The yield and cost of colonoscopy in patients with metastatic cancer of unknown primary.

BACKGROUND: Although gastroenterologists are asked to perform colonoscopy in patients with metastatic cancer of unknown primary (MCUP), studies evaluating this practice are lacking. AIM: To determine the yield and cost of colonoscopy in patients referred for colonoscopy with an indication of MCUP. METHODS: We prospectively and retrospectively assessed colonoscopies performed from 2000 to 2011 at a county, a university, and a Veterans Administration medical centre to identify patients referred for colonoscopy for the indication of MCUP. Exclusion criteria included overt or occult bleeding, iron-deficiency anaemia, familial-colon-cancer syndrome, prior colon cancer, imaging suggesting colorectal lesion, and palpable rectal mass. Outcomes were the number of primary colon cancers and costs based on 2012 Medicare reimbursements. RESULTS: Two (1%) of the 160 patients meeting enrollment criteria had a primary colon cancer identified, and both died within 1 month after diagnosis without receiving therapy targeted at colon cancer. One patient without colon cancer had a perforation because of colonoscopy, which required surgery and colostomy. The cost of a strategy of routinely performing colonoscopy in patients referred with MCUP was $84 736 per colon primary identified. CONCLUSIONS: Primary colon cancer was rarely identified at colonoscopy in patients with MCUP and no standard indications for diagnostic colonoscopy. Furthermore, the cost to diagnose one additional colon primary was very high. Those with colon cancer had advanced disease and were unable to benefit from targeted therapy. Routine colonoscopy for MCUP cannot be recommended at present.

Role of endothelin and nitric oxide imbalance in the pathogenesis of hypoxia-induced arterial hypertension.

BACKGROUND: We have recently demonstrated that prolonged hypobaric hypoxia can lead to a hematocrit-independent sustained arterial hypertension (HTN) in genetically normotensive Sprague-Dawley rats. The rise in blood pressure in the hypoxic animals was accompanied by a marked but transient increase in plasma endothelin level. In addition, hypoxia has been shown to decrease nitric oxide (NO) production by cultured endothelial cells. This study was designed to test the hypothesis that hypoxia-induced HTN may be mediated by increased endothelin and/or decreased NO production. METHODS: Blood pressure, plasma endothelin and urinary NO metabolites (NOx)were monitored in rats during a 24-hour exposure to hypobaric hypoxia (air pressure = 390 mm Hg). The results were compared with hypoxia (air pressure = 390 mm Hg). The results were compared with those obtained in animals maintained under normoxic condition (control group). To test the possible role of excess endothelin and depressed NO production, the studies were repeated using subgroups of animals treated with either an endothelin receptor ET-A/B blocker (L-754,142) or L-arginine. RESULTS: The untreated hypoxic group exhibited a threefold rise in plasma endothelin and a threefold fall in urinary NOx, prior to the onset of HTN. Endothelin receptor blockade led to a further fall in urinary NOx excretion and failed to mitigate HTN. In contrast, L-arginine supplementation improved the urinary NOx excretion and prevented HTN. Neither therapy affected the hypoxia-induced erythrocytosis. CONCLUSIONS: We conclude that hypoxia-induced HTN is associated with depressed NO production and can be mitigated by L-arginine supplementation.

Effects of experimental hemosiderosis on intestinal morphology, permeability, and tissue iron content.

Effects of iron overload on intestinal function and structure are unknown and were, therefore, investigated. Sprague-Dawley rats were randomized into an iron-overloaded group, which received a single subcutaneous injection of 1.2 g/kg elemental iron-dextran complex, and placebo-treated pair-fed controls. Animals were studied after a 10-month observation period. Intestinal permeability was assessed by measuring the urinary excretion of lactulose, rhamnose, and mannitol after oral administration. In addition, tissue nonheme iron content was measured, and histologic examination and morphometric measurements were carried out. The chronic iron-overloaded group showed a significant increase in intestine tissue iron content and stainable iron in the submucosa and muscularis propria and adipose tissue of the small intestine and lamina propria and muscularis mucosa of the large intestine. There was a significant decrease in the crypt depths without discernible change in the intestine permeability to any of the markers used. In addition, the iron-overloaded animals showed a significant number of iron-laden cells, which primarily consisted of macrophages, fibroblasts, myocytes, and adipocytes. In contrast, no iron-laden cells were present in tissues obtained from the normal control group. Thus, chronic experimental iron overload in rats leads to significant morphologic, but no permeability, alterations of the alimentary tract.