Nonmetastatic pancreatic cancer : Improved survival with chemoradiotherapy > 40 Gy after systemic treatment.

PURPOSE: The role of radiotherapy (RT) for nonmetastatic pancreatic cancer is still a matter of debate since randomized control trials have shown inconsistent results. The current retrospective single-institution study includes both resected and unresected patients with nonmetastasized pancreatic cancer. The aim is to analyze overall survival (OS) after irradiation combined with induction chemotherapy. PATIENTS AND METHODS: Of the 73 patients with nonmetastatic pancreatic cancer eligible for the present analysis, 42 (58%) patients had adjuvant chemoradiotherapy (CRT), while 31 (42%) received CRT as primary treatment. In all, 65 (89%) had chemotherapy at any time before, during, or after RT, and 39 (53%) received concomitant CRT. The median total dose was 50 Gy (range 12-77 Gy), while 61 (84%) patients received >40 Gy. RESULTS: With a median follow-up of 22 months (range 1.2-179.8 months), 14 (19%) are still alive and 59 (81%) of the patients have died, whereby 51 (70%) were cancer-related deaths. Median OS and the 2­year survival rate were 22.9 months (1.2-179.8 months) and 44%, respectively. In addition, 61 (84%) patients treated with >40 Gy had a survival advantage (median OS 23.7 vs. 17.3 months, p = 0.026), as had patients with 4 months minimum of systemic treatment (median OS 27.5 vs. 14.3 months, p = 0.0004). CONCLUSION: CRT with total doses >40 Gy after induction chemotherapy leads to improved OS in patients with nonmetastatic pancreatic cancer.

A sex-specific propensity-adjusted analysis of colonic adenoma detection rates in a screening cohort.

The prevalence of colorectal adenoma and advanced adenoma (AA) differs between sexes. Also, the optimal age for the first screening colonoscopy is under debate. We, therefore, performed a sex-specific and age-adjusted comparison of adenoma, AA and advanced neoplasia (AN) rates in a real-world screening cohort. In total, 2824 asymptomatic participants between 45- and 60-years undergoing screening colonoscopy at a single-centre in Austria were evaluated. 46% were females and mean age was 53 ± 4 years. A propensity score for being female was calculated, and adenoma, AA and AN detection rates evaluated using uni- and multivariable logistic regression. Sensitivity analyses for three age groups (group 1: 45 to 49 years, n = 521, 41% females, mean age 47 ± 1 years; group 2: 50 to 54 years, n = 1164, 47% females, mean age 52 ± 1 years; group 3: 55 to 60 years, n = 1139, 46% females, mean age 57 ± 2 years) were performed. The prevalence of any adenoma was lower in females (17% vs. 30%; OR 0.46, 95% CI 0.38-0.55; p < 0.001) and remained so after propensity score adjustment for baseline characteristics and lifestyle factors (aOR 0.52, 95% CI 0.41-0.66; p < 0.001). The same trend was seen for AA with a significantly lower prevalence in females (3% vs. 7%; OR 0.38, 95% CI 0.26-0.55; p < 0.001) that persisted after propensity score adjustment (aOR 0.54, 95% CI 0.34-0.86; p = 0.01). Also, all age-group sensitivity analyses showed lower adenoma, AA and AN rates in females. Similar numbers needed to screen to detect an adenoma, an AA or AN were found in female age group 3 and male age group 1. Colorectal adenoma, AA and AN were consistently lower in females even after propensity score adjustment and in all age-adjusted sensitivity analyses. Our study may add to the discussion of the optimal age for initial screening colonoscopy which may differ between the sexes.

Machine Learning Models Cannot Replace Screening Colonoscopy for the Prediction of Advanced Colorectal Adenoma.

Screening for colorectal cancer (CRC) continues to rely on colonoscopy and/or fecal occult blood testing since other (non-invasive) risk-stratification systems have not yet been implemented into European guidelines. In this study, we evaluate the potential of machine learning (ML) methods to predict advanced adenomas (AAs) in 5862 individuals participating in a screening program for colorectal cancer. Adenomas were diagnosed histologically with an AA being ≥ 1 cm in size or with high-grade dysplasia/villous features being present. Logistic regression (LR) and extreme gradient boosting (XGBoost) algorithms were evaluated for AA prediction. The mean age was 58.7 ± 9.7 years with 2811 males (48.0%), 1404 (24.0%) of whom suffered from obesity (BMI ≥ 30 kg/m²), 871 (14.9%) from diabetes, and 2095 (39.1%) from metabolic syndrome. An adenoma was detected in 1884 (32.1%), as well as AAs in 437 (7.5%). Modelling 36 laboratory parameters, eight clinical parameters, and data on eight food types/dietary patterns, moderate accuracy in predicting AAs with XGBoost and LR (AUC-ROC of 0.65-0.68) could be achieved. Limiting variables to established risk factors for AAs did not significantly improve performance. Moreover, subgroup analyses in subjects without genetic predispositions, in individuals aged 45-80 years, or in gender-specific analyses showed similar results. In conclusion, ML based on point-prevalence laboratory and clinical information does not accurately predict AAs.

Nonalcoholic Fatty Liver Disease in Lean Subjects: Associations With Metabolic Dysregulation and Cardiovascular Risk-A Single-Center Cross-Sectional Study.

INTRODUCTION: Although a milder metabolic phenotype of nonalcoholic fatty liver disease (NAFLD) in lean patients (body mass index [BMI] <25 kg/m2) compared to overweight/obese patients with NAFLD is assumed, the relevance of NAFLD among lean subjects remains a matter of debate. We aimed to characterize the metabolic/cardiovascular phenotype of lean patients with NAFLD. METHODS: In total, 3,043 subjects (cohort I) and 1,048 subjects (cohort II) undergoing screening colonoscopy between 2010 and 2020 without chronic liver disease other than NAFLD were assigned to one of the following groups: lean patients without NAFLD, lean NAFLD, overweight NAFLD (BMI 25-30 kg/m2), and obese NAFLD (BMI >30 kg/m2). Diagnosis of NAFLD was established using ultrasound (cohort I) and controlled attenuation parameter (cohort II). RESULTS: The prevalence of lean patients with NAFLD was 6.7%/16.1% in the overall cohort I/II and 19.7%/40.0% in lean subjects of cohort I/II. Compared with lean subjects without NAFLD, lean patients with NAFLD had a higher prevalence of dyslipidemia, dysglycemia, and the metabolic syndrome, together with a higher median Framingham risk score in both cohorts (all P < 0.001). On multivariable analyses, NAFLD in lean subjects was associated with higher odds of metabolic syndrome (adjusted odds ratio cohort I: 4.27 [95% confidence interval (CI): 2.80-6.51], P < 0.001; cohort II: 2.97 [95% CI: 1.40-6.33], P < 0.001), and higher Framingham risk score (regression coefficient B cohort I: 1.93 [95% CI: 0.95-2.92], P < 0.003; cohort II: 1.09 [95% CI: 0.81-2.10], P = 0.034), among others. Only 69.8% of lean patients with NALFD in cohort I and 52.1% in cohort II fulfilled the novel criteria for metabolic associated fatty liver disease. DISCUSSION: NAFLD in lean patients is associated with the metabolic syndrome and increased cardiovascular risk. Novel metabolic associated fatty liver disease criteria leave a considerable proportion of patients unclassified.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)-Rather a Bystander Than a Driver of Mortality.

CONTEXT: Recently, the novel metabolic dysfunction-associated fatty liver disease (MAFLD) definition has been introduced. OBJECTIVE: To assess the relevance of MAFLD for mortality. METHODS: Single-center cohort-study using colorectal cancer screening program involving 4718 subjects aged 45 to 80 who were grouped according to their body mass index (BMI) and the presence or absence of MAFLD. Mortality was compared among these groups by performing a systematic read-out of the national health insurance system, fatty liver (FL) was diagnosed using ultrasound. RESULTS: Overall prevalence of FL was 47.9%: 1200 (25.4%) patients were lean (BMI < 25 kg/m2) and did not have MAFLD, 73 (1.5%) patients were lean and had nonalcoholic fatty liver disease but did not fulfill criteria for MAFLD, and 221 (4.7%) patients were lean and fulfilled criteria for MAFLD. Additionally, 1043 (22.1%) and 925 (19.6%) subjects had MAFLD with overweight (BMI 25-30 kg/m2) and obesity (BMI ≥ 30 kg/m2), respectively, while 1041 (22.1%) and 215 (4.6%) had overweight and obesity, respectively, without FL. During a median follow-up of 7.5 (interquartile range: 4.0-9.6) years, 278 deaths (5.9%) occurred. Of these, 98 (2.1%) were cancer-related, 65 (1.4%) were cardiovascular, and 17 (0.4%) were liver-related. Overall survival was similar between patient strata (after 5 years: 93.9%-98.2%) with lean MAFLD having the numerically worst survival. Although lean and overweight patients with MAFLD had a numerically worse outcome compared to their non-MAFLD counterparts, this association was driven by age and metabolic comorbidities (predominantly diabetes) rather than the presence of MAFLD. CONCLUSION: Presence of MAFLD does not increase mortality in a cohort of individuals aged 45 to 80 years.

Nut consumption and the prevalence and severity of non-alcoholic fatty liver disease.

BACKGROUND: Nut consumption has been associated with reduced inflammation, insulin resistance, and oxidative stress. However, the influence on the prevalence and severity of non-alcoholic fatty liver disease (NAFLD) has yet to be evaluated. METHODS: 4655 subjects were included as part of a colorectal carcinoma screening program (SAKKOPI) between 07/2010 and 07/2019 and analyzed 2020. Patients were characterized using biochemical and metabolic parameters, as well as a detailed questionnaire on dietary habits. The diagnosis of NAFLD was established using abdominal ultrasound. Consumption of nuts was graded as: no consumption or <1 time/week, 1-6 times/week, 1 time/day and ≥2 times/day. RESULTS: Mean age was 58.5±9.8years with a mean BMI of 26.5±4.7kg/m2. 2058 (44.2%) patients suffered from the metabolic syndrome, 2407 (51.6%) had arterial hypertension, 2287 (49.1%) showed prediabetes/diabetes, 1854 (39.4%) had dyslipidemia and 1984 patients (43.5%) were diagnosed with NAFLD. Prevalence of metabolic syndrome (1219 [48.7%] vs. 605 [40.2%] vs. 189 [37.4%] vs. 45 [31.7%], p<0.001) and NALFD (1184 [48.1%] vs. 594 [40.7%] vs. 158 [31.7%] vs. 48 [34.0%], p<0.001). On multivariable logistic regression analysis adjusting for potential confounders and dietary patterns, nut consumption ≥1time/day was inversely associated with NAFLD in the overall cohort (adjusted Odds ratio[aOR]: 0.719 [95%CI:0.558-0.926], p = 0.011). However, following subgroup analysis, this inverse association was only confirmed in male patients (aOR: 0.589 [95%CI: 0.411-0.844], p = 0.004) but not in females (aOR: 0.886 [95%CI: 0.616-1.275], p = 0.515). Moreover, patients who consumed nuts 1-6 times/week had a significantly lower prevalence of advanced fibrosis (Fib-4 score >2.67: aOR: 0.551 [95%CI: 0.338-0.898], p = 0.017; Forns-Index >6.9: aOR: 0.585 [95%CI: 0.402-0.850], p = 0.005). CONCLUSIONS: Nut consumption might exert beneficial effects on the prevalence of NAFLD in males. The negative association with advanced fibrosis warrants further investigation.

Diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD) Is Independently Associated with Cardiovascular Risk in a Large Austrian Screening Cohort.

BACKGROUND: Many patients with non-alcoholic fatty liver disease (NAFLD) simultaneously suffer from cardiovascular (CV) disease and often carry multiple CV risk factors. Several CV risk factors are known to drive the progression of fibrosis in patients with NAFLD. OBJECTIVES: To investigate whether an established CV risk score, the Framingham risk score (FRS), is associated with the diagnosis of NAFLD and the degree of fibrosis in an Austrian screening cohort for colorectal cancer. MATERIAL AND METHODS: In total, 1965 asymptomatic subjects (59 ± 10 years, 52% females, BMI 27.2 ± 4.9 kg/m2) were included in this study. The diagnosis of NAFLD was present if (1) significantly increased echogenicity in relation to the renal parenchyma was present in ultrasound and (2) viral, autoimmune or hereditary liver disease and excess alcohol consumption were excluded. The FRS (ten-year risk of coronary heart disease) and NAFLD Fibrosis Score (NFS) were calculated for all patients. High CV risk was defined as the highest FRS quartile (>10%). Both univariable and multivariable logistic regression models were used to calculate associations of FRS with NAFLD and NFS. RESULTS: Compared to patients without NAFLD (n = 990), patients with NAFLD (n = 975) were older (60 ± 9 vs. 58 ± 10 years; p < 0.001), had higher BMI (29.6 ± 4.9 vs. 24.9 ± 3.6 kg/m2; p < 0.001) and suffered from metabolic syndrome more frequently (33% vs. 7%; p < 0.001). Cardiovascular risk as assessed by FRS was higher in the NAFLD-group (8.7 ± 6.4 vs. 5.4 ± 5.2%; p < 0.001). A one-percentage-point increase of FRS was independently associated with NAFLD (OR 1.04, 95%CI 1.02-1.07; p < 0.001) after correction for relevant confounders in multivariable logistic regression. In patients with NAFLD, NFS correlated with FRS (r = 0.29; p < 0.001), and FRS was highest in patients with significant fibrosis (F3-4; 11.7 ± 5.4) compared to patients with intermediate results (10.9 ± 6.3) and those in which advanced fibrosis could be ruled-out (F0-2, 7.8 ± 5.9, p < 0.001). A one-point-increase of NFS was an independent predictor of high-risk FRS after correction for sex, age, and concomitant diagnosis of metabolic syndrome (OR 1.30, 95%CI 1.09-1.54; p = 0.003). CONCLUSION: The presence of NAFLD might independently improve prediction of long-term risk for CV disease and the diagnosis of NAFLD might be a clinically relevant piece in the puzzle of predicting long-term CV outcomes. Due to the significant overlap of advanced NAFLD and high CV risk, aggressive treatment of established CV risk factors could improve prognosis in these patients.

Atrial Fibrillation: A New Indicator for Advanced Colorectal Neoplasia in Screening Colonoscopy.

BACKGROUND: Colorectal cancer (CRC) is a common and potentially preventable malignancy. Evidence has emerged that coronary artery disease patients are at increased risk for developing CRC by shared risk factors. Here we investigated an association between CRC and atrial fibrillation (AF), a surrogate marker of cardiovascular risk, in the setting of routine screening colonoscopy. METHODS: We investigated 1949 asymptomatic participants (median age 61 [54-67] years, 49% females) undergoing screening colonoscopy within the SAKKOPI registry (Salzburg Colon Cancer Prevention Initiative). Forty-six participants with AF (2.4%) were identified, and colonoscopy findings were compared to non-AF participants. Propensity Score Matching (PSM) was used to create 1:1 and 3:1 age- and gender-matched couples. RESULTS: Abnormal findings on screening colonoscopy (any form of adenoma or carcinoma) were more common in AF participants with an odds ratios (OR) of 2.4 [1.3-4.3] in the unmatched analysis, and 2.6 [1.1-6.3] and 2.0 [1.1-4.0] in the 1:1 and 3:1 matched groups, respectively. Correspondingly, the odds of finding advanced adenomas or carcinomas was elevated about three-fold across the different matched and unmatched analyses (OR 3.3 [1.1-10.8] for 3:1 matched participants). At the same time, the prevalence and number of colonic lesions were significantly higher in AF participants (63.0% vs. 33.4% for 3:1 matched participants, p < 0.001). Non-CRC related findings on colonoscopy, like diverticulosis, were non-different between groups. CONCLUSION: Participants with AF had a higher burden of advanced premalignant adenomas and CRC in routine colonoscopy screening. Our data suggest that practitioners should monitor the CRC screening status, especially in AF patients.