Anticipating implementation of colorectal cancer screening in The Netherlands: a nation wide survey on endoscopic supply and demand

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) screening requires sufficient endoscopic resources. The present study aims to determine the Dutch endoscopic production and manpower for 2009, evaluate trends since 2004, determine additional workload which would be caused by implementation of a CRC screening program, and inventory colonoscopy rates performed in other European countries.</p> <p>Methods</p> <p>All Dutch endoscopy units (N = 101) were surveyed for manpower and the numbers of endoscopy procedures performed in 2009. Based on calculations in the report issued by the Dutch Health Council, future additional workload caused by faecal immunochemical test (FIT) screening was estimated. The number of colonoscopies performed in Europe was evaluated by a literature search and an email-inquiry.</p> <p>Results</p> <p>Compared to 2004, there was a 24% increase in total endoscopies (N = 505,226 in 2009), and a 64% increase in colonoscopies (N = 191,339 in 2009) in The Netherlands. The number of endoscopists had increased by 4.6% (N = 583 in 2009). Five years after stepwise implementation of FIT-based CRC screening, endoscopic capacity needs to be increased an additional 15%. A lack of published data on the number of endoscopies performed in Europe was found. Based on our email-inquiry, the number of colonoscopies per 100,000 inhabitants ranged from 126 to 3,031 in 15 European countries.</p> <p>Conclusions</p> <p>Over the last years, endoscopic procedures increased markedly in The Netherlands without a corresponding increase in manpower. A FIT-based CRC screening program requires an estimated additional 15% increase in endoscopic procedures. It is very likely that current colonoscopy density varies widely across European countries.</p

Does delay in diagnosing colorectal cancer in symptomatic patients affect tumor stage and survival? A population-based observational study

<p>Abstract</p> <p>Background</p> <p>Diagnosing colorectal cancer (CRC) at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear.</p> <p>Our objectives were to evaluate the association between diagnostic delay and survival in symptomatic patients with early stage CRC and late stage CRC.</p> <p>Methods</p> <p>Prospective population-based observational study evaluating daily clinical practice in Northern Holland. Diagnostic delay was determined through questionnaire-interviews. Dukes' stage was classified into two groups: early stage (Dukes A or B) and late stage (Dukes C or D) cancer. Patients were followed up for 3.5 years after diagnosis.</p> <p>Results</p> <p>In total, 272 patients were available for analysis. Early stage CRC was present in 136 patients while 136 patients had late stage CRC. The mean total diagnostic delay (SE) was 31 (1.5) weeks in all CRC patients. No significant difference was observed in the mean total diagnostic delay in early versus late stage CRC (<it>p </it>= 0.27).</p> <p>In early stage CRC, no difference in survival was observed between patients with total diagnostic delay shorter and longer than the median (Kaplan-Meier, log-rank <it>p </it>= 0.93).</p> <p>In late stage CRC, patients with a diagnostic delay shorter than the median had a shorter survival than patients with a diagnostic delay longer than the median (log-rank <it>p </it>= 0.01). In the multivariate Cox regression model with survival as dependent variable and median delay, age, open access endoscopy, number and type of symptoms as independent variables, the odd's ratio for survival in patients with long delay (>median) versus short delay (≤median) was 1.8 (95% confidence interval (CI) 1.1 to 3.0; <it>p </it>= 0.01). Tumor-site was not associated with patient survival. When separating late stage CRC in Dukes C and Dukes D tumors, a shorter delay was associated with a shorter survival in Dukes D tumors only and not in Dukes C tumors.</p> <p>Conclusion</p> <p>In symptomatic CRC patients, a longer diagnostic and therapeutic delay in routine clinical practice was not associated with an adverse effect on survival. The time to CRC diagnosis and initiation of treatment did not differ between early stage and late stage colorectal cancer.</p

Double sampling of a faecal immunochemical test is not superior to single sampling for detection of colorectal neoplasia: a colonoscopy controlled prospective cohort study

<p>Abstract</p> <p>Background</p> <p>A single sampled faecal immunochemical test (FIT) has moderate sensitivity for colorectal cancer and advanced adenomas. Repeated FIT sampling could improve test sensitivity. The aim of the present study is to determine whether any of three different strategies of double FIT sampling has a better combination of sensitivity and specificity than single FIT sampling.</p> <p>Methods</p> <p>Test performance of single FIT sampling in subjects scheduled for colonoscopy was compared to double FIT sampling intra-individually. Test positivity of double FIT sampling was evaluated in three different ways: 1) "one of two FITs+" when at least one out of two measurements exceeded the cut-off value, 2) "two of two FITs+" when both measurements exceeded the cut-off value, 3) "mean of two FITs+" when the geometric mean of two FITs exceeded the cut-off value. Receiver operator curves were calculated and sensitivity of single and the three strategies of double FIT sampling were compared at a fixed level of specificity.</p> <p>Results</p> <p>In 124 of 1096 subjects, screen relevant neoplasia (SRN) were found (i.e. early stage CRC or advanced adenomas). At any cut-off, "two of two FITs+" resulted in the lowest and "one of two FITs+" in the highest sensitivity for SRN (range 35-44% and 42%-54% respectively). ROC's of double FIT sampling were similar to single FIT sampling. At specificities of 85/90/95%, sensitivity of any double FIT sampling strategy did not differ significantly from single FIT (p-values 0.07-1).</p> <p>Conclusion</p> <p>At any cut off, "one of two FITs+" is the most sensitive double FIT sampling strategy. However, at a given specificity level, sensitivity of any double FIT sampling strategy for SRN is comparable to single FIT sampling at a different cut-off value. None of the double FIT strategies has a superior combination of sensitivity and specificity over single FIT.</p

Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.

Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.JS, DES and ARB thank the Wellcome Trust for funding.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nrd.2016.2

Digestive oncologist in the gastroenterology training curriculum

Until the late 1980s, gastroenterology (GE) was considered a subspecialty of Internal Medicine. Today, GE also incorporates Hepatology. However, Digestive Oncology training is poorly defined in the Hepatogastroenterology (HGE)-curriculum. Therefore, a Digestive Oncology curriculum should be developed and this document might be a starting point for such a curriculum. HGE-specialists are increasingly resisting the paradigm in which they play only a diagnostic and technical role in the management of digestive tumors. We suggest minimum end-points in the standard HGE-curriculum for oncology, and recommend a focus year in the Netherlands for Digestive Oncology in the HGE-curriculum. To produce well-trained digestive oncologists, an advanced Digestive Oncology training program with specific qualifications in Digestive Oncology (2 years) has been developed. The schedule in Belgium includes a period of at least 6 mo to be spent in a medical oncology department. The goal of these programs remains the production of well-trained digestive oncologists. HGE specialists are part of the multidisciplinary oncological teams, and some have been administering chemotherapy in their countries for years. In this article, we provide a road map for the organization of a proper training in Digestive Oncology. We hope that the World Gastroenterology Organisation and other (inter)national societies will support the necessary certifications for this specific training in the HGE-curriculum