1.
Diagnostic performance of 18F-choline PET-CT in prostate cancer.
Samper Ots, P, Luis Cardo, A, Vallejo Ocaña, C, Cabeza Rodríguez, MA, Glaria Enríquez, LA, Couselo Paniagua, ML, Olivera Vegas, J
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2019;(6):766-773
Abstract
OBJECTIVES To evaluate the diagnostic performance of 18F-choline PETCT in staging prostate cancer (PC) and whether the use of this imaging modality changes the therapeutic decision in patients previously staged by conventional imaging. The secondary aim was to determine the prognostic factors associated with positive choline PETCT findings in both detection of disseminated disease and in changes in the therapeutic indication. MATERIALS AND METHODS Multicentre, retrospective, observational study of 269 patients diagnosed with PC. Mean age was 69 ± 9.2 years. Of the 269 patients, 62 (23%) had high-risk localized PC (group 1), 118 (43.9%) biochemical failure after radical prostatectomy (group 2), and 89 (33.1%) biochemical failure after radiotherapy (group 3). None of the patients showed clear evidence of distant disease on computed tomography or bone scans. The following potential prognostic factors were assessed: PSA level at diagnosis; primary and secondary Gleason; Gleason score (GS); clinical and pathologic T and N stage; number of positive cylinders in the biopsy; presence of vascular or lymphatic invasion; status of surgical margins; androgen deprivation therapy (ADT); time to biochemical recurrence; and PSA, PSA doubling time (PSADT), and PSA velocity (PSAV) at failure. Univariate and multivariate analyses were performed, and receiver-operating curves calculated. RESULTS The mean PSA by groups was, group 1: 31.22 ng/ml, group 2: 2.52 ng/ml and group 3: 5.85 ng/ml. The tumor detection rate with 18F-choline PETCT was 74% (group 1: 85.5%, group 2: 55.1% and group 3: 91%). Prognostic factors for positive 18F-choline PETCT were identified only in group 2: PSA at failure and PSADT. 18F-choline PETCT changed the therapeutic indication in 62.8% (group 1: 71%, group 2: 55.2% and group 3: 70.1%). The prognostic factors for a change in treatment were identified only in group 1: secondary Gleason ≤ 4 and GS ≤ 7 and in group 2: PSA at failure, PSA nadir after surgery and pathologic stage N0. 18F-choline PETCT identified lymph node and/or metastatic disease in 32.7% (group 1: 25.8%, group 2: 29.7% and group 3: 41.6%). Prognostic factors for detecting lymph node/metastasis were identified in the group 2: PSA failure ≥ 1.37 ng/ml and PSADT < 4 months and in the group 3: PSADT < 4.6 months and time to failure < 5 years. CONCLUSION These findings support the clinical use de 18F-choline PET-CT in staging high-risk patients with a secondary Gleason ≤ 4 and GS ≤ 7, in restaging patients with biochemical recurrence after RP if PSA at failure ≥ 1.37 ng/ml or PSADT ≤ 4 months and in patients with biochemical failure after RT, if PSADT ≤ 4.6 months and time to failure < 5 years, because it determines a change in the therapeutic indication.
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Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study.
Guasch-Ferré, M, Hu, FB, Ruiz-Canela, M, Bulló, M, Toledo, E, Wang, DD, Corella, D, Gómez-Gracia, E, Fiol, M, Estruch, R, et al
Journal of the American Heart Association. 2017;(11)
Abstract
BACKGROUND The relationship between plasma concentrations of betaine and choline metabolism and major cardiovascular disease (CVD) end points remains unclear. We have evaluated the association between metabolites from the choline pathway and risk of incident CVD and the potential modifying effect of Mediterranean diet interventions. METHODS AND RESULTS We designed a case-cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography-tandem mass spectrometry to measure, at baseline and at 1 year of follow-up, plasma concentrations of 5 metabolites in the choline pathway: trimethylamine N-oxide, betaine, choline, phosphocholine, and α-glycerophosphocholine. We have calculated a choline metabolite score using a weighted sum of these 5 metabolites. We used weighted Cox regression models to estimate CVD risk. The multivariable hazard ratios (95% confidence intervals) per 1-SD increase in choline and α-glycerophosphocholine metabolites were 1.24 (1.05-1.46) and 1.24 (1.03-1.50), respectively. The baseline betaine/choline ratio was inversely associated with CVD. The baseline choline metabolite score was associated with a 2.21-fold higher risk of CVD across extreme quartiles (95% confidence interval, 1.36-3.59; P<0.001 for trend) and a 2.27-fold higher risk of stroke (95% confidence interval, 1.24-4.16; P<0.001 for trend). Participants in the higher quartiles of the score who were randomly assigned to the control group had a higher risk of CVD compared with participants in the lower quartile and assigned to the Mediterranean diet groups (P=0.05 for interaction). No significant associations were observed for 1-year changes in individual plasma metabolites and CVD. CONCLUSIONS A metabolite score combining plasma metabolites from the choline pathway was associated with an increased risk of CVD in a Mediterranean population at high cardiovascular risk. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.
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Choline intake in a large cohort of patients with nonalcoholic fatty liver disease.
Guerrerio, AL, Colvin, RM, Schwartz, AK, Molleston, JP, Murray, KF, Diehl, A, Mohan, P, Schwimmer, JB, Lavine, JE, Torbenson, MS, et al
The American journal of clinical nutrition. 2012;(4):892-900
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Abstract
BACKGROUND There is significant histologic and biochemical overlap between nonalcoholic fatty liver disease (NAFLD) and steatohepatitis associated with choline deficiency. OBJECTIVE We sought to determine whether subjects with biopsy-proven NAFLD and evidence of an inadequate intake of choline had more severe histologic features. DESIGN We performed a cross-sectional analysis of 664 subjects enrolled in the multicenter, prospective Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) with baseline data on diet composition (from a recall-based food-frequency questionnaire) within 6 mo of a liver biopsy. Food questionnaires were analyzed with proprietary software to estimate daily intakes of choline. Liver biopsies were centrally read, and consensus was scored with the NASH CRN-developed scoring system. Because choline needs vary by age, sex, and menopausal status, participants were segregated into corresponding categories (children 9-13 y old, males ≥14 y old, premenopausal women ≥19 y old, and postmenopausal women) on the basis of the Institute of Medicine's definition of adequate intake (AI) for choline. Deficient intake was defined as <50% AI. RESULTS Postmenopausal women with deficient choline intake had worse fibrosis (P = 0.002) once factors associated with NAFLD (age, race-ethnicity, obesity, elevated triglycerides, diabetes, alcohol use, and steroid use) were considered in multiple ordinal logistic regression models. Choline intake was not identified as a contributor to disease severity in children, men, or premenopausal women. CONCLUSION Decreased choline intake is significantly associated with increased fibrosis in postmenopausal women with NAFLD. The Pioglitazone vs Vitamin E vs Placebo for Treatment of Non-Diabetic Patients With Nonalcoholic Steatohepatitis trial was registered at clinicaltrials.gov as NCT00063622, and the Treatment of Nonalcoholic Fatty Liver Disease in Children trial was registered at clinicaltrials.gov as NCT00063635.