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.

Is Clinical Research in Oesophageal Cancer in South Africa in Crisis? A Systematic Review.

Oesophageal cancer (OC) is responsible for the second highest number of cancer-related deaths in South Africa (SA). Squamous cell carcinoma is the most prevalent type with an incidence of 46.7/100,000 and 19.2/100,000 for males and females. This is a systematic review of the clinical diagnosis and management of OC within the South African context. This protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration number CRD42016034053) with adherence to PRISMA guidelines. An online search was performed using MEDLINE, EBSCOHost and PubMed. Eligibility criteria for articles included published, original peer-reviewed research addressing clinical management of oesophageal cancer in South Africa. Review articles, case reports, scientific letters and studies published in languages other than English or Afrikaans were excluded. The research terms were 'etiology', 'human', 'esophageal cancer', 'esophageal carcinoma', 'oesophageal cancer', and 'oesophageal carcinoma', 'squamous cell carcinoma', 'Africa' and 'South Africa'. A total of 336 articles were identified. Of these, 146 were immediately excluded and a further 159 were excluded after review. A total of 31 appropriate articles, i.e. 9.2% of searched articles, were included. Thirteen articles addressed chemotherapy and/or radiotherapy, 9 oesophageal luminal therapy, 7 oesophageal surgery and 2 screening. OC research of in SA over the last two decades has mainly been in the form of reviews and opinion papers. Clinical research, auditing and prospectively analysing OC management and outcomes in SA hospitals are sorely needed and should be promoted by both healthcare workers and policy makers alike.

Oesophageal squamous cell cancer in a South African tertiary hospital: a risk factor and presentation analysis.

BACKGROUND: Squamous carcinoma of the oesophagus (SCO) is the most common form of oesophageal cancer in South Africa (SA). Risk factors include male gender, smoking, alcohol consumption and low socio-economic status (SES). This study assessed the risk factors for SCO in KwaZulu-Natal. METHOD: Information on patients managed at Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa, between 1 October 2013 and 31 December 2014 was retrieved from a prospective database of Oesophageal Cancer (OC). Data collected included demographics, risk factors, symptoms and clinical findings. RESULTS: One hundred and fifty-nine patients (159) with SCO were identified. The site of tumour location was in the middle 96 (60.4%), distal 42(26.4%) and proximal 17(10.6%) oesophagus. The male to female ratio was 1:1 with an age range of 22-93 years (mean 60.6; SD±12.1). Females were significantly older than males (p = 0.018). Eighty-eight per cent were Black African. Dysphagia was reported in 158 (99.4%) of patients and loss of weight in 149(95.5%). Thirty-six patients were HIV positive (age 52.8; SD±9.7) and significantly younger than those without HIV infection (age 61.2; SD±11.5). Most patients had low SES and poor dental health. Male patients were significantly more likely to use tobacco (p < 0.001; Odds Ratio (OR) 7.8) and consume alcohol (p < 0.001; OR 7.7) than females who were 2.5 times more likely to report a family history of cancer (p = 0.017; OR 2.6). CONCLUSION: An equal gender distribution was observed. Male patients with SCO reported the expected risk factors; however these were not observed amongst women. SES may contribute to the development of SCO. Poor dental health may be a surrogate marker for low SES and a possible risk factor for SCO. HIV positive individuals present a decade younger when compared with HIV negative patients.

HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in autoimmune hepatitis type-1.

The classical human leukocyte antigen (HLA)-DRB1*03:01 and HLA-DRB1*04:01 alleles are established autoimmune hepatitis (AIH) risk alleles. To study the immune-modifying effect of these alleles, we imputed the genotypes from genome-wide association data in 649 Dutch AIH type-1 patients. We therefore compared the international AIH group (IAIHG) diagnostic scores as well as the underlying clinical characteristics between patients positive and negative for these HLA alleles. Seventy-five percent of the AIH patients were HLA-DRB1*03:01/HLA-DRB1*04:01 positive. HLA-DRB1*03:01/HLA-DRB1*04:01-positive patients had a higher median IAIHG score than HLA-DRB1*03:01/HLA-DRB1*04:01-negative patients (P<0.001). We did not observe associations between HLA alleles and alanine transaminase levels (HLA-DRB1*03:01: P=0.2; HLA-DRB1*04:01; P=0.5); however, HLA-DRB1*03:01 was independently associated with higher immunoglobulin G levels (P=0.04). The HLA-DRB1*04:01 allele was independently associated with presentation at older age (P=0.03) and a female predominance (P=0.04). HLA-DRB1*03:01-positive patients received immunosuppressive medication and liver transplantation. In conclusion, the HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles are both independently associated with the aggregate diagnostic IAIHG score in type-1 AIH patients, but are not essential for AIH development. HLA-DRB1*03:01 is the strongest genetic modifier of disease severity in AIH.

Enteropathy-associated T-cell lymphoma: improving treatment strategies.

Enteropathy-associated T-cell lymphoma (EATL) is a rare and usually rapidly fatal intestinal T-cell non-Hodgkin lymphoma. It arises from intraepithelial lymphocytes and has a high association with coeliac disease. The high mortality of EATL is associated not only with the very aggressive and often chemotherapy-refractory nature of the lymphoma. The poor condition of patients due to prolonged and severe malnutrition compromises the ability to deliver chemotherapy. There are no standardized treatment protocols, and the optimal therapy for EATL remains unclear. The primary step of treatment consists of local debulking, preferably as early as possible after EATL diagnosis. Morbidity and mortality seem to rise with advanced stages of disease due to tumour size progression, worse nutritional status and a higher risk of emergency surgery due to perforation. Standard induction therapy for EATL is anthracycline-based chemotherapy, preferably resumed between 2 and 5 weeks after surgery (depending on clinical condition). Intensification of therapy using high-dose chemotherapy followed by consolidation with BEAM and autologous stem cell transplantation is associated with better outcome. Notably, this treatment strategy has only been applied in patients eligible for this aggressive regimen which might reflect selection bias. Unfortunately, prognosis of EATL remains poor; 5-year survival varies from 8 to 60% depending on the eligibility to receive additional steps of therapy. New treatment strategies are urgently needed for a better prognosis of this lethal complication of coeliac disease. Brentuximab vedotin (anti-CD30) might be promising when added to conventional chemotherapy and is suggested as upfront treatment in EATL.

Advanced glycation end products (AGEs) and the soluble receptor for AGE (sRAGE) in patients with type 1 diabetes and coeliac disease.

BACKGROUND AND AIMS: Advanced glycation end (AGE) products play a role in the progression of diabetic complications. Gluten-free diet (GFD) might affect AGE levels in patients who adhere to a GFD because of coeliac disease (CD). The aim of our study was to compare skin AGE levels and soluble receptor AGE levels (sRAGE) in patients with type 1 diabetes (T1DM) with (T1DM + CD) and without CD (T1DM - CD) and healthy controls. METHODS AND RESULTS: We recruited 25 T1DM + CD and 25 T1DM - CD patients, matched for age, gender, diabetes duration, and glycaemic control alongside 25 healthy controls. We collected demographic, clinical and biochemical characteristics, including skin autofluorescence (AF), sRAGE and hs-CRP levels. The duration of T1DM in patients was 30 ± 14 (+CD) and 29 ± 14 years (-CD), whereas CD duration in T1DM + CD patients was 14 ± 10 years. Skin AF levels in T1DM patients were higher compared to healthy controls (2.5 ± 0.6 versus 1.9 ± 0.4, p < 0.01) and skin AF was independently associated with age (r = 0.72, p < 0.01). sRAGE levels were higher in T1DM - CD patients compared to healthy controls (1554 ± 449 versus 1309 ± 400, p = 0.049) and independently associated with creatinine levels (r = 0.32, p < 0.01). CONCLUSION: Our study demonstrates that skin AGE and sRAGE levels are elevated in T1DM patients compared with healthy controls. No difference in skin AF or sRAGE levels between T1DM patients with or without CD were observed. The present study suggests that differences in microvascular complications between T1DM and T1DM + CD patients are not due to differences in skin AF or sRAGE levels.

Optimal strategies to identify aberrant intra-epithelial lymphocytes in refractory coeliac disease.

INTRODUCTION: Different strategies have been developed to identify those refractory celiac disease (RCD) patients who are at risk to develop an enteropathy associated T-cell lymphoma (EATL). Flow cytometric analysis of intra-epithelial lymphocytes (IEL) with an aberrant phenotype is considered the golden standard but is not widely available. Immunohistochemistry (IHC) and T-cell receptor (TCR) rearrangement studies are commonly available but may lack sensitivity and specificity. Here, we compared the three different methods in the workup of patients suspected for RCD. METHODS: Duodenal biopsies from control patient (n = 5), RCD patients with moderately increased aberrant IEL populations (20-50 %: n = 14), and RCD patients with high numbers of aberrant IEL (>50 %: n = 5) as determined by flow cytometry were analysed by IHC and TCR-γ chain rearrangement analysis. Three pathologists scored the slides independently. RESULTS: Sensitivity of IHC and TCR-γ rearrangement analysis in RCD patients with high numbers of aberrant IELs was 100 and 71 %, respectively. RCD patients with aberrant cells between 25 and 50 % however, were missed by IHC and TCR in 50 and 57 % of cases, respectively. In addition, inter-rater reliability analysis of the IHC scoring revealed coder-pair Kappa coefficients between 0.28 and 0.85. CONCLUSION: Immunohistochemistry and to a lesser extent TCR-γ clonality analysis are sensitive in identifying patients with high numbers of aberrant IEL populations, yet miss half of RCD patients with moderately increased numbers. In addition, IHC has a high inter-observer variability. Therefore, patients suspected for RCD should undergo flow cytometric analysis of the duodenum.

Bomb calorimetry, the gold standard for assessment of intestinal absorption capacity: normative values in healthy ambulant adults.

BACKGROUND: Intestinal absorption capacity is considered to be the best method for assessing overall digestive intestinal function. Earlier reference values for intestinal function in healthy Dutch adults were based on a study that was conducted in an inpatient metabolic unit setting in a relatively small series. The present study aimed to readdress and describe the intestinal absorption capacity of healthy adults, who were consuming their usual (Western European) food and beverage diet, in a standard ambulatory setting. METHODS: Twenty-three healthy subjects (aged 22-60 years) were included in the analyses. Nutritional intake (energy and macronutrients) was determined with a 4-day nutritional diary. Subsequently, mean faecal losses of energy (by bomb calorimetry), fat, protein and carbohydrate were determined following a 3-day faecal collection. Finally, intestinal absorption capacity was calculated from the differences between intake and losses. RESULTS: Mean (SD) daily faeces production was 141 (49) g (29% dry weight), containing 891 (276) kJ [10.7 (1.3) kJ g(-1) wet faeces; 22.6 (2.5) kJ g(-1) dry faeces], 5.2 (2.2) g fat, 10.0 (3.8) g protein and 29.7 (11.7) g carbohydrates. Mean (SD) intestinal absorption capacity of healthy subjects was 89.4% (3.8%) for energy, 92.5% (3.7%) for fat, 86.9% (6.4%) for protein and 87.3% (6.6%) for carbohydrates. CONCLUSIONS: The present study provides normative values for both stool nutrient composition and intestinal energy and macronutrient absorption in healthy adults on a regular Dutch diet in an ambulatory setting. Intestinal energy absorption was found to be approximately 90%.

Innovating Thiopurine Therapeutic Drug Monitoring: A Systematic Review and Meta-Analysis on DNA-Thioguanine Nucleotides (DNA-TG) as an Inclusive Biomarker in Thiopurine Therapy.

BACKGROUND AND OBJECTIVE: Thioguanine (TG), azathioprine (AZA), and mercaptopurine (MP) are thiopurine prodrugs commonly used to treat diseases, such as leukemia and inflammatory bowel disease (IBD). 6-thioguanine nucleotides (6-TGNs) have been commonly used for monitoring treatment. High levels of 6-TGNs in red blood cells (RBCs) have been associated with leukopenia, the cutoff levels that predict this side effect remain uncertain. Thiopurines are metabolized and incorporated into leukocyte DNA. Measuring levels of DNA-incorporated thioguanine (DNA-TG) may be a more suitable method for predicting clinical response and toxicities such as leukopenia. Unfortunately, most methodologies to assay 6-TGNs are unable to identify the impact of NUDT15 variants, effecting mostly ethnic populations (e.g., Chinese, Indian, Malay, Japanese, and Hispanics). DNA-TG tackles this problem by directly measuring thioguanine in the DNA, which can be influenced by both TPMT and NUDT15 variants. While RBC 6-TGN concentrations have traditionally been used to optimize thiopurine therapy due to their ease and affordability of measurement, recent developments in liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques have made measuring DNA-TG concentrations in lymphocytes accurate, reproducible, and affordable. The objective of this systematic review was to assess the current evidence of DNA-TG levels as marker for thiopurine therapy, especially with regards to NUDT15 variants. METHODS: A systematic review and meta-analysis were performed on the current evidence for DNA-TG as a marker for monitoring thiopurine therapy, including methods for measurement and the illustrative relationship between DNA-TG and various gene variants (such as TPMT, NUDT15, ITPA, NT5C2, and MRP4). PubMed and Embase were systematically searched up to April 2024 for published studies, using the keyword "DNA-TG" with MeSH terms and synonyms. The electronic search strategy was augmented by a manual examination of references cited in articles, recent reviews, editorials, and meta-analyses. A meta-analysis was performed using R studio 4.1.3. to investigate the difference between the coefficients (Fisher's z-transformed correlation coefficient) of DNA-TG and 6-TGNs levels. A meta-analysis was performed using RevMan version 5.4 to investigate the difference in DNA-TG levels between patients with or without leukopenia using randomized effect size model. The risk of bias was assessed using the Newcastle-Ottowa quality assessment scale. RESULTS: In this systematic review, 21 studies were included that measured DNA-TG levels in white blood cells for either patients with ALL (n = 16) or IBD (n = 5). In our meta-analysis, the overall mean difference between patients with leukopenia (ALL + IBD) versus no leukopenia was 134.15 fmol TG/µg DNA [95% confidence interval (CI) (83.78-184.35), P < 0.00001; heterogeneity chi squared of 5.62, I2 of 47%]. There was a significant difference in DNA-TG levels for patients with IBD with and without leukopenia [161.76 fmol TG/µg DNA; 95% CI (126.23-197.29), P < 0.00001; heterogeneity chi squared of 0.20, I2 of 0%]. No significant difference was found in DNA-TG level between patients with ALL with or without leukopenia (57.71 fmol TG/µg DNA [95% CI (- 22.93 to 138.35), P < 0.80]). DNA-TG monitoring was found to be a promising method for predicting relapse rates in patients with ALL, and DNA-TG levels are likely a better predictor for leukopenia in patients with IBD than RBC 6-TGNs levels. DNA-TG levels have been shown to correlate with various gene variants (TPMT, NUDT15, ITPA, and MRP4) in various studies, points to its potential as a more informative marker for guiding thiopurine therapy across diverse genetic backgrounds. CONCLUSIONS: This systematic review strongly supports the further investigation of DNA-TG as a marker for monitoring thiopurine therapy. Its correlation with treatment outcomes, such as relapse-free survival in ALL and the risk of leukopenia in IBD, underscores its role in enhancing personalized treatment approaches. DNA-TG effectively identifies NUDT15 variants and predicts late leukopenia in patients with IBD, regardless of their NUDT15 variant status. The recommended threshold for late leukopenia prediction in patients with IBD with DNA-TG is suggested to be between 320 and 340 fmol/µg DNA. More clinical research on DNA-TG implementation is mandatory to improve patient care and to improve inclusivity in thiopurine treatment.

Compromised quality of life in patients with both Type 1 diabetes mellitus and coeliac disease.

AIMS: Type 1 diabetes mellitus and coeliac disease are two chronic illnesses associated with each other. Both diseases and their treatments can seriously impair quality of life. The objective of the present study was to investigate health-related quality of life in adult patients diagnosed with both Type 1 diabetes and coeliac disease and compare this with healthy control subjects and control subjects who have Type 1 diabetes only. METHODS: A generic measure of health-related quality of life (RAND-36) and a measure of diabetes-specific quality of life (DQOL) questionnaires were sent to patients diagnosed with both Type 1 diabetes and coeliac disease. The control group consisted of patients with Type 1 diabetes without coeliac disease matched for age, gender and socio-economic status. Generic quality of life scores were compared with data from healthy Dutch control subjects. RESULTS: Fifty-seven patients with Type 1 diabetes and coeliac disease were included and no associations between clinical characteristics and quality of life were observed. Women reported a lower quality of life in social functioning, vitality and mental health than men (all P < 0.05). A lower diabetes-specific quality of life was observed regarding diabetes-related worries and social worries in patients with Type 1 diabetes and coeliac disease compared with patients with Type 1 diabetes. Compared with healthy control subjects, quality of life in patients with Type 1 diabetes and coeliac disease was significantly lower, particularly social functioning (Cohen's d = 0.76) and general health perception (Cohen's d = 0.86). CONCLUSIONS: The additional diagnosis of coeliac disease and treatment by gluten-free diet in adult patients with Type 1 diabetes has a considerable, negative impact on quality of life and diabetes-specific quality of life. Women are particularly affected and social functioning and general health perception is compromised.

Small bowel adenocarcinoma copy number profiles are more closely related to colorectal than to gastric cancers.

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare cancer and consequently, the options for clinical trials are limited. As they are treated according to either a colorectal or a gastric cancer regimen and the molecular biology of a tumor is a pivotal determinant for therapy response, chromosomal copy number aberrations were compared with the colorectal and gastric adenocarcinomas. MATERIALS AND METHODS: A total of 85 microsatellite stable (MSS) adenocarcinomas from the stomach, colorectum and small bowel were selected from existing array comparative genomic hybridization (aCGH) datasets. We compared the aCGH profiles of the three tumor sites by supervised analysis and hierarchical clustering. RESULTS: Hierarchical clustering revealed substantial overlap of 27 SBA copy number profiles with matched colorectal adenocarcinomas but less overlap with profiles of gastric adenocarcinomas. DNA copy number aberrations located at chromosomes 1p36.3-p34.3, 4p15.3-q35.2, 9p24.3-p11.1, 13q13.2-q31.3 and 17p13.3-p13.2 were the strongest features discriminating SBAs and colorectal adenocarcinomas from gastric adenocarcinomas. CONCLUSIONS: We show that MSS SBAs are more similar to colorectal than to gastric cancer, based on the 27 genome-wide DNA copy number profiles that are currently available. These molecular similarities provide added support for treatment of MSS small bowel cancers according to colorectal cancer regimens.

Critical reappraisal of anorectal function tests in patients with faecal incontinence who have failed conservative treatment.

OBJECTIVE: Anorectal function tests are often performed in patients with faecal incontinence who have failed conservative treatment. This study was aimed to establish the additive value of performing anorectal function tests in these patients in selecting them for surgery. PATIENTS AND METHODS: Between 2003 and 2009, all referred patients with faecal incontinence were assessed by a questionnaire, anorectal manometry and anal endosonography. Patients with diarrhea, inflammatory bowel disease, pouches or rectal carcinoma were excluded. RESULTS: In total, 218 patients were evaluated. Of these, 107 (49%) patients had no sphincter defects, 71 (33%) had small defects and 40 (18%) had large defects. Anorectal manometry could not differentiate between patients with and without sphincter defects. Patients with sphincter defects were only found to have a significantly shorter sphincter length and reduced rectal capacity compared to patients without sphincter defects. Forty-three patients (20%) had a normal anal pressures ≥ 40 mmHg. Seventeen patients (8%) had also a dyssynergic pelvic floor both on clinical examination and anorectal manometry. Fifteen patients (7%) had a reduced rectal capacity between 65 and 100 ml. There was no difference in anal pressures or the presence of sphincter defects in these patients compared to patients with a rectal capacity >150 ml. There was no correlation between anorectal manometry, endosonography and faecal incontinence severity scores. CONCLUSION: In patients with faecal incontinence who have failed conservative treatment, only anal endosonography can reveal sphincter defects. Anorectal manometry should be reserved for patients eligible for surgery to exclude those with suspected dyssynergic floor or reduced rectal capacity.

Exome sequencing in a family segregating for celiac disease.

Celiac disease is a multifactorial disorder caused by an unknown number of genetic factors interacting with an environmental factor. Hence, most patients are singletons and large families segregating with celiac disease are rare. We report on a three-generation family with six patients in which the inheritance pattern is consistent with an autosomal dominant model. To date, 27 loci explain up to 40% of the heritable disease risk. We hypothesized that part of the missing heritability is because of low frequency or rare variants. Such causal variants could be more prominent in multigeneration families where private mutations might co-segregate with the disease. They can be identified by linkage analysis combined with whole exome sequencing. We found three linkage regions on 4q32.3-4q33, 8q24.13-8q24.21 and 10q23.1-10q23.32 that segregate with celiac disease in this family. We performed exome sequencing on two affected individuals to investigate the positional candidate regions and the remaining exome for causal nonsense variants. We identified 12 nonsense mutations with a low frequency (minor allele frequency <10%) present in both individuals, but none mapped to the linkage regions. Two variants in the CSAG1 and KRT37 genes were present in all six affected individuals. Two nonsense variants in the MADD and GBGT1 genes were also present in 5 of 6 and 4 of 6 individuals, respectively; future studies should determine if any of these nonsense variants is causally related to celiac disease.

Description of a novel grading system to assess the quality of bowel preparation in video capsule endoscopy.

BACKGROUND AND STUDY AIMS: Inadequate bowel preparation negatively influences the reliability of examinations by video capsule endoscopy (VCE). Currently, only subjective scales are available to describe mucosal visibility. We aimed to design a score that was derived directly from the VCE images. PATIENTS AND METHODS: A computed assessment of cleansing score was developed based on color intensities of the tissue color bar. The feasibility of this score was retrospectively tested in 24 VCE studies. A prospective study was conducted using 40 VCE segments from 10 consecutive VCE studies. The computed scores were compared with three existing methods of assessing small-intestinal cleansing. Correlations between the existing scoring systems and the computed score were evaluated using the intraclass correlation coefficient and Spearman's rho correlation. RESULTS: All computed measurements were obtained twice and resulted in exactly the same results. Both overall and segmental mucosal visibility could be assessed. The computed score and the 10-point quantitative index were significantly associated for both readers (Spearman's rho: 0.68 and 0.75, respectively; P < 0.001). The intraclass correlation coefficient for the 4-point qualitative evaluation and the computed score was 0.67 for reader 1 and 0.64 for reader 2. For reader 1, the mean computed score for segments assessed as either inadequately or adequately cleansed was 5.0 and 6.4 ( P = 0.001). For reader 2 these values were 4.0 and 6.3, respectively ( P = 0.005). CONCLUSIONS: A computed assessment of small-bowel mucosal visibility based on the ratio of color intensities of the red and green channel of the tissue color bar is feasible and more reproducible than existing subjective scales. Such a computed scale could be integrated into VCE reading software. For this novel scoring system we propose the term Computed Assessment of Cleansing (CAC) score.

Inflammatory bowel disease: a systematic review on the value of diagnostic testing in primary care.

AIM: The clinical presentation of inflammatory bowel disease in primary care represents a diagnostic challenge as its symptoms are heterogeneous and common. To assist the primary care physician, we have summarized the available evidence on diagnostic tests in patients with abdominal symptoms. METHOD: We searched PubMed and Embase and screened references. Studies were selected if the design was a primary diagnostic study. Patients were adults attending with nonacute abdominal symptoms. Tests included clinical assessment, blood or faecal tests or abdominal ultrasonography. Quality assessment using a modified version of the QUADAS tool and data extraction was performed by two reviewers independently. Diagnostic two-by-two tables and pooled estimates of sensitivity and specificity are given. We refrained from pooling when there was considerable clinical or statistical heterogeneity. RESULTS: A total of 24 studies were included. While the diagnostic performance of the individual symptoms was highly variable (range sensitivity 0.0-0.96, specificity 0.09-1.0), the performance of symptom-based classification systems was both more consistent and better (sensitivity 0.65-1.0, specificity 0.17-0.82). Among faecal and blood tests, calprotectin was studied most frequently and showed the best results (sensitivity 0.61-1.0, specificity 0.71-1.0). Statistical pooling for ultrasonography resulted in a sensitivity of 0.73 (0.65-0.80) and a specificity of 0.95 (0.91-0.97). CONCLUSION: Although calprotectin and ultrasonography showed consistent and promising findings, none of the studies was performed in primary care. To assist primary care physicians in diagnostic decision making, we urgently need high quality studies performed in primary care.

Colonic work-up after incomplete colonoscopy: significant new findings during follow-up.

BACKGROUND AND STUDY AIMS: Cecal intubation is not achieved in 2 - 23 % of colonoscopies. The efforts made by physicians to visualize the remaining colon and the number of missed significant lesions are unknown. This study evaluates 1) the reasons for incomplete colonoscopy, 2) the rates of complete colonic evaluation after incomplete colonoscopy, and 3) the number of (pre-) malignant lesions missed by incomplete colonoscopy. PATIENTS AND METHODS: In this population-based cohort study index colonoscopies were performed between September and December 2005. Prospectively collected data from consecutive patients with an incomplete colonoscopy were analyzed. For up to 18 months after the index colonoscopy, any further examinations performed in these patients were identified retrospectively. These secondary examinations included: repeat colonoscopy, computed tomography (CT) colonography, barium enema, abdominal CT scan, and surgery involving the colorectum. RESULTS: Of 5278 colonoscopies, 511 were incomplete (9.7 %). The most frequent causes of incomplete colonoscopy were looping of the scope (20.4 %), patient discomfort (15.3 %), and obstructing tumor (13.9 %). Secondary examination was performed in 278 patients (54.4 %) after incomplete colonoscopy. Patients undergoing surveillance after colorectal cancer (CRC) (78.9 %) and those with anemia (73.1 %) most frequently received a secondary examination. Incomplete colonoscopies due to stenosis (78.9 %), severe inflammation (77.8 %) or an obstructing tumor (74.6 %) were most frequently followed by a secondary examination. In all of the follow-up examinations, CRC was diagnosed in 18 patients (3.5 %) and advanced adenoma in four patients (0.8 %). CONCLUSIONS: In 4.3 % of the patients, advanced neoplasia was missed by incomplete colonoscopy. Our data therefore suggest that additional imaging is obligatory to visualize the remaining colon adequately.

There is no increased risk for colorectal cancer and adenomas in patients with diverticulitis: a retrospective longitudinal study.

AIM: This study was designed to assess the relationship between diverticulitis and the development of colorectal cancer (CRC) and colonic adenomas. METHOD: A retrospective study was longitudinally conducted. Patients who had been admitted to the hospital between 1990 and 2000 with diverticulitis were retrieved and the incidence of CRC and prevalence of colonic adenomas in these patients was determined. Data were collected from the electronic clinical and pathology records. The incidence of CRC and prevalence of adenomas in this patient cohort was compared with the general population. The patients were followed until 2008. RESULTS: A total of 288 patients with diverticulitis were included (167 of whom were female patients [58%]). The mean age of patients at admittance for diverticulitis was 66 years (range: 27-92). CRC was detected in five patients (1.7%) (95% CI 0.8-3.5) with a mean age of 77 years; colonic adenomas were found in 18 patients (6.3%) (95% CI 4.3-9.0) with a mean age of 62 years. The lifetime risks of developing CRC and adenomas were presumed to be 4% and 20% respectively. Expected rates for CRC and adenomas in our patients were calculated as 17 (95% CI 4.0-8.6) and 69 patients (95% CI 20.1-28.3) respectively. CONCLUSION: This study showed a lower prevalence of CRC and colonic adenomas in patients with diverticulitis compared with the lifetime risk which means that diverticulitis is not a risk factor for development of CRC and adenomas. Long-term colonic screening after a negative colonoscopy for diverticulitis (generally performed several weeks after recovery) does not seem to be justified.