The role of tranexamic acid in reducing post-operative bleeding and seroma formation in breast surgery: A meta-analysis.

INTRODUCTION: Tranexamic acid (TXA) reduces blood loss and blood transfusion requirements in surgery. Seroma and haematoma formation occur as complications of breast surgery. We aimed to perform a meta-analysis evaluating TXA in reducing post-operative haematoma and seroma formation for breast surgery. METHODS: A systematic review was performed in accordance with PRISMA guidelines. Results were expressed as dichotomous variables pooled as odds ratios (OR) with corresponding 95% confidence intervals (CIs) using the Mantel-Haenszel method. RESULTS: Seven studies including 1446 patients were included. There were 1830 breast surgery procedures performed with TXA administered in 797 cases (43.6%). There was a significant reduction in haematoma rates in the TXA group (TXA: 3.184% (22/691) vs Control: 6.787% (64/943), OR: 0.41, 95% CI: 0.20-0.86, P = 0.020). Based on surgical procedure, haematoma rates were similar for TXA and control groups in cancer surgery (P = 0.230). Haematoma rates reduced following TXA use in cosmetic procedures (TXA: 3.807% (15/394) vs. Control: 9.091% (34/374), OR: 0.41, 95% CI: 0.22-0.75, P = 0.004). Haematoma rates were also reduced in procedures where axillary lymph node dissection (ALND) was not performed; in the TXA group, 3.379% (22/651) developed a haematoma versus 6.623% (60/906) in the control group (OR: 0.45, 95% CI 0.27-0.77, P = 0.003). TXA administration did not impact seroma formation or infection rates. CONCLUSION: Perioperative administration of TXA may impact the incidence of haematoma in breast surgery, particularly in cosmetic procedures and procedures without ALND. Well-designed randomised studies are required to determine its true efficacy. TXA has no effect on seroma formation or infection in breast surgery.

A radiomic model to classify response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Medical image analysis has evolved to facilitate the development of methods for high-throughput extraction of quantitative features that can potentially contribute to the diagnostic and treatment paradigm of cancer. There is a need for further improvement in the accuracy of predictive markers of response to neo-adjuvant chemotherapy (NAC). The aim of this study was to develop a radiomic classifier to enhance current approaches to predicting the response to NAC breast cancer. METHODS: Data on patients treated for breast cancer with NAC prior to surgery who had a pre-NAC dynamic contrast enhanced breast MRI were included. Response to NAC was assessed using the Miller-Payne system on the excised tumor. Tumor segmentation was carried out manually under the supervision of a consultant breast radiologist. Features were selected using least absolute shrinkage selection operator regression. A support vector machine learning model was used to classify response to NAC. RESULTS: 74 patients were included. Patients were classified as having a poor response to NAC (reduction in cellularity < 90%, n = 44) and an excellent response (> 90% reduction in cellularity, n = 30). 4 radiomics features (discretized kurtosis, NGDLM contrast, GLZLM_SZE and GLZLM_ZP) were identified as pertinent predictors of response to NAC. A SVM model using these features stratified patients into poor and excellent response groups producing an AUC of 0.75. Addition of estrogen receptor status improved the accuracy of the model with an AUC of 0.811. CONCLUSION: This study identified a radiomic classifier incorporating 4 radiomics features to augment subtype based classification of response to NAC in breast cancer.

Preoperative Breast Magnetic Resonance Imaging as a Predictor of Response to Neoadjuvant Chemotherapy.

Introduction: The ability to accurately predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer would improve patient selection for specific treatment strategies, would provide important information for patients to aid in the treatment selection process, and could potentially avoid the need for more extensive surgery. The diagnostic performance of magnetic resonance imaging (MRI) in predicting pCR has previously been studied, with mixed results. Magnetic resonance imaging performance may also be influenced by tumour and patient factors. Methods: Eighty-seven breast cancer patients who underwent NAC were studied. Pre-NAC and post-NAC MRI findings were compared with pathologic findings postsurgical excision. The impact of patient and tumour characteristics on MRI accuracy was evaluated. Results: The mean (SD) age of participants was 48.7 (10.3) years. The rate of pCR based on post-NAC MRI was 19.5% overall (19/87). The sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy in predicting pCR were 52.9%, 77.1%, 36.0%, 87.1%, and 72.4%, respectively. Positive predictive value was the highest in nonluminal versus Luminal A disease (45.0% vs 25.0%, P < .001), with higher rates of false positivity in nonluminal subtypes (P = .002). Tumour grade, T category, and histological subtype were all independent predictors of MRI accuracy regarding post-NAC tumour size. Conclusion: Magnetic resonance imaging alone is insufficient to accurately predict pCR in breast cancer patients post-NAC. Magnetic resonance imaging predictions of pCR are more accurate in nonluminal subtypes. Tumour grade, T category, and histological subtype should be considered when evaluating post-NAC tumour sizes.

General data protection regulations (2018) and clinical research: perspectives of patients and doctors in an Irish university teaching hospital.

BACKGROUND: Europe's General Data Protection Regulation, or GDPR, is a set of data protection rules on the acquisition, storage, use, and access of personal data. GDPR came into effect in May 2018 when it was introduced across all 27 European Union (EU) member states and the European Economic Area (EEA). Maintaining compliance with this legislation has presented significant new challenges for ongoing clinical research. AIMS: To evaluate the knowledge and expectations of patients and doctors regarding GDPR and implications for future clinical research. METHODS: An anonymous 12-item questionnaire was circulated to patients and doctors at a University Teaching Hospital. Data analysis included descriptive statistics. RESULTS: Five hundred nine participants were included: 261 females (51.3%) and 248 males (48.7%). Three hundred fifty were patients (68.8%) and 159 were doctors (31.2%). Three hundred thirty-four participants were aware of GDPR (65.7%): 116 doctors (73.0%) and 218 patients (62.3%, P = 0.018). 71.1% of doctors were willing to allow their personal data to be processed anonymously as part of a clinical research project compared to 43.4% of patients (P < 0.001). 80.2% of patients believed explicit consent is needed before using personal data in clinical research in comparison to 60.4% of doctors (P < 0.001). Level of education impacted awareness of GDPR (P < 0.001); a higher level of education among patients increased GDPR familiarity (P < 0.001), however failed to impact doctor familiarity (P = 0.117). CONCLUSION: GDPR has introduced complexity to the processing and sharing of personal data among researchers. This study has identified differences in the perception of GDPR and willingness to consent to data being used in clinical research between doctors and patients. Measures to adequately inform prospective research participants on data processing and the evolving landscape of data protection regulation should be prioritised.

Microwave Imaging in Breast Cancer - Results from the First-In-Human Clinical Investigation of the Wavelia System.

RATIONALE AND OBJECTIVES: Microwave Breast Imaging (MBI) is an emerging non-ionising technology with the potential to detect breast pathology. The investigational device considered in this article is a low-power electromagnetic wave MBI prototype that demonstrated the ability to detect dielectric contrast between tumour phantoms and synthetic fibroglandular tissue in preclinical studies. Herein, we evaluate the MBI system in the clinical setting. The capacity of the MBI system to detect and localise breast tumours in addition to benign breast pathology is assessed. Secondly, the safety profile and patient experience of this device is established. MATERIALS AND METHODS: Female patients were recruited from the symptomatic unit to 1 of 3 groups: Biopsy-proven breast cancers (Group-1), unaspirated cysts (Group-2) and biopsy-proven benign breast lesions (Group-3). Breast Density was determined by Volpara VDM (Volumetric Density Measurement) Software. MBI, radiological, pathological and histological findings were reviewed. Subjects were surveyed to assess patient experience. RESULTS: A total of 25 patients underwent MBI. 24 of these were included in final data analysis (11 Group-1, 8 Group-2 and 5 Group-3). The MBI system detected and localised 12 of 13 benign breast lesions, and 9 out of the 11 breast cancers. This included 1 case of a radiographically occult invasive lobular cancer. No device related adverse events were recorded. 92% (n = 23) of women reported that they would recommend MBI imaging to other women. CONCLUSION: The MBI system detected and localized the majority of breast lesions. This modality may have the potential to offer a non-invasive, non-ionizing and painless adjunct to breast cancer diagnosis. Further larger studies are required to validate the findings of this study.

The Wavelia Microwave Breast Imaging system-tumour discriminating features and their clinical usefulness.

OBJECTIVE: The Wavelia Microwave Breast Imaging (MBI) system, based on non-ionising imaging technology, has demonstrated exciting potential in the detection and localisation of breast pathology in symptomatic patients. In this study, the ability of the system to accurately estimate the size and likelihood of malignancy of breast lesions is detailed, and its clinical usefulness determined. METHODS: Institutional review board and Health Products Regulatory Authority (HPRA) approval were obtained. Patients were recruited from the symptomatic unit to three groups; breast cancer (Group-1), unaspirated cysts (Group-2) and biopsied benign lesions (Group-3). MBI, radiological and histopathological findings were reviewed. MBI size estimations were compared with the sizes determined by conventional imaging and histopathology. A Quadratic Discriminant Analysis (QDA) classifier was trained in a 3D feature space to discriminate malignant from benign lesions. An independent review was performed by two independent breast radiologists. RESULTS: 24 patients (11 Group-1, 8 Group-2 and 5 Group-3) underwent MBI. The Wavelia system was more accurate than conventional imaging in size estimation of breast cancers. The QDA accurately separated benign from malignant breast lesions in 88.5% of cases. The addition of MBI and the Wavelia malignancy risk calculation was deemed useful by the two radiologists in 70.6% of cases. CONCLUSION: The results from this MBI investigation demonstrate the potential of this novel system in estimating size and malignancy risk of breast lesions. This system holds significant promise as a potential non-invasive, comfortable, and harmless adjunct for breast cancer diagnosis. Further larger studies are under preparation to validate the findings of this study. ADVANCES IN KNOWLEDGE: This study details the potential of the Wavelia MBI system in delineating size and malignancy risk of benign and malignant breast lesions in a symptomatic cohort. The usefulness of the Wavelia system is assessed in the clinical setting.

Clinicopathological response to neoadjuvant therapies and pathological complete response as a biomarker of survival in human epidermal growth factor receptor-2 enriched breast cancer - A retrospective cohort study.

BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is overexpressed in 20-25% of breast cancers. Complete eradication of disease following neoadjuvant therapies and chemotherapy has been referred to as pathological complete response (pCR). AIMS: To determine clinicopathological predictors of pCR to neoadjuvant therapies and to evaluate pCR as a surrogate to enhanced survival. METHODS: Consecutive female patients with HER2 positive (HER+) breast cancer managed surgically in a single institution between 2005 and 2015 were included. Descriptive statistics and binary logistic regression were used to determine predictors of pCR. Appraisal of pCR as a predictor of survival was performed using Kaplan-Meier curves and Cox regression analysis. RESULTS: 451 patients were included with a mean age of 56.6 ± 13.4 years (range 23-95). Disease-free (DFS) and overall survival (OS) was 82.3% (371/451) and 82.6% (376/451) respectively with a median follow-up of 108.0 months (range 3-184.0). 118 were treated in the neoadjuvant setting (26.2%): tumour size <50 mm (Odds Ratio (OR): 12.156, P = 0.023) and progesterone receptor negativity (OR: 2.762, P = 0.008) independently predicted breast pCR, while ductal carcinoma (OR: 3.203, P = 0.030) and grade 3 disease (OR: 2.788, P = 0.018) predicted axillary pCR. Both breast and axillary pCR predicted enhanced DFS (Hazard Ratio (HR): 0.470 & HR: 0.449) and OS (HR: 0.383 & HR: 0.307). Axillary pCR independently predicted improved OS (HR: 0.326). CONCLUSION: pCR is sensitive biomarker and surrogate to survival outcomes in HER2+ breast cancer. Patients likely to achieve pCR may be predicted from traditional clinicopathological characteristics and molecular parameters.

Evaluating the Clinical Utility of Routine Sentinel Lymph Node Biopsy and the Value of Adjuvant Chemotherapy in Elderly Patients Diagnosed With Oestrogen Receptor Positive, Clinically Node Negative Breast Cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) provides staging information and guides adjuvant therapy in early breast cancer (EBC). Routine SLNB in oncogeriatricians with low-risk EBC remains controversial. AIMS: To evaluate axillary management in elderly patients diagnosed with oestrogen receptor positive (ER+), clinically lymph node negative (cLN-) EBC, and to assess whether SLNB affects further axillary management or adjuvant chemotherapy (ACTX) decision making. METHODS: Female patients aged > 65 years, diagnosed with ER+, human epidermal growth factor receptor-2 negative (HER2-), and cLN- breast cancer (BC), who underwent surgery and SLNB were included. Clinicopathological predictors of ACTX and completion axillary lymph node dissection (CALND) were determined. Kaplan-Meier analyses assessed survival outcomes. RESULTS: A total of 253 patients were included (median age: 72 years, range: 66-90), all underwent SLNB; 50 (19.8%) had lymphatic metastasis on SLNB (SLNB+). Of these, 19 proceeded to CALND (38.0%), 10 (52.6%) of whom had further axillary disease (ALND+). 20 of the 50 SLNB+ patients received ACTX (40.0%) as did 31 of the 203 SLNB- patients (15.2%) (P < .001). Oncotype DX (ODX) testing was utilized in 82 cases (32.8%). Younger age (P < .001), SLNB+ (P < .001) and ODX score (P = .003) were all associated with ACTX prescription. ODX > 25 (OR: 4.37, 95% CI: 1.38-13.80, P = .012) independently predicted receiving ACTX. Receiving ACTX and proceeding to CALND did not improve disease-free (P = .485 and P = .345) or overall survival (P = .981 and P = .646). CONCLUSIONS: Routine SNLB may not be necessary in elderly patients diagnosed with ER+, cLN- EBC. Future oncogeriatric practice is likely to see genomic testing guiding ACTX prescription in this group.

Clinicopathological correlates, oncological impact, and validation of Oncotype DX™ in a European Tertiary Referral Centre.

Oncotype DX™ (ODX) score estimates prognosis and predicts breast cancer recurrence. It also individualizes patient adjuvant chemotherapy prescription in breast cancer. This assay relies on genetic and molecular markers; the clinicopathological phenotype of which are tested routinely. The aim of this study was determine whether clinicopathological and immunohistochemical information predicts ODX recurrence score (RS). Secondly, to assess the impact on adjuvant chemotherapy (AC) and oncological outcome of ODX testing in patients in a European tertiary referral center. Estrogen receptor positive (ER+), human epidermal growth factor receptor-2 negative (HER2-), lymph node negative (LN-), and female breast cancer patients with ODX testing performed between 2007 and 2015 were categorized into low- (<11), intermediate- (11-25), and high-risk (>25) groups. Clinicopathological and immunohistochemical correlates of RS were determined. Predictors of RS were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analyses. ODX was performed in 400 consecutive ER+LN- patients. Median follow-up was 74.1 months (3.0-144.4). Low grade (odds ratio [OR]:2.39; 95% confidence interval [CI]:1.04-5.51, p = 0.041) independently predicted low ODX, while high grade (OR:2.04; 95% CI: 1.19-3.49, p = 0.009) and reduced progesterone receptor (PgR) expression (OR: 2.57, 95% CI: 1.42-4.65, p = 0.002) independently predicted high ODX. Omission of AC in intermediate- (p = 0.159) and high-risk (p = 0.702) groups did not negatively impact survival. In conclusion, tumor grade independently predicts low and high RS, while PgR negativity predicts high RS. ODX reduced AC prescription without compromising oncological outcome.

C-Reactive Protein-Lymphocyte Ratio Identifies Patients at Low Risk for Major Morbidity after Oesophagogastric Resection for Cancer.

INTRODUCTION: Complications following oesophagogastric surgery have significant implications for patient recovery. OBJECTIVE: identify cost-effective biomarkers which can predict morbidity. METHODS: Analysis of all upper gastrointestinal resections in Galway University Hospital from 2014 to 2018 was performed. The ability of C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), and CRP-lymphocyte ratio (CLR) to predict morbidity, including anastomotic leak (AL), was assessed and compared. RESULTS: Seventy-one oesophagectomies and 77 gastrectomies were performed. There were 2 (1%) 30-day mortalities and 83 (56%) morbidities of which 30 (20%) were of Clavien-Dindo grade 3 or higher. The rate of major morbidity within the oesophagectomy cohort was 27% and was 14% in the gastrectomy cohort. There were 11 (7%) ALs, 7 in the oesophagectomy cohort, and 4 in the gastrectomy cohort. From post-operative day (POD) 2 onwards, CRP could predict AL (POD2 AUC = 0.705, p = 0.025; POD3 AUC = 0.757, p = 0.005, POD4 AUC = 0.811, p = 0.001; and POD5 AUC = 0.824, p = 0.001). CLR predicted AL on POD2 onwards (POD2 AUC = 0.722, p = 0.005; POD3 AUC = 0.736, p = 0.01; POD4 AUC = 0.775, p = 0.003; and POD5 AUC = 0.817, p = 0.001). CRP level of 218 mg/dL and CLR level of 301 at POD 2 generated negative predictive values of 97 and 98%, respectively, for AL. Post-operative NLR did not display sufficient discriminatory ability for the outcomes. CONCLUSION: CRP and CLR are reliable negative predictors of major morbidity, including AL, after oesophagogastric resection. Their use can inform patient intervention and recovery.

The Impact of Preoperative Breast Magnetic Resonance Imaging on Surgical Management in Symptomatic Patients With Invasive Lobular Carcinoma.

OBJECTIVE: Due to an insidious proliferative pattern, invasive lobular breast cancer (ILC) often fails to form a defined radiological or palpable lesion and accurate diagnosis remains challenging. This study aimed to determine the value of preoperative magnetic resonance imaging (MRI) for ILC and its impact on surgical outcomes. METHODS: Consecutive symptomatic patients diagnosed with ILC in a tertiary centre over a 9-year period were reviewed. The time from diagnosis until surgery, initial type of surgery/index operation (breast-conserving surgery [BCS]/mastectomy) and the rates of reoperation (re-excision/completion mastectomy) were recorded. Patients were grouped into those who received conventional imaging and preoperative MRI (MR+) and those who received conventional imaging alone (MR-). RESULTS: There were 218 cases of ILC, and 32.1% (n = 70) had preoperative MRI. Time from diagnosis to surgery was longer in the MR+ than the MR- group (32.5 vs 21.1 days, P < .001) even when adjusting for age and breast density. Initial BCS was performed on 71.4% (n = 50) of MR+ patients and 72.3% (n = 107) of the MR- group. While the rate of completion mastectomy following initial BCS was higher in the MR+ group (30.0%, n = 15 vs 14.0%, n = 15; χ2 = 5.63; P = .018), this association was not maintained in multivariable analysis. No difference was recorded in overall (initial and completion) mastectomy rate between the MR+ and MR- group (50.0%, n = 35 vs 37.8%, n = 56; χ2 = 2.89; P = .089). Margin re-excision following BCS was comparable between groups (8.0%, n =4, vs 9.3%, n = 10; χ2 = 0.076, P = .783) despite the selection bias for borderline conservable cases in the MR+ group. The rate of usage of MRI for ILC cases declined over the study period. CONCLUSION: While MRI was associated with minor delays in treatment and did not reduce overall rates of margin re-excision or completion mastectomy, it altered the choice of surgical procedure in almost a quarter of MR+ cases. The benefit of preoperative breast MRI appears to be confined to select (younger, dense breast, borderline conservable) cases in symptomatic ILC.

Serial CRP levels following oesophagectomy: a marker for anastomotic dehiscence.

BACKGROUND: Following oesophagectomy, the most concerning complication is that of anastomotic leak (AL). Prompt diagnosis and intervention are crucial to facilitate an optimal outcome. Other complications, particularly respiratory, are not infrequent. Early identification of AL versus other sources of the inflammatory response can be problematic. AIMS: To evaluate the role of serial CRP as a prognosticator for oesophagogastric AL. METHODS: All oesophagectomies carried out at our institution from 2010 to 2017 were included. Serial C-reactive protein (CRP) and white cell count (WCC) were recorded pre-operatively and on each consecutive day up to day 10 post-op. All complications were recorded and the timing of diagnosis compared with serial CRP and WCC measurements to determine any correlation. RESULTS: One hundred and two patients underwent oesophagectomy (84 male, 18 female) with a mean age of 62.5 years (± 9.8). Forty-seven patients developed post-operative complications, with pulmonary (n = 28) the most common. There were 5 cases of AL. Patients in the AL group (n = 5) had a significantly higher mean CRP compared to those who did not develop AL (n = 97) pre-operatively (50 vs. 14, p = 0.046), on post-op day 3 (300 vs. 218, p = 0.02) and on post-op day 4 (279 vs. 184, p = 0.009). There was no significant difference in mean daily CRP between patients with pulmonary complications (PC, n = 29) and those who did not develop complications (NC, n = 54). CONCLUSIONS: Elevated CRP may be a useful marker in facilitating the prompt diagnosis of AL following oesophagectomy. Serial CRP may not contribute to identifying lower respiratory tract infections, partly as a result of the pro-inflammatory response following surgery.

Circulating microRNAs miR-331 and miR-195 differentiate local luminal a from metastatic breast cancer.

BACKGROUND: Breast cancer is the leading cause of cancer related death in women, with metastasis the principle cause of mortality. New non-invasive prognostic markers are needed for the early detection of metastasis, facilitating treatment decision optimisation. MicroRNA (miRNA) are small, non-coding RNAs regulating gene expression and involved in many cellular processes, including metastasis. As biomarkers, circulating miRNAs (in blood) hold great promise for informing diagnosis or monitoring treatment responses. METHODS: Plasma extracted RNA from age matched local Luminal A (n = 4) or metastatic disease (n = 4) were profiled using Next Generation Sequencing. Selected differentially expressed miRNA were validated on a whole blood extracted miRNA cohort [distant metastatic disease (n = 22), local disease (n = 31), healthy controls (n = 21)]. Area Under the Curve (AUC) in Receiver Operating Characteristic (ROC) analyses was performed. RESULTS: Of 4 miRNA targets tested (miR-181a, miR-329, miR-331, miR-195), mir-331 was significantly over-expressed in patients with metastatic disease, compared to patients with local disease (p < 0.001) or healthy controls (p < 0.001). miR-195 was significantly under-expressed in patients with metastatic disease, compared to patients with local disease (p < 0.001) or healthy controls (p = 0.043). In combination, miR-331 and miR-195 produced an AUC of 0.902, distinguishing metastatic from local breast cancer. CONCLUSIONS: We identified and validated two circulating miRNAs differentiating local Luminal A breast cancers from metastatic breast cancers. Further investigation will reveal the molecular role of these miRNAs in metastasis, and determine if they are subtype specific. This work demonstrates the ability of circulating miRNA to identify metastatic disease, and potentially inform diagnosis or treatment effectiveness.

Correction to: Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options.

It has been highlighted that the original manuscript [1] contains a typesetting error regarding the authorship.

Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options.

BACKGROUND: Recent studies have shown that breast cancer subtype can change from the primary tumour to the recurrence. Discordance between primary and recurrent breast cancer has implications for further treatment and ultimately prognosis. The aim of the study was to determine the rate of change between primary and recurrence of breast cancer and to assess the impact of these changes on survival and potential treatment options. METHODS: Patient demographics were collected on those who underwent surgery for breast cancer between 2001 and 2014 and had a recurrence with biopsy results and pathology scoring of both the primary and recurrence. RESULTS: One hundred thirty two consecutive patients were included. There were 31 (23.5%) changes in subtype. Discordance occurred most frequently in luminal A breast cancer (n = 20), followed by triple negative (n = 4), luminal B (n = 3) and HER2 (n = 3). Patients who changed from luminal A to triple negative (n = 18) had a significantly worse post-recurrence survival (p < 0.05) with overall survival approaching significance (p = 0.064) compared to concordant luminal A cases (n = 46). Overall receptor discordance rates were: estrogen receptor 20.4% (n = 27), progesterone receptor 37.7% (n = 50) and HER2 3% (n = 4). Loss of estrogen receptor and progesterone receptor was more common than gain (21 vs. 6 (p = 0.04) and 44 vs. 6 (p = 0.01) respectively). Nine patients (6.8%) gained receptor status potentially impacting treatment options. CONCLUSION: Discordance in subtype and receptor status occurs between primary and recurrent breast cancer, ultimately affecting survival and potentially impacting treatment options.

Circulating Nucleosomes and Nucleosome Modifications as Biomarkers in Cancer.

Traditionally the stratification of many cancers involves combining tumour and clinicopathological features (e.g., patient age; tumour size, grade, receptor status and location) to inform treatment options and predict recurrence risk and survival. However, current biomarkers often require invasive excision of the tumour for profiling, do not allow monitoring of the response to treatment and stratify patients into broad heterogeneous groups leading to inconsistent treatment responses. Here we explore and describe the benefits of using circulating biomarkers (nucleosomes and/or modifications to nucleosomes) as a non-invasive method for detecting cancer and monitoring response to treatment. Nucleosomes (DNA wound around eight core histone proteins) are responsible for compacting our genome and their composition and post-translational modifications are responsible for regulating gene expression. Here, we focus on breast and colorectal cancer as examples where utilizing circulating nucleosomes as biomarkers hold real potential as liquid biopsies. Utilizing circulating nucleosomes as biomarkers is an exciting new area of research that promises to allow both the early detection of cancer and monitoring of treatment response. Nucleosome-based biomarkers combine with current biomarkers, increasing both specificity and sensitivity of current tests and have the potential to provide individualised precision-medicine based treatments for patients.

Diagnostic imaging of deep vein thrombosis secondary to osteochondroma formation.

Deep vein thrombosis (DVT) is a condition classically associated with blood stasis, hypercoagulability or injury to the vasculature. As blood stasis is usually associated with patient immobility, DVT occurrence in young active patients with no underlying haematological conditions is a rarity. An exostosis, also known as osteochondroma, is a cartilage capped lesion. If solitary, they represent low malignant potential and unless symptomatic, they are rarely excised. A 23-year-old, active male, presented to hospital with pain and swelling in the left lower leg. It was a deep, non-radiating pain, exacerbated by exercise. Wells' criteria score for DVT was 2. An ultrasound was performed which identified thrombosis in the superficial femoral, and popliteal veins. Haematological causes of thrombosis were ruled out. X-ray showed a posterior femoral exostosis. It was determined that compression by the exostosis was the cause of the thrombosis. We present a case of a DVT secondary to osteochondroma formation in a young male. Isolated DVT in this setting is uncommon with fewer than five previously reported cases identified in the literature. We also discuss the current literature and management of this rare entity.

Aerosolized intraperitoneal local anesthetic for laparoscopic surgery: a randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Postoperative pain remains a significant challenge following laparoscopy. Aerosolized intraperitoneal local anesthetic (AILA) is a novel method to deliver local anesthetic. The aim was to evaluate aerosolized ropivacaine in pain management following laparoscopic Nissen fundoplication (LNF) and cholecystectomy (LC). METHODS: This prospective randomized double-blinded placebo-controlled trial enrolled consecutive patients undergoing LNF and LC. The treatment group (TG) received intraperitoneal ropivacaine (5 mL 1 % Naropin(®)) at CO2 insufflation via the AeroSurge(®) aerosolizer device through the camera port. The control group (CG) received 5 mL of saline in the same manner. Postoperative shoulder tip pain at rest 6 h postoperatively was the primary study endpoint, with secondary endpoints of shoulder and abdominal pain within the first 24 h, recovery room stay, hospital stay, and postoperative analgesia use. Pain scores were collected using the Verbal Rating Score. RESULTS: Eighty-seven patients were included in the final analysis (TG n = 40, CG n = 47). There was no significant difference between CG and TG at the primary endpoint. In the LC group, AILA significantly reduced shoulder tip pain at rest at 10 (p = 0.030) and 30 min (p = 0.040) and shoulder tip pain on movement at 10 (p = 0.030) and 30 min (p = 0.037). In the LNF group, AILA significantly reduced postoperative abdominal pain at rest at 6 h (p = 0.009). AILA reduced overall incidence of shoulder tip pain in the LC group (11.8 vs. 57.9 %, p = 0.004). CONCLUSION: This study did not demonstrate a significant difference between TG and CG in the primary endpoint, pain at 6 h postoperatively.