Objective We aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals. Design From 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit. Results 366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1–32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001). Conclusion The diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.

Background Endoscopic ultrasound (EUS)-guided tissue acquisition is extensively used, but the optimal sampling device is still a matter of debate. We performed meta-analyses on studies comparing fine-needle aspiration (FNA) with fine-needle biopsy (FNB) needles, and studies comparing different FNB needles.Methods Online databases were searched for randomized controlled trials (RCTs) of at least 50 cases with a suspected solid pancreatic or nonpancreatic lesion that compared FNA with FNB needles. Outcome measures included diagnostic accuracy, adequacy, number of passes, presence of tissue cores, and adverse events. We also performed meta-regression analysis on the effect of FNB design on diagnostic accuracy. Quality was assessed using the QUADAS-2 tool.Results 18 RCTs comparing FNA with FNB needles were included. FNB provided a higher pooled diagnostic accuracy (87 % vs. 80 %; P = 0.02) and tissue core rate (80 % vs. 62 %; P = 0.002), and allowed diagnosis with fewer passes (P = 0.03), in both pancreatic and nonpancreatic lesions. A total of 93 studies were included comparing different FNB devices. Pooled diagnostic accuracy was higher for forward-facing bevel needles than for the reverse bevel needle. In this analysis, study quality was low and heterogeneity was high (I2 = 80 %).Conclusion FNB outperformed FNA when sampling pancreatic and nonpancreatic lesions. Forward-facing bevel FNB needles seemed to outperform the reverse bevel FNB needle, but the low quality of evidence prevents us from making strong recommendations on the optimal FNB design.

Objective: A healthy lifestyle is the first-line treatment in non-alcoholic fatty liver disease (NAFLD), but specific dietary recommendations are lacking. Therefore, we aimed to determine whether dietary macronutrient composition is associated with NAFLD.Design: Participants from the Rotterdam Study were assessed on (1) average intake of macronutrients (protein, carbohydrate, fat, fibre) using a Food Frequency Questionnaire and (2) NAFLD presence using ultrasonography, in absence of excessive alcohol, steatogenic drugs and viral hepatitis. Macronutrients were analysed using the nutrient density method and ranked (Q1–Q4). Logistic regression analyses were adjusted for sociodemographic, lifestyle and metabolic covariates. Moreover, analyses were adjusted for and stratified by body mass index (BMI) (25 kg/m²). Also, substitution models were built.Results: In total, 3882 participants were included (age 70±9, 58% female). NAFLD was present in 1337 (34%) participants of whom 132 were lean and 1205 overweight. Total protein was associated with overweight NAFLD after adjustment for sociodemographic and lifestyle covariates (OR_Q4vsQ1 1.40; 95% CI 1.11 to 1.77). This association was driven by animal protein (OR_Q4vsQ1 1.54; 95% CI 1.20 to 1.98). After adjustment for metabolic covariates, only animal protein remained associated with overweight NAFLD (OR_Q4vsQ1 1.36; 95% CI 1.05 to 1.77). Monosaccharides and disaccharides were associated with lower overall NAFLD prevalence (OR_Q4vsQ1 0.66; 95% CI 0.52 to 0.83) but this effect diminished after adjustment for metabolic covariates and BMI. No consistent associations were observed for fat subtypes or fibre. There were no substitution effects.Conclusion: This large population-based study shows that high animal protein intake is associated with NAFLD in overweight, predominantly aged Caucasians, independently of well-known risk factors. Contrary to previous literature, our results do not support a harmful association of monosaccharides and disaccharides with NAFLD.

Background: Creatinine is the most widely used test to estimate the glomerular filtration rate (GFR), but muscle mass as key determinant of creatinine next to renal function may confound such estimates. We explored effects of 24‐h height‐indexed creatinine excretion rate (CER index) on GFR estimated with creatinine (eGFR_Cr), muscle mass‐independent cystatin C (eGFR_Cys), and the combination of creatinine and cystatin C (eGFR_Cr‐Cys) and predicted probabilities of discordant classification given age, sex, and CER index.Methods: We included 8076 adults enrolled in the PREVEND study. Discordant classification was defined as not having eGFR_Cr <60 mL/min per 1.73 m² when eGFR_Cys was <60 mL/min/1.73 m². Baseline effects of age and sex on CER index were quantified with linear models using generalized least squares. Baseline effects of CER index on eGFR were quantified with quantile regression and logistic regression. Effects of annual changes in CER index on trajectories of eGFR were quantified with linear mixed‐effects models. Missing observations in covariates were multiply imputed.Results: Mean (SD) CER index was 8.0 (1.7) and 6.1 (1.3) mmol/24 h per meter in male and female participants, respectively (P_difference < 0.001). In male participants, baseline CER index increased until 45 years of age followed by a gradual decrease, whereas a gradual decrease across the entire range of age was observed in female participants. For a 70‐year‐old male participant with low muscle mass (CER index of 2 mmol/24 h per meter), predicted baseline eGFR_Cr and eGFR_Cys disagreed by 24.7 mL/min/1.73 m² (and 30.1 mL/min/1.73 m² when creatinine was not corrected for race). Percentages (95% CI) of discordant classification in male and female participants aged 60 years and older with low muscle mass were 18.5% (14.8–22.1%) and 15.2% (11.4–18.5%), respectively. For a 70‐year‐old male participant who lost muscle during follow‐up, eGFR_Cr and eGFR_Cys disagreed by 1.5, 5.0, 8.5, and 12.0 mL/min/1.73 m² (and 6.7, 10.7, 13.5, and 15.9 mL/min/1.73 m² when creatinine was not corrected for race) at baseline, 5 years, 10 years, and 15 years of follow‐up, respectively.Conclusions: Low muscle mass may cause considerable overestimation of single measurements of eGFR_Cr. Muscle wasting may cause spurious overestimation of repeatedly measured eGFR_Cr. Implementing muscle mass‐independent markers for estimating renal function, like cystatin C as superior alternative to creatinine, is crucial to accurately assess renal function in settings of low muscle mass or muscle wasting. This would also eliminate the negative consequences of current race‐based approaches.