Clínica Universidad de Navarra
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- 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) predictive score for complete resection in primary cytoreductive surgery(2022) Boria, F. (Félix); Chiva, L. (Luis); Sin Autoridad; Gutierrez, M. (Monica); Sancho-Rodriguez, L. (Lidia); Alcázar, A. (Andrés); Zapardiel, I. (Ignacio)Objective To assess the value of preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan, combined with clinical variables, in predicting complete cytoreduction in selected patients with advanced ovarian cancer. Methods We carried out a multicenter, observational, retrospective study evaluating patients who underwent primary cytoreductive surgery for advanced ovarian cancer in two Spanish centers between January 2017 and January 2022. Inclusion criteria were histological confirmation of invasive epithelial ovarian carcinoma; preoperative International Federation of Gynecology and Obstetrics (FIGO) stage III or IV; upfront cytoreductive surgery; and 18F-FDG PET/CT performed 1 month prior to surgery. A modified 18F-FDG PET/CT peritoneal cancer index score was calculated for all patients. Clinical variables and preoperative 18F-FDG PET/CT findings were analyzed and a multivariate model was constructed. A predictive score based on the odds ratio of the variables was calculated to determine patient selection. Results A total of 45 patients underwent primary cytoreductive surgery. Complete resection was achieved in 36 (80%) patients. On multivariate analysis, two clinical variables (age ≥58 years and American Society of Anesthesiology score ≥3) and two preoperative 18F-FDG PET/CT scan findings (presence of extra-abdominal lymph node involvement and modified peritoneal cancer index value of 6 or more) were associated with gross residual disease. For this multivariate model predictive of non-complete cytoreduction, the area under the curve was 0.881. A predictive value of ≥5 was the most predictive cut-off for gross residual disease. Complete resection rate was 91.7% in patients with a score of ≤4 and 33.3% in patients with a score of ≥5 points on the predictive score. Conclusions In selected patients, a predictive score value ≥5 may be consider as a cut-off point for triaging patients to diagnostic laparoscopy before the primary surgery or neoadjuvant chemotherapy.
- 11C-Methionine PET/CT in Assessment of Multiple Myeloma Patients: Comparison to 18F-FDG PET/CT and Prognostic Value(MDPI, 2022) Sin Autoridad; Rodriguez-Otero, P. (Paula); Sancho-Rodriguez, L. (Lidia); Nuñez-Cordoba, J.M. (Jorge M.); Prieto, E. (Elena); Marcos-Jubilar, M. (María); Rosales, J.J. (Juan José); Alfonso-Piérola, A. (Ana); Guillén-Valderrama, E.F. (Edgar Fernando); San-Miguel, J.F. (Jesús F.); Garcia-Velloso, M. J. (María José)Multiple myeloma (MM) is the second most common haematological malignancy and remains incurable despite therapeutic advances. 18F-FDG (FDG) PET/CT is a relevant tool MM for staging and it is the reference imaging technique for treatment evaluation. However, it has limitations, and investigation of other PET tracers is required. Preliminary results with L-methyl-[11C]- methionine (MET), suggest higher sensitivity than 18F-FDG. This study aimed to compare the diagnostic accuracy and prognostic value of 1FDG and MET in MM patients. We prospectively compared FDG and MET PET/CT for assessment of bone disease and extramedullary disease (EMD) in a series of 52 consecutive patients (8 smoldering MM, 18 newly diagnosed MM and 26 relapsed MM patients). Bone marrow (BM) uptake patterns and the detection of focal lesions (FLs) and EMD were compared. Furthermore, FDG PET parameters with known MM prognostic value were explored for both tracers, as well as total lesion MET uptake (TLMU). Median patient age was 61 years (range, 37–83 years), 54% were male, 13% of them were in stage ISS (International Staging System) III, and 31% had high-risk cytogenetics. FDG PET/CT did not detect active disease in 6 patients, while they were shown to be positive by MET PET/CT. Additionally, MET PET/CT identified a higher number of FLs than FDG in more than half of the patients (63%). For prognostication we focussed on the relapsed cohort, due to the low number of progressions in the two other cohorts. Upon using FDG PET/CT in relapsed patients, the presence of more than 3 FLs (HR 4.61, p = 0.056), more than 10 FLs (HR 5.65, p = 0.013), total metabolic tumor volume (TMTV) p50 (HR 4.91, p = 0.049) or TMTV p75 (HR 5.32, p = 0.016) were associated with adverse prognosis. In MET PET/CT analysis, TMTV p50 (HR 4.71, p = 0.056), TMTV p75 (HR 6.27, p = 0.007), TLMU p50 (HR 8.8, p = 0.04) and TLMU p75 (HR 6.3, p = 0.007) adversely affected PFS. This study confirmed the diagnostic and prognostic value of FDG in MM. In addition, it highlights that MET has higher sensitivity than FDG PET/CT for detection of myeloma lesions, including FLs. Moreover, we show, for the first time, the prognostic value of TMTV and TLMU MET PET/CT in the imaging evaluation of MM patients.
- A proof-of-concept study of the in-vivo validation of a computational fluid dynamics model of personalized radioembolization(2021) Antón, R. (Raúl); Antoñana, J. (Javier); Aramburu-Montenegro, J. (Jorge); Ezponda, A. (Ana); Prieto, E. (Elena); Andonegui-Isasa, A. (Asier); Ortega, J. (Julio); Vivas, I. (Isabel); Sancho-Rodriguez, L. (Lidia); Sangro, B. (Bruno); Bilbao-Jaureguízar, J. (José Ignacio); Rodriguez-Fraile, M. (Macarena)Radioembolization (RE) with yttrium-90 (90Y) microspheres, a transcatheter intraarterial therapy for patients with liver cancer, can be modeled computationally. The purpose of this work was to correlate the results obtained with this methodology using in vivo data, so that this computational tool could be used for the optimization of the RE procedure. The hepatic artery three-dimensional (3D) hemodynamics and microsphere distribution during RE were modeled for six 90Y-loaded microsphere infusions in three patients with hepatocellular carcinoma using a commercially available computational fluid dynamics (CFD) software package. The model was built based on in vivo data acquired during the pretreatment stage. The results of the simulations were compared with the in vivo distribution assessed by 90Y PET/CT. Specifically, the microsphere distribution predicted was compared with the actual 90Y activity per liver segment with a commercially available 3D-voxel dosimetry software (PLANET Dose, DOSIsoft). The average difference between the CFD-based and the PET/CT-based activity distribution was 2.36 percentage points for Patient 1, 3.51 percentage points for Patient 2 and 2.02 percentage points for Patient 3. These results suggest that CFD simulations may help to predict 90Y-microsphere distribution after RE and could be used to optimize the RE procedure on a patient-specific basis.
- 3D voxel-based dosimetry to predict contralateral hypertrophy and an adequate future liver remnant after lobar radioembolization(Springer, 2021) Grisanti-Vollbracht, F. (Fabiana); Prieto, E. (Elena); Bastidas, J.F. (Juan Fernando); Sancho-Rodriguez, L. (Lidia); Rodrigo, P. (Pablo); Beorlegui, C. (Carmen); Iñarrairaegui, M. (Mercedes); Bilbao-Jaureguízar, J. (José Ignacio); Sangro, B. (Bruno); Rodriguez-Fraile, M. (Macarena)Introduction: Volume changes induced by selective internal radiation therapy (SIRT) may increase the possibility of tumor resection in patients with insufficient future liver remnant (FLR). The aim was to identify dosimetric and clinical parameters associated with contralateral hepatic hypertrophy after lobar/extended lobar SIRT with 90Y-resin microspheres. Materials and methods: Patients underwent 90Y PET/CT after lobar or extended lobar (right + segment IV) SIRT. 90Y voxel dosimetry was retrospectively performed (PLANET Dose; DOSIsoft SA). Mean absorbed doses to tumoral/non-tumoral-treated volumes (NTL) and dose-volume histograms were extracted. Clinical variables were collected. Patients were stratified by FLR at baseline (T0-FLR): < 30% (would require hypertrophy) and ≥ 30%. Changes in volume of the treated, non-treated liver, and FLR were calculated at < 2 (T1), 2–5 (T2), and 6–12 months (T3) post-SIRT. Univariable and multivariable regression analyses were performed to identify predictors of atrophy, hypertrophy, and increase in FLR. The best cut-off value to predict an increase of FLR to ≥ 40% was defined using ROC analysis. Results: Fifty-six patients were studied; most had primary liver tumors (71.4%), 40.4% had cirrhosis, and 39.3% had been previously treated with chemotherapy. FLR in patients with T0-FLR < 30% increased progressively (T0: 25.2%; T1: 32.7%; T2: 38.1%; T3: 44.7%). No dosimetric parameter predicted atrophy. Both NTL-Dmean and NTL-V30 (fraction of NTL exposed to ≥ 30 Gy) were predictive of increase in FLR in patients with T0 FLR < 30%, the latter also in the total cohort of patients. Hypertrophy was not significantly associated with tumor dose or tumor size. When ≥ 49% of NTL received ≥ 30 Gy, FLR increased to ≥ 40% (accuracy: 76.4% in all patients and 80.95% in T0-FLR < 30% patients). Conclusion: NTL-Dmean and NTL exposed to ≥ 30 Gy (NTL-V30) were most significantly associated with increase in FLR (particularly among patients with T0-FLR < 30%). When half of NTL received ≥ 30 Gy, FLR increased to ≥ 40%, with higher accuracy among patients with T0-FLR < 30%.
- Evaluation of the role of thyroid scintigraphy in the differential diagnosis of thyrotoxicosis(Wiley, 2020) Perdomo-Zelaya, C.M. (Carolina M.); Sin Autoridad; Sancho-Rodriguez, L. (Lidia); Paricio, J.J. (J. J.); Lozano, M.D. (María Dolores); Higuera, M. (Magdalena) de la; Arbizu, J. (Javier); Galofre, J.C. (Juan Carlos)Objective: A differential diagnosis of thyrotoxicosis is crucial as the treatment of the main causes of this condition can vary significantly. Recently published diagnostic guidelines on thyrotoxicosis embrace the presence of thyrotropin receptor (TSH-R) antibodies (TRAb) as the primary and most important diagnostic step. The application of diagnostic algorithms to aid in the treatment of hyperthyroidism supports using thyroid radionuclide scintigraphy (TRSt) in baffling clinical scenarios, when TRAb are absent or when third-generation TRAb are not available. First-generation TRAb measurement may have limitations. Consequently, patients with thyrotoxicosis and first-generation TRAb results may be misdiagnosed and consequently improperly treated. Our purpose was to compare first-generation TRAb values to TRSt in the differential diagnosis of hyperthyroidism. Methods: We conducted a retrospective study of 201 untreated outpatients with overt or subclinical hyperthyroidism on whom first-generation TRAb and TRSt had been performed at the time of diagnosis. Histological specimens were analysed in patients who had previously undergone thyroid surgery at our centre. SPSS 20.0 was used in statistical analysis. Results: Seventy-three out of 201 (36.3%) patients had positive TRAb. A diffuse uptake was present in 83.5% (61/73), whereas 13.7% (10/73) had a heterogeneous uptake and 2.7% (2/73) had an absent uptake. Thirty out of 91 (33%) patients with diffuse uptake were negative for positive TRAb and were diagnosed with Graves’ disease. Analysis of 37 histological specimens indicated that TRSt had greater accuracy (81% vs 75.7%) and specificity (79.2% vs 57.1%) when compared to TRAb in the differential diagnosis of thyrotoxicosis. However, TRSt sensitivity was inferior to TRAb (84.6% vs 92.3%). Conclusions: Our study endorses that initial differential diagnosis of thyrotoxicosis should not be based solely on first-generation TRAb as this approach may leave nearly 20% of the patients misdiagnosed and, consequently, improperly treated. Our results underscore that thyroid scintigraphy should also be performed when only first-generation TRAb assays are available during the initial differential diagnosis of thyrotoxicosis.
- Diagnostic accuracy of visual analysis versus dual time-point imaging with 18F-FDG PET/CT for the characterization of indeterminate pulmonary nodules with low uptakePrecisión diagnóstica del análisis visual frente al protocolo de imagen tardía con 18F-FDG PET/TC para la caracterización de nódulos pulmonares indeterminados con baja captación(Elsevier, 2021) Grisanti-Vollbracht, F. (Fabiana); Zulueta, J. (Javier); Rosales, J.J. (Juan José); Sin Autoridad; Sancho-Rodriguez, L. (Lidia); Lozano, M.D. (María Dolores); Mesa-Guzmán, M.A. (Miguel Alejandro); Garcia-Velloso, M. J. (María José)Objective: To determine the accuracy of visual analysis and the retention index (RI) with dual-time point 18F-FDG PET/CT for the characterization of indeterminate pulmonary nodules (IPN) with low FDG uptake. Materials and methods: A retrospective analysis was performed on 43 patients (28 men, 64 ± 11 years old, range 36–83 years) referred for IPN characterization with 18F-FDG-PET/CT and maximum standard uptake value ≤2.5 at 60 min post-injection (SUVmax1). Nodules were analyzed by size, visual score for FDG uptake on standard (OSEM 2,8) and high definition (HD) reconstructions, SUVmax1, SUVmax at 180 min post-injection (SUVmax2), and RI was calculated. The definitive diagnosis was based on histopathological confirmation (n = 28) or ≥2 years of follow-up. Results: Twenty-four nodules (56%) were malignant. RI ≥ 10% on standard reconstruction detected 18 nodules that would have been considered negative using the standard SUVmax ≥ 2.5 criterion for malignancy. RI ≥ 10% had a sensitivity, specificity, PPV, NPV and accuracy of 75%, 73.7%, 78.3%, 70%, and 74.4%, respectively, while for FDG uptake > liver on HD these were 79.1%, 63.2%, 73.1%, 70.6%, and 72.1%, respectively. SUVmax1 ≥ 2, SUVmax2 > 2.5 and FDG uptake > liver on standard reconstruction had a PPV of 100%. FDG uptake > mediastinum on HD had a NPV of 100%. Conclusions: RI ≥ % was the most accurate criterion for malignancy, followed by FDG uptake > liver on HD reconstruction. On standard reconstruction, SUVmax1 ≥ 2 was highly predictive of malignancy, as well as SUVmax2 > 2.5 and FDG uptake > liver. FDG uptake < mediastinum on HD was highly predictive of benign nodules.
- The Pattern of Progression Defines Post-progression Survival in Patients with Hepatocellular Carcinoma Treated with SIRT(Springer, 2020) de la Torre-Aláez, M. (Manuel Antonio); Sin Autoridad; Casadei-Gardini, A. (Andrea); Lorente-Bilbao, J.I. (José Ignacio); Rodriguez-Fraile, M. (Macarena); Sancho-Rodriguez, L. (Lidia); D'Avola, D. (Delia); Herrero, J.I. (José Ignacio); Iñarrairaegui, M. (Mercedes); Sangro, B. (Bruno)Purpose In patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib, post-progression survival (PPS) is marked by the pattern of progression. Our aim was to assess the influence of the pattern of progression to selective internal radiotherapy (SIRT) in PPS among patients with HCC. Methods A retrospective analysis of patients treated with SIRT between 2003 and 2015 was conducted, excluding those with a single nodule < 5 cm or with metastases. Four patterns of progression to SIRT were defined: target tumour growth, non-target tumour growth, new intrahepatic disease, and new extrahepatic disease. PPS was calculated from the time of progression based on RECIST 1.1 criteria. Results Out of the 102 patients who met the selection criteria, 76 progressed after a median follow-up of 15 months. Median PPS was 6.5 months (95% CI 3.8–9.3 months). Patients who progressed at pre-existing lesions had a better PPS (median 12.5 months) than those who progressed with new lesions inside or outside the liver (median 4.2 months) (p = 0.02). In a Cox model adjusted by liver function and systemic inflammation, the pattern of progression had a hazard ratio of 1.64 (95% CI 0.92–2.93; p = 0.093). Conclusion In a cohort of HCC patients treated with SIRT, the pattern of progression associated with worst survival was the development of new intrahepatic lesions or extrahepatic metastases.
- Ultraprocessed food intake and body mass index change among youths: a prospective cohort study(Elsevier, 2024) Sin Autoridad; Martín‐Calvo, N. (Nerea); Fung, T.T. (Teresa T.); Chavarro, J.E. (Jorge E.); Sun, Q. (Qi)Background Suboptimal diets may promote undesired weight gain in youths, with high ultraprocessed food (UPF) intake becoming a significant concern in the United States. Objectives We evaluated the association between UPF intake and body mass index [BMI (in kg/m2)] change in large United States youth cohorts. Methods Participants included children and adolescents (7–17 y) from the Growing Up Today Study (GUTS1 and GUTS2) who completed baseline and ≥1 follow-up diet and anthropometrics assessment (GUTS1 1996–2001: N = 15,797; GUTS2 2004–2011: N = 9720). Follow-up years were based on diet assessment availability. UPFs were categorized using the Nova system, with intakes evaluated as the cumulative mean percent energy from UPFs and subgroups. BMI was assessed using self-reported body weight/height. Changes in BMI annually and over 2, 4–5, and 7 y in association with UPF intake were examined using multivariable repeated-measure linear mixed models. Results At baseline, the mean percentage of energy from UPFs was 49.9% in GUTS1 and 49.5% in GUTS2 participants; mean BMI was 18.7 and 19.8, respectively. After multivariable adjustments for sociodemographic and lifestyle factors, each 10% increment in UPF intake was associated with a 0.01 (95% confidence interval: 0.003, 0.03) increase annually and a 0.07 (0.01, 0.13) increase over 5 y in GUTS1 participants. In GUTS2, increases were 0.02 (0.003, 0.04) annually and 0.09 (0.01, 0.18) over 4 y. Among GUTS1, statistically significant annual BMI increases of 0.02–0.07 were associated with elevated intake of ultraprocessed breakfast cereals, savory snacks, and ready-to-eat/heat foods, especially pizza, burgers, and sandwiches. No association was found between UPF intake and overweight/obesity risk. Conclusions A higher UPF intake was associated with a modest yet significant increase in BMI in large prospective cohorts of United States youths, calling for public health efforts to promote healthful food intake among youths to prevent excessive weight gain.
- Epicardial and liver fat implications in albuminuria: a retrospective study(Springer, 2024) Perdomo-Zelaya, C.M. (Carolina M.); Martin-Calvo, N. (Nerea); Ezponda, A. (Ana); Mendoza-Ferradas, F.J. (Francisco Javier); Bastarrika, G. (Gorka); García-Fernández, N. (Nuria); Herrero, J.I. (José Ignacio); Colina, I. (Inmaculada); Escalada, J. (Javier); Frühbeck, G. (Gema)Background Albuminuria is considered an early and sensitive marker of kidney dysfunction, but also an independent cardiovascular risk factor. Considering the possible relationship among metabolic liver disease, cardiovascular disease and chronic kidney disease, we aimed to evaluate the risk of developing albuminuria regarding the presence of epicardial adipose tissue and the steatotic liver disease status. Methods A retrospective long-term longitudinal study including 181 patients was carried out. Epicardial adipose tissue and steatotic liver disease were assessed by computed tomography. The presence of albuminuria at follow-up was defined as the outcome. Results After a median follow up of 11.2 years, steatotic liver disease (HR 3.15; 95% CI, 1.20–8.26; p = 0.02) and excess amount of epicardial adipose tissue (HR 6.12; 95% CI, 1.69–22.19; p = 0.006) were associated with an increased risk of albuminuria after adjustment for visceral adipose tissue, sex, age, weight status, type 2 diabetes, prediabetes, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, and cardiovascular prevention treatment at baseline. The presence of both conditions was associated with a higher risk of developing albuminuria compared to having steatotic liver disease alone (HR 5.91; 95% CI 1.15–30.41, p = 0.033). Compared with the first tertile of visceral adipose tissue, the proportion of subjects with liver steatosis and abnormal epicardial adipose tissue was significantly higher in the second and third tertile. We found a significant correlation between epicardial fat and steatotic liver disease (rho = 0.43 [p < 0.001]). Conclusions Identification and management/decrease of excess adiposity must be a target in the primary and secondary prevention of chronic kidney disease development and progression. Visceral adiposity assessment may be an adequate target in the daily clinical setting. Moreover, epicardial adipose tissue and steatotic liver disease assessment may aid in the primary prevention of renal dysfunction.
- Diagnostic performance of serum interleukin-6 in pediatric acute appendicitis: a systematic review(2022) Arredondo-Montero, J. (Javier); Bardají-Pascual, C. (Carlos); Bronte-Anaut, M. (Mónica); Lopez-Andres, N. (Natalia); Antona, G. (Giuseppa); Martín-Calvo, N. (Nerea)Background Despite the radiological and analytical advances of the last decades, there is still a significant rate of diagnostic error in pediatric acute appendicitis. In recent years, multiple biomarkers have emerged as potential diagnostic tools. This study aimed to examine the diagnostic performance of serum interleukin-6 in pediatric acute appendicitis. Methods We conducted a systematic review of the literature that involved an extensive search in the main databases of medical bibliography (Medline, PubMed, Web of Science and SciELO). Two independent reviewers selected the relevant articles based on the previously defined inclusion and exclusion criteria. Methodological quality of the selected article was rated using the QUADAS2 index. Data extraction was performed by two independent reviewers. Results The research in the medical bibliography databases resulted in 68 articles. We removed 26 duplicates. Among the remaining 42 articles, we excluded 33 following the inclusion and exclusion criteria. Of the final 9 studies included in this review, 8 provided measured serum interleukin-6 values, and all of them reported significant differences between groups, but inconsistent results regarding sensitivity and specificity. Conclusions The diagnostic performance of interleukine-6 alone for the diagnosis of acute appendicitis in children is limited. The sensitivity and specificity of interleukine-6 for the diagnosis of non-complicated acute appendicitis in the pediatric population are moderate but increased in complicated appendicitis. There seems to be a direct relationship between serum level of interleukin-6 and the hours of evolution of abdominal pain in children with acute appendicitis. The increasingly widespread use of non-operative management of acute appendicitis warrants further exploration of the classificatory potential of this marker between complicated and uncomplicated appendicitis. We consider that this may be an avenue of research to explore in the future.