BackgroundThe use of biomarkers to target anti-EGFR treatments for metastatic colorectal cancer (CRC) is well-established, requiring molecular analysis of primary or metastatic biopsies. We aim to review concordance between primary CRC and its metastatic sites.MethodsA systematic review and meta-analysis of all published studies (1991–2018) reporting on biomarker concordance between primary CRC and its metastatic site(s) was undertaken according to PRISMA guidelines using several medical databases. Studies without matched samples or using peripheral blood for biomarker analysis were excluded.Findings61 studies including 3565 patient samples were included. Median biomarker concordance for KRAS (n = 50) was 93.7% [[67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100]], NRAS (n = 11) was 100% [[90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100]], BRAF (n = 22) was 99.4% [[80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100]], and PIK3CA (n = 17) was 93% [[42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100]]. Meta-analytic pooled discordance was 8% for KRAS (95% CI = 5–10%), 8% for BRAF (95% CI = 5–10%), 7% for PIK3CA (95% CI = 2–13%), and 28% overall (95% CI = 14–44%). The liver was the most commonly biopsied metastatic site (n = 2276), followed by lung (n = 438), lymph nodes (n = 1123), and peritoneum (n = 132). Median absolute concordance in multiple biomarkers was 81% (5–95%).InterpretationMetastatic CRC demonstrates high concordance across multiple biomarkers, suggesting that molecular testing of either the primary or liver and lung metastasis is adequate. More research on colorectal peritoneal metastases is required.

The optimal flap cover for managing open lower limb fractures is debated. Most studies have reported on surgical outcome but clinical outcome is not well recognised. We aimed to determine whether there are differences in patient-reported quality of life (QoL) outcome between local flap versus free flap.All patients admitted with lower limb open fractures were retrospectively reviewed. Patient notes were assessed for demographics, time to fracture union, wound healing and patient-reported QoL with EQ-5D-5L alongside a novel flap assessment tool.A total of 40 patients had flap reconstruction of their lower limb injury; 23 local flap (Group I) and 17 free flap (Group II). Average length of follow-up was 33.8 months. Group I -10 revisions of flaps (43.5%) and 14 surgical complications (60.9%). Fracture union was 171 days and wound healing 130 days. EQ-5D index and EQ-VAS scores were 0.709 and 79.3, respectively. Group II -8 revision of flaps (47.1%) and 12 surgical complications (70.6%). Fracture union was 273 days and wound healing 213 days. EQ-5D index and EQ-VAS scores were 0.525 and 57.2, respectively. Aesthetic appeal -48% Group I vs. 66% Group II. Significant differences were found between the two flap groups with higher scores for daily living in Group I (p = 0.007) compared to higher overall flap ratings in Group II (p = 0.049). Both groups were comparable in terms of complications; while flap congestion and dehiscence were more common with free flaps statistical interrogation did not elicit significance (p > 0.05).Local flap and free flap techniques offer distinct advantages. Local flaps have better surgical outcome and patient-reported QoL in the first few years post soft tissue reconstruction. Differences between local and free reconstructive techniques in terms of patient health and function are ameliorated in the longer term.

Background Genetic biomarkers guide systemic anti-cancer treatment (SACT) in metastatic colorectal cancer. It has been suggested they have a role in selecting patients with colorectal peritoneal metastases (CRPM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). This study aims to quantify the effect of mutation status on overall survival (OS), adjusting for confounders such as pre-operative systemic anticancer treatment (SACT). Patients and Methods Retrospective analysis of patients undergoing CRS/HIPEC for CRPM at a national peritoneal tumour centre (2004–2017) was performed. Demographics, treatment history and operative data were extracted. Known biomarker gene mutation status was noted including: KRAS, NRAS, BRAF, PIK3CA and MMR. Cox regression analysis and Kaplan–Meier curves were used to determine overall survival. Results One hundred ninety-five patients were included. Median follow-up time was 34.7 months (range 5.4–184.9 months) and median OS was 38.7 months (95% CI 32.4–44.9 months). Biomarker status was as follows: KRAS (n = 114), NRAS (n = 85), BRAF (n = 44), PIK3CA (n = 15) and MMR (n = 21). Mutation rates were 45.6%, 3.5%, 13.6%, 13.3% and 14.3%, respectively. Seventy-four per cent underwent complete cytoreduction (CC = 0), 81% received SACT pre-CRS/HIPEC and 65% post-CRS/HIPEC. RAS (p = 0.21) or BRAF (p = 0.109) mutation status did not predict OS. Nodal involvement, extramural vascular invasion, Peritoneal Cancer Index (PCI) score, CC score, SACT post-HIPEC and NRAS mutation were significant negative predictors of OS in univariate analysis (p < 0.05). Multivariate Cox regression confirmed CC-score > 1 (HR: 7.599, 95% CI 3.402–16.974, p < 0.0001) as a negative predictor of OS. RAS mutation status did not affect outcome (HR: 1.682, 95% CI 0.995–2.843, p = 0.052). Conclusions RAS mutation status should not in isolation be used to select patients for CRS/HIPEC.