Population-based colorectal cancer screening by colonoscopy or CT colonography

In 1968 at request of the World Health Organization (WHO), Wilson and Jungner defined 10 criteria for informed population-based screening.(1) In subsequent years, these criteria have been reevaluated and revised several times. In their most recent version, they can be summarized as follows: screening has to aim at an important health issue, and it has to result in substantial health gain or lead to other healthcare benefits. Besides, the method of screening must be reliable and valid. Finally, participation in screening has to be based on informed choice and must be completely voluntarily. Colorectal cancer can be considered an important healthcare problem. Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer-related mortality.(2) The lifetime risk in the US population is 5%-6% without screening(3), which is similar in the Netherlands.(4) More than 400 000 persons are diagnosed with colorectal cancer each year in Europe.(5) The prognosis of CRC depends on the stage at the time of diagnosis; in the Netherlands, the 5-year-survival rate of stage I CRC is 94% compared to 8% for stage IV.(4) Several studies have shown that colorectal cancer screening is effective in the average risk population.(6-8) Besides, screening for CRC is thought to be cost-effective.(9) Screening can be performed with a range of different methods and strategies. Available methods for colorectal-cancer screening fall into two broad categories; stool tests (guaiac fecal occult blood test (gFOBT), fecal immunochemical test (FIT) and DNA tests) and structural examinations (flexible sigmoidoscopy, colonoscopy, and computed tomographic colonography)

De effectiviteit van horizontaal belastingtoezicht

Abstract Esther A.M. Huiskers-Stoop onderzoekt de effectiviteit van horizontaal belastingtoezicht. Zij omschrijft horizontaal toezicht als een vorm van belastingtoezicht gebaseerd op wederzijds vertrouwen, begrip en transparantie tussen belastingplichtigen en de Belastingdienst, waarbij belastingplichtigen in ruil voor vrijwillige en actuele verstrekking van fiscaal relevante gegevens snel zekerheid krijgen over hun belastingpositie en de Belastingdienst hen niet belast met veel tijd en aandacht vergende boekenonderzoeken en andere controlemaatregelen achteraf. Huiskers-Stoop wil weten of horizontaal toezicht werkt, en vooral of het beter werkt dan traditioneel belastingtoezicht. Traditioneel toezicht kenmerkt zich door een sterke hiërarchische verhouding tussen belastingplichtigen en de Belastingdienst, waarbij de Belastingdienst gebruik kan maken van vergaande publiekrechtelijke bevoegdheden om fiscaal relevante gegevens te verzamelen en, zo nodig, af te dwingen. Huiskers-Stoop heeft niet alleen een raamwerk ontwikkeld van randvoorwaarden waaronder horizontaal toezicht in theorie zou moeten werken en het Nederlandse model daaraan getoetst, maar zij heeft ook door interviews en een enquête onderzocht of horizontaal toezicht in de praktijk van middelgrote ondernemingen een verbetering laat zien ten opzichte van traditioneel belastingtoezicht. Zij concludeert de aannemelijkheid dat horizontaal toezicht in vergelijking tot het traditionele belastingtoezicht, leidt tot een betere fiscale compliance, meer fiscale zekerheid, minder fiscale compliancekosten en een betere relatie met de Belastingdienst. Naarmate ondernemingen groter zijn werkt horizontaal toezicht nog beter. De vraag of horizontaal toezicht werkt is volgens Huiskers-Stoop onlosmakelijk verbonden met de vraag hoe het werkt. Daarom behandelt zij tevens de inbedding van horizontaal toezicht in het fiscaal wettelijke systeem en het fiscale uitvoeringsproces. Zij gaat nader in op de fiscale samenwerking op basis van een convenant, de juridische kwalificatie van het convenant, de toetsing van het beleid aan het gelijkheidsbeginsel, de (ontbrekende) noodzaak tot codificatie, de totstandkoming en toetsing van convenantaangiften, gebruik van onder het convenant verkregen informatie, de invordering van convenantaanslagen, het herstel van fouten evenals het opleggen van fiscale boetes. Ook kijkt zij over de grens om te zien wat internationale ervaringen met horizontale vormen van belastingtoezicht kunnen leren over de werking ervan

Face-to-face vs telephone pre-colonoscopy consultation in colorectal cancer screening; A randomised trial

Background: A pre-colonoscopy consultation in colorectal cancer (CRC) screening is necessary to assess a screenees general health status and to explain benefits and risks of screening. The first option allows for personal attention, whereas a telephone consultation does not require travelling. We hypothesised that a telephone consultation would lead to higher response and participation in CRC screening compared with a face-to-face consultation. Methods:A total of 6600 persons (50-75 years) were 1: 1 randomised for primary colonoscopy screening with a pre-colonoscopy consultation either face-to-face or by telephone. In both arms, we counted the number of invitees who attended a pre-colonoscopy consultation (response) and the number of those who subsequently attended colonoscopy (participation), relative to the number invited for screening. A questionnaire regarding satisfaction with the consultation and expected burden of the colonoscopy (scored on five-point rating scales) was sent to invitees. Besides, a questionnaire to assess the perceived burden of colonoscopy was sent to participants, 14 days after the procedure.Results:In all, 3302 invitees were allocated to the telephone group and 3298 to the face-to-face group, of which 794 (24%) attended a telephone consultation and 822 (25%) a face-to-face consultation (P=0.41). Subsequently, 674 (20%) participants in the telephone group and 752 (23%) in the face-to-face group attended colonoscopy (P=0.018). Invitees and responders in the telephone group expected the bowel preparation to be more painful than those in the face-to-face group while perceived burden scores for the full screening procedure were comparable. More subjects in the face-to-face group than in the telephone group were satisfied by the consultation in general: (99.8% vs 98.5%, P=0.014).Conclusion:Using a telephone rather than a face-to-face consultation in a population-based CRC colonoscopy screening progr

Study protocol: Population screening for colorectal cancer by colonoscopy or CT colonography: A randomized controlled trial

Background: Colorectal cancer (CRC) is the second most prevalent type of cancer in Europe. Early detection and removal of CRC or its precursor lesions by population screening can reduce mortality. Colonoscopy and computed tomography colonography (CT colonography) are highly accurate exams and screening options that examine the entire colon. The success of screening depends on the participation rate. We designed a randomized trial to compare the uptake, yield and costs of direct colonoscopy population screening, using either a telephone consultation or a consultation at the outpatient clinic, versus CT colonography first, with colonoscopy in CT colonography positives.Methods and design: 7,500 persons between 50 and 75 years will be randomly selected from the electronic database of the municipal administration registration and will receive an invitation to participate in either CT colonography (2,500 persons) or colonoscopy (5,000 persons) screening. Those invited for colonoscopy screening will be randomized to a prior consultation either by telephone or a visit at the outpatient clinic. All CT colonography invitees will have a prior consultation by telephone. Invitees are instructed to consult their general practitioner and not to participate in screening if they have symptoms suggestive for CRC. After provid

Multitarget Stool DNA Test Performance in an Average-Risk Colorectal Cancer Screening Population

INTRODUCTION: We set out to evaluate the performance of a multitarget stool DNA (MT-sDNA) in an average-risk colonoscopy-controlled colorectal cancer (CRC) screening population. MT-sDNA stool test results were evaluated against fecal immunochemical test (FIT) results for the detection of different lesions, including molecularly defined high-risk adenomas and several other tumor characteristics. METHODS: Whole stool samples (n = 1,047) were prospectively collected and subjected to an MT-sDNA test, which tests for KRAS mutations, NDRG4 and BMP3 promoter methylation, and hemoglobin. Results for detecting CRC (n = 7), advanced precancerous lesions (advanced adenoma [AA] and advanced serrated polyps; n = 119), and non-AAs (n = 191) were compared with those of FIT alone (thresholds of 50, 75, and 100 hemoglobin/mL). AAs with high risk of progression were defined by the presence of specific DNA copy number events as measured by low-pass whole genome sequencing. RESULTS: The MT-sDNA test was more sensitive than FIT alone in detecting advanced precancerous lesions (46% (55/119) vs 27% (32/119), respectively, P < 0.001). Specificities among individuals with nonadvanced or negative findings (controls) were 89% (791/888) and 93% (828/888) for MT-sDNA and FIT testing, respectively. A positive MT-sDNA test was associated with multiple lesions (P = 0.005), larger lesions (P = 0.03), and lesions with tubulovillous architecture (P = 0.04). The sensitivity of the MT-sDNA test or FIT in detecting individuals with high-risk AAs (n = 19) from individuals with low-risk AAs (n = 52) was not significantly different. DISCUSSION: In an average-risk screening population, the MT-sDNA test has an increased sensitivity for detecting advanced precancerous lesions compared with FIT alone. AAs with a high risk of progression were not detected with significantly higher sensitivity by MT-sDNA or FIT

Mycobacterium marinum MMAR_2380, a predicted transmembrane acyltransferase, is essential for the presence of the mannose cap on lipoarabinomannan

Lipoarabinomannan (LAM) is a major glycolipid in the mycobacterial cell envelope. LAM consists of a mannosylphosphatidylinositol (MPI) anchor, a mannan core and a branched arabinan domain. The termini of the arabinan branches can become substituted with one to three α(1→2)-linked mannosyl residues, the mannose cap, producing ManLAM. ManLAM has been associated with a range of different immunomodulatory properties of Mycobacterium tuberculosis during infection of the host. In some of these effects, the presence of the mannose cap on ManLAM appears to be crucial for its activity. So far, in the biosynthesis of the mannose cap on ManLAM, two enzymes have been reported to be involved: a mannosyltransferase that adds the first mannosyl residue of the mannose caps to the arabinan domain of LAM, and another mannosyltransferase that elongates the mannose cap up to three mannosyl residues. Here, we report that a third gene is involved, MMAR_2380, which is the Mycobacterium marinum orthologue of Rv1565c. MMAR_2380 encodes a predicted transmembrane acyltransferase. In M. marinum ΔMMAR_2380, the LAM arabinan domain is still intact, but the mutant LAM lacks the mannose cap. Additional effects of mutation of MMAR_2380 on LAM were observed: a higher degree of branching of both the arabinan domain and the mannan core, and a decreased incorporation of [1,2-14C]acetate into the acyl chains in mutant LAM as compared with the wild-type form. This latter effect was also observed for related lipoglycans, i.e. lipomannan (LM) and phosphatidylinositol mannosides (PIMs). Furthermore, the mutant strain showed increased aggregation in liquid cultures as compared with the wild-type strain. All phenotypic traits of M. marinum ΔMMAR_2380, the deficiency in the mannose cap on LAM and changes at the cell surface, could be reversed by complementing the mutant strain with MMAR_2380. Strikingly, membrane preparations of the mutant strain still showed enzymic activity for the arabinan mannose-capping mannosyltransferase similar to that of the wild-type strain. Although the exact function of MMAR_2380 remains unknown, we show that the protein is essential for the presence of a mannose cap on LAM

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin