Citations

The critical decisions regarding thoracotomy for trauma occur soon after the injury, when decisions have to be made that may influence survival or have an impact on morbidity if operation is delayed. Roadside thoracotomy is impractical, and should not be considered; instead, patients should be taken rapidly to the nearest hospital. Endotracheal intubation prior to transport appears to be beneficial, but the application of MAST trousers and the infusion of large volumes of fluid for hypovolaemia before control of haemorrhage offers no advantage and may be hazardous. On the whole, resuscitative thoracotomy is associated with a low salvage rate, especially for the patient sustaining blunt trauma, but may be worthwhile in the patient with penetrating trauma. Urgent, as opposed to immediate thoracotomy, should be undertaken once the patient has been stabilized. This may occur in most patients with penetrating injuries of the heart who survive to reach hospital, those with continuing, significant haemorrhage through chest drains, and those with tracheal, oesophageal and diaphragmatic injuries. Extensive open chest wounds require considerable ingenuity in closure, often with plastic surgical help. Patients with blunt traumatic rupture of the aorta often have multiple injuries, which may also be life threatening. If bleeding into the abdomen is demonstrated, then laparotomy should precede thoracotomy: musculoskeletal injuries and neurological injuries can usually be dealt with after the aortic rupture has been repaired.

Abstract Paget's disease is a chronic nonmetabolic bone disorder that is characterized by increased bone resorption, bone formation, and remodeling. This unbalanced process may lead to osseous deformities, structural weakness, and altered joint biomechanics, all of which can make surgical reconstruction difficult. Although few patients with Paget's disease ever need surgical treatment, successful surgical management of orthopedic manifestations of the disease has improved the quality of life for these patients. Surgical options include corrective osteotomy for long bone deformity, fracture fixation, joint arthroplasty, spinal decompression, and tumor resection. Patients are at increased risk for surgical complications such as blood loss and heterotopic bone formation. Issues relating to the surgical management of patients with Paget's disease such as appropriate preoperative diagnosis, technical challenges of surgery, and strategies to improve the long-term outcome of surgical intervention are discussed.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Cardinal pathologic features of AD are amyloid plaques and neurofibrillary tangles, and most in the field believe that the initiating events ultimately leading to clinical AD center on disordered metabolism of amyloid beta protein. Mouse models of AD have been created by inserting one or more human mutations associated with disordered amyloid metabolism and that cause early onset familial AD into the mouse genome. Human-like amyloid plaque formation increases dramatically with age in these transgenic mice. Amyloid reduction in humans is a major therapeutic objective, and AD transgenic mice allow controlled study of this biology. Recent work has shown that amyloid plaques as small as 35 μm can be detected using in vivo magnetic resonance microimaging (MRMI) at high magnetic field (9.4 T). In addition, age-dependent changes in metabolite concentration analogous to those that have been identified in human AD patients can be detected in these transgenic mice using single-voxel 1 H magnetic resonance spectroscopy ( 1 H MRS) at high magnetic field. These MR-based techniques provide a new set of tools to the scientific community engaged in studying the biology of AD in transgenic models of the disease. For example, an obvious application is evaluating therapeutic modification of disease progression. Toward the end of this review, the authors include results from a pilot study demonstrating feasibility of using MRMI to detect therapeutic modification of plaque progression in AD transgenic mice.

Controversy exists regarding the pathogenic or predictive role of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with multiple sclerosis (MS). Four immunopathological patterns (IP) have been recognized in early active MS lesions, suggesting heterogeneous pathogenic mechanisms. Whether MOG antibodies contribute to this pathological heterogeneity and potentially serve as biomarkers to identify specific pathological patterns is unknown. Here we report the frequencies of antibodies to human recombinant MOG (identified by Western blot and enzymelinked immunoabsorbent assay (ELISA)) in patients with pathologically proven demyelinating disease, and investigate whether antibody status is associated with clinical course, HLA-DR2 genotype, IP or treatment response to plasmapheresis. The biopsy cohort consisted of 72 patients: 12 pattern I, 43 pattern II and 17 pattern III. No association was found between MOG antibody status and conversion to clinically definite MS, DR-2 status, IP or response to plasmapheresis. There was poor agreement between Western blot and ELISA (kappa=0.07 for MOG IgM). Fluctuations in antibody seropositivity were seen for 3/4 patients tested serially by Western blot. This study does not support a pathologic pattern-specific role for MOG-antibodies. Variable MOG-antibody status on serial measurements, coupled with the lack of Western blot and ELISA correlations, raises concern regarding the use of MOG-antibody as an MS biomarker and underscores the need for methodological consensus.

Purpose The role of high-degree microsatellite instability (MSI-H) as a marker to predict benefit from adjuvant chemotherapy remains unclear. Patients and Methods To help define its impact, we conducted an analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) patients who were randomly assigned to a surgery-alone group (untreated cohort) and patients assigned to an adjuvant fluorouracil (FU) -treated group (treated cohort). MSI-H and other potential markers were assessed (TGF-BRII, p53, thymidylate synthase, and Ki67). Results In all, 98 (18.1%) of 542 patients exhibited MSI-H, and there was a strong inverse relationship between MSI-H and mutant p53 status (P < .001). The prognostic analyses showed increased recurrence-free survival (RFS) for MSI-H patients versus MSS/MSI-L patients (P = .10), but showed no difference in overall survival (OS; P = .67). There was a potential interaction between MSI-H and mutant p53 in terms of improved RFS (P = .03). In the predictive marker analysis, we observed no interaction between MSI status and treatment for either RFS (P = .68) or OS (P = .62). Hazard ratios (HR) for RFS for MSI-H versus MSS/MSI-L patients were 0.77 (95% CI, 0.40 to 1.48) in the untreated-patients group and 0.60 (95% CI, 0.30 to 1.19) in the treated-patients group. HRs for OS were 0.82 (95% CI, 0.44 to 1.51) and 1.02 (95% CI, 0.56 to 1.85) for the respective groups. There was a trend toward improved RFS in patients with MSI-H and mutant p53. Conclusion These results do not support the use of MSI-H as a predictive marker of chemotherapy benefit.

Learning ObjectivesAfter completing this course, the reader should be able to: Discuss recent progress in the treatment of patients with advanced colorectal cancer.Define the continuum-of-care approach and how it may differ from our current approach to the treatment of patients with advanced colorectal cancer.Identify key factors in treatment selection for patients with advanced colorectal cancer.Explain the impact of each active drug in the treatment of advanced colorectal cancer and the impact of treatment with multiple agents over the course of the disease.CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com