Value of a 21-gene expression assay on core biopsy to predict neoadjuvant chemotherapy response in breast cancer: systematic review and meta-analysis.

BACKGROUND: A recurrence score based on a 21-gene expression assay predicts the benefit of adjuvant chemotherapy in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This systematic review aimed to determine whether the 21-gene expression assay performed on core biopsy at diagnosis predicted pathological complete response (pCR) to neoadjuvant chemotherapy. METHODS: The study was performed according to PRISMA guidelines. Relevant databases were searched to identify studies assessing the value of the 21-gene expression assay recurrence score in predicting response to neoadjuvant chemotherapy in patients with breast cancer. The Newcastle-Ottawa Scale was used to assess the quality of the studies. Results are reported as risk ratio (RR) with 95 per cent confidence interval using the Cochrane-Mantel-Haenszel method for meta-analysis. Sensitivity analyses were carried out where appropriate. RESULTS: Seven studies involving 1744 patients reported the correlation between pretreatment recurrence score and pCR. Of these, 777 patients (44.6 per cent) had a high recurrence score and 967 (55.4 per cent) a low-intermediate score. A pCR was achieved in 94 patients (5.4 per cent). The pCR rate was significantly higher in the group with a high recurrence score than in the group with a low-intermediate score (10.9 versus 1.1 per cent; RR 4.47, 95 per cent c.i. 2.76 to 7.21; P < 0.001). A significant risk difference was observed between the two groups (risk difference 0.10, 0.04 to 0.15; P = 0.001). CONCLUSION: A high recurrence score is associated with higher pCR rates and a low-intermediate recurrence score may indicate chemoresistance. Routine assessment of recurrence score by the 21-gene expression assay on core biopsy might be of value when considering neoadjuvant chemotherapy in patients with ER-positive, HER2-negative breast cancer.

Intracorporeal vs extracorporeal anastomosis following neoplastic right hemicolectomy resection: a systematic review and meta-analysis of randomized control trials.

PURPOSE: While minimally invasive surgery is the preferred approach for right hemicolectomy, the choice of anastomotic technique is still debated. Both intracorporeal (ICA) and extracorporeal anastomosis (ECA) are described, with conflicting reports on safety and efficacy seen. This study aimed to examine impact of ICA and ECA on outcomes in right hemicolectomy. METHODS: A meta-analysis of randomized control trials (RCT) was performed. The primary outcome was overall morbidity. The secondary outcomes included both perioperative and post-operative outcomes. RESULTS: Four RCTs were included incorporating 399 patients (199 patients (49.9%) ICA Vs 200 (50.1%) ECA). There was no significant difference in overall morbidity (RR 0.79, 95% CI 0.43, 1.48, p = 0.47), anastomotic leak (RR 1.34, 95% CI 0.58, 3.13, p = 0.5) or surgical site infections (RR 0.53, 95% CI 0.17, 1.64, p = 0.27). ICA patients had a significantly less post-operative ileus (RR 0.53, 95% CI 0.3-0.94, p = 0.03) quicker return to first flatus (WMD - 0.71, 95% CI - 1.12, 0.31, p = 0.0005), first bowel motion (WMD - 0.53, 95% CI - 0.69, - 0.37, p < 0.00001) and first meal (WMD - 0.68, 95% CI - 1.33, - 0.03, p = 0.04). Pain scores were significantly better for ICA patients on POD 3 (WMD - 0.76, 95% CI - 1.23, - 0.28, p = 0.002), POD 4 (WMD - 0.90, 95% CI - 1.71, - 0.09, p = 0.03) and POD 5 (WMD - 0.67, 95% CI - 1.22, - 0.13, p = 0.01). Length of hospital stay was similar (WMD - 0.46, 95% CI - 1.14, 0.22, p = 0.19). CONCLUSION: ICA is associated with a quicker return to normal physiological function with equivalent post-operative morbidity. Both ECA and ICA are safe and feasible for restoring normal bowel continuity.

Meta-analysis of the diagnostic accuracy of ultrasound-guided fine-needle aspiration and core needle biopsy in diagnosing axillary lymph node metastasis.

BACKGROUND: Axillary lymph node status remains a significant prognostic indicator in breast cancer. Here, the diagnostic accuracy of ultrasound-guided fine-needle aspiration (US-FNA) and ultrasound-guided core needle biopsy (US-CNB) in axillary staging was compared. METHODS: A comprehensive search was undertaken of all published studies comparing the diagnostic accuracy of US-CNB and US-FNA of axillary lymph nodes in breast cancer. Studies were included if raw data were available on the diagnostic performance of both US-FNA and US-CNB, and compared with final histology results. Relevant data were extracted from each study for systematic review. Meta-analysis was performed using a random-effects model. The pooled sensitivity and specificity of US-FNA and US-CNB were obtained using a bivariable model. Summary receiver operating characteristic (ROC) graphs were created to confirm diagnostic accuracy. RESULTS: Data on a total of 1353 patients from six studies met the inclusion criteria and were included in the final analysis. US-CNB was superior to US-FNA in diagnosing axillary nodal metastases: sensitivity 88 (95 per cent c.i. 84 to 91) versus 74 (70 to 78) per cent respectively. Both US-CNB and US-FNA had a high specificity of 100 per cent. Reported complication rates were significantly higher for US-CNB compared with US-FNA (7·1 versus 1·3 per cent; P < 0·001). Conversely, the requirement for repeat diagnostic procedures was significantly greater for US-FNA (4·0 versus 0·5 per cent; P < 0·001). CONCLUSION: US-CNB is a superior diagnostic technique to US-FNA for axillary staging in breast cancer.

Microsatellite instability is associated with reduced disease specific survival in stage III colon cancer.

BACKGROUND: Up to 15% of colorectal cancers exhibit microsatellite instability (MSI), where errors in replication go unchecked due to defects in the mismatch repair system. This study aimed to determine survival in a large single-centre series of 1250 consecutive colorectal cancers subjected to universal MSI testing. METHODS: Clinical and pathological features of patients with colorectal cancer identified on prospectively maintained colorectal and pathology databases at St. Vincent's University Hospital from 2004 to May 2012 were examined. Mismatch repair (MMR) status was determined by immunohistochemistry. Kaplan-Meier curves, the log-rank test and Cox regression were used to associate survival with clinical and pathological characteristics. RESULTS: Of the 1250 colorectal cancers in the study period, 11% exhibited MSI (n = 138). Patients with MSI tumours had significantly lower rates of lymph node and distant metastases (MSI N+ rate: 24.8% compared with MSS N+ rate: 46.2%, p < 0.001). For Stage I and II disease MSI was associated with improved disease free survival (DSS) compared with MSS colon cancer. However, patients with Stage III MSI colon cancers had a worse DSS than those with MSS tumours. Stage III MSI tumours exhibited higher rates of lymphovascular invasion and perineural invasion than Stage I/II MSI tumours. CONCLUSION: MSI is associated with a reduced risk of nodal and distant metastases, with an improved DSS in Stage I/II colon cancer. However, when MSI tumours progress to Stage III these patients had worse outcomes and pathological features. New strategies for this cohort of patients may be required to improve outcomes.

Restructuring an evolving Irish trauma system: What can we learn from Europe and Australia?

AIM: Major trauma is a leading cause of mortality and disability. Internationally, major trauma centres and comprehensive trauma networks are associated with improved outcomes. This study aimed to examine selected international trauma systems in Europe and Australia to identify common themes that may aid reconfiguration of the Irish trauma service. METHODS: An electronic search strategy was utilised using Medline, and a search of the grey literature using Google and Google Scholar. Search terms included "trauma systems", "trauma care", "major trauma centre" and "trauma network". Relevant articles were reviewed and data summarised in a narrative format. RESULTS: Republic of Ireland currently lacks designated major trauma centres and surrounding trauma networks. Lessons from international models and data from the on-going national trauma audit may guide reconfiguration. Well-functioning trauma systems internationally bear striking similarities, and involve a hub and spoke model. This model has a central major trauma centre, surrounded by a co-ordinated trauma network with trauma units. Concentration of major trauma into high volume centres is key, but these centres must be adequately resourced to deliver a high quality service. Investment in and co-ordination of prehospital care is essential to overcome geographical impediments to centralising trauma care. Funding of rehabilitation infrastructure and resources is also an integral part of a well-functioning trauma system. Trauma outcome data is key to informing trauma system design, with dissemination of this data and public engagement critical for change. CONCLUSION: International models of trauma care provide valuable lessons for countries currently in process of reconfiguring trauma services.