Placental Chorangiosis: Increased Risk for Cesarean Section

We describe a patient with Class C diabetes who presented for nonstress testing at 36 weeks and 4 days of gestation with nonreassuring fetal heart tones (NRFHT) and oligohydramnios. Upon delivery, thrombosis of the umbilical cord was grossly noted. Pathological analysis of the placenta revealed chorangiosis, vascular congestion, and 40% occlusion of the umbilical vein. Chorangiosis is a vascular change of the placenta that involves the terminal chorionic villi. It has been proposed to result from longstanding, low-grade hypoxia in the placental tissue and has been associated with such conditions such as diabetes, intrauterine growth restriction (IUGR), and hypertensive conditions in pregnancy. To characterize chorangiosis and its associated obstetric outcomes we identified 61 cases of chorangiosis on placental pathology at Henry Ford Hospital from 2010 to 2015. Five of these cases were omitted due to lack of complete records. Among the 56 cases, the cesarean section rate was 51%, indicated in most cases for nonreassuring fetal status. Thus, we suggest that chorangiosis, a marker of chronic hypoxia, is associated with increased rates of cesarean sections for nonreassuring fetal status because of long standing hypoxia coupled with the stress of labor

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC

Definitive radiation therapy for cervical cancer: Non-white race and public insurance are risk factors for delayed completion, a pilot study.

This is a pilot study to assess whether racial disparities exist in time to initiation and completion of external beam pelvic radiation therapy and brachytherapy in cervical cancers treated with definitive chemoradiation. A retrospective analysis was conducted on all cervical cancer patients treated with definitive radiotherapy between 2006 and 2016 at a single institution. Patient demographics including age, race, insurance status and stage at diagnosis were obtained. Analyses were performed according to the following definitions of wait times: interval from pathologic diagnosis of cervical cancer to (Siegel et al., 2016) initiation of radiation therapy, (Yoo et al., 2017) completion of external beam radiation therapy and (DeSantis et al., 2016) completion of external beam radiation therapy plus brachytherapy if indicated. Of 50 women, 21 self-identified as white, 25 as black and 4 as Hispanic. Due to small numbers, Hispanic women were included with black women as a non-white group. The average age was 52 years for women in this cohort. Mean days to initiation of radiation therapy were 41.8 days: 33.7 days among white patients versus 47.8 days for non-white patients (p-value 0.101). Mean days from diagnosis to completion of external beam pelvic radiation therapy were 81.3 days: 70.9 days among white patients versus 88.9 days among non-white patients (p-value 0.006). Non-white patients were more likely to have public insurance, which was also associated with a longer time to completion of radiation treatment. We conclude that non-white patients experienced delays to completing external beam radiation therapy, which was no longer present after adjusting for insurance status

Multi-disciplinary clinic discussion associated with decreased performance of breast MRI and increased eligibility for breast conservation

Background/Objective: The management of breast cancer benefits from a multi-disciplinary approach as this leads to better adherence to management guidelines. There is much variability in the utilization of MRI in the management of breast cancer. This study examines the effect of implementation of a multi-disciplinary clinic (MDC) on the utilization of MRI and breast-conserving therapy (BCT). Methods: We conducted a retrospective review of patients who were diagnosed with invasive breast cancer 1 year prior to and after the implementation of an MDC at our institution. We examined various clinical factors including age, sex, tumor characteristics, radiologic studies, surgical and medical treatment, and rates of BCT. We performed univariate analysis to compare differences among rates of pre-treatment MRI and BCT between patients who were and were not presented at the MDC. Results: A total of 539 patients were eligible for the study. There were 122 patients who were diagnosed prior to MDC, and 419 patients discussed at MDC. There was no difference in the average age (59.9 vs 62.2, p=0.1). There were no differences between the non-MDC and MDC patients among rates of BCT offered if eligible (96.8% vs 96.7%, p=0.95) and BCT performed if eligible (98.8% vs 93.9%, p=0.07). There was, however, a significant difference between the 2 groups in rates of pre-treatment MRI performed (32.2% vs 14.4%, p\u3c0.001). When comparing the groups that did not have a pre-treatment MRI and those that did, there was a decrease in the rate of BCT eligibility (82% vs 72.9%, p=0.02), BCT offered (98.6% vs 87.0%, p\u3c0.001), but not in the rates of BCT performed if eligible (95% vs 94.2%, p=0.82). Conclusions: Having a pre-treatment MRI resulted in patients more likely to be considered ineligible for BCT, and also less likely to be offered BCT. Having lower rates of BCT offered is a negative repercussion that may be mitigated through an MDC approach because patients are less likely to have a pretreatment MRI when presented at MDC. Further research is warranted, and more detailed conclusions may be obtained through prospective trials such as the ALLIANCE-MRI trial

Rate of Urologic Injury with Robotic Hysterectomy

STUDY OBJECTIVE: To evaluate rates of urologic injury in patients who underwent robotic hysterectomy compared with laparoscopic, vaginal, and open hysterectomy. DESIGN: A retrospective analysis (Canadian Task Force classification II-2). SETTING: Henry Ford Health System, 2013 to 2016. PATIENTS: Women who underwent robotic, vaginal, laparoscopic, and open abdominal hysterectomy. INTERVENTIONS: Robotic hysterectomy, laparoscopic-assisted vaginal hysterectomy, total laparoscopic hysterectomy, laparoscopic supracervical hysterectomy, vaginal hysterectomy, and abdominal hysterectomy. MEASUREMENTS AND MAIN RESULTS: To identify patients with urologic injury, a departmental database for quality improvement was searched for reported urologic injuries. In addition, patients who had urology consultation within 90 days of hysterectomy were screened for injury. A total of 3114 hysterectomies were identified by retrospective chart review. One thousand eighty-eight robotic, 782 laparoscopic, 304 vaginal, and 940 abdominal hysterectomies were analyzed for urologic complications. A total of 27 injuries were confirmed (7 during laparoscopic hysterectomy, 10 during robotic hysterectomy, 1 during vaginal hysterectomy, and 9 during abdominal hysterectomy). The overall rate of urologic injury was 0.87% with a 0.55% risk of bladder injury and a 0.32% risk of injury to the ureter. When the route of hysterectomy was taken into account, the risk of urologic injury was 0.92% for robotic hysterectomy, 0.90% for laparoscopic hysterectomy, 0.33% for vaginal hysterectomy, and 0.96% for open hysterectomy. The mean body mass index (BMI) for all patients was 32.7 kg/m2; injured patients had a mean BMI of 34.6 kg/m2, and noninjured patients had a mean BMI of 32.0 kg/m2 (p = .10). CONCLUSION: Rates of urologic injury with robotic hysterectomy are similar to those of laparoscopic hysterectomy in our population. BMI was not significantly different in patients who had urologic injuries. Surgeon volume was not associated with risk for urologic injury

Rate of Urologic Injury with Robotic Hysterectomy.

STUDY OBJECTIVE: To evaluate rates of urologic injury in patients who underwent robotic hysterectomy compared with laparoscopic, vaginal, and open hysterectomy. DESIGN: A retrospective analysis (Canadian Task Force classification II-2). SETTING: Henry Ford Health System, 2013 to 2016. PATIENTS: Women who underwent robotic, vaginal, laparoscopic, and open abdominal hysterectomy. INTERVENTIONS: Robotic hysterectomy, laparoscopic-assisted vaginal hysterectomy, total laparoscopic hysterectomy, laparoscopic supracervical hysterectomy, vaginal hysterectomy, and abdominal hysterectomy. MEASUREMENTS AND MAIN RESULTS: To identify patients with urologic injury, a departmental database for quality improvement was searched for reported urologic injuries. In addition, patients who had urology consultation within 90 days of hysterectomy were screened for injury. A total of 3114 hysterectomies were identified by retrospective chart review. One thousand eighty-eight robotic, 782 laparoscopic, 304 vaginal, and 940 abdominal hysterectomies were analyzed for urologic complications. A total of 27 injuries were confirmed (7 during laparoscopic hysterectomy, 10 during robotic hysterectomy, 1 during vaginal hysterectomy, and 9 during abdominal hysterectomy). The overall rate of urologic injury was 0.87% with a 0.55% risk of bladder injury and a 0.32% risk of injury to the ureter. When the route of hysterectomy was taken into account, the risk of urologic injury was 0.92% for robotic hysterectomy, 0.90% for laparoscopic hysterectomy, 0.33% for vaginal hysterectomy, and 0.96% for open hysterectomy. The mean body mass index (BMI) for all patients was 32.7 kg/m CONCLUSION: Rates of urologic injury with robotic hysterectomy are similar to those of laparoscopic hysterectomy in our population. BMI was not significantly different in patients who had urologic injuries. Surgeon volume was not associated with risk for urologic injury

MARCH ubiquitin ligases alter the itinerary of clathrin-independent cargo from recycling to degradation

The MARCH family of proteins are membrane-associated E3 ubiquitin ligases that down-regulate surface membrane proteins. Expression of MARCH8 in cells causes the ubiquitination and down-regulation of surface CD98 and CD44—cargo proteins that enter cells by clathrin-independent endocytosis and are usually routed to recycling, not degradation

CCNE1 and survival of patients with tubo‐ovarian high‐grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

BackgroundCyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.MethodsWithin the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.ResultsHigh-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss.ConclusionThis study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC