Background:KRAS codons 12 and 13 mutations predict resistance to anti-EGFR monoclonal antibodies (moAbs) in metastatic colorectal cancer. Also, BRAF V600E mutation has been associated with resistance. Additional KRAS mutations are described in CRC.Methods:We investigated the role of KRAS codons 61 and 146 and BRAF V600E mutations in predicting resistance to cetuximab plus irinotecan in a cohort of KRAS codons 12 and 13 wild-type patients.Results:Among 87 KRAS codons 12 and 13 wild-type patients, KRAS codons 61 and 146 were mutated in 7 and 1 case, respectively. None of mutated patients responded vs 22 of 68 wild type (P=0.096). Eleven patients were not evaluable. KRAS mutations were associated with shorter progression-free survival (PFS, HR: 0.46, P=0.028). None of 13 BRAF-mutated patients responded vs 24 of 74 BRAF wild type (P=0.016). BRAF mutation was associated with a trend towards shorter PFS (HR: 0.59, P=0.073). In the subgroup of BRAF wild-type patients, KRAS codons 61/146 mutations determined a lower response rate (0 vs 37%, P=0.047) and worse PFS (HR: 0.45, P=0.023). Patients bearing KRAS or BRAF mutations had poorer response rate (0 vs 37%, P=0.0005) and PFS (HR: 0.51, P=0.006) compared with KRAS and BRAF wild-type patients.Conclusion:Assessing KRAS codons 61/146 and BRAF V600E mutations might help optimising the selection of the candidate patients to receive anti-EGFR moAbs.

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PTEN loss in metastases may be predictive of resistance to cetuximab plus irinotecan. The combination of PTEN IHC and KRAS mutational analyses could help to identify a subgroup of patients with mCRC who have higher chances of benefiting from EGFR inhibition.

A pharmacogenetic approach may be an innovative strategy for optimizing palliative chemotherapy in patients with advanced colorectal cancer. These findings deserve confirmation in additional prospective studies.

IMPORTANCETo date, only a few studies have directly compared nonpenetrating surgery (NPS) and trabeculectomy (TE). Therefore, there is no strong evidence as to which surgical technique leads to the best results in terms of ocular hypotensive effect and safety.OBJECTIVE To compare the hypotensive effect and safety of NPS and TE in terms of intraocular pressure (IOP) reduction and incidence of complications.DATA SOURCES The MEDLINE and EMBASE databases were searched for studies potentially eligible in any language published up to March 31, 2013.STUDY SELECTION Systematic review and meta-analysis of comparative studies of 2 or more surgical techniques (1 of which had to be TE), including patients with open-angle glaucoma. DATA EXTRACTION AND SYNTHESISThe considered interventions were TE, deep sclerectomy (DS), viscocanalostomy, and canaloplasty. MAIN OUTCOMES AND MEASURESThe primary outcome was the mean between-group difference in the reduction in diurnal IOP from baseline to the 6-or 12-month follow-up evaluation. We also considered the incidence of complications, expressed as relative risk.RESULTS Eighteen articles, accounting for 20 comparisons, were selected for data extraction and analysis. Analysis of the 6-month follow-up data showed that the pooled estimate of the mean between-group difference was −2.15 mm Hg (95% CI, −2.85 to −1.44) in favor of TE. There was no difference between the NPS subgroups. In the subgroup antimetabolite analysis, the addition of mitomycin C to TE and DS decreased the difference in the reduction in IOP (TE and DS without mitomycin C: −2.65 mm Hg [95% CI, −3.90 to −1.39]; TE and DS with mitomycin C: −0.83 mm Hg [95% CI, −2.40 to 0.74]). In the subgroup analysis by implant addition, no significant difference induced by DS with or without drainage devices was detected (test for subgroup differences: χ 2 1 = 0.24; P = .62). The absolute risk of hypotony, choroidal effusion, cataract, and flat or shallow anterior chamber was higher in the TE group than in the NPS group. CONCLUSIONS AND RELEVANCE Trabeculectomy seems to be the most effective surgical procedure for reducing IOP in patients with open-angle glaucoma. However, as expected, it was associated with a higher incidence of complications when compared with NPS.

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Surgery of liver metastases can be effective, and the appropriate selection of surgical candidates relies first on imaging. Different techniques are available, but information on their relative performance is unclear. The aim of this overview is to assess the imaging modality performance in the diagnosis of colorectal cancer (CRC) liver metastases. MEDLINE and EMBASE were searched for articles published from January 2000 to August 2008. Eligible trials had to be conducted on patients with diagnosis/suspicion of CRC liver metastases, comparing more than two modalities among MRI, computed tomography (CT), positron emission tomography using fluoro-18-deoxyglucose (FDG-PET), ultrasonography (US). Pooled estimates of sensitivity, specificity were calculated and pairwise comparisons were performed. Of 6030 screened articles, 25 were eligible. Sensitivity and specificity on a per-patient basis for US, CT, MRI, and FDG-PET were 63.0% and 97.6%, 74.8% and 95.6%, 81.1% and 97.2, and 93.8% and 98.7%, respectively. On a per-lesion basis, sensitivity was 86.3%, 82.6%, 86.3%, and 86.0%, respectively. Specificity was reported in few studies. MRI showed a better sensitivity than CT in per-patient (odds ratio [OR]: 0.69; 95% confidence interval [CI]: 0.47-0.99; P ¼ 0.05) and in per-lesion analysis (OR: 0.66; 95% CI: 0.55-0.80; P < 0.0001). In per-lesion analysis, the difference was higher when liver-specific contrast agents were administered. Available evidence supports the MRI use for the detection of CRC liver metastases. SURGICAL TREATMENT OF colorectal cancer (CRC) liver metastases is the only treatment associated with demonstrated long-term survival (1). Patients with untreated but potentially resectable metastases show a median survival of 6 to 12 months (2), while 5-year survival rate of 45-60% can be achieved in appropriate selected patients (3) and this selection relies first on imaging. Although in the past 20 years the role of diagnostic imaging has gained an increasing importance, due to a rapid improvement both in imaging technology and in its clinical application, no consensus has yet emerged on the optimal imaging strategy for the preoperative staging of patients with CRC liver metastases (3). Moreover, after preoperative imaging, intraoperative ultrasonography (IOUS) has been reported to identify at least one additional lesion in 10-12% of cases (4). These data indicate that intensive efforts should be used to improve staging to avoid unnecessary laparotomy and nontherapeutic resection procedures, especially because nowadays resection of liver metastases is pursued with increasing aggressiveness.The diagnostic value of ultrasound with contrast agents, multi-detector computed tomography (MDCT), and MRI with extra-cellular contrast media (ECCM) and liver-specific contrast media (LSCM) is debated. Nowadays MDCT is the mainstay of staging and follow-up of these patients, because it provides good coverage of the liver and the complete abdomen and chest in one session. MRI has been shown to be also useful in the preope...

LEARNING OBJECTIVESAfter completing this course, the reader should be able to:1. Describe the importance of KRAS mutations in CRC patients.2. Explain the relevance to cancer treatment of concordance of KRAS status between primary tumors and metastases in CRC patients.3. Discuss the impact of KRAS mutations as a predictive/prognostic factor in CRC patients.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTPurpose. Several studies have suggested that KRAS somatic mutations may predict resistance to cetuximaband panitumumab-based treatments in metastatic colorectal cancer (CRC) patients. Nevertheless, most experiences were conducted on samples from primaries. The aim of this study was to evaluate the grade of concor-