Routes to diagnosis for sarcoma - Describing the sarcoma patient journey.

BACKGROUND: Understanding the route to diagnosis for patients with cancer is important to improve the diagnostic pathway and therefore outcomes. We aimed to investigate routes to diagnosis for patients with sarcoma in England. METHODS: National patient level datasets relating to 7716 soft tissue and 1240 bone sarcoma patients diagnosed between 2006 and 2008 were analysed. Routes to diagnosis were defined as: "Two Week Wait Referral", "GP Referral", "Other Outpatient", "Inpatient Elective", "Emergency Presentation", "Death Certificate Only" and "Unknown". RESULTS: Patients with sarcoma are most likely to be diagnosed after "GP Referral" or "Emergency Presentation" and are less likely to be referred under a two week wait compared with other malignancies. Patients with bone sarcoma under 10 or over 80 years of age were more likely to present by emergency routes, as were patients with vertebral column, pelvis or unspecified site tumours and those with Ewing's sarcoma or sarcoma NOS. Patients with soft tissue sarcoma under 19 or over 80 years of age and patients with GI tract tumours were more likely to present by emergency routes. Patients presenting by emergency routes more often had metastases and had lower 1 year survival. Patients from least deprived quintiles more often presented by unknown routes: those from more deprived quintiles more often presented by emergency routes. CONCLUSION: Routes to diagnosis for sarcoma patients differ from other cancers. Interventions to improve the diagnostic experience should consider the very young and elderly, tumours in abdominal, pelvic or spinal locations and on reducing emergency presentations.

Subunit interactions change the heme active-site geometry in p-cresol methylhydroxylase.

The enzyme p-cresol methylhydroxylase [4-cresol: (acceptor) oxidoreductase (methyl-hydroxylating), EC 1.17.99.1] contains two subunits: a cytochrome c (electron transfer) subunit (cytochrome cpc) and a flavin (catalytic) subunit. When these subunits are separated by isoelectric focusing, a stable cytochrome subunit is obtained. Significant differences are observed between the one-dimensional NMR spectra of oxidized cytochrome cpc and of oxidized p-cresol methylhydroxylase. Analysis of the two-dimensional nuclear Overhauser enhancement and exchange spectroscopy (NOESY) spectrum of reduced cytochrome cpc suggests that the axial ligand, Met-50, of the stable subunit reorients by a rotation about the C gamma-S delta bond when cytochrome cpc binds to the flavin subunit. This reorientation must result in a change in bonding at the heme, which is reflected both in the para-magnetically shifted resonances and in the redox potential. p-Cresol methylhydroxylase thereby provides an interesting example of the coupling of subunit interactions to active-site structure and reactivity.

Bronchorrhoea.

Bronchorrohea has been defined as a condition in which more than 100 ml of sputum is produced within 24 hours, an amount in excess of that seen in chronic lung diseases. The rheological and chemical characteristics of the sputum are here described. Levels of viscosity, dry weight, N-acetyl neuraminic acid (NANA), fucose, and sulphate fall between those in saliva and mucoid sputum from chronic lung diseases. These levels were always higher in bronchorrhoea sputum than in saliva and therefore may be used in the differential diagnosis of bronchorrhoea and hypersalivation. Bronchorrhoea sputum has the constituents of a bronchial secretion but is low in acid glycoprotein. Certain other features are commonly found - a large amount of froth, increase in viscosity with time, and separation into two phases. Some cases respond to steroids, particularly when the levels of NANA in the sputum are low.

Bronchorrhoea in a case of alveolar cell carcinoma.

In a case of bronchorrhoea associated with alveolar cell carcinoma thf rheological and chemical features of the sputum indicated that it was bronchial fluid and not saliva and part bronchial secretion, partly serum transudate. The viscosity and chemical constituents were similar to those found in bronchorrhoea when associated with chronic bronchitis, asthma, or bronchiectasis. The surfactant studies suggested an alveolar origin for most of thf fluid, while the failure of fluid restriction, corticosteroids, atropine, or cytotoxic drugs to influence the sputum volume and properties indicated that the cells responsible are "autonomous".