Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis

OBJECTIVE: Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. DESIGN: In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. RESULTS: In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). CONCLUSION: The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias

Folic Acid Transport to the Human Fetus Is Decreased in Pregnancies with Chronic Alcohol Exposure

During pregnancy, the demand for folic acid increases since the fetus requires this nutrient for its rapid growth and cell proliferation. The placenta concentrates folic acid into the fetal circulation; as a result the fetal levels are 2 to 4 times higher than the maternal level. Animal and in vitro studies have suggested that alcohol may impair transport of folic acid across the placenta by decreasing expression of transport proteins. We aim to determine if folate transfer to the fetus is altered in human pregnancies with chronic alcohol consumption.Serum folate was measured in maternal blood and umbilical cord blood at the time of delivery in pregnancies with chronic and heavy alcohol exposure (n = 23) and in non-drinking controls (n = 24). In the alcohol-exposed pairs, the fetal:maternal serum folate ratio was ≤ 1.0 in over half (n = 14), whereas all but one of the controls were >1.0. Mean folate in cord samples was lower in the alcohol-exposed group than in the controls (33.15 ± 19.89 vs 45.91 ± 20.73, p = 0.04).Our results demonstrate that chronic and heavy alcohol use in pregnancy impairs folate transport to the fetus. Altered folate concentrations within the placenta and in the fetus may in part contribute to the deficits observed in the fetal alcohol spectrum disorders

Quality of life before and after TVT, a prospective multicentre cohort study, results from the Netherlands TVT database

Objective To asses the long term outcome of tension-free vaginal tape procedure in women with isolated stress urinary incontinence (SUI). Design Prospective cohort study. Setting Twenty-eight teaching hospitals and 13 local hospitals, with 54 gynaecologists and urologists performing the surgery. Sample Eight hundred and nine participants. Methods The Incontinence Impact Questionnaire (lIQ-7) and the Urogenital Distress Inventory (UDI-6) were used to measure the results of the TVT procedure (pre-operative at 2, 6, 12 and 24 months post-operative). According the recommendation of the International Continence Society (ICS), the question `Do you experience urinary leakage during physical activity, coughing or sneezing?' was selected from the UDI to asses SUI. Main outcome measures Incontinence Impact Questionnaire (IIQ-7) and the Urogenital Distress Inventory (UDI-6). Results Both IIQ and UDI mean scores decreased significantly after TVT, indicating an improvement in quality of life. Subjective improvement can improve for up to two years post-operatively. Conclusions This is the largest prospective study that used these validated disease-specific questionnaires to asses the long term outcome of the TVT procedure. This study shows a statistically significant and clinically relevant long term improvement of the quality of life after a TVT for women with SUI

Associations of Height With the Risks of Colorectal and Endometrial Cancer in Persons With Lynch Syndrome

Persons with Lynch syndrome (LS - carrying a pathogenic mutation in a DNA mismatch repair gene) have an increased colorectal cancer (CRC) and endometrial cancer (EC) risk. A high reported variability in cancer risk suggests the existence of factors that modify cancer risk for LS. We aimed to investigate the association between height and CRC and EC for persons with LS using two large studies. Information of 1,213 men and 1,636 women with LS from the Colon Cancer Family Registry (1998-2007) and the GEOLynch cohort study (2006-2017) was harmonized. We used weighted Cox proportional hazard regression models with age on the time-axis to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for each 5 cm increment in self-reported height. CRC was diagnosed in 947 persons during 65,369 person-years of observation and 171 women were diagnosed with EC during 39,227 person-years of observation. Height was not associated with CRC for men (HR 1.00 per 5 cm, 95%CI: 0.91, 1.11) or women (HR 1.01 per 5 cm, 95%CI: 0.92, 1.11). Nor was height associated with EC (HR 1.08 per 5 cm, 95%CI: 0.94, 1.24). Hence, we observed no evidence for an association of height with either CRC or EC for persons with LS

Inulin significantly improves serum magnesium levels in proton pump inhibitor-induced hypomagnesaemia

Proton pump inhibitors (PPI) are among the most widely prescribed drugs to treat gastric acid-related disorders. PPI-induced hypomagnesaemia, a defect in intestinal absorption of Mg(2+) , can be a severe side effect of chronic PPI use.To restore serum Mg(2+) concentrations in PPI-induced hypomagnesaemia patients by dietary supplementation with inulin fibres.Eleven patients with PPI-induced hypomagnesaemia and 10 controls were treated with inulin (20 g/day). Each trial consisted of two cycles of 14-day inulin treatment followed by a washout period of 14 days. Patients continued to use their PPI. Serum Mg(2+) levels served as the primary endpoint.Inulin significantly enhanced serum Mg(2+) levels from 0.60 to 0.68 mmol/L in PPI-induced hypomagnesaemia patients, and from 0.84 to 0.93 mmol/L in controls. As a consequence 24 h urinary Mg(2+) excretion was significantly increased in patients with PPI-induced hypomagnesaemia (0.3-2.2 mmol/day). Symptoms related to hypomagnesaemia, including muscle cramps and paraesthesia, were reduced during intervention with inulin. Inulin increases serum Mg(2+) concentrations under PPI maintenance in patients with PPI-induced hypomagnesaemia

Development and validation of the WASP classification system for optical diagnosis of adenomas, hyperplastic polyps and sessile serrated adenomas/polyps

Objective Accurate endoscopic differentiation would enable to resect and discard small and diminutive colonic lesions, thereby increasing cost-efficiency. Current classification systems based on narrow band imaging (NBI), however, do not include neoplastic sessile serrated adenomas/polyps (SSA/Ps). We aimed to develop and validate a new classification system for endoscopic differentiation of adenomas, hyperplastic polyps and SSA/Ps < 10 mm. Design We developed the Workgroup serrAted polypS and Polyposis (WASP) classification, combining the NBI International Colorectal Endoscopic classification and criteria for differentiation of SSA/Ps in a stepwise approach. Ten consultant gastroenterologists predicted polyp histology, including levels of confidence, based on the endoscopic aspect of 45 polyps, before and after participation in training in the WASP classification. After 6 months, the same endoscopists predicted polyp histology of a new set of 50 polyps, with a ratio of lesions comparable to daily practice. Results The accuracy of optical diagnosis was 0.63 (95% CI 0.54 to 0.71) at baseline, which improved to 0.79 (95% CI 0.72 to 0.86, p< 0.001) after training. For polyps diagnosed with high confidence the accuracy was 0.73 (95% CI 0.64 to 0.82), which improved to 0.87 (95% CI 0.80 to 0.95, p< 0.01). The accuracy of optical diagnosis after 6 months was 0.76 (95% CI 0.72 to 0.80), increasing to 0.84 (95% CI 0.81 to 0.88) considering high confidence diagnosis. The combined negative predictive value with high confidence of diminutive neoplastic lesions (adenomas and SSA/Ps together) was 0.91 (95% CI 0.83 to 0.96). Conclusions We developed and validated the first integrative classification method for endoscopic differentiation of small and diminutive adenomas, hyperplastic polyps and SSA/Ps. In a still image evaluation setting, introduction of the WASP classification significantly improved the accuracy of optical diagnosis overall as well as SSA/P in particular, which proved to be sustainable after 6 months

Diagnostic yield of colonoscopy surveillance in testicular cancer survivors treated with platinum-based chemotherapy: study protocol of a prospective cross-sectional cohort study

Background: Testicular cancer (TC) survivors have an increased risk of various second primary malignancies. A recent cohort study detected an increased risk of colorectal cancer (CRC) in TC survivors treated with platinum-based chemotherapy with a hazard ratio of 3.9. CRC risk increased with higher cisplatin-dose. We know that colonoscopy surveillance in high-risk populations results in reduced incidence and mortality of CRC. TC survivors treated with platinum-based chemotherapy can potentially benefit from colonoscopy surveillance; however, to which extent is unknown. Furthermore, the pathogenesis of these secondary CRCs is unknown, and better insights into the carcinogenesis may affect surveillance decisions. Methods: This prospective multicenter study will be performed in four Dutch hospitals. TC survivors are eligible if treated with ≥ 3 cycles of cisplatin before age 50. Colonoscopy will be performed ≥ 8 years after initial treatment (minimum and maximum ages at colonoscopy, 35 and 75 years, respectively). The primary aim of the study is the diagnostic yield of advanced neoplasia detected during colonoscopy. As secondary aim, we will evaluate the molecular profile of advanced colorectal neoplasia and will assess current platinum levels in blood and urine and correlate blood-platinum levels with prevalence of colorectal lesions. Furthermore, we will investigate effectiveness of fecal immunochemical testing (FIT) and burden of colonoscopy by two questionnaires. Demographic data, previous history, results of colonoscopy, hemoglobin level of FIT and results of molecular and platinum levels will be obtained. Yield of colonoscopy will be determined by detection rate of adenoma and serrated lesions, advanced adenoma detection rate and CRC detection rate. The MISCAN model will be used for cost-effectiveness analyses of CRC surveillance. With 234 participants undergoing colonoscopy, we can detect an absolute difference of 6% of advanced neoplasia with 80% power. Discussion: TC survivors treated with cisplatin-based chemotherapy can benefit from CRC surveillance. Evaluation of the diagnostic performance and patient acceptance of CRC surveillance is of importance to develop surveillance recommendations. Insight into the carcinogenesis of cisplatin-related advanced colorectal lesions will contribute to CRC prevention in the increasing number of TC survivors. The results may also be important for the many other cancer survivors treated with platinum-based chemotherapy. Trial registration: Clinical Trials: NCT04180033, November 27, 2019, https://clinicaltrials.gov/ct2/show/NCT04180033