Receptor Discordance in Metastatic Breast Cancer; a review of clinical and genetic subtype alterations from primary to metastatic disease.

PURPOSE: Receptor and subtype discordance between primary breast tumours and metastases is a frequently reported phenomenon. The aim of this article is to review the current evidence on receptor discordance in metastatic breast cancer and to explore the benefit of performing a repeat biopsy in this context. METHODS: Searches were undertaken on PubMed and Clinicaltrials.gov for relevant publications and trials. CONCLUSION: The current guidelines recommend offering to perform a biopsy of a metastatic lesion to evaluate receptor status. The choice of systemic therapy in metastatic disease is often based on the receptor status of the primary lesion. As therapeutic decision making is guided by subtype, biopsy of the metastatic lesion to determine receptor status may alter treatment. This article discusses discordance rates, the mechanisms of receptor discordance, the effect of discordance on treatment and survival outcomes, as well as highlighting some ongoing clinical trials in patients with metastatic breast cancer.

The impact of timing on outcomes in appendicectomy: a systematic review and network meta-analysis.

INTRODUCTION: Appendicectomy remains the standard treatment for appendicitis. There is a lack of clarity on the timeframe in which surgery should be performed to avoid unfavourable outcomes. AIM: To perform a systematic review and network meta-analysis to evaluate the impact the (1)time-of-day surgery is performed (2), time elapsed from symptom onset to hospital presentation (patient time) (3), time elapsed from hospital presentation to surgery (hospital time), and (4)time elapsed from symptom onset to surgery (total time) have on appendicectomy outcomes. METHODS: A systematic review was performed as per PRISMA-NMA guidelines. The time-of-day which surgery was done was divided into day, evening and night. The other groups were divided into < 24 h, 24-48 h and > 48 h. The rate of complicated appendicitis, operative time, perforation, post-operative complications, surgical site infection (SSI), length of stay (LOS), readmission and mortality rates were analysed. RESULTS: Sixteen studies were included with a total of 232,678 patients. The time of day at which surgery was performed had no impact on outcomes. The incidence of complicated appendicitis, post-operative complications and LOS were significantly better when the hospital time and total time were < 24 h. Readmission and mortality rates were significantly better when the hospital time was < 48 h. SSI, operative time, and the rate of perforation were comparable in all groups. CONCLUSION: Appendicectomy within 24 h of hospital admission is associated with improved outcomes compared to patients having surgery 24-48 and > 48 h after admission. The time-of-day which surgery is performed does not impact outcomes.

Diagnostic accuracy of intraoperative methods for margin assessment in breast cancer surgery: A systematic review & meta-analysis.

PURPOSE: There are a wide variety of intraoperative techniques available in breast surgery to achieve low rates for positive margins of excision. The objective of this systematic review was to determine the pooled diagnostic accuracy of intraoperative breast margin assessment techniques that have been evaluated in clinical practice. METHODS: This study was performed in accordance with PRISMA guidelines. A systematic search of the literature was conducted to identify studies assessing the diagnostic accuracy of intraoperative margin assessment techniques. Only clinical studies with raw diagnostic accuracy data as compared with final permanent section histopathology were included in the meta-analysis. A bivariate model for diagnostic meta-analysis was used to determine overall pooled sensitivity and specificity. RESULTS: Sixty-one studies were eligible for inclusion in this systematic review and meta-analysis. Cytology demonstrated the best diagnostic accuracy, with pooled sensitivity of 0.92 (95 % CI 0.77-0.98) and a pooled specificity of 0.95 (95 % CI 0.90-0.97). The findings also indicate good diagnostic accuracy for optical spectroscopy, with a pooled sensitivity of 0.86 (95 % CI 0.76-0.93) and a pooled specificity of 0.92 (95 % CI 0.82-0.97). CONCLUSION: Pooled data indicate that optical spectroscopy, cytology and frozen section have the greatest diagnostic accuracy of currently available intraoperative margin assessment techniques. However, long turnaround time for results and their resource intensive nature has prevented widespread adoption of these methods. The aim of emerging technologies is to compete with the diagnostic accuracy of these established techniques, while improving speed and usability.