Mary Catherine Tolcher

Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas

Mucinous ovarian carcinomas (MCs) typically do not respond to current conventional therapy. We have previously demonstrated amplification of HER2 in 6 of 33 (18.2%) mucinous ovarian carcinomas (MCs) and presented anecdotal evidence of response with HER2‐targeted treatment in a small series of women with recurrent HER2‐amplified (HER2+) MC. Here, we explore HER2 amplification and KRAS mutation status in an independent cohort of 189 MCs and 199 mucinous borderline ovarian tumours (MBOTs) and their association to clinicopathological features. HER2 status was assessed by immunohistochemistry (IHC), FISH, and CISH, and interpreted per ASCO/CAP guidelines, with intratumoural heterogeneity assessment on full sections, where available. KRAS mutation testing was performed with Sanger sequencing. Stage and grade were associated with recurrence on both univariate and multivariate analysis (p < 0.001). Assessment of HER2 status revealed overexpression/amplification of HER2 in 29/154 (18.8%) MCs and 11/176 (6.2%) MBOTs. There was excellent agreement between IHC, FISH, and CISH assessment of HER2 status (perfect concordance of HER2 0 or 1+ IHC with non‐amplified status, and 3+ IHC with amplified status). KRAS mutations were seen in 31/71 (43.6%) MCs and 26/33 (78.8%) MBOTs, and were near mutually exclusive of HER2 amplification. In the 189 MC cases, a total of 54 recurrences and 59 deaths (53 of progressive disease) were observed. Within MCs, either HER2 amplification/overexpression or KRAS mutation was associated with decreased likelihood of disease recurrence (p = 0.019) or death (p = 0.0041) when compared to cases with neither feature. Intratumoural heterogeneity was noted in 26% of HER2‐overexpressing cases. These data support the stratification of MCs for the testing of new treatments, with HER2‐targeted therapy as a viable option for HER2+ advanced or recurrent disease. Further research is required to delineate the molecular and clinical features of the ∼34% of MC cases with neither HER2 amplification nor KRAS mutations.

Decision-to-incision time and neonatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the literature on the proportion of emergent cesarean deliveries accomplished within 30 minutes, the mean time from decision-to-incision or delivery, and differences in neonatal outcomes in deliveries accomplished within 30 minutes compared to beyond 30 minutes. DATA SOURCES: Electronic databases (Ovid MEDLINE and EMBASE and www.clinicaltrials.gov) were searched from inception to January 2013. METHODS OF STUDY SELECTION: Eligible studies reported decision-to-incision time or delivery time intervals for nonelective cesarean deliveries. Both emergent and urgent deliveries (also known as category 1 and category 2 deliveries) were included. Two reviewers independently identified studies for inclusion. TABULATION, INTEGRATION, AND RESULTS: Out of 737 reports identified in the primary search, 34 studies (22,936 women) met eligibility criteria. Seventy-nine percent (95% confidence interval [CI] 61–97%) of category 1 deliveries and 36% (95% CI 24–48%) of category 2 deliveries were achieved within 30 minutes, with significantly shorter time in category 1 compared to category 2 deliveries (21.2 compared with 42.6 minutes; P<.001). In the 13 studies that included neonatal outcomes, there was a higher risk of overall 5-minute Apgar score less than 7 (odds ratio [OR] 3.10; 95% CI 1.93–4.96) and umbilical artery pH level less than 7.10 (OR 3.40; 95% CI 2.38–4.87) in cases involving shorter delivery intervals. However, analyses limited to category 1 deliveries did not show a statistically greater risk of Apgar score less than 7 (OR 0.69; 95% CI 0.11–4.51) or umbilical artery pH level less than 7.10 (OR 1.10; 95% CI 0.28–4.40) with shorter delivery intervals. There was no difference by delivery interval in admission to neonatal intensive care units or special newborn units (OR 1.23; 95% CI 0.90–1.68). CONCLUSION: Delivery within 30 minutes was not achieved in a substantial proportion of cases. The clinical significance of failing to achieve this standard remains uncertain.

Safety of culdotomy as a surgical approach: implications for natural orifice transluminal endoscopic surgery.

Data from this study support the feasibility and safety of utilizing the cul-de-sac as an access port to the peritoneal cavity for natural orifice transluminal endoscopic surgery.

Predicting Cesarean Delivery After Induction of Labor Among Nulliparous Women at Term

OBJECTIVE: To identify independent risk factors for cesarean delivery after induction of labor and to develop a nomogram for predicting cesarean delivery among nulliparous women undergoing induction of labor at term. METHODS: This is a retrospective cohort study including nulliparous women with singleton, term (37 0/7 weeks of gestation or greater), cephalic pregnancies undergoing induction of labor from July 1, 2006, through May 31, 2012, at a tertiary care academic center. Inductions were identified using International Classification of Diseases, 9th Revision codes. Demographic, delivery, and outcome data were abstracted manually from the medical record. Women with a contraindication to vaginal delivery (malpresentation, abnormal placentation, prior myomectomy) were excluded. Independent risk factors for cesarean delivery were identified using logistic regression. RESULTS: During the study period, there were 785 nulliparous inductions that met study criteria; 231 (29.4%) underwent cesarean delivery. Independent risk factors associated with an increased risk of cesarean delivery included older maternal age, shorter maternal height, greater body mass index, greater weight gain during pregnancy, older gestational age, hypertension, diabetes mellitus, and initial cervical dilation less than 3 cm. A nomogram was constructed based on the final model with a bias-corrected c-index of 0.709 (95% confidence interval 0.671–0.750). CONCLUSION: We identified independent risk factors that can be used to predict cesarean delivery among nulliparous women undergoing induction of labor at term. If validated in other populations, the nomogram could be useful for individualized counseling of women with a combination of identifiable antepartum risk factors. LEVEL OF EVIDENCE: II

Characterization of precursor lesions in the endometrium and fallopian tube epithelium of early-stage uterine serous carcinoma.

To determine if selected cases of uterine serous carcinoma (USC) arise from tubal rather than endometrial epithelium. Bilateral fallopian tubes from 38 women with pure USC were entirely submitted for histopathologic examination using the protocol Sectioning and Extensively Examining the FIMbria (SEE-FIM). Non-neoplastic endometrium was extensively sampled. Immunohistochemistry for p53 was performed on all paraffin blocks of fallopian tube and non-neoplastic endometrium. Endometrial intraepithelial carcinoma (EIC) was present in 22 cases (58%). Endometrial p53 foci were identified in 3 patients. There were 11 cases (29%) with fallopian tube involvement; 9 of 11 had tubal wall invasion or lymphatic involvement without serous tubal intraepithelial carcinoma (STIC) and were, therefore, classified as metastatic from the endometrium. STIC was identified in 3 patients (8%). There were 3 cases with tubal p53 foci in non-neoplastic epithelium. EIC was present in 58% of patients, further supporting EIC as a precursor lesion to USC. STIC was present in 8%, suggesting that the fallopian tube may in fact represent the primary lesion in a minority of patients with USC. This finding may account for the early multifocal disease distribution observed in these patients.

Impact of a labor and delivery safety bundle on a modified adverse outcomes index.

BACKGROUND The Obstetrics Adverse Outcomes Index was designed to measure the quality of perinatal care and includes 10 adverse events that may occur at or around the time of delivery. We hypothesized that adverse outcomes in the labor and delivery suite, including hypoxic ischemic encephalopathy, could be decreased with a combination of interventions, even among high-risk pregnancies. OBJECTIVE The objective of the study was to evaluate the impact of a labor and delivery care bundle on adverse obstetrics outcomes as measured by a modified Obstetrics Adverse Outcomes Index, Weighted Adverse Outcomes Index, and Severity Index. STUDY DESIGN This is a retrospective cohort study including all women who delivered at our academic, tertiary care institution over a 3 year period of time, before and after the implementation of an intervention to decrease adverse outcomes. Outcome measures consisted of previously reported indices that were modified including the addition of hypoxic ischemic encephalopathy. The adverse outcomes index is a percentage of deliveries with 1 or more adverse events, the weighted adverse outcomes index is the sum of the points assigned to cases with adverse outcomes divided by the number of deliveries, and the severity index is the sum of the adverse outcome scores divided by the number of deliveries with an identified adverse outcome. A segmented regression analysis was utilized to evaluate the differences in the level and trend of each index before and after our intervention using calendar month as the unit of analysis. RESULTS During the study period, 5826 deliveries met inclusion criteria. Comparing the pre- and postintervention periods, high-risk pregnancy was more common in the postintervention period (73.5% vs 79.4%, P < .001). Overall, there was a decrease in both the Modified Weighted Adverse Outcomes Index (P = .0497) and the Modified Severity Index (P = 0.01) comparing the pre- and postintervention periods; there was no difference in the Modified Adverse Outcomes Index (P = .43). For low-risk pregnancies, there was no significant difference in the levels for any of the measured indices over the study period (P = .61, P = .41, and P = .34 for the Modified Adverse Outcomes Index, Modified Weighted Adverse Outcomes Index, and Modified Severity Index, respectively). Among the high-risk pregnancies, the monthly Modified Weighted Adverse Outcomes Index decreased by 4.2 ± 1.8 (P = .03). The monthly Modified Severity Index decreased by 53.9 ± 17.7 points from the pre- to the postintervention periods (P = .01) and was < 50% of the predicted Modified Severity Index had the intervention not been implemented. The cesarean delivery rate was increasing prior to the intervention, but the rate was stable after the intervention, and the absolute rate did not differ between the pre- and the postintervention periods (28.4% vs 30.0%, P = .20). CONCLUSION Overall and for high-risk pregnancies, the implementation of the labor and delivery care bundle had a positive impact on the Modified Weighted Adverse Outcomes Index and Modified Severity Index but not the Modified Adverse Outcomes Index.

Delivery of an Impacted Fetal Head During Cesarean: A Literature Review and Proposed Management Algorithm.

&NA; Effective and expedient management of an impacted fetal head (IFH) at cesarean delivery is essential to avoid maternal and neonatal morbidity. The incidence of an IFH at the time of cesarean may increase because of changing practice guidelines regarding the acceptable duration of the second stage of labor. Based on limited available evidence comparing the “push,” “pull,” and other methods for delivery of the IFH, we suggest the primary disengagement technique be selected based on surgeon experience and propose a management algorithm “ALERT” for clinical application. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this activity, the learner will be better able to identify risk factors for an impacted fetal head during cesarean delivery, list potential complications associated with an impacted fetal head, describe the “push” and “pull” methods of delivery of an impacted fetal head, and understand the concepts in the ALERT algorithm.

Clinical Impact of a Restrictive Labor Induction Approval Process

Background/Aims: The aim of this study was to evaluate the impact of a restrictive labor induction approval process on induction and primary cesarean delivery rates. Methods: A retrospective cohort study was conducted at a tertiary care academic center from 2006 through 2012. The cohort of deliveries before (pre-intervention) and after (post-intervention) the process included term, singleton pregnancies with no contraindication to vaginal delivery. The primary outcome was induction of labor rates, subgrouped on the basis of whether it was medically or nonmedically indicated. Secondary outcomes included the primary cesarean rate and other maternal and neonatal outcomes. Results: Of 13,753 deliveries, 6,746 met study inclusion criteria. There was a significant decrease in induction rates comparing the pre- and post-intervention periods (21.0 vs. 18.5%, p = 0.01). Nonmedically indicated induction rates also decreased significantly (2.9 vs. 0.6%, p < 0.001). No difference was observed in medically indicated induction (18.1 vs. 17.9%, p = 0.84), the primary cesarean rate (14.4 vs. 15.8%, p = 0.12), or any of the measured neonatal outcomes (p > 0.05). Conclusions: Implementation of a labor induction approval process was associated with a significant reduction in overall and non-indicated induction rates but did not affect the primary cesarean rate or neonatal outcomes.

Intrapartum factors associated with neonatal hypoxic ischemic encephalopathy: A case-controlled study

BackgroundNeonatal encephalopathy (NE) affects 2–4/1000 live births with outcomes ranging from negligible neurological deficits to severe neuromuscular dysfunction, cerebral palsy and death. Hypoxic ischemic encephalopathy (HIE) is the sub cohort of NE that appears to be driven by intrapartum events. Our objective was to identify antepartum and intrapartum factors associated with the development of neonatal HIE.MethodsHospital databases were searched using relevant diagnosis codes to identify infants with neonatal encephalopathy. Cases were infants with encephalopathy and evidence of intrapartum hypoxia. For each hypoxic ischemic encephalopathy case, four controls were randomly selected from all deliveries that occurred within 6 months of the case.ResultsTwenty-six cases met criteria for hypoxic ischemic encephalopathy between 2002 and 2014. In multivariate analysis, meconium-stained amniotic fluid (aOR 12.4, 95% CI 2.1–144.8, p = 0.002), prolonged second stage of labor (aOR 9.5, 95% CI 1.0–135.3, p = 0.042), and the occurrence of a sentinel or acute event (aOR 74.9, 95% CI 11.9-infinity, p < 0.001) were significantly associated with hypoxic ischemic encephalopathy. The presence of a category 3 fetal heart rate tracing in any of the four 15-min segments during the hour prior to delivery (28.0% versus 4.0%, p = 0.002) was more common among hypoxic ischemic encephalopathy cases.ConclusionProlonged second stage of labor and the presence of meconium-stained amniotic fluid are risk factors for the development of HIE. Close scrutiny should be paid to labors that develop these features especially in the presence of an abnormal fetal heart tracing. Acute events also account for a substantial number of HIE cases and health systems should develop programs that can optimize the response to these emergencies.

Does Regional Anesthesia for External Cephalic Version Increase the Risk of Emergent Cesarean Delivery? [8C]

INTRODUCTION: Previous studies have shown improved success without additional complications when external cephalic version (ECV) is performed with neuraxial anesthesia (NA). The purpose of this study was to evaluate the effect of NA at the time of ECV on emergent cesarean delivery (CD), procedure success, and subsequent vaginal delivery. METHODS: Women who underwent ECV at Mayo Clinic between January 1, 2010 and December 31, 2014 with and without NA were retrospectively studied. The primary outcome was the rate of emergency CD (delivery within 4 hours of ECV). Secondary outcomes were ECV success and ultimate mode of delivery. Outcomes were compared using the chi-square test. RESULTS: A total of 135 patients underwent 144 ECV procedures with NA use in 65 (45.1%) procedures. Increased rates of emergent CD were found with NA compared to procedures without NA (6 [9.2%] versus 0 [0%], P=.006). ECV success was unaffected by NA (36 [55.4%] successful ECV with NA versus 38 [48.1%] without NA, P=.38). Successful ECV led to subsequent vaginal delivery in only 55 (38.2%) women. CONCLUSION: NA for ECV increased the risk of emergent CD without impacting ECV success. These findings differ from previous randomized controlled trials (RCTs). The increased risk and decreased success of our ECVs compared to ECVs performed in the context of RCTs could be explained by patient selection, variation in operator experience or technique, or variation in anesthetic management. Future studies should further evaluate the risk of NA for ECV in true practice scenarios outside of RCTs.