Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study.

OBJECTIVE: The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients. METHODS: Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods. RESULTS: 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion. CONCLUSIONS: Patients with SLNs-isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs-isolated tumor cells was not associated with worse overall survival.

Fetal Doppler monitoring during maternal open-heart surgery: Case report and key aspects of a multidisciplinary challenge.

CASE REPORT: Herein we present the case of a 33-year nulliparous woman at 21 weeks of gestation with mitral valve vegetation resulting from infective endocarditis. Due to the mother's critical condition caused by consecutive thromboembolic events, surgery with cardiopulmonary bypass was indicated. During surgery the fetus was monitored by a specialized obstetrician who repetitively measured the Doppler indices of the umbilical artery, Ductus venosus and uterine artery. Right after CO2 was insufflated into the operating area, the Doppler monitoring showed an increased Pulsatility Index of the Umbilical artery right before fetal distress with bradycardia occurred. A subsequent maternal arterial blood gas analysis showed an acidosis with hypercapnia. Consequently, the CO2 insufflation was stopped and the gas flow on the Heart Lung Machine increased. After regaining homeostasis of acidosis, the Doppler Indices and fetal heart rate recovered. The remaining surgery and postoperative course were uneventful. At the 37 weeks of gestation a healthy boy was delivered by Cesarean section and at the age of two years, the neurodevelopment was assessed, which indicated normal development in mental cognition, language and motoric. This report presents a periodic Doppler examination of the maternal and fetal circulation during surgery on CPB while also discussing the possible impact of fetal monitoring in managing open cardiac surgery in pregnancy.

Variability in endometrial carcinoma pathology practice: opportunities for improvement with molecular classification.

We assessed the landscape of diagnostic pathology practice and how molecular classification could potentially impact management of patients with endometrial cancer by collecting patient samples, clinicopathologic data, and patient outcomes from EC patients diagnosed in 2016 at 10 Canadian tertiary cancer centers and 19 community hospitals. ProMisE molecular subtype (POLEmut, MMRd, p53abn, No Specific Molecular Profile (NSMP)) was assigned retrospectively. 1357 patients were fully evaluable including 85 POLEmut (6.3%), 380 MMRd (28.0%), 643 NSMP (47.4%), and 249 p53abn ECs (18.3%). Immunohistochemistry (IHC) for MMR proteins was undertaken at the time of primary diagnosis in 2016 in only 42% of the cohort (570/1357; range 3.5-95.4%/center). p53 IHC had only been performed in 21.1% of the cohort (286/1357; range 10.1-41.9%/center). Thus, based on the retrospective molecular subtype assignment, 54.7% (208/380) of MMRd EC had not been tested with MMR IHC (or MSI) and 48.2% (120/249) of p53abn ECs were not tested with p53 IHC in 2016. Molecular subtype diversity within histotypes was profound; most serous carcinomas were p53abn (91.4%), but only 129/249 (51.8%) p53abn EC were serous. Low-grade (Gr1-2) endometrioid carcinomas were mostly NSMP (589/954, 61.7%) but included all molecular subtypes, including p53abn (19/954, 2.0%). Molecular subtype was significantly associated with clinical outcomes (p < 0.001) even in patients with stage I disease (OS p = 0.006, DSS p < 0.001, PFS p < 0.001). Assessment of national pathologic practice in 2016 shows highly variable use of MMR and p53 IHC and demonstrates significant opportunities to improve and standardize biomarker reporting. Inconsistent, non-reflexive IHC resulted in missed opportunities for Hereditary Cancer Program referral and Lynch Syndrome diagnosis, and missed potential therapeutic implications (e.g., chemotherapy in p53abn EC, immune blockade for MMRd EC). Routine integration of molecular subtyping into practice can improve the consistency of EC pathology assessment and classification.

CA-125 Levels Are Predictive of Survival in Low-Grade Serous Ovarian Cancer-A Multicenter Analysis.

OBJECTIVE: Studies on low-grade serous ovarian cancer (LGSC) are limited by a low number of cases. The aim of this study was to define the prognostic significance of age, stage, and CA-125 levels on survival in a multi-institutional cohort of women with pathologically confirmed LGSC. METHODS: Women with LGSC were identified from the collaborative Ovarian Cancer Association Consortium (OCAC). Cases of newly diagnosed primary LGSC were included if peri-operative CA-125 levels were available. Age at diagnosis, FIGO stage, pre- and post-treatment CA-125 levels, residual disease, adjuvant chemotherapy, disease recurrence, and vital status were collected by the participating institutions. Progression-free (PFS) and overall survival (OS) were calculated. Multivariable (MVA) Cox proportional hazard models were used and hazard ratios (HR) calculated. RESULTS: A total of 176 women with LGSC were included in this study; 82% had stage III/IV disease. The median PFS was 2.3 years and the median OS was 6.4 years. Age at diagnosis was not significantly associated with worse PFS (p = 0.23) or OS (p = 0.3) (HR per year: 0.99; 95%CI, 0.96-1.01 and 0.98; 95%CI 0.95-1.01). FIGO stage III/IV was independently associated with PFS (HR 4.26, 95%CI 1.43-12.73) and OS (HR 1.69, 95%CI 0.56-5.05). Elevated CA-125 (≥35 U/mL) at diagnosis was not significantly associated with worse PFS (p = 0.87) or OS (p = 0.78) in MVA. Elevated CA-125 (≥35 U/mL) after completion of primary treatment was independently associated with worse PFS (HR 2.81, 95%CI 1.36-5.81) and OS (HR 6.62, 95%CI 2.45-17.92). In the MVA, residual disease was independently associated with PFS (0.022), but not OS (0.85). CONCLUSION: Advanced LGSC was associated with poor long-term prognosis. FIGO stage and abnormal post-treatment CA-125 level are key prognostic factors inversely associated with PFS and OS. HIGHLIGHTS: 1. Through a multi-center collaborative effort, data from 176 women with low-grade serous ovarian cancer were analyzed. 2. Although low-grade serous ovarian cancer is often considered indolent, the progression-free and overall survival are poor. 3. Elevated post-treatment CA-125 levels are independently associated with poor survival.

Diagnosis and Therapy of Iron Deficiency Anemia During Pregnancy: Recommendation of the Austrian Society for Gynecology and Obstetrics (OEGGG).

This overview analyzes the data on the controversial therapy of iron substitution during pregnancy, the diagnosis of iron deficiency anemia and the indication-related therapy, and is the first recommendation issued by the OEGGG on the appropriate therapy. The effects of anemia during pregnancy on postnatal outcomes have been intensively investigated with heterogeneous results. A final scientific conclusion with regards to the "optimal" maternal hemoglobin level is limited by the heterogeneous results of various studies, many of which were conducted in emerging nations (with different dietary habits and structural differences in the respective healthcare systems). The current literature even suggests that there may be a connection between both decreased and increased maternal serum hemoglobin concentrations and unfavorable short-term and long-term neonatal outcomes. In Austria, 67 percent of pregnant women take pharmacological supplements or use a variety of dietary supplements. Clinically, the prevalence of maternal anemia is often overestimated, leading to overtreatment of pregnant women (iron substitution without a medical indication). To obtain a differential diagnosis, a workup of the indications for treatment should be carried out prior to initiating any form of iron substitution during pregnancy. If treatment is medically indicated, oral iron substitution is usually sufficient. Because of the restricted approval and potential side effects, medical indications for intravenous iron substitution should be limited. Intravenous iron substitution without a prior detailed diagnostic workup is an off-label use and should only be used in very limited cases, and women should be advised accordingly.

Oncologic outcomes of endometrial cancer in patients with low-volume metastasis in the sentinel lymph nodes: An international multi-institutional study.

OBJECTIVE: To assess oncologic outcomes in endometrial cancer patients with low-volume metastasis (LVM) in the sentinel lymph nodes (SLNs). METHODS: Patients with endometrial cancer and SLN-LVM (≤2 mm) from December 3, 2009, to December 31, 2018, were retrospectively identified from 22 centers worldwide. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV, adnexal involvement, or unknown adjuvant therapy (ATx) were excluded. RESULTS: Of 247 patients included, 132 had isolated tumor cell (ITC) and 115 had micrometastasis (MM). Overall 4-year recurrence-free survival (RFS) was 77.6% (95% CI, 70.2%-85.9%); median follow-up for patients without recurrence was 29.6 (interquartile range, 19.2-41.5) months. At multivariate analysis, Non-endometrioid (NE) (HR, 5.00; 95% CI, 2.50-9.99; P < .001), lymphovascular space invasion (LVSI) (HR, 3.26; 95% CI, 1.45-7.31; P = .004), and uterine serosal invasion (USI) (HR, 3.70; 95% CI, 1.44-9.54; P = .007) were independent predictors of recurrence. Among 47 endometrioid ITC patients without ATx, 4-year RFS was 82.6% (95% CI, 70.1%-97.2). Considering 18 ITC patients with endometrioid grade 1 disease, without LVSI, USI, or ATx, only 1 had recurrence (median follow-up, 24.8 months). CONCLUSIONS: In patients with SLN-LVM, NE, LVSI, and USI were independent risk factors for recurrence. Patients with any risk factor had poor prognosis, even when receiving ATx. Patients with ITC and grade 1 endometrioid disease (no LVSI/USI) had favorable prognosis, even without ATx. Further analysis (with more patients and longer follow-up) is needed to assess whether ATx can be withheld in this low-risk subgroup.

Vulvar Melanoma: Molecular Characteristics, Diagnosis, Surgical Management, and Medical Treatment.

Ten percent of all women have pigmented vulvar lesions. Fortunately, most of these are benign but 1% of all melanomas in women affect the vulva. While the mortality rate of cutaneous melanoma has dropped by 7% annually during the last 5 years, the prognosis of vulvar melanoma remains dismal: the 5-year overall survival rate is 47% compared with 92% for cutaneous melanoma. The current evidence suggests that this likely results from a combination of delayed diagnosis and different tumor biology, treatment strategies, and treatment response. Although many landmark trials on checkpoint inhibitors included mucosal and vulvar melanomas, the results were often not reported separately. Post-hoc analyses indicate overall response rates between 19 and 37% for checkpoint inhibitors. A recently published retrospective study on vulvar melanomas suggests an objective response in 33.3% with a similar safety profile to cutaneous melanoma. Tyrosine kinase inhibitors may be considered in recurrent disease if a c-KIT mutation is present.

Gynecologic Malignancies in Children and Adolescents: How Common is the Uncommon?

The aim of this study is to assess the projected incidence and prognostic indicators of gynecologic malignancies in the pediatric population. In this population-based retrospective cohort study, girls ≤18 years with ovarian, uterine, cervical, vaginal and vulvar malignancies diagnosed between 2000 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER)-18 registry. The Kaplan-Meier method was used to analyze overall survival (OS). The age-adjusted annual incidence of gynecologic malignancies was 6.7 per 1,000,000 females, with neoplasms of the ovary accounting for 87.5%, vagina 4.5%, cervix 3.9%, uterus 2.5% and vulva 1.6% of all gynecologic malignancies. Malignant germ-cell tumors represented the most common ovarian neoplasm, with an increased incidence in children from 5-18 years. Although certain subtypes were associated with advanced disease stages, the 10-year OS rate was 96.0%. Sarcomas accounted for the majority of vaginal, cervical, uterine and vulvar malignancies. The majority of vaginal neoplasms were observed in girls between 0-4 years, and the 10-year OS rate was 86.1%. Overall, gynecologic malignancies accounted for 4.2% of all malignancies in girls aged 0-18 years and the histologic subtypes and prognosis differed significantly from patients in older age groups.

Cytology-based screening for anal intraepithelial neoplasia in women with a history of cervical intraepithelial neoplasia or cancer.

BACKGROUND: High-risk human papillomavirus (HPV) has been identified in the pathogenesis of anal cancer. The purpose of this study was to assess the prevalence of abnormal anal cytology and HPV in women aged ≥40 years who have a history of high-grade cervical squamous intraepithelial lesion (SIL) or cancer and to estimate the prevalence of anal intraepithelial neoplasia (AIN) using cytology as the primary screening modality. METHODS: Women who had a history of high-grade cervical SIL or cancer and were ≥40 years of age were included in this prospective study. Anal cytology with HPV-DNA testing was performed. All patients with abnormal anal cytology were referred for high-resolution anoscopy (HRA), and abnormal lesions were biopsied and treated if pathologically confirmed. Abnormal anal cytology correlated with HPV status, HRA findings, and clinical and demographic characteristics. RESULTS: A total of 317 women completed the study. Of these, 96 (30.3%) had abnormal anal cytology (high-grade SIL, 12.5%; low-grade SIL, 19.8%; atypical squamous cells, cannot exclude high-grade SIL, 6.3%; atypical squamous cells of undetermined significance, 61.5%) and 101 (31.9%) were HPV-DNA-positive. There was a significant association between abnormal cytology results and the presence of high-risk HPV. Of the 96 patients with abnormal cytology, 30 (31.3%) had biopsy-proven AIN on HRA, representing 9.5% of the total patient cohort; of these, 10 (33.3%) had low-grade AIN and 20 (66.7%) had high-grade AIN. Older age and smoking were significant risk factors for abnormal anal cytology. CONCLUSION: Women aged ≥40 years with a history of high-grade cervical SIL or cancer have a high rate of AIN. Screening for anal cancer may therefore be considered in this patient population. The optimal screening approach should be addressed in future studies.

Clinical Characteristics and Treatment Response With Checkpoint Inhibitors in Malignant Melanoma of the Vulva and Vagina.

OBJECTIVES: The aims of the study were to assess the clinical and histopathological characteristics of a comprehensive cohort of women with vulvovaginal melanoma (VVM) treated at our institution and to study the treatment response of checkpoint inhibitors in this patient cohort. MATERIALS AND METHODS: This is a retrospective study of women with invasive VVM treated at the Princess Margaret Cancer Centre in Toronto, Ontario, Canada, over a period of 15 years. Clinical and histopathological characteristics, treatment, as well as treatment-related outcome were analyzed in 32 women. Treatment response was evaluated retrospectively using the "response criteria for use in trials testing immunotherapeutics" (iRECIST). The objective response rate was defined as the proportion of patients with complete or partial response based on the best overall response. RESULTS: At a median follow-up of 37.8 months (5.8-110.4), 26 women (81.3%) had disease progression and 16 (50%) died. Thirteen patients with locally unresectable or metastatic melanoma were treated with immune checkpoint inhibitors. Ten additional cases were identified from previously published reports. The best objective response rate for immune checkpoint inhibitors was 30.4% (95% CI = 11.6%-49.2%) and the clinical benefit rate was 52.2% (95% CI = 31.8%-72.6%). The clinical benefit rate was significantly better for programmed cell death protein 1 inhibitors (or a combination) compared with ipilimumab alone (Fisher exact, p = .023). Grade 3/4 adverse events were observed in 3 (13.0%) of the 23 patients. CONCLUSIONS: Women with VVM constitute a high-risk group with poor overall prognosis. Immune checkpoint inhibitors are effective in the treatment of metastatic melanoma in this patient cohort.

High-throughput approaches for precision medicine in high-grade serous ovarian cancer.

High-grade serous carcinoma (HGSC) is the most prevalent and aggressive subtype of ovarian cancer. The large degree of clinical heterogeneity within HGSC has justified deviations from the traditional one-size-fits-all clinical management approach. However, the majority of HGSC patients still relapse with chemo-resistant cancer and eventually succumb to their disease, evidence that further work is needed to improve patient outcomes. Advancements in high-throughput technologies have enabled novel insights into biological complexity, offering a large potential for informing precision medicine efforts. Here, we review the current landscape of clinical management for HGSC and highlight applications of high-throughput biological approaches for molecular subtyping and the discovery of putative blood-based biomarkers and novel therapeutic targets. Additionally, we present recent improvements in model systems and discuss how their intersection with high-throughput platforms and technological advancements is positioned to accelerate the realization of precision medicine in HGSC.

Ultrasound Markers in Fetal Hydronephrosis to Predict Postnatal Surgery.

PURPOSE: Parents confronted with the finding of antenatal hydronephrosis (ANH) are particularly interested in whether their baby will need postnatal surgery. The objective of this study was to predict ANH requiring surgery on the basis of the fetal anteroposterior renal pelvic diameter (APRPD) and the Society for Fetal Urology (SFU) grading system. MATERIALS AND METHODS: The medical records of 179 patients with the finding of ANH were reviewed retrospectively. ANH was graded according to the SFU grading system. Prenatal ultrasound examinations were correlated to postnatal outcome, which was divided into three groups: prenatal resolution, conservative management and surgical treatment. RESULTS: 58 (32.4 %) cases were classified as prenatal resolution, 89 (49.7 %) babies were assigned to the conservative outcome group and 32 (17.9 %) patients needed surgical repair. Postnatal surgery was best predicted in the second trimester (area under the receiver operating characteristics curve: 0.839) by an APRPD cut-off of 8.3 mm (sensitivity: 77.8 %; specificity: 85.7 %; PPV of 53.9 %, NPV of 94.7 %). The combination of the parameters "progression of SFU grade" and SFU grade 3 or 4 achieved a sensitivity of 84.4 % and a specificity of 80.3 % for the prediction of surgery. CONCLUSION: Second-trimester APRPD is a useful parameter for predicting the risk for postnatal surgery. The SFU grade should be assessed in every prenatal ultrasound examination as some further risk estimates can be made based on its dynamics over time.

Malignant Melanoma of the Vulva and Vagina: A US Population-Based Study of 1863 Patients.

BACKGROUND: Vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of malignant melanomas with important differences in biology and treatment. OBJECTIVE: The objective of this study was to describe the epidemiology and prognosis of VuM and VaM in a large representative cohort. METHODS: Women with invasive VuM or VaM were identified from the Surveillance, Epidemiology and End Results-18 population representing 27.8% of the US population. Data on age, ethnicity, stage, location, histopathology, primary surgery, and lymphadenectomy were collected. The Kaplan-Meier method was used to analyze disease-specific and overall survival. Univariate and multivariate regression models were used to identify factors with a significant association with disease-specific survival. RESULTS: A total of 1400 VuM and 463 VaM were included for further analysis; 78.6% and 49.7% of women with VuM and VaM underwent surgery, but only 52.9% of women with non-metastatic VuM and 42.9% of women with non-metastatic VaM undergoing surgery had lymph node assessment; one third of these had positive nodes. Superficial spreading was the most common subtype in VuM, and nodular melanoma in VaM (p < 0.001). The median disease-specific survival was 99 months (95% confidence interval 60-138) and 19 months (95% confidence interval 16-22), respectively. Survival was significantly associated with age at diagnosis, ethnicity, stage, surgery, lymph node metastases, histologic subtype, ulceration, mitotic count, and tumor thickness in VuM, and stage, surgery, and lymph node involvement in VaM. In the Cox model, lymph node status and number of mitoses remained independent predictors of outcome in VuM; in VaM, only lymph node status remained significant. CONCLUSIONS: The overall prognosis of VuM and VaM remains poor. The American Joint Committee on Cancer staging system is applicable and should be used for VuM; however, lymph node status and mitotic rate are the most important predictors of survival. Lymph node status should be assessed and patients with positive nodes may be candidates for adjuvant treatment.

Vulvar malignancies: an interdisciplinary perspective.

Vulvar cancer represents the fourth most common gynecologic malignancy and is often encountered by the general Dermatologist or Gynecologist. Dermatooncologists and Gynecologic Oncologists share expertise in this field and the diagnosis and treatment should ideally be interdisciplinary. All subtypes are typically seen in the later decades of life, although all histologic subtypes have been described in women younger than 30 years. The diagnosis is often delayed. Exact mapping of biopsies is of high importance, as the location and distance from the midline guides the surgical approach depending on the underlying histology. Squamous cell carcinoma accounts for more than 76 % of vulvar cancer with vulvar intraepithelial neoplasia being an important precursor. Basal cell carcinoma is the second most common vulvar malignancy. Melanoma accounts for 5.7 % of vulvar cancer and has a worse prognosis compared to cutaneous melanoma. Most of the trials on checkpoint inhibitors and targeted therapy have not excluded patients with vulvar melanoma and the preliminary evidence is reviewed in the manuscript. Surgery remains the primary treatment modality of locally resectable vulvar cancer. In view of the rarity, the procedure should be performed in dedicated cancer centers to achieve optimal disease control and maintain continence and sexual function whenever possible.

Vulvamalignome: eine interdisziplinäre Betrachtung.

Vulvamalignome stellen die vierthäufigste Gruppe von gynäkologischen Krebserkrankungen dar. Erste Ansprechpartner sind typischerweise niedergelassene Dermatologen und Gynäkologen. Mit der jeweiligen Fachexpertise findet die Diagnose und Therapie idealerweise interdisziplinär zwischen spezialisierten Dermatoonkologen und gynäkologischen Onkologen statt. Vulvamalignome sind überwiegend Erkrankungen des höheren Lebensalters, obwohl alle histologischen Subtypen auch bei Frauen unter 30 Jahren vorkommen. Die Diagnose erfolgt oft verzögert. Eine genaue Kartierung von Biopsien (Mapping) ist von großer Bedeutung, da Lokalisation und Entfernung von der Mittellinie in Abhängigkeit von der zugrunde liegenden Histologie das operative Vorgehen bestimmen. Plattenepithelkarzinome machen mehr als 76 % der Vulvamalignome aus und vulväre intraepitheliale Neoplasien (VIN) sind dabei wichtige Vorstufen. Der zweithäufigste Typ der Vulvakarzinome ist das Basalzellkarzinom. Melanome machen 5,7 % der vulvären Malignome aus und ihre Prognose ist schlechter als die der kutanen Melanome. Die meisten Studien zu Checkpoint-Inhibitoren und zielgerichteten Therapien haben Patientinnen mit vulvären Melanomen nicht ausgeschlossen. Die vorliegende Evidenz wird im folgenden diskutiert. Die Methode der Wahl bei lokal resezierbaren Vulvamalignomen ist die Exzision. Angesichts ihrer Seltenheit sollte die Behandlung in spezialisierten Zentren erfolgen, um eine optimale Krankheitskontrolle zu erreichen und Kontinenz und sexuelle Funktion bestmöglich zu erhalten.

Clinical Monitoring of Sacrococcygeal Teratoma.

BACKGROUND: Sacrococcygeal teratomas (SCT) are often highly vascularized and may result in high-output cardiac failure, polyhydramnios, fetal hydrops, and demise. Delivery is guided by the SCT to fetus volume ratio (SCTratio), SCT growth rate, and cardiac output indexed for weight (CCOi). METHODS: We compared measurements and outcome in 12 consecutive fetuses referred with SCT. Adverse outcomes were: fetal surgery, delivery < 32 gestational weeks or neonatal demise. Only SCTratio and CCOi were used to manage the cases. SCT vascularization index (VI%) was derived from the 3D virtual organ computer-aided analysis (VOCAL) software. The SCTModel (modified from acardiac twins) calculated a hypothetical SCT draining vein size and derived a risk line, using diameters of the superior and inferior vena cava, the azygous and umbilical veins. VI% and a model of systemic and umbilical venous volumes (SCTModel) were tested as indicators for outcome in SCT. RESULTS: Fetuses were monitored from 20.1 to 36.4 gestational weeks and 5/12 had adverse outcomes: 1 had successful open fetal surgery at 23.8 weeks and delivered at term, 4 delivered at < 32 weeks with 3/4 having neonatal demise between 25 and 29 weeks. VI% was significantly higher in cases with adverse outcomes (mean 10.3 [8.9-11.6] vs. 4.4 [3.4-5.3], p < 0.0001). The additional fraction of the fetal cardiac output required to perfuse the SCT-draining vein (XSCO%) (p = 0.46), SCTratio (p = 0.08), and CCOi (p = 0.64) were not significant. All cases with adverse outcome had VI% > 8%. The SCTModel risk line predicted nonadverse outcomes well but lacked data in 2/5 cases with adverse outcomes. CONCLUSIONS: VI% is a significant indicator of SCT cases with adverse outcomes and combined with SCTratio may guide timing of delivery better than current measures.

The Influence of Blood Pressure on Fetal Aortic Distensibility: An Animal Validation Study.

BACKGROUND/AIMS: Aortic distension waveforms describe the change in diameter or cross-sectional area over the cardiac cycle. We aimed to validate the association of aortic fractional area change (AFAC) with blood pressure (BP) in a fetal lamb model. METHODS: Four pregnant ewes underwent open fetal surgery under general anesthesia at 107-120 gestational days. A 4-Fr catheter was introduced into the fetal femoral artery and vein, or the carotid artery and jugular vein. The thoracic aorta was imaged using real-time ultrasound; AFAC was calculated using offline speckle tracking software. Measurements of invasive BP and AFAC were obtained simultaneously and averaged over 10 cardiac cycles. BP was increased by norepinephrine infusion and the association of aortic distensibility with BP was assessed. RESULTS: Baseline measurements were obtained from 4 lambs, and changes in aortic distensibility with increasing BP were recorded from 3 of them. A positive correlation was found between AFAC and systolic BP (r = 0.692, p = 0.001), diastolic BP (r = 0.647, p = 0.004), mean BP (r = 0.692, p = 0.001), and BP amplitude (r = 0.558, p = 0.016) controlled for heart rate. No association was found between BP and maximum or minimum aortic area. CONCLUSION: AFAC provides a quantifiable measure of aortic distensibility and correlates with systolic BP, diastolic BP, mean BP, and BP amplitude in a fetal lamb model.

Recipient umbilical artery elongation (redundancy) in twin-twin transfusion syndrome.

BACKGROUND: Chronic hypertension in adults causes arterial lengthening in major arteries, but the effects of early fetal hypertension on the twin-twin transfusion syndrome recipient's vascular architecture remains unknown. OBJECTIVE: We hypothesize that arterial cord redundancy is related to recipient hypertension and subsequent heart failure. Our objectives were to: (1) establish a 3-dimensional color Doppler ultrasound method of measuring umbilical arterial length relative to its corresponding venous segment in the umbilical cord using artery vein angle; (2) compare recipient artery vein angle to gestational age-matched controls; and (3) test the association of artery vein angle with recipient heart failure. STUDY DESIGN: We compared 3 groups prospectively: twin-twin transfusion syndrome pregnancies undergoing fetoscopic laser surgery (preoperatively) and 2 groups of gestational age-matched controls: uncomplicated monochorionic-diamniotic twin pregnancies and healthy singletons. Using a 3-dimensional color-Doppler volume image of 5 cm of cord near the placental insertion, we traced the umbilical artery and vein producing umbilical artery:vein length, (artery vein index) and measured the artery vein angle between umbilical artery and vein. Correlation of artery vein angle to twin-twin transfusion syndrome stage, maximum vertical pocket, umbilical arterial indices, ductus venosus Doppler, and brain natriuretic peptide were performed. We used pulsed-wave and tissue Doppler to measure tissue Doppler velocities and indexed cardiac output and correlated these with artery vein angle. Comparative statistics, including multivariable linear regression, examined the relationship between umbilical arterial Doppler indices and artery vein angle. RESULTS: Artery vein angle and artery vein index correlated significantly (R2, 0.86; P < .0001), hence, artery vein angle was used for analysis. Mean artery vein angle was 33.1 ± 31.5 degrees in recipients (n = 44), 9.5 ± 6 degrees in monochorionic-diamniotic (n = 11; 22 fetuses), and 8.9 ± 8.3 degrees in singleton controls (n = 16) (P < .001). An artery vein angle ≥26 degrees (>95th percentile for controls) was measured in 52% recipients. Artery vein angle was higher in twin-twin transfusion syndrome stage 3R vs 1 (P = .001). Artery vein angle increased with increasing umbilical arterial pulsatility index (P < .001), and decreased with increasing resistance index (P = .02) after adjusting for gestational age. Interrater agreements to categorize abnormal artery vein angle values was 95% (P < .001). Abnormal ductus venosus Doppler and elevated recipient amniotic fluid N-terminal pro-brain natriuretic peptide/protein levels correlated significantly with artery vein angle. Abnormal artery vein angles were associated with decreased indexed cardiac output, lower tissue Doppler velocities, higher right-sided Tei indices, and severe tricuspid regurgitation. CONCLUSION: Umbilical arterial lengthening occurs in 52% of recipients and is associated with abnormal Doppler flows, low systolic tissue Doppler velocities, reduced cardiac output, and elevated markers of cardiac failure. This may reflect chronicity and severity of hypertension in the recipient fetus. Further research is needed to explore the mechanisms of elongation and long-term implications.

Granulomatous Mycosis Fungoides in an Adolescent-A Rare Encounter and Review of the Literature.

Granulomatous mycosis fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by an infiltrate of atypical lymphocytes, histiocytes, and multinucleated giant cells. Clinically, GMF has a slowly progressing course with a worse prognosis than other forms of MF. With its peak incidence being in the fifth to sixth decade, GMF is rare in children and adolescents. Herein we describe a 14-year-old boy with GMF.