Fish bone perforation mimicking colon cancer: A case report.

Most patients who ingest fish bones do not develop any complications. The small proportion of patients who do complicate, present with non-specific symptoms. A 64-year-old female patient presented with a 2-month history of abdominal pain. Following clinical evaluation and computed tomography scan of the abdomen, a provisional diagnosis of colon cancer was made. Histology of the resected bowel at hemicolectomy demonstrated a perforation by fish bone with an associated abscess. The case illustrates how fish bone perforation may mislead unsuspecting clinicians and may be misdiagnosed as colonic cancer.

HER3 and downstream pathways are involved in colonization of brain metastases from breast cancer.

INTRODUCTION: Metastases to the brain from breast cancer have a high mortality, and basal-like breast cancers have a propensity for brain metastases. However, the mechanisms that allow cells to colonize the brain are unclear. METHODS: We used morphology, immunohistochemistry, gene expression and somatic mutation profiling to analyze 39 matched pairs of primary breast cancers and brain metastases, 22 unmatched brain metastases of breast cancer, 11 non-breast brain metastases and 6 autopsy cases of patients with breast cancer metastases to multiple sites, including the brain. RESULTS: Most brain metastases were triple negative and basal-like. The brain metastases over-expressed one or more members of the HER family and in particular HER3 was significantly over-expressed relative to matched primary tumors. Brain metastases from breast and other primary sites, and metastases to multiple organs in the autopsied cases, also contained somatic mutations in EGFR, HRAS, KRAS, NRAS or PIK3CA. This paralleled the frequent activation of AKT and MAPK pathways. In particular, activation of the MAPK pathway was increased in the brain metastases compared to the primary tumors. CONCLUSIONS: Deregulated HER family receptors, particularly HER3, and their downstream pathways are implicated in colonization of brain metastasis. The need for HER family receptors to dimerize for activation suggests that tumors may be susceptible to combinations of anti-HER family inhibitors, and may even be effective in the absence of HER2 amplification (that is, in triple negative/basal cancers). However, the presence of activating mutations in PIK3CA, HRAS, KRAS and NRAS suggests the necessity for also specifically targeting downstream molecules.

Current and future approach to the pathologist's assessment for targeted therapy in breast cancer.

Breast cancer is a common disease in the population. Contrary to public perception, it is a heterogeneous disease with varying morphology, prognosis and response to therapy. The pathological analysis is at the heart of information provided to surgeons and oncologists to plan further management. The pathologist is increasingly asked to test for biomarkers that provide prognostic and predictive information to direct treatment. Staining cancers for ER, PgR and HER2 has become routine and it is likely that addition of other biomarkers including 'basal markers', VEGF and growth factor receptors such as HER1 (EGFR) will soon follow. Microarray based genomic, transcription and proteomic methods are changing our classification systems and identifying novel targets for the development of new therapeutics. It is important for pathologists to appreciate and embrace the new developments as they will impact on daily clinical practice and require accurate assessment of biomarkers to determine treatment options as part of multidisciplinary teams.

Hemodynamic effects of recombinant human erythropoietin on the central nervous system after subarachnoid hemorrhage: reduction of microcirculatory impairment and functional deficits in a rabbit model.

OBJECT: The authors investigated the hemodynamic effects of recombinant human erythropoietin (rhEPO) after subarachnoid hemorrhage (SAH) in rabbits. METHODS: The authors used male New Zealand White rabbits in this study divided into the following groups: SAH plus saline (16 rabbits), SAH plus low-dose rhEPO (16 rabbits; 1500 IU/kg on Day 0 and 500 IU/kg on Days 2 and 4), SAH plus high-dose rhEPO (10 rabbits; 1500 IU/kg on Days 0, 2, 4, and 6), and sham (6 rabbits). Computed tomography perfusion studies and CT angiography were performed for 1 hour after SAH on Day 0, and once each on Days 2, 4, 7, 9, and 16 after SAH. Assessments of neurological function and tissue histology were also performed. RESULTS: The mortality rate was significantly lower after rhEPO treatment (12%) than after saline treatment (44%) (p < 0.05). Neurological outcomes in the low-dose and high-dose rhEPO groups were better than in the saline group after SAH (p < 0.05), and the cerebral blood flow in the high-dose rhEPO group was greater than that in the saline group (p < 0.05). The mean transit time was significantly lower on Days 2 and 4 in the low-dose and high-dose rhEPO groups than in the saline group, but increased significantly on Day 7 in both groups (p < 0.05). The hematocrit increased significantly from baseline values in the high-dose and low-dose rhEPO groups on Days 4 and 7, respectively (p < 0.05). CONCLUSIONS: Treatment with rhEPO after experimental SAH is associated with improved cerebral blood flow and microcirculatory flow as reflected by lower mean transit times. Improved tissue perfusion correlated with reduced mortality and improved neurological outcomes. Further investigation of the impact of increasing hematocrit on hemodynamic changes is needed.

Measurements of aneurysm morphology determined by 3-d micro-ultrasound imaging as potential quantitative biomarkers in a mouse aneurysm model.

Aneurysms remain a significant medical problem and our current understanding of aneurysm formation and developmental stages remains incomplete. Noninvasive 3-D micro-ultrasound (3-D micro-US) imaging technologies designed for noninvasive evaluation of small laboratory animals diminish risks associated with invasive examination and provide in-situ (live) analysis of vascular morphological changes, which enables quantitative measurements of live biological specimens. We demonstrate here that aneurysm morphology can be quantified using 3-D micro-US, and we validate this methodology through comparison of geometric measures with those obtained from 3-D serial histologic records in a mouse model of accelerated aneurysm formation. Aneurysms were induced in Balb/C mice after C57Bl/6 mouse aortic transplant with injections of a pro-inflammatory viral serpin with a mutated reactive site. Aortic transplant segments were imaged 28 days after transplant using 3-D micro-US. Upon sacrifice, the aortas were excised and histology sections (5-microm thick) were digitized, co-registered using mutual information and stacked to form 3-D images. Surfaces of the mouse aorta and aneurysm were manually segmented from the 3-D micro-US and histology images. Comparisons with 3-D histology images demonstrated that 3-D micro-US allowed in-vivo analysis of aneurysm morphology, including total aneurysm area, plaque growth and lumen size. Linear regression of 3-D US-derived aneurysm and plaque volumes vs. 3-D histology-derived volumes resulted in slopes of 1.30 (R(2) = 0.96) and 1.20 (R(2) = 0.98), respectively, demonstrating that 3-D micro-US measurements can be used to track aneurysm growth in a mouse aortic transplant model.