What drives centralisation in cancer care?

Background: To improve quality of care, centralisation of cancer services in high-volume centres has been stimulated. Studies linking specialisation and high (surgical) volumes to better outcomes already appeared in the 1990’s. However, actual centralisation was a difficult process in many countries. In this study, factors influencing the centralisation of cancer services in the Netherlands were determined. Material and methods: Centralisation patterns were studied for three types of cancer that are known to benefit from high surgical caseloads: oesophagus-, pancreas- and bladder cancer. The Netherlands Cancer Registry provided data on tumour and treatment characteristics from 2000–2013 for respectively 8037, 4747 and 6362 patients receiving surgery. By plotting timelines of centralisation of cancer surgery, relations with the appearance of (inter)national scientific evidence, actions of medical specialist societies, specific regulation and other important factors on the degree of centralisation were ascertained. Results: For oesophagus and pancreas cancer, a gradual increase in centralisation of surgery is seen from 2005 and 2006 onwards following (inter)national scientific evidence. Centralisation steps for bladder cancer surgery can be seen in 2010 and 2013 anticipating on the publication of norms by the professional society. The most influential stimulus seems to have been regulations on minimum volumes. Conclusion: Scientific evidence on the relationship between volume and outcome lead to the start of centralisation of surgical cancer care in the Netherlands. Once a body of evidence has been established on organisational change that influences professional practice, in addition some form of regulation is needed to ensure widespread implementation

A piece of the human heart: variance of protein phosphorylation in left ventricular samples from end-stage primary cardiomyopathy patients

Cardiomyocyte contraction is regulated by phosphorylation of sarcomeric proteins. Throughout the heart regional and transmural differences may exist in protein phosphorylation. In addition, phosphorylation of sarcomeric proteins is altered in cardiac disease. Heterogeneity in protein phosphorylation may be larger in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) as it may be caused by multiple mutations in genes encoding different sarcomeric proteins. Moreover, HCM is characterized by asymmetric remodelling of the heart. In the present study we assessed if local differences in sarcomeric protein phosphorylation are more evident in primary HCM or DCM than in non-failing donors. Thereto, phosphorylation of the two main target proteins of the beta-adrenergic receptor pathway, troponin I (cTnI) and myosin binding protein C (cMyBP-C) was analysed in different parts in the free left ventricular wall of end–stage failing HCM and DCM patients and donors obtained during transplant surgery. Intra-patient variability in protein phosphorylation within tissue samples of approximately 2 g wet weight was comparable between donor, HCM and DCM samples and could partly be attributed to the precision of the technique. Thus, our data indicate that within the precision of the measurements small, biopsy-sized cardiac tissue samples are representative for the region of the free left ventricular wall from which they were obtained

Contractile Dysfunction Irrespective of the Mutant Protein in Human Hypertrophic Cardiomyopathy With Normal Systolic Function

Background-Hypertrophic cardiomyopathy (HCM), typically characterized by asymmetrical left ventricular hypertrophy, frequently is caused by mutations in sarcomeric proteins. We studied if changes in sarcomeric properties in HCM depend on the underlying protein mutation. Methods and Results-Comparisons were made between cardiac samples from patients carrying a MYBPC3 mutation (MYBPC3(mut); n = 17), mutation negative HCM patients without an identified sarcomere mutation (HCM(mn); n = 11), and nonfailing donors (n = 12). All patients had normal systolic function, but impaired diastolic function. Protein expression of myosin binding protein C (cMyBP-C) was significantly lower in MYBPC3(mut) by 33 +/- 5%, and similar in HCM(mn) compared with donor. cMyBP-C phosphory Conclusions-Changes in sarcomere function reflect the clinical HCM phenotype rather than the specific MYBPC3 mutation. Hypocontractile sarcomeres are a common deficit in human HCM with normal systolic left ventricular function and may contribute to HCM disease progression. (Circ Heart Fail. 2012; 5: 36-46.