Citations

Abstract Quantifying lymph nodes in vascularized lymph node transfer (VLNT) has been performed using preoperative percutaneous ultrasound. The higher resolution and accuracy of intraoperative ultrasound (IOUS) over transcutaneous ultrasound has been demonstrated in the radiology literature for the identification and characterization of finer structures including hepatic lesions, pancreatic lesions, and biliary or pancreatic ducts. We hypothesize that IOUS during VLNT would be a superior method to quantify and map lymph nodes in our flaps. A prospectively collected database of patients undergoing VLNT over 3 years (October 2014 to October 2017) was reviewed. Patients who underwent IOUS during flap harvest, before pedicle ligation to simultaneously map and quantify the number of lymph nodes were included in the study. Twenty-one patients with an average age of 58.7 years and a mean BMI of 32.3 underwent VLNT with IOUS for chronic lymphedema during the study period. Extremity lymphedema was classified as Campisi IB (n = 7), IIA (n = 7), IIB (n = 5), and IIIA (n = 2). There were 14 superficial circumflex iliac artery flaps, including 4 performed concomitantly with a deep inferior epigastric perforator flap, 1 transverse cervical artery flap, and 6 omental flaps. The average number of lymph nodes transferred per IOUS was 4.3 for superficial circumflex iliac artery flaps, 4 for the transverse cervical artery flap, and 5.2 for the omental flaps. Intraoperative ultrasound allows the lymphatic surgeon to precisely map the location of lymph nodes which can guide intraoperative decision making. As there is no data correlating the number of lymph nodes transferred and outcomes after VLNT, developing a precise intraoperative quantification method is important.

AbstractIntroductionPrevious reports have shown that suboptimal antenatal corticosteroids administration occurs in most cases. However, as multifetal gestations were either excluded or constituted a small proportion of the participants in these studies, little is known about the patterns of use of antenatal corticosteroids in twin pregnancies.Material and methodsWe reviewed the records of women who received antenatal corticosteroids and delivered between 240/7 and 346/7 weeks of gestation during 2015‐2017 at 2 university hospitals. Optimal antenatal corticosteroids timing was defined as delivery ≥24 hours ≤7 days from the previous antenatal corticosteroids course.ResultsOf 424 pregnancies, 307 (72.4%) were singleton and 117 were (27.6%) twin. For twin compared with singleton pregnancies, gestational age at initial antenatal corticosteroids administration was lower (P = 0.02), the proportion of deliveries within the optimal window of the initial antenatal corticosteroids course was lower (19.7% vs 33.2%, P = 0.001), and the proportion of women eligible for a rescue antenatal corticosteroids course was higher (58.1% vs 32.9%, P < 0.0001). However, despite similar rates of rescue antenatal corticosteroids administration (P = 0.64), the overall rate of delivery within any optimal window (either initial or rescue course) was lower in twin than singleton pregnancies (26.5% vs 42.3%, P = 0.004), and the antenatal corticosteroids‐to‐delivery interval was longer (median 6.9 vs 4.2 days, P = 0.0009). In multivariate analysis, optimal antenatal corticosteroids administration was negatively associated with twin pregnancy (P = 0.04) and preterm labor (P = 0.05), and positively associated with the presence of gestational hypertensive disorders (P = 0.03).ConclusionsTwin pregnancy is an independent risk factor for suboptimal antenatal corticosteroids administration. Directed efforts should be made to improve the utilization of antenatal corticosteroids in this vulnerable group of women.

Introduction and aim: Combined hepatocellular-cholangiocarcinoma (HCC-CCA) is a rare liver malignancy distinct from either hepatocellular carcinoma (HCC) or cholangiocarcinoma. Liver transplantation (LT) is not recommended for HCC-CCA because of suboptimal outcomes. Because non-invasive diagnosis of HCC-CCA is extremely challenging, some HCC-CCAs are presumed as HCC on imaging and listed for LT with the correct diagnosis ultimately made on explant pathology. We compared HCC-CCA with HCC to determine the utility of response to pre-transplant loco-regional therapy (LRT) in predicting outcomes for HCC-CCA after LT as a potential means of identifying appropriate HCC-CCA patients for LT. Materials and methods: Retrospective review of 19 patients with pathologically confirmed HCC-CCA individually matched to 38 HCC patients based on age, sex, and Milan criteria at listing was performed. The modified response evaluation criteria in solid tumors was used to categorize patients as responders or non-responders to pre-transplant LRT based on imaging performed before and after LRT. Overall survival (OS) and recurrence-free survival (RFS) were examined. Results: OS at 3 years post-transplant was 74% for HCC-CCA and 87% for HCC. RFS at 3 years was 74% for HCC-CCA, and 87% for HCC. Among responders to LRT, the 3-year OS was 92% for HCC-CCA and 88% for HCC; among non-responders, 3-year OS was 43% for HCC-CCA and 83% for HCC. Higher 3-year OS was observed among HCC-CCA responders (77%) compared with HCC-CCA non-responders (23%). Conclusions: OS was similarly high among responders to pre-transplant LRT irrespective of tumor type. Radiologic response to LRT could potentially be used to select appropriate HCC-CCA patients for LT if the findings are validated in independent studies.

Abstract Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P &lt; 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P &lt; 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis. Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.

Abstract Rationale Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) are commonly used for the diagnosis and mediastinal staging of lung cancer. Molecular markers are becoming increasingly important in patients with lung cancer to define targetable mutations suitable for personalized therapy, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species proto-oncogene (ROS1), and programmed death-ligand 1 (PD-L1). Objectives To evaluate the adequacy of EBUS-TBNA–derived tissue for molecular analysis. Methods We searched the MEDLINE, LILACS, www.clinicaltrials.gov, and Epistemonikos databases through January 2018. Data Extraction Two independent reviewers performed the data search, quality assessment, and data extraction. We included both prospective and retrospective studies; risk of bias was evaluated using the ROBINS-I tool. The primary outcome was the proportion of adequate samples obtained by EBUS-TBNA for molecular analysis. Data were pooled by using a binary random effects model. Finally, evidence was rated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Results A total of 33 studies including 2,698 participants were analyzed. In 28 studies that evaluated EBUS-TBNA for the identification of EGFR mutations, the pooled probability of obtaining a sufficient sample was 94.5% (95% confidence interval CI], 93.2–96.4%). For identification of ALK mutations, the pooled probability was 94.9% (95% CI, 89.4–98.8%). Finally, the prevalence of EGFR mutation was 15.8% (95% CI, 12.1–19.4%), and the prevalence of ALK mutation was 2.77% (95% CI, 1.0–4.8%). Data for ROS1 and PD-L1 mutations were not suitable for meta-analysis. Conclusions EBUS-TBNA has a high yield for molecular analysis of both EGFR and ALK mutations. However, the suitability of TBNA samples for next-generation sequencing is uncertain and should be explored in further studies. Clinical trial registered with PROSPERO (CRD42017080008).

Background Current thermal ablation methods for atrial fibrillation, including radiofrequency and cryoablation, have a suboptimal success rate. To avoid pulmonary vein (PV) stenosis, ablation is performed outside of the PV, despite the importance of triggers inside the vein. We previously reported on the acute effects of a novel direct current electroporation approach with a balloon catheter to create lesions inside the PVs in addition to the antrum. In this study, we aimed to determine whether the effects created by this nonthermal ablation method were associated with irreversible lesions and whether PV stenosis or other adverse effects occurred after a survival period. Methods and Results Initial and survival studies were performed in 5 canines. At the initial study, the balloon catheter was inflated to contact the antrum and interior of the PV. Direct current energy was delivered between 2 electrodes on the catheter in ECG‐gated 100 μs pulses. A total of 10 PVs were treated demonstrating significant acute local electrogram diminution (mean amplitude decrease of 61.2±19.8%). After the survival period (mean 27 days), computed tomography imaging showed no PV stenosis. On histologic evaluation, transmural, although not circumferential, lesions were seen in each treated vein. No PV stenosis or esophageal injury was present. Conclusions Irreversible, transmural lesions can be created inside the PV without evidence of stenosis after a 27‐day survival period using this balloon‐based direct current ablation approach. These early data show promise for an ablation approach that could directly treat PV triggers in addition to traditional PV antrum ablation.