Methylation, Lifestyle and Genes in the Pathogenesis and Prevention of Human Congenital Heart Diseases

Up until now, only approximately 15% of the CHD can be attributed to a known cause. The remaining 85% is thought to result from interactions between genetic predispositions and periconception environmental exposures. Folate, a B vitamin involved i

Nationwide treatment and outcomes of intrahepatic cholangiocarcinoma

Background: Most data on the treatment and outcomes of intrahepatic cholangiocarcinoma (iCCA) derives from expert centers. This study aimed to investigate the treatment and outcomes of all patients diagnosed with iCCA in a nationwide cohort. Methods: Data on all patients diagnosed with iCCA between 2010 and 2018 were obtained from the Netherlands Cancer Registry. Results: In total, 1747 patients diagnosed with iCCA were included. Resection was performed in 292 patients (17%), 548 patients (31%) underwent palliative systemic treatment, and 867 patients (50%) best supportive care (BSC). The OS median and 1-, and 3-year OS were after resection: 37.5 months (31.0–44.0), 79.2%, and 51.6%,; with systemic therapy, 10.0 months (9.2–10.8), 38.4%, and 5.1%, and with BSC 2.2 months (2.0–2.5), 10.4%, and 1.3% respectively. The resection rate for patients who first presented in academic centers was 33% (96/292) compared to 13% (195/1454) in non-academic centers (P < 0.001). Discussion: Half of almost 1750 patients with iCCA over an 8 year period did not receive any treatment with a 1-year OS of 10.4%. Three-year survival was about 50% after resection, while long-term survival was rare after palliative treatment. The resection rate was higher in academic centers compared to non-academic centers

Curriculum for diagnostic endoscopic ultrasound training in Europe : European Society of Gastrointestinal Endoscopy (ESGE) Position Statement

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Preoperative endoscopic biliary drainage by metal versus plastic stents for resectable perihilar cholangiocarcinoma

Background and Aims: Adequate preoperative biliary drainage (PBD) is recommended in most patients with resectable perihilar cholangiocarcinoma (pCCA). Most expert centers use endoscopic plastic stents rather than self-expandable metal stents (SEMSs). In the palliative setting, however, use of SEMSs has shown longer patency and superior survival. The aim of this retrospective study was to compare stent dysfunction of SEMSs versus plastic stents for PBD in resectable pCCA patients. Methods:In this multicenter international retrospective cohort study, patients with potentially resectable pCCAs who underwent initial endoscopic PBD from 2010 to 2020 were included. Stent failure was a composite end point of cholangitis or reintervention due to adverse events or insufficient PBD. Other adverse events, surgical outcomes, and survival were recorded. Propensity score matching (PSM) was performed on several baseline characteristics. Results: A total of 474 patients had successful stent placement, of whom 61 received SEMSs and 413 plastic stents. PSM (1:1) resulted in 2 groups of 59 patients each. Stent failure occurred significantly less in the SEMSs group (31% vs 64%; P &lt; .001). Besides less cholangitis after SEMSs placement (15% vs 31%; P = .012), other PBD-related adverse events did not differ. The number of patients undergoing surgical resection was not significantly different (46% vs 49%; P = .71). Complete intraoperative SEMSs removal was successful and without adverse events in all patients. Conclusions: Stent failure was lower in patients with SEMSs as PBD compared with plastic stents in patients with resectable pCCA. Removal during surgery was quite feasible. Surgical outcomes were similar.</p

Diagnostic accuracy of endoscopic ultrasonography-guided tissue acquisition prior to resection of pancreatic carcinoma:a nationwide analysis

Introduction: Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM). Aim: assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands. Patients and methods: Results of all EUS + TA prior to resection of pancreatic carcinoma from 2014–2018, were extracted from the national Dutch Pathology Registry (PALGA). Pathology reports were classified as: insufficient for analysis (b1), benign (b2), atypia (b3), neoplastic other (b4), suspected malignant (b5), and malignant (b6). RAS was defined as the proportion of EUS procedures yielding specimen sufficient for analysis. SFM was calculated using a strict definition (malignant only, SFM-b6), and a broader definition (SFM-b5+6). Results: 691 out of 1638 resected patients (42%) underwent preoperative EUS + TA. RAS was 95% (range 89–100%), SFM-b6 was 44% (20–77%), and SFM-b5+6 was 65% (53–90%). All centers met the performance target RAS&gt;85%. Only 9 out of 17 met the performance target SFM-b5+6 &gt; 85%. Conclusion: This nationwide study detected significant practice variation regarding KPI of EUS + TA procedures prior to surgical resection of pancreatic carcinoma. Therefore, quality improvement of EUS + TA is indicated

Body Mass Index Is an Important Determinant of Methylation Biomarkers in Women of Reproductive Ages

B vitamin deficiencies lead to moderate hyperhomocysteinemia, which has been associated with health and disease. However, concomitant derangements in cellular methylation, reflected by altered plasma S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) concentrations, may be the primary cause. Therefore, we identified determinants of homocysteine, SAM, and SAH concentrations in 336 women, aged 20-48 y, as part of a large study focusing on risk factors for reproductive disorders, Blood was obtained to determine plasma SAM, SAH, and total homocysteine (tHcy), serum vitamin B-12 and folate, RBC folate concentrations, and the related single nucleotide polymorphisms 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C > T and 1298A > C, methionine synthase reductase (MTRR) 66A > G, and nicotinamide A methyltransferase IVS1-151G > A. Questionnaires provided information on demographics, lifestyles, and nutrient intakes. Correlation coefficients were calculated and multivariable associations were assessed with a general linear model. Serum folate was positively correlated with SAM concentrations (r = 0.159; P = 0.004). Folate and vitamin B-12 were not correlated with SAH concentrations or the SAM:SAH ratio but were inversely correlated with tHcy concentrations (serum folate r = -0.324; RBC folate r = -0.294; vitamin B-12 r = -0.307; P < 0.01). From the multivariable analysis, BMI was the strongest determinant of SAM (standardized beta = 19.145; P < 0.001) and SAH concentrations (standardized beta = 3.241; P = 0.010). MTHFR 677TT (standardized beta = 0.195; P = 0.001), B vitamin supplement use (standardized beta = -0.156; P < 0.001) and dietary protein intake (standardized beta = -0.011; P < 0.001) were the strongest determinants of tHcy concentrations. Thus, the determinants of SAM and SAH differ from those of tHcy concentrations. Given that BMI was a strong determinant of SAM concentrations, it should be included in future studies on cellular methylation. J. Nutr. 139: 2315-2321, 2009