results, thirty patients (17.3%) underwent immediate IFLD. Median follow up was 38.0 (1-137.8) months. The 3-year groin RFS was 91.6% (95% CI 86.2-97.4%) for negative SLNs and 64.6% (95% CI 46.5-89.7%) for positive SLNs on frozen section. Similarly, the 3-year groin RFS was 91.7% (95% CI 86.3-97.4%) for negative, 58.4% (95% CI 38.5-87.7%) for macrometastases and 100% for micrometastases/ITCs on final pathology. CONCLUSIONS: Intraoperative assessment of SLNs is accurate to determine need for IFLD and does not compromise patient outcomes in vulvar cancer.

Incorporating Molecular Diagnostics into Treatment Paradigms for Endometrial Cancer.

OPINION STATEMENT: The treatment of endometrial cancer has recently undergone a paradigm shift from using traditional clinical-pathologic factors to molecular characterization for prognosis and selection of treatment. Recent approval of pembrolizumab, dostarlimab, and the combination of lenvatinib and pembrolizumab has drastically changed the treatment options and response rate for advanced and recurrent endometrial cancer, especially for DNA mismatch repair-deficient (MMRd) tumors. For p53 abnormal tumors, which have the worst prognosis, there are several new treatment approaches including lenvatinib and pembrolizumab, trastuzumab, and possibly a future role for PARP inhibitors in the homologous recombination deficiency (HRD) p53 abnormal population. In DNA polymerase epsilon-mutated (POLEmut) tumors which have an excellent prognosis, there's a possibility to de-escalate treatment, and in the small chance of recurrence, these tumors may be susceptible to immune checkpoint inhibitors. Further research is needed to better characterize biomarkers for prognosis and identify targeted treatments within the p53 wild-type (p53 WT)/no specific molecular profile (NSMP) cohort. Upcoming studies are evaluating adjuvant treatment by molecular subtype and will determine the next steps for precision medicine in endometrial cancer.

Oncologic and pregnancy outcomes after fertility-sparing surgery for stage I, low-grade endometrioid ovarian cancer.

OBJECTIVE: To evaluate oncologic outcomes in patients with stage I endometrioid ovarian cancer treated with fertility-sparing compared with conventional surgery and to describe reproductive outcomes. METHODS: A retrospective cohort study was carried out of patients aged 18-45 with stage I, grade 1 and 2 (low-grade) endometrioid ovarian cancer treated at two cancer centers between July 2001 and December 2019. Clinical and pathologic characteristics were compared using Fisher's exact test for categorical and the Mann-Whitney U test for continuous variables. Recurrence-free and overall survival were calculated from Kaplan-Meier curves and compared for fertility-sparing and conventional surgery using the log rank test. Pregnancy outcomes are described. RESULTS: There were 230 patients with endometrioid ovarian cancer. After exclusion of patients with stage greater than I and those older than 45 years, there were 31 patients with stage I cancer aged 18-45. Of these patients, 11 (35.5%) underwent fertility-sparing surgery and 20 (64.5%) underwent conventional surgery. The median follow-up was 6.0 years (range 1.8-17.3). The median age was 36 years (range 26-42) in the fertility-sparing group and 42 years (range 35-45) in the conventional surgery group (p=0.001), with no difference in other clinical and pathologic characteristics. The 5-year recurrence-free survival was 90.9% (95% CI 73.9% to 100%) for the fertility-sparing group and 84.0% (95% CI 67.3% to 100%) for the conventional surgery group (p=0.65). The 5-year overall survival was 100% for patients in the fertility-sparing group and 92.6% (95% CI 78.7% to 100%) for patients treated with conventional surgery (p=0.49). Four (12.9%) patients had disease recurrence: three (15%) after conventional surgery and one (9.1%) in the contralateral ovary after fertility-sparing surgery and embryo cryopreservation. After fertility-sparing surgery, seven (63.6%) patients attempted pregnancy, of which five (71.4%) conceived with four (57.1%) using in vitro fertilization. Of the five patients who conceived, there were three spontaneous abortions and five live births. CONCLUSION: Fertility-sparing surgery appears safe and may be considered in young women with stage I, low-grade endometrioid ovarian cancer when fertility preservation is desired.

The effect of complete surgical staging and adjuvant chemotherapy on survival in stage I, grade 1 and 2 endometrioid ovarian carcinoma.

OBJECTIVES: To assess the effect of complete surgical staging and adjuvant chemotherapy on survival in stage I, low grade endometrioid ovarian cancer. METHODS: This retrospective study was conducted at two cancer centers from July 2001 to December 2019. Inclusion criteria were all stage I, grade 1 and 2 endometrioid ovarian cancer patients. Patients with mixed histology, concurrent endometrial cancer, neoadjuvant chemotherapy, and patients who did not undergo follow-up at our centers were excluded. Clinical, pathologic, recurrence, and follow-up data were collected. Cox proportional hazard model evaluated predictive factors. Recurrence-free survival and overall survival were calculated using the Kaplan-Meier method. RESULTS: There were 131 eligible stage I patients: 83 patients (63.4%) were stage IA, 5 (3.8%) were stage IB, and 43 (32.8%) were stage IC, with 80 patients (61.1%) having grade 1 and 51 (38.9%) patients having grade 2 disease. Complete lymphadenectomy was performed in 34 patients (26.0%), whereas 97 patients (74.0%) had either partial (n=22, 16.8%) or no (n=75, 57.2%) lymphadenectomy. Thirty patients (22.9%) received adjuvant chemotherapy. Median follow-up was 51.5 (95% CI 44.3 to 57.2) months. Five-year recurrence-free survival was 88.0% (95% CI 81.6% to 94.9%) and 5 year overall survival was 95.1% (95% CI 90.5% to 99.9%). In a multivariable analysis, only grade 2 histology had a significantly higher recurrence rate (HR 3.42, 95% CI 1.03 to 11.38; p=0.04). There was no difference in recurrence-free survival (p=0.57) and overall survival (p=0.30) in patients with complete lymphadenectomy. In stage IA/IB, grade 2 there was no benefit of adjuvant chemotherapy (p=0.19), and in stage IA/IB, low grade without complete surgical staging there was no benefit of adjuvant chemotherapy (p=0.16). Twelve patients (9.2%) had recurrence; 3 (25%) were salvageable at recurrence and are alive with no disease. CONCLUSIONS: Patients with stage I, low grade endometrioid ovarian cancer have a favorable prognosis, and adjuvant chemotherapy and staging lymphadenectomy did not improve survival.

Ruptured Degenerating Fibroid Causing Preterm Labour and Systemic Inflammatory Response Syndrome.

BACKGROUND: Fibroids are present in at least 10% of pregnancies and are recognized to cause a variety of complications. A few case reports have described fibroids as an etiological factor in uterine rupture, sometimes with life-threatening hemorrhage. CASE: A 28-year-old G1, P0 woman at 20 weeks gestation developed systemic inflammatory response syndrome with acute renal failure and massive ascites secondary to a ruptured degenerated fibroid. This resulted in preterm delivery and neonatal death. At 6 weeks postpartum, she successfully underwent an abdominal myomectomy. CONCLUSION: This is a rare case of uterine fibroid rupture causing preterm labour and systemic inflammatory response syndrome. This report discusses the diagnosis of uterine rupture related to the fibroid with imaging and subsequent management, which included fertility-preserving surgery.

Risk of Recurrence After Treatment for Cervical Intraepithelial Neoplasia 3 and Adenocarcinoma In Situ of the Cervix: Recurrence of CIN 3 and AIS of Cervix.

OBJECTIVES: The aim of the study was to evaluate recurrence risk of cervical intraepithelial neoplasia (CIN) 3+ and adenocarcinoma in situ (AIS)+ in a large population cohort of women previously treated for CIN 3/AIS. METHODS: Merging administrative databases with information on health services utilization and jurisdictional cancer registry, we identified all women undergoing treatment for CIN 3 or AIS from 2006 to 2010. Recurrence rate 1-5 years after treatment was defined as a biopsy finding of CIN 3/AIS or retreatment (loop electrosurgical excision procedure [LEEP], laser, cone, hysterectomy). Logistic regression was used to determine odds of recurrence. RESULTS: A total of 15,177 women underwent treatment for CIN 3 (n = 14,668) and AIS (n = 509). The recurrence rate for 5 years was greater for AIS (9.0%) compared with CIN 3 (6.1%). In a multivariate analysis, increased risk of recurrence was shown for age older than 45 years (hazard ratio (HR) = 1.3, 95% CI = 1.1-1.6), AIS compared with CIN 3 (HR = 2.2, 95% CI = 1.5-3.5) first cytology after treatment showing high grade (HR = 12.4, 95% CI = 9.7-15.7), and no normal Pap smears after treatment (HR = 2.8, 95% CI = 2.2-3.7). There was no difference in recurrence risk with treatment type (cone vs LEEP: HR = 1.0, 95% CI = 0.8-1.2, and laser vs LEEP: HR = 1.1, 95% CI = 0.8-1.4) or number of procedures per year performed by physicians (<40 vs >40 procedures: HR = 1.1, 95% CI = 0.9-1.3). CONCLUSIONS: Recurrence risk of CIN 3 and AIS is related to age, histology, and posttreatment cytology, which should assist with discharge planning from colposcopy. Definitive treatment with hysterectomy should be considered in women older than 45 years with additional risk factors for recurrence.

Sonographic lower uterine segment thickness after prior cesarean section to predict uterine rupture: A systematic review and meta-analysis.

INTRODUCTION: Cesarean section rates are increasing with a decrease in the rate of trial of labor after cesarean section. The objective of this study was to systematically review the predictive characteristics of sonographic measurement of lower uterine segment thickness for uterine rupture during labor. MATERIAL AND METHODS: The review was carried out in agreement with PRISMA and SEDATE guidelines. MEDLINE, EMBASE, ClinicalTrials.gov and Cochrane Library were searched from 1990 until November 2018. Quality of included studies was assessed using the QUADAS-2 tool. Data were extracted to construct 2 × 2 tables from each study comparing ultrasound measurement with uterine defect at time of delivery. The data were plotted as a summary receiver-operating characteristic (SROC) curve using the hierarchical SROC model. RESULTS: Twenty-eight observational cohort studies met the selection criteria for inclusion. Sonographic lower uterine segment thickness was measured at a gestational age of 36-40 weeks in women with a previous cesarean section. The risk of bias and concerns regarding applicability were low among most studies. The sonographic measurement was correlated with either delivery outcome or lower uterine segment thickness at the time of repeat cesarean section. The cut-off value for lower uterine segment thickness ranged from 1.5 to 4.05 mm across all studies. An association between thin lower uterine segment measurement and uterine dehiscence and uterine rupture was shown in 27 and four studies, respectively. Nineteen studies were included in a meta-analysis with a subgroup analysis by ultrasound methodology. In the subgroup using the ultrasound methodology associated with uterine rupture, the cut-off value is more precise (2.0-3.65 mm) among these 12 studies. There were 18 cases (1.0%) of uterine rupture, 120 (6.6%) of uterine dehiscence and 1674 (92.4%) women with no uterine defect. The SROC curve showed a sensitivity of 0.88 (95% CI 0.83-0.92) and specificity of 0.77 (95% CI 0.70-0.83). The negative likelihood ratio was 0.11 (95% CI 0.08-0.16) and the diagnostic odds ratio was 34.0 (95% CI 18.2-63.5). CONCLUSIONS: Lower uterine segment thickness >3.65 mm, measured using a standardized ultrasound technique, is associated with a lower likelihood of uterine rupture.

The effect of age, ethnicity, and level of education on fertility awareness and duration of infertility.

OBJECTIVE: An increasing number of Canadian women are delaying child-bearing, despite a decrease in fertility with age. A longer duration of infertility is associated with a significant decrease in live birth rate, reinforcing the need for prompt access to fertility treatment. This study aimed to assess the fertility awareness of women attending a fertility clinic to determine whether fertility awareness is a factor in accessing treatment. METHODS: A quantitative cross-sectional survey evaluated fertility awareness and collected information about ethnicity, education level, and the duration of infertility for new patients. Fertility awareness was evaluated with questions about prevalence, causes, and treatment of infertility. RESULTS: The mean age of participants in the study was 34 years (range 23 to 44; n = 140). The duration of infertility before new patients first sought medical advice for infertility was less than one year in 52.9%, one to two years in 28.6%, two to three years in 12.9%, and four or more years in 5.0% of study participants. Fertility awareness was calculated as the percentage of correct responses to the survey questions. The mean fertility awareness for all study participants was 49.9% and this ranged from the lowest score of 9.1% to the highest score of 90.9% correct. Women waiting for longer than two years to seek medical help had lower fertility awareness (P = 0.038). In addition, fertility awareness was greater in women who had previously sought medical help for infertility from a family doctor, a gynaecologist, or another fertility clinic (P = 0.001). Higher fertility awareness correlated with a higher level of education (linear trend P < 0.001). Finally, fertility awareness also varied with ethnicity (ANOVA P = 0.025), but the age at which women of different ethnicities sought treatment was similar (ANOVA P = 0.13). CONCLUSION: Fertility awareness is associated with time to seek treatment, ethnicity, and level of education among new patients seeking medical treatment. This study demonstrates the need to educate women of reproductive age and identifies particular patient populations in Canada that would most benefit from further education about infertility.

Objectif : Un nombre croissant de Canadiennes reportent la grossesse, et ce, malgré la baisse de la fertilité qui est constatée avec l'âge. La prolongation de la durée de l'infertilité est associée à une baisse marquée du taux de naissance vivante, ce qui souligne la nécessité d'assurer un accès rapide au traitement contre l'infertilité. Cette étude cherchait à évaluer les connaissances en matière de fertilité chez des femmes consultant une clinique de fertilité, en vue de déterminer si de telles connaissances constituent un facteur pour ce qui est de l'accès au traitement. Méthodes : Une enquête transversale quantitative a évalué les connaissances en matière de fertilité chez de nouvelles patientes et a recueilli des données au sujet de leur ethnicité, de leur scolarité et de la durée de leur infertilité. Les connaissances en matière de fertilité ont été évaluées par l'intermédiaire de questions portant sur la prévalence, les causes et la prise en charge de l'infertilité. Résultats : L'âge moyen des participantes à l'étude était de 34 ans (plage : 23-44; n = 140). La durée de l'infertilité avant que ces nouvelles patientes aient pour la première fois cherché à obtenir l'avis d'un médecin à ce sujet était de moins d'un an chez 52,9 % d'entre elles; d'un à deux ans, chez 28,6 %; de deux à trois ans, chez 12,9 %; et de quatre ans ou plus, chez 5,0 %. Le pourcentage de bonnes réponses aux questions de l'enquête a été utilisé pour définir les connaissances en matière de fertilité. Pour l'ensemble des participantes à l'étude, le score moyen pour ce qui est des connaissances en matière de fertilité était de 49,9 % (plage : de 9,1 % à 90,9 %). Les femmes qui avaient attendu pendant plus de deux ans avant de chercher à obtenir l'aide d'un médecin comptaient des connaissances moindres en matière de fertilité (P = 0,038). De plus, les connaissances en matière de fertilité étaient supérieures chez les femmes qui avaient déjà cherché à obtenir de l'aide pour contrer leur infertilité auprès d'un médecin de famille, d'un gynécologue ou d'une autre clinique de fertilité (P = 0,001). Le fait de détenir des connaissances élevées en matière de fertilité était en corrélation avec une scolarité accrue (tendance linéaire P < 0,001). Enfin, les connaissances en matière de fertilité ont également varié en fonction de l'ethnicité (ANOVA P = 0,025); toutefois, l'âge auquel les femmes de différentes ethnicités ont cherché à obtenir un traitement était semblable (ANOVA P = 0,13). Conclusion : Chez de nouvelles patientes cherchant à obtenir un traitement médical, les connaissances en matière de fertilité ont été associées avec le délai avant la mise en œuvre de la démarche visant l'obtention d'un traitement, l'ethnicité et le niveau de scolarité. Cette étude démontre la nécessité de renseigner les femmes en âge de procréer et identifie les populations particulières de patientes canadiennes qui tireraient le plus profit d'une sensibilisation accrue au sujet de l'infertilité.

Characterization of biologically active insulin-loaded alginate microparticles prepared by spray drying.

BACKGROUND: Spray drying has been used as a means to encapsulate therapeutics in polymeric matrices to improve stability and alter pharmacokinetics. This research aims to characterize alginate microparticles formed by spray drying to encapsulate insulin for therapeutic delivery applications. METHODS: Particle size was characterized by laser diffraction spectroscopy, morphology by scanning electron microscopy, and protein and polymer distribution by confocal laser scanning microscopy. In addition, particle fines collected from the spray-dryer exhaust unit were characterized for size and morphology. The insulin encapsulation efficiency (EE) was determined after particle dissolution through quantification by spectrophotometric analysis. An in-vitro bioassay involving stimulation of rat L6 myoblasts was developed to confirm the bioactivity of released insulin. RESULTS: Mean diameter of the product was 2.1 ± 0.3 µm. Larger particles appeared spherical, with some smaller particles presenting surface topography variability and divoting. Protein EE was 38.2% ± 9.5%, with confocal microscopy showing the protein and polymer concentrated at the surface of larger particles, but more evenly distributed throughout smaller particles. A bioassay for the in-vitro quantification of insulin bioactivity was developed by calibrating the ratio of phosphorylated to total cellular protein kinase B (PKB; also known as AKT). in insulin-stimulated rat L6 myoblasts. Insulin released from the particles was 88% ± 15% bioactive, showing that spray drying had minimal impact on protein structure. CONCLUSION: Spray drying was effective in producing microparticles containing bioactive insulin. Future studies will focus on the improvement of the EE and particle uniformity with the aim of developing this technology further for the encapsulation and delivery of peptide or protein-based therapeutics.

Natural killer cell lines preferentially kill clonogenic multiple myeloma cells and decrease myeloma engraftment in a bioluminescent xenograft mouse model.

BACKGROUND: Novel therapies capable of targeting drug resistant clonogenic MM cells are required for more effective treatment of multiple myeloma. This study investigates the cytotoxicity of natural killer cell lines against bulk and clonogenic multiple myeloma and evaluates the tumor burden after NK cell therapy in a bioluminescent xenograft mouse model. DESIGN AND METHODS: The cytotoxicity of natural killer cell lines was evaluated against bulk multiple myeloma cell lines using chromium release and flow cytometry cytotoxicity assays. Selected activating receptors on natural killer cells were blocked to determine their role in multiple myeloma recognition. Growth inhibition of clonogenic multiple myeloma cells was assessed in a methylcellulose clonogenic assay in combination with secondary replating to evaluate the self-renewal of residual progenitors after natural killer cell treatment. A bioluminescent mouse model was developed using the human U266 cell line transduced to express green fluorescent protein and luciferase (U266eGFPluc) to monitor disease progression in vivo and assess bone marrow engraftment after intravenous NK-92 cell therapy. RESULTS: Three multiple myeloma cell lines were sensitive to NK-92 and KHYG-1 cytotoxicity mediated by NKp30, NKp46, NKG2D and DNAM-1 activating receptors. NK-92 and KHYG-1 demonstrated 2- to 3-fold greater inhibition of clonogenic multiple myeloma growth, compared with killing of the bulk tumor population. In addition, the residual colonies after treatment formed significantly fewer colonies compared to the control in a secondary replating for a cumulative clonogenic inhibition of 89-99% at the 20:1 effector to target ratio. Multiple myeloma tumor burden was reduced by NK-92 in a xenograft mouse model as measured by bioluminescence imaging and reduction in bone marrow engraftment of U266eGFPluc cells by flow cytometry. CONCLUSIONS: This study demonstrates that NK-92 and KHYG-1 are capable of killing clonogenic and bulk multiple myeloma cells. In addition, multiple myeloma tumor burden in a xenograft mouse model was reduced by intravenous NK-92 cell therapy. Since multiple myeloma colony frequency correlates with survival, our observations have important clinical implications and suggest that clinical studies of NK cell lines to treat MM are warranted.

Laparoscopic ovarian transposition prior to pelvic radiation for gynecologic cancer.

This study evaluates a novel technique of laparoscopic ovarian transposition performed by Gynecologic Oncologists prior to pelvic radiation for gynecologic cancer. A retrospective review was completed of all patients that underwent laparoscopic ovarian transposition from February 2007 to June 2017 at one tertiary care cancer. The technique involves salpingectomy, followed by retroperitoneal dissection to move the ovaries lateral to the hepatic and splenic flexures of the colon. Normal ovarian function was defined by the absence of vasomotor symptoms, FSH and menstrual history (if menstruating). The radiation dose to the ovary was calculated through dose volume histograms from three-dimensional image planning. Ten patients had laparoscopic ovarian transposition, of which, eight patients received post-operative external beam radiation to the pelvis (45-59.4 Gy). Four had additional brachytherapy (35.5-40 Gy). Median age and follow up were 29 years (18-37), and 20 months (6-103). Nine patients had cervical and one had vaginal cancer. Four patients were treated with primary radiation, three had radical trachelectomy with adjuvant radiation, and three had radical hysterectomy with one of three receiving adjuvant radiation. No patients developed vasomotor symptoms (0/8 (95% CI 0-19%)). FSH was normal in 2/2 patients. Menses continued post-radiation in 5/7 women who retained their uterus. The median radiation dose to the right and left ovary was 0.51 (0.23-1.1) Gy and 0.53 (0.23-1.1) Gy, respectively. Laparoscopic ovarian transposition with mobilization to the hepatic and splenic flexures of the colon achieves preservation of ovarian function in women prior to pelvic radiation.