Human colon cancers often start as benign adenomas through loss of APC, leading to enhanced βCATENIN (βCAT)/TCF function. These early lesions are efficiently managed but often progress to invasive carcinomas and incurable metastases through additional changes, the nature of which is unclear. We find that epithelial cells of human colon carcinomas (CCs) and their stem cells of all stages harbour an active HH-GLI pathway. Unexpectedly, they acquire a high HEDGEHOG-GLI (HH-GLI) signature coincident with the development of metastases. We show that the growth of CC xenografts, their recurrence and metastases require HH-GLI function, which induces a robust epithelial-to-mesenchymal transition (EMT). Moreover, using a novel tumour cell competition assay we show that the self-renewal of CC stem cells in vivo relies on HH-GLI activity. Our results indicate a key and essential role of the HH-GLI1 pathway in promoting CC growth, stem cell self-renewal and metastatic behavior in advanced cancers. Targeting HH-GLI1, directly or indirectly, is thus predicted to decrease tumour bulk and eradicate CC stem cells and metastases.

Three risk factors for anastomotic leak have been identified, one is patient-related (ASA score), one is disease-related (rectal location), the third being surgery-related (prolonged operative time). These factors should be considered in perioperative decision-making regarding defunctioning stoma formation.

Context Experts and policy makers have repeatedly called for universal screening at hospital admission to reduce nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection. Objective To determine the effect of an early MRSA detection strategy on nosocomial MRSA infection rates in surgical patients. Design, Setting, and Patients Prospective, interventional cohort study conducted between July 2004 and May 2006 among 21 754 surgical patients at a Swiss teaching hospital using a crossover design to compare 2 MRSA control strategies (rapid screening on admission plus standard infection control measures vs standard infection control alone). Twelve surgical wards including different surgical specialties were enrolled according to a prespecified agenda, assigned to either the control or intervention group for a 9-month period, then switched over to the other group for a further 9 months. Interventions During the rapid screening intervention periods, patients admitted to the intervention wards for more than 24 hours were screened before or on admission by rapid, multiplex polymerase chain reaction. For both intervention (n=10 844) and control (n=10 910) periods, standard infection control measures were used for patients with MRSA in all wards and consisted of contact isolation of MRSA carriers, use of dedicated material (eg, gown, gloves, mask if indicated), adjustment of perioperative antibiotic prophylaxis of MRSA carriers, computerized MRSA alert system, and topical decolonization (nasal mupirocin ointment and chlorhexidine body washing) for 5 days. Main Outcome Measures Incidence of nosocomial MRSA infection, MRSA surgical site infection, and rates of nosocomial acquisition of MRSA. Results Overall, 10 193 of 10 844 patients (94%) were screened during the intervention periods. Screening identified 515 MRSA-positive patients (5.1%), including 337 previously unknown MRSA carriers. Median time from screening to notification of test results was 22.5 hours (interquartile range, 12.2-28.2 hours). In the intervention periods, 93 patients (1.11 per 1000 patient-days) developed nosocomial MRSA infection compared with 76 in the control periods (0.91 per 1000 patient-days; adjusted incidence rate ratio, 1.20; 95% confidence interval, 0.85-1.69; P=.29). The rate of MRSA surgical site infection and nosocomial MRSA acquisition did not change significantly. Fifty-three of 93 infected patients (57%) in the intervention wards were MRSA-free on admission and developed MRSA infection during hospitalization. Conclusion A universal, rapid MRSA admission screening strategy did not reduce nosocomial MRSA infection in a surgical department with endemic MRSA prevalence but relatively low rates of MRSA infection.

Clinical variables associated with prolonged survival after surgery for LM in CRC patients include prolonged disease-free interval between primary tumor and metastatic spread, normal prethoracotomy carcinoembryonic antigen, absence of thoracic node involvement, and a single pulmonary lesion.