Mammographic density has been shown to be a strong independent predictor of breast cancer and a causative factor in reducing the sensitivity of mammography. There remain questions as to the use of ...mammographic density information in the context of screening and risk management, and of the association with cancer in populations known to be at increased risk of breast cancer.
To assess the association of breast density with presence of cancer by measuring mammographic density visually as a percentage, and with two automated volumetric methods, Quantra™ and VolparaDensity™.
The TOMosynthesis with digital MammographY (TOMMY) study of digital breast tomosynthesis in the Breast Screening Programme of the National Health Service (NHS) of the United Kingdom (UK) included 6020 breast screening assessment cases (of whom 1158 had breast cancer) and 1040 screened women with a family history of breast cancer (of whom two had breast cancer). We assessed the association of each measure with breast cancer risk in these populations at enhanced risk, using logistic regression adjusted for age and total breast volume as a surrogate for body mass index (BMI).
All density measures showed a positive association with presence of cancer and all declined with age. The strongest effect was seen with Volpara absolute density, with a significant 3% (95% CI 1–5%) increase in risk per 10 cm3 of dense tissue. The effect of Volpara volumetric density on risk was stronger for large and grade 3 tumours.
Automated absolute breast density is a predictor of breast cancer risk in populations at enhanced risk due to either positive mammographic findings or family history. In the screening context, density could be a trigger for more intensive imaging.
•Three different breast density measures compared: visual, Quantra and Volpara.•All density measures showed a positive association with presence of cancer.•The strongest effect was seen with Volpara absolute density measure.•A stronger effect of Volpara density on risk was observed for large and grade 3 cancers.
Aims To assess the feasibility of undertaking microbubble-guided vacuum-assisted biopsy (VAB) of the sentinel lymph node (SLN) and determine its sensitivity in detecting metastases. Patient ...experience and the impact of VAB on subsequent axillary surgery were also evaluated. Materials and methods Patients with a normal axillary ultrasound or benign core biopsy planned for surgical SLN biopsy were recruited. Part 1 of the study was used to establish the technique of ultrasound microbubble contrast to detect the SLN. In Part 2 microbubble detection of the SLN was followed by 13 G VAB. All patients subsequently had surgical histological correlation. Results One hundred and thirty-nine patients were recruited: 36 to Part 1 and 103 to Part 2. Of the 100 patients in Part 2 included for analysis, 82 (82%) underwent successful biopsy. Sensitivity for detecting metastases was 58.8% (95% confidence interval: 32.9%, 81.6%). The procedure was generally well tolerated; however, VAB interfered adversely with subsequent surgical SLN biopsy with surgeons reporting moderate or severe interference in 48% of patients and an additional 8.3% with complete failure of SLNB. Conclusion It is possible to perform VAB of microbubble-detected SLNs. Although the sensitivity for detecting metastases was reasonable, the adverse effect on subsequent surgery was significant.
Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical morbidity/mortality. NAXIVA assessed ...the response of VTT to axitinib, a potent tyrosine kinase inhibitor.
NAXIVA was a single-arm, multi-centre, Phase 2 study. In total, 20 patients with resectable clear cell RCC and VTT received upto 8 weeks of pre-surgical axitinib. The primary endpoint was percentage of evaluable patients with VTT improvement by Mayo level on MRI. Secondary endpoints were percentage change in surgical approach and VTT length, response rate (RECISTv1.1) and surgical morbidity.
In all, 35% (7/20) patients with VTT had a reduction in Mayo level with axitinib: 37.5% (6/16) with IVC VTT and 25% (1/4) with RV-only VTT. No patients had an increase in Mayo level. In total, 75% (15/20) of patients had a reduction in VTT length. Overall, 41.2% (7/17) of patients who underwent surgery had less invasive surgery than originally planned. Non-responders exhibited lower baseline microvessel density (CD31), higher Ki67 and exhausted or regulatory T-cell phenotype.
NAXIVA provides the first Level II evidence that axitinib downstages VTT in a significant proportion of patients leading to reduction in the extent of surgery.
NCT03494816.
Abstract Synthesis of influenza virus mRNA by the viral RNA polymerase complex is primed by capped RNA fragments generated by endonuclease cleavage of host pre-mRNA by the polymerase subunit PB1. In ...previous studies, endonuclease and promoter-binding sites have been described in the C-terminal region of PB1. Here, we have identified an additional region near the C-terminus of PB1 involved in producing capped RNA primers for viral transcription. In particular, mutations of basic amino acids K669, R670, and R672 inhibited primer-dependent viral mRNA synthesis. In contrast, primer-independent cRNA and vRNA syntheses were only marginally affected. Additionally, recombinant viruses containing the K669A or R672A mutations expressed reduced amounts of mRNA compared to cRNA during infection and were attenuated in cell culture. Further in vitro analysis showed that these mutations inhibited the ability of the polymerase to initiate mRNA synthesis by causing a reduction in binding to the vRNA promoter and capped RNA. These results suggest that this region plays a critical role in the regulation of viral mRNA transcription.
Pre-treatment oestrogen receptor (ER) expression in breast cancer predicts for rate of response to endocrine therapy but not for the quality or duration of response (DofR). ER is known to be ...down-regulated by anti-oestrogens. This study has tested the hypothesis that the degree of down-regulation of ER and the ER-regulated marker bcl-2 are associated with the quality and duration of tamoxifen response. 80 patients with ER+ve breast cancer (H-score > 10) receiving primary tamoxifen (n = 51 Stage I-II elderly; n = 29 Stage III) underwent sequential tumour biopsies for immunocytochemical assessment of ER, bcl-2 and the proliferation marker MIB1. Median follow-up is 45 months. By 6-months on therapy three patients had attained complete response (CR), 27 partial response (PR); 44 static disease (SD) and six progression (PD) by UICC criteria. Greater decrease in ER and bcl-2 H-score from pre-treatment to 6 weeks (p = 0.035, p = 0.037) and ER and bcl-2 H-score from pre-treatment to 6 months (p = 0.058, p = 0.036) were significantly associated with better quality of response (CR/PR vs SD/PD). Greater 6-week and 6-month reduction in bcl-2 H-score (p = 0.041, p = 0.036) and 6-week reduction in MIB1 (p = 0.013) were significantly correlated with longer DofR. This study demonstrates that greater down-regulation of ER and the ER-regulated protein bcl-2 on primary tamoxifen are significantly associated with a better quality of response and bcl-2 and the proliferation marker MIB1 a longer duration of response in ER+ve breast cancer.
Acute cholecystitis is increasingly managed by laparoscopic cholecystectomy. Some reports have shown conversion and complication rates that are increased in comparison to elective laparoscopic ...cholecystectomy. This study reviews the combined experience of two hospitals where the intention was to perform early laparoscopic cholecystectomy for acute cholecystitis. A total of 152 cases of laparoscopic cholecystectomy for acute cholecystitis (evidence of acute inflammation clinically and pathologically) were identified. Conversion to open cholecystectomy was required in 14 cases (9%) in the total series. Laparoscopic cholecystectomy was performed within 2 days of admission in 76% (115 of 152) of patients. Conversion was significantly less likely in patients undergoing laparoscopic cholecystectomy within 2 days of admission (4 of 115) compared to those undergoing surgery beyond 2 days (10 of 37;
P <0.0001). Eleven patients (7%) had postoperative complications; however, there were no cases of injury to the biliary system and no perioperative deaths. This series shows that laparoscopic cholecystectomy can be performed safely in patients with acute cholecystitis and suggests that early laparoscopic cholecystectomy is preferable to delaying surgery. Although the conversion rate to open surgery is higher than for elective cholecystectomy, the majority of patients (91%) still derive the well-recognized benefits of laparoscopic cholecystectomy. Early laparoscopic cholecystectomy is an acceptable approach to acute cholecystitis for the experienced laparoscopic surgeon.
This open access book explores cultural competence in the higher education sector from multi-disciplinary and inter-disciplinary perspectives. It addresses cultural competence in terms of leadership ...and the role of the higher education sector in cultural competence policy and practice. Drawing on lessons learned, current research and emerging evidence, the book examines various innovative approaches and strategies that incorporate Indigenous knowledge and practices into the development and implementation of cultural competence, and considers the most effective approaches for supporting cultural competence in the higher education sector. This book will appeal to researchers, scholars, policy-makers, practitioners and general readers interested in cultural competence policy and practice.
A prospective clinical trial of the transperitoneal laparoscopic approach to the lumbar spine in a consecutive series of patients undergoing anterior lumbar interbody fusion.
To determine safety and ...effectiveness, and to document technique and perioperative complications of a laparoscopic exposure for lumbar interbody fusion.
With the widespread adoption of laparoscopic techniques, the benefits of minimal access surgery are now well recognized--in general, gynecologic and urologic surgery. Only recently have minimal access techniques been applied to spinal procedures.
Forty-seven patients with symptomatic degenerative disc disease underwent transperitoneal laparoscopic exposure of the lumbar spine to facilitate implantation of cylindrical threaded interbody fusion cages. These patients were prospectively followed and all perioperative considerations and complications were documented and analyzed. The surgical technique of laparoscopic exposure will be described.
The laparoscopic approach was attempted in 47 consecutive patients. Forty-four were completed laparoscopically--36 single level fusions, seven two level fusions, and one three level fusion. Early in the series, conversion to open surgery was required in one patient (case #3) because of bleeding from the presacral veins which hindered the view. In one case, mobilization of the great vessels proved to be difficult, and in one other case the patient could not tolerate abdominal insufflation. The mean blood loss for the entire group was 105 mls. Complications related to the endoscopic exposure were few. There were no injuries to major vascular structures or to bowel, and no mortalities. In two patients, the cages were malpositioned necessitating repeat endoscopic exposure for cage realignment. One patient required a laparotomy for a postoperative small bowel obstruction. The median postoperative stay was 4 days.
Transperitoneal laparoscopic exposure for single or multiple level, anterior lumbar interbody fusion can be performed with low risk. Experience in open anterior spinal surgery and laparoscopic general surgery is vital in minimizing the risks.
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