Screening for variants in TPMT did not reduce the proportions of patients with hematologic ADRs during thiopurine treatment for IBD. However, there was a 10-fold reduction in hematologic ADRs among variant carriers who were identified and received a dose reduction, compared with variant carriers who did not, without differences in treatment efficacy. ClinicalTrials.gov number: NCT00521950.

The complication rate with PEG placement is high with both the push and pull methods. The complication rate with the pull method is significantly reduced when antibiotic prophylaxis is used.

NTR5561.

Adequate folate availability is necessary to sustain normal DNA synthesis and normal patterns of DNA methylation and these features of DNA can be modified by methylenetetrahydrofolate reductase (MTHFR) C677T genotype. This study investigated the effect of MTHFR C677T genotype and daily supplementation with 5 mg folic acid and 1.25 mg vitamin B-12 on uracil misincorporation into DNA and promoter methylation. Subjects (n = 86) with a history of colorectal adenoma and MTHFR CC or TT genotype were randomly assigned to receive folic acid plus vitamin B-12 or placebo for 6 mo. Uracil misincorporation and promoter methylation of 6 tumor suppressor and DNA repair genes were assessed in DNA from rectal biopsies at baseline and after the intervention. The biomarkers did not differ between the treated group and the placebo group after 6 mo compared with baseline. The uracil concentration of DNA increased in the treated group (5.37 fmol/microg DNA, P = 0.02), whereas it did not change in the placebo group (P = 0.42). The change from baseline of 4.01 fmol uracil/microg DNA tended to differ between the groups (P = 0.16). An increase in promoter methylation tended to occur more often in the intervention group than in the placebo group (OR = 1.67; P = 0.08). This study suggests that supplementation with high doses of folic acid and vitamin B-12 may not favorably influence uracil incorporation and promoter methylation in subjects with previous colorectal adenomas. Because such alterations may potentially increase the risk of neoplastic transformation, more research is needed to fully define the consequences of these molecular alterations.

BackgroundIn patients with stage II colorectal cancer (CRC) the number of surgically retrieved lymph nodes (LNs) is associated with prognosis, resulting in a minimum of 10–12 retrieved LNs being recommended for this stage. Current guidelines do not provide a recommendation regarding LN yield in T1 CRC. Studies evaluating LN yield in T1 CRC suggest that such high LN yields are not feasible in this early stage, and a lower LN yield might be appropriate. We aimed to validate the cut-off of 10 retrieved LNs on risk for recurrent cancer and detection of LN metastasis (LNM) in T1 CRC, and explored whether this number is feasible in clinical practice.MethodsPatients diagnosed with T1 CRC and treated with surgical resection between 2000 and 2014 in thirteen participating hospitals were selected from the Netherlands Cancer Registry. Medical records were reviewed to collect additional information. The association between LN yield and recurrence and LNM respectively were analyzed using 10 LNs as cut-off. Propensity score analysis using inverse probability weighting (IPW) was performed to adjust for clinical and histological confounding factors (i.e., age, sex, tumor location, size and morphology, presence of LNM, lymphovascular invasion, depth of submucosal invasion, and grade of differentiation).ResultsIn total, 1017 patients with a median follow-up time of 49.0 months (IQR 19.6–81.5) were included. Four-hundred five patients (39.8%) had a LN yield ≥ 10. Forty-one patients (4.0%) developed recurrence. LN yield ≥ 10 was independently associated with a decreased risk for recurrence (IPW-adjusted HR 0.20; 95% CI 0.06–0.67; P = 0.009). LNM were detected in 84 patients (8.3%). LN yield ≥ 10 was independently associated with increased detection of LNM (IPW-adjusted OR 2.27; 95% CI 1.39–3.69; P = 0.001).ConclusionsIn this retrospective observational study, retrieving < 10 LNs was associated with an increased risk of CRC recurrence, advocating the importance to perform an appropriate oncologic resection of the draining LNs and diligent LN search when patients with T1 CRC at high-risk for LNM are referred for surgical resection. Given that both gastroenterologists, surgeons and pathologists will encounter T1 CRCs with increasing frequency due to the introduction of national screening programs, awareness on the consequences of an inadequate LN retrieval is of utmost importance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0892-7) contains supplementary material, which is available to authorized users.