FDG PET and PET/CT for the detection of the primary tumour in patients with cervical non-squamous cell carcinoma metastasis of an unknown primary.

In patients with a neck metastasis from an unknown primary with non-squamous cell cancer (non-SCC) histology, the primary is often located outside the head and neck area. We retrospectively evaluated 326 patient records and found 14 patients with non-SCC neck lymph node metastasis from an unknown primary undergoing whole body F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) with or without coregistered computed tomography (PET/CT). The PET or PET/CT findings were verified by pathological work-up, additional imaging tests, and clinical follow-up. PET detected pathological FDG uptake suspicious for the primary in eight patients. PET or PET/CT findings were true positive in seven patients, true negative in 4, false positive in 1, and false negative in two patients. In one patient PET/CT revealed a synchronous ovarian carcinoma. The results suggest that whole body imaging with FDG PET and PET/CT can be useful to identify unknown primaries of non-SCC origin. However, the work-up of patients undergoing PET or PET/CT in our study was very heterogeneous and the primary was more likely found in patients without extensive imaging before PET scanning. Further studies should evaluate if the histology of a neck nodal metastasis should influence the choice of the imaging method and the role of PET and PET/CT imaging for the work up of patients with a non-SCC neck lymph node metastasis of an unknown primary.

HIF at the crossroads between ischemia and carcinogenesis.

Tissue hypoxia occurs where there is an imbalance between oxygen supply and consumption in both, solid tumors as a result of exponential cellular proliferation and in atherosclerotic diseases as a result of inefficient blood supply. Hypoxia-inducible factor 1 (HIF-1) is central in normal angiogenesis and cancer angiogenesis. HIF-1 is a transcriptional activator composed of an O(2)- and growth factor-regulated HIF-1alpha subunit and a constitutively expressed HIF-1beta subunit. Upon activation, HIF-1 drives the expression of genes controlling cell survival and governing the formation of new blood vessels. A better understanding of the regulation of HIF-1alpha levels by the receptor tyrosine kinases/phosphatidylinositol 3-kinase signaling pathway and by the HIF prolyl hydoxylases has provided new insights into the development of anticancer and revascularization therapeutics. We will focus on the potential of a new pharmacology for regulating HIF pathways in both, cancer and ischemic cardiac diseases. The consequences of the switch of HIF activation in these two disease states and the signaling pathway overlap that atherosclerosis and cancer angiogenesis share are discussed.

Xenogeneic transplantation of porcine hepatocytes into the CCl4 cirrhotic rat model.

Liver support using extracorporeal devices and hepatocyte transplantation has received renewed interest for the management of acute and chronic liver failure. The aim of this study was to determine whether xenogeneic porcine hepatocytes could integrate into the liver parenchyma of cirrhotic Lewis rats when administered by an intrasplenic route. Cirrhosis was induced by carbon tetrachloride (CCl4) inhalation and confirmed histologically. Freshly isolated porcine hepatocytes were infused directly into the splenic pulp at laparotomy over a 5-15-min interval. Using (111)In-labeled hepatocytes, the degree of localization of porcine hepatocytes to the spleen and liver was found to be greater than 60% in both control and cirrhotic rats. Integration of porcine hepatocytes into the rat liver parenchyma was determined by immunohistochemical staining for porcine albumin in rat liver sections. Further confirmation was provided by in situ hybridization using a porcine-specific probe that binds to a distinct repetitive element (PRE) in porcine DNA. Evidence of integrated porcine hepatocytes was seen for over 50 days in animals under cyclosporine immunosuppression. These data demonstrate the integration of xenogeneic porcine hepatocytes into the liver of the cirrhotic rat and their ability to produce porcine albumin for up to 50 days.

Early indicators of prognosis in upper gastrointestinal hemorrhage.

OBJECTIVE: Endoscopy allows accurate risk stratification of patients presenting with gastrointestinal bleeding; frequently, however, it is not immediately available. Initial management and triage of patients thus depends on nonendoscopic information. We sought to risk stratify patients with upper gastrointestinal bleeding using variables available on initial presentation (ie., before endoscopy). METHODS: A retrospective observational study was performed using data from 335 admissions with an initial diagnosis of upper gastrointestinal hemorrhage. All patients underwent endoscopy and were evaluated for an adverse outcome during their hospitalization. An adverse outcome was defined as death, the need for any operation, recurrent hematemesis, recurrent melena after initial clearing, or a hematocrit falling despite transfusion. RESULTS: Univariate analysis identified 17 distinct variables associated (p < 0.05) with an adverse outcome. A stepwise logistic regression identified five variables as independent predictors (p < 0.05) of an adverse outcome: an initial hematocrit <30%, initial systolic blood pressure < 100 mm Hg, red blood in the nasogastric lavage, history of cirrhosis or ascites on exam, and a history of vomiting red blood. We derived a decision rule based on patients having 0-5 of these independent predictors. This decision rule allowed identification of a large patient population with a <10% chance of an adverse outcome. CONCLUSION: Risk stratification is possible from information available at the time of initial presentation. If confirmed in other populations, these predictors can be used to identify patients who require a less intensive level of care.