Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer.

BACKGROUND: Activating mutations in KRAS have been suggested as potential predictive and prognostic biomarkers. However, the prognostic impact of specific point mutations remains less clear. This study assessed the prognostic impact of specific KRAS mutations on survival for patients with colorectal cancer. METHODS: Retrospective review of patients KRAS typed for advanced and recurrent colorectal cancer between 2010 and 2015 in a UK Cancer Network. RESULTS: We evaluated the impact of KRAS genotype in 392 patients. Mutated KRAS was detected in 42.9% of tumours. KRAS mutations were more common in moderate vs well-differentiated tumours. On multivariate analysis, primary tumour T stage (HR 2.77 (1.54-4.98), P=0.001), N stage (HR 1.51 (1.01-2.26), P=0.04), curative intent surgery (HR 0.51 (0.34-0.76), P=0.001), tumour grade (HR 0.44 (0.30-0.65), P=0.001) and KRAS mutation (1.54 (1.23-2.12), P=0.005) were all predictive of overall survival. Patients with KRAS codon 12 mutations had worse overall survival (HR 1.76 (95% CI 1.27-2.43), P=0.001). Among the five most common codon 12 mutations, only p.G12C (HR 2.21 (1.15-4.25), P=0.01) and p.G12V (HR 1.69 (1.08-2.62), P=0.02) were predictive of overall survival. CONCLUSIONS: For patients with colorectal cancer, p.G12C and p.G12V mutations in codon 12 were independently associated with worse overall survival after diagnosis.

Chemotherapy induced hepatotoxicity in metastatic colorectal cancer: a review of mechanisms and outcomes.

Colorectal cancer remains one of the most common cancers worldwide. The treatment of metastatic disease has advanced considerably in the past 10 years both in terms of surgical technique and development of novel chemotherapeutic agents. The widespread use of multiple chemotherapeutic agents has lead to recognition of distinct patterns of hepatotoxicity associated with specific drugs. These side-effects have potential implications for both the patient and medical professional, but the underlying mechanisms involved in these conditions remains poorly understood. This review explores the mechanisms of action of the commonly used chemotherapeutic agents and the potential mechanisms for their hepatotoxicity. It is important that all medical professionals involved in the management of metastatic colorectal cancer understand the problems of hepatotoxicity and the impact they have on the patient.

Duodenal rupture following trauma in a child.

We present a case of delayed presentation of a traumatic duodenal rupture in a 15-year-old boy. He presented 12 hours after falling six feet and sustaining blunt trauma to his anterior abdominal wall. On arrival in the Emergency Department he was shocked and peritonitic. After initial resuscitation he was stable and transferred to computed tomography where free retroperitoneal air and duodenal rupture was found. He was transferred to theatre where he underwent laparotomy and successful repair of the rupture. He made an uneventful recovery and was discharged nine days later. Duodenal rupture is a rare but serious complication of blunt abdominal trauma. Diagnosis is difficult but missed diagnosis and delayed presentation is associated with high morbidity and mortality. A high index for suspicion must be kept when dealing with blunt abdominal trauma to ensure this is not missed.

Parenteral nutrition line sepsis: the difficulty in diagnosis.

Parenteral nutrition (PN) line sepsis is a common and yet poorly managed complication in hospitalised patients receiving PN. Making a clinical diagnosis is difficult as the clinical picture can be very non-specific and definitions of what constitutes line infection can vary. Once there is clinical suspicion, proving it with microbiological techniques is not an exact science. Traditional techniques have required the removal of the PN line to allow microbiologists to perform analysis of it for infection. This has obvious drawbacks as it is often not easy to replace the line in these patients and the line is often later proven not to be the source of the sepsis. Although the gold-standard technique still requires removal of the line, there has been development in the field of diagnosis line infection while conserving the line. These include intra-luminal brushings of the line, differential blood cultures and simple swabs of the line hub. These techniques are not as sensitive but reduce the problems caused by removing and re-inserting the line in these patients. The definition of PN line sepsis varies between institutions. Rates can be expressed as a true number of cases, or can be expressed correctly as a number of cases per 1000 line days to standardise rates between units of differing sizes. Rates can also be altered if the diagnostic criteria are too strict or too lax. Accurate diagnosis of PN line sepsis remains difficult in modern medical practice.