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Colorectal cancer screening guidelines are identical for men and women despite reported differences in epidemiology, endoscopy performance, screening preferences, and screening uptake. High-quality research is needed to determine whether gender aspects may in real world increase acceptance and overcome screening barriers, which may lead to better use of limited resources allocated for public health.

Randomized Comparison of Three Palliative Regimens Including Brachytherapy, Photodynamic Therapy, and APC in Patients With Malignant Dysphagia (CONSORT 1a) (Revised II)

Currently colorectal cancer (CRC) screening guidelines are based on age and to some extent on family history of screenees only. Potentially CRC screening could be also customised according to gender, race, ethnicity, smoking habits, presence of obesity, diabetes and metabolic syndrome. The factors that could be individually modified are: choice of screening test, age of initiation of screening and screening intervals. Gender is probably the easiest factor to be included. One of the professional societies has already included the race into guidelines in order to lower the age of starting screening in African-Americans. Targeting persons at higher than average-risk aims at optimising the use of available resources. However, an important drawback of such approach exists; it is the risk of making guidelines too complex and incomprehensible for both eligible screenees and physicians.

In light of the huge population at risk for colorectal cancer (CRC) and limited screening resources, shifting the use of screening tests from low-risk to high-risk groups is a valid option. This study reviews the gender of potential screenees as a factor influencing CRC screening yield and overall results. The higher risk of advanced neoplasia, better endoscopy performance, and greater endoscopy screening uptake in men should be taken into consideration when planning an optimized CRC screening program.

Sedation for endoscopy provides comfort for the patient and better examination conditions for the endoscopist. The high costs of providing anaesthesia by specialists and the relative lack of specialist personnel in many countries have led to the wider introduction of sedation delivered by non-anaesthesiologists. Such sedation should be targeted for moderate levels of sedation; however, personnel should be able to avoid - and rescue patients from - deeper sedation levels. Several conditions have to be fulfilled to provide proper and safe non-anaesthesiologist sedation for endoscopy, especially when propofol is to be used. These conditions include formal training, supervision by anaesthesiology staff, and definition of standard operating procedures on the national as well as local levels.

Gastroesophageal reflux disease is regarded as a spectrum of diseases: non-erosive reflux disease (NERD), erosive reflux disease (ERD), and the far end of the spectrum represented by patients with Barrett's esophagus. Among predisposing factors, both risk and protective polymorphic variants of several genes may influence the clinical outcomes of reflux disease. Consequently, different molecular mechanisms are likely to underlie the development of clinical variants of reflux disease. Ninety six patients with reflux disease were screened for polymorphisms of CARD15, SLC22A4 (OCTN1), SLC22A5 (OCTN2), DLG5, ATG16L1 and IL23R genes which had previously been found to associate with immune-mediated chronic inflammatory disorders. While none of the polymorphisms were associated with NERD or ERD, the 1142G/A variant of the IL23R gene was found to be a risk variant in Barrett's esophagus patients. The IL23/IL23R pathway may modulate STAT3 transcriptional activity which is an essential regulator not only of immune-mediated inflammation, but also of inflammatory-associated apoptosis resistance. Although the mechanisms of metaplastic transition of inflamed squamous epithelium are undetermined as yet, our findings suggest potential involvement of alternations in the IL23/IL23R pathway as a molecular background of Barrett's esophagus development.

This article summarizes the most important recent articles on colonoscopy as a screening tool for colorectal cancer, presenting screening outcomes and quality issues. We also refer to the first published results of CT colonography screening in the United States and cost-effectiveness analyses of this method. Also discussed are recent progress in fecal DNA testing and studies of the impact of screening on mortality and lifestyle.

Barrett's esophagus represents a well-defined precursor lesion of esophageal adenocarcinoma, although only a subset of patients with these lesions advances to invasive cancer. Currently, reliable markers predicting neoplastic progression in Barrett's esophagus are lacking. The only clinically useful risk factor is the presence of dysplasia in Barrett's epithelium, but its use as a prognostic marker of disease progression has several significant limitations. Thus, identification of biomarkers of potential prognostic value in dysplasia development in Barrett's esophagus is highly important. The aim of the study was to determine if expression levels of selected genes support histologic diagnosis of dysplastic changes in Barrett's esophagus. Upon rigorous sampling and independent histopathologic examination of endoscopic specimens by two experienced gastrointestinal pathologists, 56 patients with Barrett's esophagus (16 negative for dysplasia, 15 with indefinite, 21 with low-grade, and 4 with high-grade dysplasia) were selected for molecular analysis. The relative mRNA levels of ten selected genes were estimated by quantitative real-time polymerase chain reaction (PCR) analysis. Although expression of nine genes showed trends toward down- or upregulation during progression from Barrett's esophagus without dysplasia to Barrett's esophagus with high-grade dysplasia, only a decrease in S100A2 mRNA levels was statistically significant (P

Barrett's esophagus is characterized by the replacement of squamous epithelium with specialized intestinal metaplastic mucosa. The exact mechanisms of initiation and development of Barrett's metaplasia remain unknown, but a hypothesis of "successful adaptation" against noxious reflux components has been proposed. To search for the repertoire of adaptation mechanisms of Barrett's metaplasia, we employed high-throughput functional genomic and proteomic methods that defined the molecular background of metaplastic mucosa resistance to reflux. Transcriptional profiling was established for 23 pairs of esophageal squamous epithelium and Barrett's metaplasia tissue samples using Affymetrix U133A 2.0 GeneChips and validated by quantitative real-time polymerase chain reaction. Differences in protein composition were assessed by electrophoretic and mass-spectrometry-based methods. Among 2,822 genes differentially expressed between Barrett's metaplasia and squamous epithelium, we observed significantly overexpressed metaplastic mucosa genes that encode cytokines and growth factors, constituents of extracellular matrix, basement membrane and tight junctions, and proteins involved in prostaglandin and phosphoinositol metabolism, nitric oxide production, and bioenergetics. Their expression likely reflects defense and repair responses of metaplastic mucosa, whereas overexpression of genes encoding heat shock proteins and several protein kinases in squamous epithelium may reflect lower resistance of normal esophageal epithelium than Barrett's metaplasia to reflux components. Despite the methodological and interpretative difficulties in data analyses discussed in this paper, our studies confirm that Barrett's metaplasia may be regarded as a specific microevolution allowing for accumulation of mucosal morphological and physiological changes that better protect against reflux injury.

Background and study aims: Colonoscopy screening for colorectal cancer has been implemented without evidence from randomized controlled trials quantifying its benefit and invariably as an opportunistic program, both of which are contrary to the European Union guideline recommendations. The aim of this paper is to describe the rationale and design of the first population-based colonoscopy screening program (PCSP), which was launched in Poland in 2012 as a randomized health services (RHS) study. Methods: The PCSP is a natural extension of opportunistic colonoscopy screening implemented in 2000. It uses colonoscopy capacity, a quality assurance program, and a network of 92 centers built up during the opportunistic screening phase to develop a countrywide PCSP. Within the PCSP, single screening colonoscopy is offered to a target population aged 55 – 64 years. The PCSP uses an RHS design, which means that eligible individuals drawn from population registries are randomly assigned to immediate or postponed invitation to screening. Individuals from birth cohorts that will reach the upper age limit for screening before full implementation of the PCSP are randomly assigned, in a 1:1:1 ratio, to “immediate” screening, “postponed” screening, or a “never invited” control group. The RHS design is a natural platform that will evaluate the effectiveness of screening, and compare different age ranges for screening, invitation procedures, and quality improvement interventions. Up to 2015, 24 centers have been developed, with 34.2 % geographic coverage and 851 535 individuals enrolled. Conclusions: The PCSP sets an example for implementation of population-based colonoscopy screening with experimental design to ensure proper evaluation of its effectiveness. RHS registration number: 007_2015_1_RHS.

In order to update the previous version of the European Code against Cancer and formulate evidence-based recommendations, a systematic search of the literature was performed according to the methodology agreed by the Code Working Groups. Based on the review, the 4th edition of the European Code against Cancer recommends: "Take part in organized cancer screening programmes for: Bowel cancer (men and women) Breast cancer (women) Cervical cancer (women)." Organized screening programs are preferable because they provide better conditions to ensure that the Guidelines for Quality Assurance in Screening are followed in order to achieve the greatest benefit with the least harm. Screening is recommended only for those cancers where a demonstrated life-saving effect substantially outweighs the potential harm of examining very large numbers of people who may otherwise never have, or suffer from, these cancers, and when an adequate quality of the screening is achieved. EU citizens are recommended to participate in cancer screening each time an invitation from the national or regional screening program is received and after having read the information materials provided and carefully considered the potential benefits and harms of screening. Screening programs in the European Union vary with respect to the age groups invited and to the interval between invitations, depending on each country's cancer burden, local resources, and the type of screening test used For colorectal cancer, most programs in the EU invite men and women starting at the age of 50-60 years, and from then on every 2 years if the screening test is the guaiac-based fecal occult blood test or fecal immunochemical test, or every 10 years or more if the screening test is flexible sigmoidoscopy or total colonoscopy. Most programs continue sending invitations to screening up to the age of 70-75 years. For breast cancer, most programs in the EU invite women starting at the age of 50 years, and not before the age of 40 years, and from then on every 2 years until the age of 70-75 years. For cervical cancer, if cytology (Pap) testing is used for screening, most programs in the EU invite women starting at the age of 25-30 years and from then on every 3 or 5 years. If human papillomavirus testing is used for screening, most women are invited starting at the age of 35 years (usually not before age 30 years) and from then on every 5 years or more. Irrespective of the test used, women continue participating in screening until the age of 60 or 65 years, and continue beyond this age unless the most recent test results are normal. (C) 2015 International Agency for Research on Cancer; Licensee ELSEVIER Ltd

The diagnosis of celiac disease (CD) in patients with different autoimmune diseases including Graves disease (GD) remains a challenge. The aims of our study were to: (1) assess the prevalence of CD in Polish patients with GD and (2) evaluate the prevalence of CD in the subgroups of patients with GD divided on the basis of clinical and human leukocyte antigen (HLA) typing criteria.The prospective study was conducted at an academic referral center. The study groups consisted of consecutive, euthyroid patients with GD (n = 232) and healthy volunteers without autoimmune thyroid diseases (n = 122). The diagnosis of CD was based on elevated immunoglobulin A autoantibodies to the enzyme tissue transglutaminase (IgA-TTG) and small intestine biopsy findings.CD was diagnosed in 8 patients with GD (3.4%) and 1 healthy volunteer (0.8%). The development of CD in patients with GD was strongly associated with HLA-DQ2 haplotype (as predicted from linkage disequilibria, 14.6% vs. 1.5%, P = .009; odds ratio [OR] = 11.3; 95% confidence interval [CI] 1.3-252.7): 6 patients with CD carried HLA-DRB1(*)03, 1 carried an HLA-DRB1(*)04 allele, and 1 had an HLA-DRB1(*)07/(*)11 genotype. Multivariate analysis showed independent associations between CD and early GD onset (P = .014, OR = 9.6), autoimmunity in family (P = .029, OR = 6.3) and gastroenterologic symptoms (P = .031, OR = 8.1).The results of our study suggest that serologic screening for CD may be considered in GD patients (1) with the HLA alleles typical for CD, (2) with an early onset of GD, or (3) a family history of autoimmunity. Moreover, the diagnosis of CD should be explored in euthyroid GD patients with nonspecific gastrointestinal symptoms.

The aim of this analysis was to retrospectively review video recordings of malignant polyps10 mm in search for suspicious macroscopic features in white light endoscopy.Database entries and recordings of screening colonoscopies from a single tertiary referral center between June 2009 and December 2012 were reviewed. Malignant polyps10 mm were analyzed. The recordings were reviewed by two expert endoscopists in search for suspicious morphological features: irregular contours, central depression, contact bleeding, shape deformity, central depression, chicken skin sign, circumscribed area with abnormal vascular and/or surface pattern. Then, six experienced endoscopists watched the recordings in search of listed features. Next, video recordings of these malignant polyps were mixed with randomly drawn video recordings of 20 non-malignant polyps matched by size and reviewed by 14 blinded endoscopists to assess the sensitivity and specificity for the diagnosis of malignant polyps.Five of the 8651 (0.06%) subjects who underwent screening colonoscopy during the study period were diagnosed with a malignant polyp10 mm. Only one of them was ad hoc identified by performing endoscopist as suspicious. On recordings review performed by the experts, each of the four remaining polyps presented at least one suspicious macroscopic feature. Presence of these features was confirmed by experienced endoscopists. The sensitivity and specificity for the diagnosis of malignant polyp were 73.21% and 85.35%, respectively, if at least two suspicious macroscopic features defined malignant polyp.On careful white light endoscopy examination small malignant colorectal polyps show suspicious macroscopic features, which were frequently unrecognized by examining endoscopists.

This overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or to participate in organised intervention programmes. The Code should also form a base to guide national health policies in cancer prevention. The 12 recommendations are: not smoking or using other tobacco products; avoiding second-hand smoke; being a healthy body weight; encouraging physical activity; having a healthy diet; limiting alcohol consumption, with not drinking alcohol being better for cancer prevention; avoiding too much exposure to ultraviolet radiation; avoiding cancer-causing agents at the workplace; reducing exposure to high levels of radon; encouraging breastfeeding; limiting the use of hormone replacement therapy; participating in organised vaccination programmes against hepatitis B for newborns and human papillomavirus for girls; and participating in organised screening programmes for bowel cancer, breast cancer, and cervical cancer.

BACKGROUND Recommendations for colorectal-cancer screening are based solely on age and family history of cancer, not sex. METHODS We performed a cross-sectional analysis of the data from a large colonoscopy-based screening program that included 50,148 participants who were 40 to 66 years of age. People 40 to 49 years of age were eligible only if they had a family history of cancer of any type. Of the 43,042 participants 50 to 66 years of age, 13.3% reported a family history of colorectal cancer, as did 66.3% of the 7106 participants who were 40 to 49 years of age. We defined advanced neoplasia as cancer or adenoma that was at least 10 mm in diameter, had high-grade dysplasia, or had villous or tubulovillous histologic characteristics, or any combination thereof. We used multivariate logistic regression to identify associations between participants' characteristics and advanced neoplasia in a primary (or derivation) data set, and we confirmed the associations in a secondary (or validation) data set. RESULTS Advanced neoplasia was detected in 2553 (5.9%) participants 50 to 66 years of age and in 243 (3.4%) participants 40 to 49 years of age. The rate of complications during colonoscopy was 0.1%, and no participants died. In the validation set, a logistic-regression model showed that male sex was independently associated with advanced neoplasia (adjusted odds ratio, 1.73; 95% confidence interval, 1.52 to 1.98; P

To investigate tolerability and efficacy of pantoprazole 20 mg, once daily (o.d.), pantoprazole 40 mg o.d., and omeprazole 20 mg o.d., in patients taking nonsteroidal anti-inflammatory drug(s) (NSAIDs).Included in this randomized, double-blind, multicenter, parallel-group study were rheumatic patients (55 yr) on continual NSAIDs and with at least one more recognized risk factor that contributes to the development of gastrointestinal (GI) injury. Study duration was 6 months, and the treatment consisted of pantoprazole 20 mg o.d. (N = 196), pantoprazole 40 mg o.d. (N = 199), or omeprazole 20 mg o.d. (N = 200). Patients took NSAID(s) (except COX-2 inhibitors), had no more than five erosions/petechiae in the upper GI tract, no current peptic ulcers or reflux esophagitis, and had at most moderate intensity GI symptoms. Endoscopy was performed at baseline, 3, and 6 months. The primary end points were lack of "therapeutic failure" and lack of "endoscopic failure" at 6 months.After 6 months, the probabilities to remain in remission were 90% pantoprazole 20 mg o.d., 93% pantoprazole 40 mg o.d., and 89% omeprazole 20 mg o.d. for lack of "therapeutic failure;" 91% pantoprazole 20 mg o.d., 95% pantoprazole 40 mg o.d., and 93% omeprazole 20 mg o.d. for lack of "endoscopic failure."For patients taking NSAIDs continually, pantoprazole 20 mg o.d., pantoprazole 40 mg o.d., or omeprazole 20 mg o.d. provide equivalent, effective, and well-tolerated prophylaxis against GI lesions, including peptic ulcers.

There is no direct evidence that colonoscopy screening reduces mortality from colorectal cancer. However, results from studies using fecal occult blood testing and sigmoidoscopy, along with the fact that colonoscopy is performed after positive primary screening tests, support this assumption. Colonoscopy every 10 years is the preferred strategy in terms of clinical outcomes and cost effectiveness. The purpose of this article is to present the methodology used for the implementation of an opportunistic colonoscopy colorectal cancer screening program in Poland. We also review recent literature on challenges related to colonoscopy screening including recruitment, acceptance, and quality of the procedure.

Since the implementation of screening programmes, both the incidence and mortality of colorectal cancer have been decreasing. The choice of the preferred screening tool, however, is divergent and the adherence to screening programmes in most countries is still low. Cancer detection tests such as the guaiac faecal occult blood test (gFOBT) and the immunohistochemical FOBT (iFOBT) achieve higher acceptance than endoscopy. The sensitivity and specificity of iFOBT are higher than those of gFOBT, but gFOBT is cheaper and easier to perform. Endoscopic screening, which represents cancer prevention tests, has higher sensitivity for premalignant lesions than gFOBT and iFOBT and enables diagnosis and therapy in one single procedure. Since screening colonoscopy and sigmoidoscopy are invasive procedures with potentially severe adverse events, the highest possible quality must be provided. High-tech equipment, experience, training, quality control programmes, excellent bowel preparation and low adverse event rates are pivotal. Alternative screening tools such as CT colonography, barium enema CT and multitarget stool DNA tests have not been established as routine screening tools to date.

Background: Although Helicobacter pylori is a significant etiologic factor of peptic ulcer disease, it remains unknown why ulcers develop only in the minority of infected individuals. Aim: The aim of this cross-sectional study was to evaluate the association between the presence of duodenal ulcer in H. pylori-infected patients and different risk factors. Methods: A total of 122 H. pylori-infected patients were enrolled; 79 had duodenal ulcer and 43 gastritis. Univariate analysis was conducted using either Fisher’s exact test or exact Cochrane-Armitage trend test. In multivariate analysis the logistic model was used. Results: Univariate analysis indicated six factors (male sex, smoking, antral H. pylori density, cagA presence in antrum, and vacA s1a presence in antrum and corpus). Four factors (sex, smoking-alcohol index, H. pylori density index, and cagA index) were found to be significant in multivariate analysis. The best model predicting duodenal ulcer included male sex, smoking, presence of H. pylori on histopathology in antrum and cagA presence in corpus. Conclusion: Although several risk factors were significantly associated with duodenal ulcer, we failed in the identification of either a single risk factor or a set of factors that can unequivocally differentiate patients with ulcer from those with gastritis.

Colorectal cancer (CRC) is the second most common newly diagnosed cancer and the second most common cause of death in the European Union (EU). CRC is an enormous health and economic burden. Early detection and prevention have the possibility of reducing this burden significantly. Many cancer-associated deaths can be avoided through early detection by high-quality colorectal screening programs followed by appropriate treatment. Under the auspices of the United European Gastroenterology Federation (UEGF), the European Association for Gastroenterology and Endoscopy, the Hungarian Society of Gastroenterology and the Hungarian College of Gastroenterology, the ‘Budapest Declaration’ (2011) was an accepted official scientific program during the Hungarian Presidency of the Council of the European Union. The Budapest Declaration follows the Munich Declaration (2001), the Brussels Declaration (2007), the Transatlantic Declaration (2009), the Barcelona Declaration (2010), the written declaration of CRC screening, a joint initiative with European Parliamentarians coordinated by the UEGF, and finally, the ‘European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis’. The ‘Budapest Declaration’ together with previous declarations aims to urge the national and supranational healthcare decision makers to launch new Europe-wide initiatives to establish high-quality CRC programs to achieve optimal efficiency in CRC screening. In case of implementation of the proposals, actions and conditions recommended, we can achieve that one of the basic principles of the EU – the chance of equal access – be realized in member states with respect to the prevention of CRC and reduction of cancer-related mortality. To better achieve this goal, we propose to establish an UEGF joint committee, with one participant representing each EU member state to coordinate and supervise the implementation of CRC screening.

Background Aberrant DNA methylation in gene promoters is associated with aging and cancer, but the circumstances determining methylation change are unknown. We investigated the impact of lifestyle modulators of colorectal cancer (CRC) risk on the stability of gene promoter methylation in the colonic mucosa. Methods We measured genome-wide promoter CpG methylation in normal colon biopsies (n = 1092) from a female screening cohort, investigated the interaction of lifestyle factors with age-dependent increase in methylation with log-linear multivariable regression, and related their modifying effect to hypermethylation in CRC. All statistical tests were two-sided. Results Of 20025 promoter-associated CpGs analyzed, 1713 showed statistically significant age-dependent methylation gains. Fewer CpGs acquired methylation in users of aspirin (≥2 years) and hormonal replacement therapy (HRT age ≥50 years) compared with nonusers (43 vs 1355; 1 vs1377, respectively), whereas more CpGs were affected in smokers (≥20 years) and individuals with a body mass index (BMI) of 25kg/m2 and greater compared with control groups (180 vs 39; 554 vs 144, respectively). Fifty percent of the CpGs showing age-dependent methylation were found hypermethylated in CRC (odds ratio [OR] = 20; 95% confidence interval [CI] = 18 to 23; P < 2×10–16). These loci gained methylation with a higher median rate compared with age-only methylated sites (P = 2×10–76) and were enriched for polycomb regions (OR = 3.67). Importantly, aspirin (P < .001) and HRT use (P < .001) reduced the methylation rate at these cancer-related genes, whereas smoking (P < .001) and high BMI (P = .004) increased it. Conclusions Lifestyle, including aspirin use, modulates age-associated DNA methylation change in the colonic epithelium and thereby impacts the evolution of cancer methylomes.

Screening for colorectal cancer (CRC) holds unusual position in the current public health policy of many countries. Reasons for that are numerous. Firstly, CRC is a serious epidemiological problem in aging societies. Cancer occurs in both genders unlike in other cancers for which screening programmes are accepted. Secondly, it has not been yet decided universally which of the screening methods is optimal. There are several methods available, which have been studied and introduced into practice in different parts of the world; but it seems everyone is doing different thing. The plethora of methodological opportunities is striking. On one side of the spectrum there is a faecal occult blood testing using old guaiac method repeated as often as every year, with colonoscopy for positive stool test. On the other side of the spectrum, a once-in-a-lifetime primary screening colonoscopy is suggested as a possible option.1 Good news is that despite diverse methodology of CRC screening, it is not only cost-effective but also cost-saving – an exceptional feature compared with other screenings.2 It appeared over the last few years, that public health policy makers have currently the choice between the two main options. One is the faecal testing using different methods requiring usually frequent repetitions. The other is infrequent endoscopic screening using sigmoidoscopy (followed by colonoscopy for polyp bearers in the distal colon) or colonoscopy (every 10 years or once-in-a-lifetime). The recent high-quality randomized controlled trials performed in the UK, Italy, and the USA3–5 have shown surprising and unforeseen effect: a SINGLE sigmoidoscopy examination provides a very long-lasting effect, up to 11–13 years, with regard to CRC mortality and incidence reduction. The curves showing this effect comparing CRC mortality for intervention group and control group are diverging still at the moment of 11–13 years, suggesting that the effect may be even much longer than only that period of time. In this issue, the study by Geir Hoff et al.6 started in Norway 30 years ago provides data with as long as 26 years of follow up. This is the longest follow-up period available in the literature concerning CRC-screening randomized controlled trials and is an important piece of information providing insight into the effectiveness of endoscopic screening for CRC. Unfortunately, the number of patients recruited was not sufficient to provide statistical significance in all analyses and also probably for ethical reasons it was not possible to avoid colonoscopy in patients of control group 13 years after initial randomization. But even despite that, the 60% reduction of CRC incidence in the intervention group after 26 years of follow up is impressive. The mortality reduction (84%) sounds even better, but the lack of statistical significance slightly disappoints. The intervention in this study over the period of 26 years sounds a bit complex, but in fact it was nearly in full accordance with current knowledge and recommendations. It consisted of: (a) initial sigmoidoscopy with clearing colonoscopy for polyp bearers in the distal colon; (b) two surveillance colonoscopies for polyp bearers only, 2 and 6 years after initial examination; and (c) colonoscopy 13 years after initial examination, with subsequent surveillance colonoscopies only for patients with advanced findings either 18 years or 23 years after initial sigmoidoscopy. The study provides other notable observations that may shed light on future design of screening programmes. In the screening group, the authors observed a sustained reduction in CRC incidence for the first 20 years, with a starting raise in the incidence in the last 6 years of follow-up. It has been courageously interpreted as an effect of a less stringent surveillance protocol following polypectomy in the second half of the follow-up period (time period II). Although this is one of a plausible explanations, it is rather poorly documented in this study. First, only two out of the seven cancers in the screening group were diagnosed in screening attendees during follow-up period (one cancer was diagnosed at first screening examination and other four cancers in non-attendees). Second, before time period II, both screening and control groups were offered screening colonoscopy, with comparable attendance rates. Therefore, we would expect that the relative reduction in CRC incidence was attenuated in time period II, but in fact it was maintained (hazard ratios: period I: 0.30, 95% CI 0.06–1.44; period II: 0.43, 95% CI 0.15–1.22). So, it not only suggests that the effect on incidence in the screening group was maintained with less stringent surveillance protocol, but also that the effect of screening colonoscopy at a mean age of 66.9 years could have been less potent that the effect of flexible sigmoidoscopy with subsequent surveillance at a mean age of 54.5 years. Despite offering screening colonoscopy in both groups at the mean age of 66.9 years, the cumulative hazard ratios for CRC continue to diverge as if there was no colonoscopy in the control group. Although a microsimulation modelling study has shown that beginning screening at age 50 was consistently better that at age 60,7 the relatively poor effect of screening colonoscopy at age 66.9 is really unexpected and striking. We have no good explanation for this phenomenon and think that it requires immediate further studies. All previous screening sigmoidoscopy randomized controlled trials, together with Hoff’s study here, speak for the unique value of endoscopic screening for CRC. We only need formal and final confirmation of CRC mortality and incidence reduction of primary screening colonoscopy from randomized controlled trials which are underway.8,9 The exceptional feature of endoscopic screening, confirmed in the current study, is that its effect is very long lasting and it may be probably performed only once in a life time, providing that a quality of examination is high.10 The emerging issue that needs to be addressed thoroughly is the choice of optimal age to begin endoscopy screening.

Physician recommendation is a strong predictor of colorectal cancer (CRC) screening adherence, but there are no sufficient data specific to primary colonoscopy screening programs. The primary objective was to compare the effect of primary care physician's (PCP) counseling with information leaflet about CRC screening on participation rate in opportunistic primary colonoscopy screening program. Secondary objective was to determine the impact of this counseling on a decision to choose unsedated colonoscopy.Six hundred consecutive subjects 50-65 years of age visiting PCP group practice for routine medical consultation were randomly assigned in a 1:1 ratio either to discuss CRC screening with PCP or to receive an information leaflet on CRC screening only. The outcome measures were the participation rate and the proportion of unsedated colonoscopies assessed on subjects' self-reports collected six months after the intervention. Multivariate logistic regression model with backward selection was used to investigate the association between independent covariates and binary endpoints.Participation rate was 47.0% (141 subjects) in the counseling group and 13.7% (41 patients) in the information leaflet group. The rates of unsedated colonoscopies were 77.0% and 39.0%, respectively. In a multivariate analyses, PCP's counseling was associated with higher participation in CRC screening (adjusted odds ratio [OR] 5.33, 95% confidence intervals [95% CI] 3.55-8.00) and higher rate of unsedated colonoscopies (OR 7.75, 95% CI 2.94-20.45).In opportunistic primary colonoscopy screening, PCP's counseling significantly increases participation rate and decreases demand for sedation compared to recruitment with information materials only. NCT01688817.

Objective This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. Design We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Results Advanced colorectal neoplasia was detected in 2544 of the 35 918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p

To identify reasons for the high incidence rates of stomach cancer in Poland, we conducted a population-based case-control study in Warsaw. Cases were residents aged 21 to 79 years who were newly diagnosed with stomach cancer between March 1, 1994, and April 30, 1997. Controls were randomly selected from Warsaw residents registered at the nationwide Polish Electronic System of Residence Evidency, frequency-matched to cases by age and sex. Information on demographic characteristics; consumption of cigarettes, alcohol, tea and coffee; diet; medical history; family history of cancer; occupational history; and living conditions during adolescence was elicited by trained interviewers using a structured questionnaire. Included were 464 cases (90% of eligible) and 480 controls (87% of eligible). Among men, the risk of stomach cancer was significantly elevated among current smokers (OR = 1.7, 95% CI = 1.1-2.7) but not among former smokers. The excess risk was largely confined to long-term and heavy smokers, with significant 2-fold excess risk among men who smoked 40 or more pack-years. Among women, an 80% increase in risk was observed in both current and former smokers but dose-response trends were less consistent than among men. Alcohol consumption was not clearly related to risk, and no association was found for drinking regular coffee or herbal tea or using milk/cream in coffee or tea. A significant reduction in risk was linked to daily tea drinking among women, but not among men. Our findings confirm an association with cigarette smoking, which is estimated to account for approximately 20% of stomach cancers diagnosed among Warsaw residents during the study period.

Background: A novel 1-h topical method eradicated Helicobacter pylori in 96% of dyspeptic patients. The eradication rate of amoxycillin/omeprazole therapy varies from 0 to 93%. Aim: To compare both methods in patients with endoscopically proven duodenal ulcer. Methods: Eighty patients (59 males, 21 females; median age 43 years) were randomized into two therapeutic groups. The first group (group A) was treated with a 6-week course of ranitidine 300 mg/day, then omeprazole 20 mg b.d. with pronase 36 000 units/day for 2 days, followed by 1-h topical therapy with a solution of bismuth, metronidazole, amoxycillin and pronase. The second group (group B) consisted of patients treated with omeprazole 20 mg b.d. and amoxycillin 2 g/day for 2 weeks, followed by a 4-week course of ranitidine 300 mg/day. Eradication of H.␣pylori was assessed by urease test, histology, a polymerase chain reaction and a 13C-urea breath test, all of which were performed 4 weeks after discontinuation of the antibacterial treatment. Results: Eradication rates in groups A and B were 2.5% and 35% in an intention-to-treat analysis, respectively. Side-effects were encountered in 40.5% and 12.5% of subjects in groups A and B, respectively. Treatment tolerance was rated as poor by 54% of patients in group A and 2.5% of patients in group B. Conclusions: Both treatment regimens, the 1-h topical method and amoxycillin with omeprazole, have low eradication rates in patients with duodenal ulcer. In addition, the topical treatment is characterized by a high rate of side-effects and poor tolerance. Based on the results of our study, neither method can be recommended for eradication of H. pylori in patients with duodenal ulcer.

Photodynamic therapy (PDT) using 5-aminolaevulinic-acid-(ALA)-induced protoporphyrin IX (PPIX) increases survival in hamsters with pancreatic cancer. However, experiments with other photosensitizers on this model show a high risk of duodenal perforation. In this paper, the pharmacokinetics and PDT effects of ALA on normal tissues in the pancreatobiliary region are presented. Using quantitative fluorescence microscopy, maximum PPIX fluorescence was seen in the bile ducts, less in the duodenal mucosa and least in the muscularis propria and pancreas. For PDT, light was delivered either using a bare fibre touching the tissue (single-point illumination), or irradiating a 1.5 cm diameter circular area. Single-point PDT (50 J) produced only localized reversible damage without perforation. Surface irradiation of the whole periampullary region (50 J cm−2) caused extensive damage, sometimes with perforation. Before PDT can be used safely to treat tumours of the pancreas and bile duct, further studies are necessary to understand its effect on larger areas of normal tissue.

Aim Following treatment with argon plasma coagulation (APC), rectal ulceration is seen in approximately 50% of patients with haemorrhagic chronic radiation proctitis (CRP). This study aimed to assess the frequency of rectal ulcers (defined as a mucosal defect of 3 mm or more in diameter) in relation to the use of antiplatelet treatment for concomitant cardiovascular disease. Method Sixty-two patients with CRP were included in this retrospective study. Patients underwent pelvic irradiation due to prostate cancer (n = 28), cervical cancer (n = 16), endometrial cancer (n = 17) or rectal cancer (n = 1). APC was performed in all patients. Control endoscopies were performed at 8 and 16 weeks after enrolment. Results Rectal ulcers were observed after APC in 35 (56%) patients. They were symptomatic in 5 and asymptomatic in 30. The 20 (32%) patients who were on antiplatelet therapy had a significantly lower risk of ulceration after APC (OR = 0.21; 95% CI 0.049–0.91; P = 0.019). The number of symptomatic ulcers (5% vs 10%; P = 1.0) and asymptomatic ulcers alone (30% vs 58%; P = 0.06) was also lower in patients respectively taking and not taking antiplatelet therapy, but these differences did not reach statistical significance. Conclusion Argon plasma coagulation-related ulceration in patients treated for CRP is less common when concomitant antiplatelet treatment is administered. This preliminary finding suggests that antiplatelet therapy may benefit patients treated with APC for CRP.

The authors discuss concerns about the updated recommendations for colorectal cancer screening from the USPSTF. They advocate for integration of high-quality clinical trials into ongoing screening ...

Contains fulltext : 111010pub.pdf (Publisher’s version ) (Closed access) Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.

5-aminolevulinic acid (5-ALA) is an interesting photosensitizing substance for photodynamic therapy (PDT), successfully applied topically for urological malignancy. In gastroenetrology it has proven efficacy for treatment of some GI neoplasms after systemic administration This study was aimed at investigating the possibility of topical 5-ALA administration also for the PDT of gut cancer in a mice model. 5-ALA solution at different concentrations (5%, 1.5%, and 0.5%) was instilled in the colon of mice, which was later removed and examined by fluorescence microscopy. The results of fluorescence studies were compared with those obtained in a control group treated with 5-ALA given systemically. Satisfactory epithelial fluorescence levels and good selectivity between gut layers was obtained after intracolonic 5-ALA instillation. However, mean fluorescence intensity was higher after systemic drug application. Our results suggest that 5-ALA may probably be used topically for the PDT of some gut neoplasms. (C) 1999 Society of Photo-Optical Instrumentation Engineers. [S1083-3668(99)00803-5].

Colorectal cancer (CRC) is the second most common newly diagnosed cancer and the second most common cause of death in the European Union (EU). CRC is an enormous health and economic burden. Early detection and prevention have the possibility of reducing this burden significantly. Many cancer-associated deaths can be avoided through early detection by high-quality colorectal screening programs followed by appropriate treatment. Under the auspices of the United European Gastroenterology Federation (UEGF), the European Association for Gastroenterology and Endoscopy, the Hungarian Society of Gastroenterology and the Hungarian College of Gastroenterology, the 'Budapest Declaration' (2011) was an accepted official scientific program during the Hungarian Presidency of the Council of the European Union. The Budapest Declaration follows the Munich Declaration (2001), the Brussels Declaration (2007), the Transatlantic Declaration (2009), the Barcelona Declaration (2010), the written declaration of CRC screening, a joint initiative with European Parliamentarians coordinated by the UEGF, and finally, the 'European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis'. The 'Budapest Declaration' together with previous declarations aims to urge the national and supranational healthcare decision makers to launch new Europe-wide initiatives to establish high-quality CRC programs to achieve optimal efficiency in CRC screening. In case of implementation of the proposals, actions and conditions recommended, we can achieve that one of the basic principles of the EU - the chance of equal access - be realized in member states with respect to the prevention of CRC and reduction of cancer-related mortality. To better achieve this goal, we propose to establish an UEGF joint committee, with one participant representing each EU member state to coordinate and supervise the implementation of CRC screening.

BackgroundProstate cancer (PCa) and colorectal cancer (CRC) are the most commonly diagnosed cancers and cancer-related causes of death in Poland. To date, numerous single nucleotide polymorphisms (SNPs) associated with susceptibility to both cancer types have been identified, but their effect on disease risk may differ among populations.MethodsTo identify new SNPs associated with PCa and CRC in the Polish population, a genome-wide association study (GWAS) was performed using DNA sample pools on Affymetrix Genome-Wide Human SNP 6.0 arrays. A total of 135 PCa patients and 270 healthy men (PCa sub-study) and 525 patients with adenoma (AD), 630 patients with CRC and 690 controls (AD/CRC sub-study) were included in the analysis. Allele frequency distributions were compared with t-tests and χ(2)-tests. Only those significantly associated SNPs with a proxy SNP (p0.7) were selected. GWAS marker selection was conducted using PLINK. The study was replicated using extended cohorts of patients and controls. The association with previously reported PCa and CRC susceptibility variants was also examined. Individual patients were genotyped using TaqMan SNP Genotyping Assays.ResultsThe GWAS selected six and 24 new candidate SNPs associated with PCa and CRC susceptibility, respectively. In the replication study, 17 of these associations were confirmed as significant in additive model of inheritance. Seven of them remained significant after correction for multiple hypothesis testing. Additionally, 17 previously reported risk variants have been identified, five of which remained significant after correction.ConclusionPooled-DNA GWAS enabled the identification of new susceptibility loci for CRC in the Polish population. Previously reported CRC and PCa predisposition variants were also identified, validating the global nature of their associations. Further independent replication studies are required to confirm significance of the newly uncovered candidate susceptibility loci.

Background & Aims Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett's esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. Methods We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. Results Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. Conclusions We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.

Experimental studies have been carried out using 5-aminolaevulinic acid (ALA) to induce transient porphyrin photosensitisation for photodynamic therapy (PDT) in a pancreatic cancer model in Syrian golden hamsters. ALA was given either intravenously or orally (in bolus or fractionated doses) with the laser light delivered by means of a bare fibre touching the tissue surface or external irradiation using a light-integrating cylindrical applicator. Animals were killed 1-24 h after ALA administration for pharmacokinetic studies and 3-7 days after light exposure to study PDT-induced necrosis. A separate survival study was also performed after a fractionated oral dose of ALA and external irradiation. Protoporphyrin IX sensitisation in the tumour tissue as measured by quantitative fluorescence microscopy was highest after intravenous administration of 200 mg kg-1 ALA and then in decreasing order after oral fractionated and oral bolus doses (both 400 mg kg-1). Laser light application at 630 nm to give 12-50 J from the bare fibre or 50 J cm-2 using surface illumination with the cylindrical applicator resulted in tumour necrosis up to 8 mm in depth. In larger tumours a rim of viable tumour was observed on the side opposite to illumination. In a randomised study, survival of treated animals was significantly longer than in the untreated control group (log-rank test, P < 0.02), although all animals died of recurrent tumour. This technique shows promise in the treatment of small volumes of tumour in the pancreas. Images Figure 2 Figure 3 Figure 4

Endogenously synthesised protoporphyrin IX (PpIX) following the administration of 5-amino-laevulinic acid (ALA) is an effective photosensitiser for photodynamic therapy (PDT). Following intravenous administration, PpIX accumulates predominantly in mucosa of hollow viscera and on light exposure, mucosal ablation results with relative sparing of the submucosa and muscularis layers. Oral administration is effective with ALA in contrast to conventional exogenous photosensitisers such as haematoporphyrin derivative and phthalocyanines. Oral administration of ALA is also simpler, safer, cheaper and more acceptable to patients. We studied the porphyrin sensitisation kinetics profile in the stomach, colon and bladder in normal rats following enterally and parenterally administered ALA using microscopic fluorescence photometric studies of frozen tissue sections. Mucosal cells in all three organs exhibit higher fluorescence levels as compared with underlying smooth muscle following both intravenous and oral administration. Peak concentration were seen 4 h after sensitisation at the highest doses used (200 mg kg-1 i.v., 400 mg kg-1 oral), and slightly earlier with lower doses. The temporal kinetics of both routes of administration were similar although a higher oral dose was required to achieve the same tissue concentration of PpIX. The highest level of fluorescence was achieved in the gastric mucosa and in decreasing levels, colonic and bladder mucosa. A similar degree of mucosal selectivity was achieved in each organ with each route of administration but an oral dose in excess of 40 mg kg-1 was required to achieve measurable PpIX sensitisation. In a pilot clinical study, two patients with inoperable rectal adenocarcinomas were given 30 mg kg-1 and one patient with sigmoid colon carcinoma was given 60 mg kg-1 ALA orally. Serial biopsies of normal and tumour areas were taken over the subsequent 24 h. Fluorescence microscopy of these specimens showed maximum accumulation of PpIX 4 to 6 h after administration of 30 mg kg-1 ALA. There was greater PpIX accumulation in tumour than adjacent normal mucosa in two patients. Preferential PpIX accumulation in tumour was greater in the patient receiving 60 mg kg-1 ALA. Images Figure 2 Figure 10

United European Gastroenterology is a successful federation of gastroenterological societies (called member societies). Thanks to its organizational success it may allocate as much as half a million Euro to support postgraduate teaching in gastroenterology in Europe. Every gastroenterological society that is a member of UEG (16 specialist societies “Ordinary Members” and 46 national societies “National Society Members”) may apply. This is a great opportunity! Two main forms of postgraduate teaching are supported. One is the support of a single regular educational meeting (up to 25,000 euro may be granted). Second is the support of a long-term educational project planned for three consecutive years with the intention to develop stand-alone long-term educational event. In this type of event, the first year is granted with up to € 50,000 and the subsequent two years with up to €25,000 euro each year. For the last two years a specially designed scoring system to evaluate applications is in place. It promotes several aspects of teaching that are regarded by UEG to be very important. Namely, the high scores are applied for such aspects like interactivity and multidisciplinarity. Therefore we check whether organizers allowed enough time for discussion, whether they are planning to use voting interactive system or include in the programme case presentation with participation of the audience in solving clinical problems. We also look at such aspects as balance in geographical distribution of speakers and attendees, age and gender of speakers, location of the postgraduate course and planned cooperation with other society. Of course, the typical and obvious criteria are also applied as justification of undertaking the course, the topic of the course, well-structured budget etc. Well visible is also such preparation of the course that the materials (e.g. recordings) may be used by the UEG e-learning platform. All applications are scored by the members of the Educational Committee that consists of one representative from each Ordinary Member Society of UEG. Of course, members are excluded from judging their own society application. The system of voting and democratic methodology is regarded as fair and valuable. For example the number of applications per society as well as number of granted support per society is not limited. So, if there are many good proposals from a given society they all could be granted. In order to keep the high standards it was decided that the score below the 50% of attainable scoring will not be considered for support. Of course, nothing is ideal; but we think that such evaluation system is better than the old, opinion-based system. Results of the last two years application process are presented in Table 1. Table 1. Statistics of the last two years after introduction of new scoring system There are several criteria that have to be fulfilled not only during application process but also during and after the education event. Examples are: a need to place a logo of UEG at all event materials and the event website, or a need to submit a report after the meeting has taken place. These points and others are required and if not fulfilled the grant will not be paid. Details for those who want to place application may be found at www.ueg.eu/education/ts/.. This year application is open from February 17 until May 12 for 2015 events. We invite all gastroenterological societies to try. We want to sponsor the best education in gastroenterology.