To evaluate the detection rate of local and whole-body recurrence by integrated [18F]F-PSMA-1007 PET/MR assessment of prostate cancer patients treated with prostatectomy with very low biochemical recurrence (<0.5 ng/ml). Therapeutic implications.

OBJECTIVE: To analyse the efficacy of integrated assessment of [18F]F-PSMA-1007 PET/MRI on the early detection of local recurrence (LR) for prostate cancer patients with PSA levels <0.5 ng/ml after radical prostatectomy. To assess the location of recurrence so that therapy may be tailored to patient. METHODS: Prospective study including 35 patients with prostate cancer (PCa), who were referred for a [18F]F-PSMA-1007 PET/MR after prostatectomy with a very initial PSA value increase (PSA < 0,5 ng/ml). Simultaneous acquisition in a PET/MRI hybrid equipment (SIGNA-GE), 1 hour after administration of 370 ± 10% MBq of [18F]F-PSMA-1007: Prostate selective imaging (20 min): multiparametric PET + MRI (MRImp): DIXON, T1, T2, diffusion sequences post-gadolinium administration. Whole body image (30 min): PET + MRI: DIXON, T1, T2, diffusion, STIR sequences. A Nuclear Physician and a Radiologist jointly reviewed the studies: In order to assess LR, the "Prostate Imaging for Recurrence Reporting" system was used on MRI, as well as the Likert scale on the PET prostate imaging. The remaining lesions were classified as N1 and M1a. RESULTS: PET/MRI was positive in 25 patients (71,4%) and negative in 10 patients (28,6%). RL was detected in 15 patients (42.9%): in 2 (5.7%) MRI was superior; in 3 (8.6%) PET was superior; integrated PET/MRI showed improved results in 5 patients (14.3%) for the detection of LR. Location of recurrences: LR in 11 patients (44.0%); N1 in 10 (40.0%); LR + N1 (8.0%) in 2; LR + N1 + M1a in 2 (8.0%). In 20 patients (80%) the PET/MRI findings allowed radioguided radiotherapy implementation (11 on LR, and 9 on N1), whereas hormonal treatment was decided in 5 patients (20%) due to multimetastases/spread disease. CONCLUSION: [18F]F-PSMA-1007 PET/MRI has a 71.4% recurrence detection rate after prostatectomy with PSA < 0.5 ng/ml. Its combined PET and MRI study increases the detection of LR by 14.3%, with a high N1+M1a detection rate (56%), allowing radioguided radiotherapy in 80% of patients.

Detección de la infiltración de la cadena mamaria interna en pacientes con cáncer de mama mediante PET/RM con 18F-FDG y sus implicaciones terapéuticas / Detection of internal mammary chain infiltration in breast cancer patients by [18F]FDG PET/MRI: Therapy implications

Objetivo: Evaluar la tasa de detección y la implicación terapéutica de la infiltración de la cadena mamaria interna (ICMI) mediante tomografía por emisión de positrones (PET) y resonancia magnética (RM) con 18F-fluorodesoxiglucosa (18F-PET/RM) en la estadificación de pacientes con cáncer de mama. Método: Estudio prospectivo, 41 mujeres con cáncer de mama (estadio ≥ IIB) estadificadas mediante 18F-FDG-PET/RM. Estudio en dos fases: imágenes mamarias (decúbito prono), cuerpo completo (supino). Estadificación TNM por consenso entre especialista en Medicina Nuclear y Radiología. Estudio vaso aferente (VA) a cadena mamaria interna (CMI) por RM mamaria. Correlación ICMI con edad, VA-CMI, estadificación T, cuadrante, infiltración axilar y a distancia. Revaloración terapéutica en comité multidisciplinar. Resultados: Tasa de detección de ICMN de 34% (14/41), siendo 8/14 < 55 años. Todas las 14 pacientes con ICMI muestran VA-CMI, en seis de ellas (43,9%) sin VA-axilar. De 27/41 sin ICMI, en 13 (48,1%) solo VA-axilar, en los 14 restantes (51,9%) VA-axilar y VA-CMI. Un total de 57% (8/14) son multicéntricos y 42% (6/14) focales, en cuadrantes internos en 4/6 (66,7%). En 1/14 (7,1%) solo ICMI, en 9/14 (64,3%) axilar y CMI y en 4/14 (28,6%) lesiones a distancia. Decisión del comité: sin tratamiento adicional en 27/41 (65,8%), radioterapia torácica en 10/41 (24,4%) y terapia sistémica en 4/41 (9,7%). Conclusión: La tasa de detección de la ICMI en la estadificación del cáncer de mama mediante 18F-FDG PET/RM es de 34%. Son factores asociados la edad, los tumores multicéntricos, los de cuadrantes internos, la existencia de VA-CMI, la estadificación NM. La evidencia de ICMI permite la individualización de la terapia, indicando la radioterapia torácica en 24,4%.(AU)

Objective: To evaluate the detection rate and therapeutic implication of the infiltration of the internal mammary chain (IMCI) by [18F]FDG PET/MRI for staging of patients with breast cancer. Methods: Prospective study including 41 women with breast cancer (stage ≥IIB) staged by [18F]FDG PET/MR. Two-phase exam: breast imaging (prone), whole-body (supine). TNM stage assessed by peer consensus with Nuclear Medicine and Radiology specialists. Study of the afferent vessel (AV) to IMC by breast MRI. IMCI was correlated with age, AV-IMC, T stage, breast quadrants, axillary and distant infiltration. Therapeutic re-evaluation by a multidisciplinary committee. Results: IMCI detection rate of 34% (14/41), with 8/14 patients under 55 years of age. All 14 patients with IMCI showed AV-IMC, 6 of them (43.9%) without VA-axillary. Of 27/41 patients without IMCI, in 13 (48.1%) only AV-axillary was found, in the remaining 14 (51.9%), AV-axillary and AV-IMC was found. In 57% (8/14) tumours were multicentric and 42% (6/14) focal, in inner quadrants in 4/6 (66.7%). In 1/14 patient (7.1%) only IMCI was found, in 9/14 (64.3%) axillary and IMC, in 4/14 patients (28.6%) distant lesions were detected. Committee re-evaluation: no further treatment in 27/41 patients (65.8%), thoracic radiotherapy in 10/41 patients (24.4%), systemic therapy in 4/41 patients (9.7%). Conclusion: Our detection rate of IMCI in breast cancer staging by [18F]FDG PET/MR was 34%. Related factors were age, multicentric tumours, inner quadrants, detection of AV-IMC, NM staging.The evidence of IMCI allowed tailored therapy, with thoracic radiotherapy implementation in 24.4% of patients.(AU)

Detection of internal mammary chain infiltration in breast cancer patients by [18F]FDG PET/MRI. Therapy implications.

OBJECTIVE: To evaluate the detection rate and therapeutic implication of the infiltration of the internal mammary chain (IMCI) by [18F]FDG PET/MRI for staging of patients with breast cancer. METHODS: Prospective study including 41 women with breast cancer (stage ≥ IIB) staged by [18F]FDG PET/MR. Two-phase exam: breast imaging (prone), whole-body (supine). TNM stage assessed by peer consensus with Nuclear Medicine and Radiology specialists. Study of the afferent vessel (AV) to IMC by breast MRI. IMCI was correlated with age, AV-IMC, T stage, breast quadrants, axillary and distant infiltration. Therapeutic re-evaluation by a multidisciplinary committee. RESULTS: IMCI detection rate of 34% (14/41), with 8/14 patients under 55 years of age. All 14 patients with IMCI showed AV-IMC, 6 of them (43.9%) without VA-axillary. Of 27/41 patients without IMCI, in 13 (48.1%) only AV-axillary was found, in the remaining 14 (51.9%), AV-axillary and AV-IMC was found. In 57% (8/14) tumours were multicentric and 42% (6/14) focal, in inner quadrants in 4/6 (66.7%). In 1/14 patient (7.1%) only IMCI was found, in 9/14 (64.3%) axillary and IMC, in 4/14 patients (28.6%) distant lesions were detected. Committee re-evaluation: no further treatment in 27/41 patients (65.8%), thoracic radiotherapy in 10/41 patients (24.4%), systemic therapy in 4/41 patients (9.7%). CONCLUSION: Our detection rate of IMCI in breast cancer staging by [18F]FDG PET/MR was 34%. Related factors were age, multicentric tumours, inner quadrants, detection of AV-IMC, NM staging. The evidence of IMCI allowed tailored therapy, with thoracic radiotherapy implementation in 24.4% of patients.

Long-term outcome predictors after functional remediation in patients with bipolar disorder.

BACKGROUND: Improving functioning in patients with bipolar disorder (BD) is one of the main objectives in clinical practice. Of the few psychosocial interventions that have been specifically developed to enhance the psychosocial outcome in BD, functional remediation (FR) is one which has demonstrated efficacy. The aim of this study was to examine which variables could predict improved functional outcome following the FR intervention in a sample of euthymic or subsyndromal patients with BD. METHODS: A total of 92 euthymic outpatients were included in this longitudinal study, with 62 completers. Partial correlations controlling for the functional outcome at baseline were calculated between demographic, clinical and neurocognitive variables, and functional outcome at endpoint was assessed by means of the Functioning Assessment Short Test scale. Next, a multiple regression analysis was run in order to identify potential predictors of functional outcome at 2-year follow-up, using the variables found to be statistically significant in the correlation analysis and other variables related to functioning as identified in the previous scientific literature. RESULTS: The regression model revealed that only two independent variables significantly contributed to the model (F(6,53): 4.003; p = 0.002), namely verbal memory and inhibitory control. The model accounted for 31.2% of the variance. No other demographic or clinical variable contributed to the model. CONCLUSIONS: Results suggest that patients with better cognitive performance at baseline, especially in terms of verbal memory and executive functions, may present better functional outcomes at long term follow-up after receiving functional remediation.

Identifying social cognition subgroups in euthymic patients with bipolar disorder: a cluster analytical approach.

BACKGROUND: Bipolar disorder (BD) is associated with social cognition (SC) impairments even during remission periods although a large heterogeneity has been described. Our aim was to explore the existence of different profiles on SC in euthymic patients with BD, and further explore the potential impact of distinct variables on SC. METHODS: Hierarchical cluster analysis was conducted using three SC domains [Theory of Mind (ToM), Emotional Intelligence (EI) and Attributional Bias (AB)]. The sample comprised of 131 individuals, 71 patients with BD and 60 healthy control subjects who were compared in terms of SC performance, demographic, clinical, and neurocognitive variables. A logistic regression model was used to estimate the effect of SC-associated risk factors. RESULTS: A two-cluster solution was identified with an adjusted-performance group (N = 48, 67.6%) and a low-performance group (N = 23, 32.4%) with mild deficits in ToM and AB domains and with moderate difficulties in EI. Patients with low SC performance were mostly males, showed lower estimated IQ, higher subthreshold depressive symptoms, longer illness duration, and poorer visual memory and attention. Low estimated IQ (OR 0.920, 95% CI 0.863-0.981), male gender (OR 5.661, 95% CI 1.473-21.762), and longer illness duration (OR 1.085, 95% CI 1.006-1.171) contributed the most to the patients clustering. The model explained up to 35% of the variance in SC performance. CONCLUSIONS: Our results confirmed the existence of two discrete profiles of SC among BD. Nearly two-thirds of patients exhibited adjusted social cognitive abilities. Longer illness duration, male gender, and lower estimated IQ were associated with low SC performance.

18F-choline PET/MRI on initial staging of prostate cancer. Impact on therapy approach. / La PET/RM con 18F-colina en el diagnóstico inicial del cáncer de próstata. Impacto en la estrategia terapéutica.

AIM: Evaluate the therapy impact of initial staging in patients diagnosed with prostate cancer by 18 F-choline PET/MRI hybrid technique. MATERIAL: A prospective study which included 31 patients diagnosed with prostate cancer; Gleason > 7; mean PSA 13.6 ng/mL (range 6.3-20.6). PET/MRI studies were acquired simultaneously with hybrid equipment (SIGNA.3T, GE) following intravenous injection of 185 ± 18.5MBq of 18F-choline: - Early/prostate imaging: PET emission + multiparametric MR: DIXON-T1-T2-diffusion-gadolinium. - Late/whole-body imaging: PET emission + MR: DIXON-T1-T2-diffusion-STIR sequences. Images were visually evaluated. SUV & ADC & textures were also calculated. Treatment selection was based upon Oncology Committee consensus decision. RESULTS: Procedure was well tolerated in all patients, and no artifacts were reported. MRI was superior in T staging in eight patients (25.8%) (Likert: 2-3), whereas PET increased MRI sensitivity in three patients (9.7%) (PIRADS: 3). PROSTATE LESION LOCATION: Peripheral 91.4%, transitional 8.6%. SUVmax threshold: 2.95: sensitivity 92.9%, specificity 66.7%. No correlation SUV vs. ADC. Better distinction between stage T2 vs. T3 using the DiscrLin model with NG = 16 (AUC 0.7767 ± 0.3386). PET was superior to T2 in textures analysis (0.588 vs. 0.412). Seventeen patients (54.8%) were staged ≥ T3, with surgical treatment being contraindicated. Fifteen patients (48.4%) presented with extra-prostatic disease: 8/31 oligometastatic and 7/31 multiple metastasis. Therapy approach following PET/MRI was: radical treatment in 24/31 patients (77.4%), 14 radical prostatectomy and 10 MRI-guided radiotherapy; systemic treatment in 7/31 patients (22.6%). CONCLUSION: 18F-choline PET/MRI had a complementary role for the T staging, with a high detection rate for NM infiltration. PET/MRI findings allowed patients to be directed either to prostatectomy or MRI-guided radiotherapy, and thus avoiding radicaltreatment in 22.6% of patients.

Impacto de la tecnología híbrida PET/RM con 18F-colina en la estrategia terapéutica de los pacientes con cáncer de próstata tratados con prostatectomía que presentan elevación del antígeno prostático específico inferior a 1 ng/ml / Value of 18F-Choline PET/MRI hybrid technique on the therapeutic approach for patients with prostate cancer treated with prostatectomy and rising prostate specific antigen levels below 1 ng/ml

OBJETIVO: Evaluar la tasa de detección de la PET/RM con 18F-colina y los cambios en el manejo terapéutico de los pacientes con cáncer de próstata tratados con prostatectomía que presentan elevación del PSA <1 ng/ml. MÉTODO: Estudio prospectivo de los 36 primeros pacientes con cáncer de próstata tratados con prostatectomía, con elevación de PSA<1 ng/ml, a los que hemos realizado una PET/RM con 18F-colina. Tras la administración de 185±10% MBq de 18F-colina se ha adquirido un estudio en dos fases: 1) precoz prostática (inmediatamente tras la administración del trazador): emisión PET/RM multiparamétrica. 2) Estudio una hora postinyección de cuerpo completo: emisión PET/RM: T1, T2, STIR, difusión. El comité oncológico ha decidido la estrategia terapéutica de los pacientes según los hallazgos de la PET/RM con 18F-colina. RESULTADOS: De los 36 pacientes, 20 (55,6%) han mostrado positividad del estudio PET/RM con 18F-colina: en 8 (22,2%) lecho de prostatectomía, en 7 (19,4%) adenopatías infradiafragmáticas, en 4 (11,1%) recidiva local y adenopatías infradiafragmáticas, en 1 (2,8%) una metástasis ósea. De los 36 pacientes, en 16 (44,4%) el estudio PET/RM con 18F-colina ha sido negativo. Los hallazgos de la PET/RM con 18F-colina han condicionado la estrategia terapéutica: en 15 pacientes (41,6%) enfermedad oligometastásica tratada con radioterapia guiada por la imagen, en 5 (13,9%) enfermedad multimetastásica tratada con privación androgénica, en 16 (44,4%) negativo en vigilancia activa. CONCLUSIÓN: La técnica híbrida PET/RM con 18F-colina ha demostrado una elevada tasa de detección de la recidiva en los pacientes tratados con prostatectomía que presentan PSA <1 ng/ml, permitiendo una estrategia terapéutica personalizada según los hallazgos de la exploración

OBJECTIVE: To assess the detection rate of 18F-Choline PET/MRI and subsequent changes in therapy approach for patients with prostate cancer treated by prostatectomy and with rising levels of PSA <1 ng/ml. METHODS: Prospective study with our first 36 patients with prostatectomy for prostate cancer and rising levels of PSA, who were referred for an 18F-Choline PET/MRI study. A dual-phase study was acquired after intravenous administration of 185±10% MBq of 18F-Choline: 1) early imaging (immediately after tracer administration) of prostate area (emission PET/Multiparametric MRI). 2) whole-body imaging 1 h after tracer injection (emission PET/MRI: T1, T2, STIR, diffusion). The therapy approach for patients was decided upon the Oncology Committee consensus based on 18F-Choline PET/MRI findings. RESULTS: Twenty out of 36 patients (55.6%) were positive for the 18F-Choline PET/MRI study: 8 (22.2%) within the prostatectomy bed, 7 (19.4%) with infradiaphragmatic lymph nodes, 4 (11.1%) with local recurrence and infradiaphragmatic lymph nodes, and 1 (2.8%) with bone metastasis. Sixteen out of the 36 patients (44.4%) were negative for the 18F-Choline PET/MRI study. 18F-Choline PET/MRI findings had an impact on the therapy approach to follow: 15 patients (41.6%) showed oligometastatic disease which was treated by imaging-guided radiotherapy, 5 (13.9%) with multiple metastatic disease were treated by androgen deprivation therapy, 16 (44.4%) negative were under active surveillance. CONCLUSION: Hybrid 18F-Choline PET/MRI procedure showed a high detection rate for recurrence in prostate cancer patients treated with prostatectomy and rising PSA levels <1 ng/ml, and 18F-Choline PET/MRI findings resulted in a better tailored therapy approach delivered to our patients

Estandarización de los protocolos de adquisición mediante PET/TC con 18F-Colina en el cáncer de próstata / Standardization of acquisition protocols using PET/CT with 18F-Choline in prostate cancer

INTRODUCCIÓN: Estandarizar los protocolos de adquisición de 18F-Colina PET/TC, que permitan evitar la interferencia urinaria, evaluar el mejor tiempo del estudio de cuerpo completo y valorar si la «doble fase» permite la diferenciación entre lesiones benignas frente a malignas. MÉTODO: Estudio prospectivo que incluye 100 pacientes con cáncer de próstata: 31 estadificación y 69 recidiva bioquímica (32 posprostatectomía y 37 posradioterapia). Adquisición pélvica inmediatamente tras inyección de 18F-Colina y estudio de cuerpo completo, 1 y 2h p.i. Cálculo de media SUVmáx por territorios en todos los estudios secuenciales. Análisis de medias (χ2) y porcentaje de cambio del SUV (2/1h; 1h/0min). Patrón de dinámica metabólica: acumulativo frente a aclaramiento. Seguimiento tras tratamiento en todos los pacientes y de forma dirigida, cuando éticamente es posible. RESULTADOS: Cincuenta y tres focos prostáticos, en ninguna de las imágenes precoces actividad urinaria: Patrón acumulativo en 42, porcentaje de aumento: 0min/1h: +16,7% (X20,94); 1/2h: +10,0% (X20,83). Patrón aclaramiento en 11, porcentaje de reducción: 0min/1h: 21,4% (X20,91); 1/2h: −7,7% (X20,85), correspondiendo en 7 a estadificación y 4 a posradioterapia. Todos los focos infradiafragmáticos (n: 24) mostraron dinámica acumulativa, porcentaje de aumento: +9,1% (χ20,97), todas ellas visibles en el primer estudio. De los 12 focos supradiafragmáticos, 8 mostraron aclaramiento, porcentaje de reducción: −13,0% (χ2 0,95). Los otros 4 dinámica acumulativa, porcentaje de aumento: +13,0% (χ2 0,96), siendo valorados invasivamente. Todos los focos óseos (n: 18) mostraron dinámica acumulativa, porcentaje de aumento: +17,1% (χ20,95), todas ellas visibles en el estudio 1h. CONCLUSIONES: En la valoración prostática la mejor técnica doble fase es 0min/1h. En la diferenciación de adenopatías supradiafragmáticas es aconsejable la técnica de doble fase: 1/2h. Para la infiltración infradiafragmática y ósea, ante hallazgos dudosos, las imágenes 2h aumentan la confianza diagnóstica

AIM: To standardize acquisition protocols for 18F-Choline PET/CT to prevent from urine interference, to determine the best time point for the whole-body study, and to assess whether "dual point" acquisition allows for differentiating malignant vs. benign lesions. METHODS: One hundred consecutive patients with prostate cancer were prospectively studied. Immediately after 18F-Choline injection, a pelvis study was acquired, and a whole-body was subsequently obtained 1 and 2 hours p.i. Mean SUVmax was obtained in regions and for every sequential imaging. Mean analysis (χ2) and SUV percentage change (2/1 hours; 1 hours/0 min) were obtained. Metabolic pattern dynamics were assessed: accumulative vs. clearance. Patient follow-up after therapy and directed classification whenever ethically possible were performed. RESULTS: Fifty-three prostate foci, without disturbing urinary activity was ever found on early images. Accumulative pattern in 42, with percentage increase was: 0 min/1 hour: +16.7% (χ20.94); 1/2 hours: +10,0% (χ2 0.83). Clearance pattern in 11, with percentage decrease: 0 min/1 hour: −21.4% (χ20.91): −7.7% (χ20.85), corresponding in 7 to initial staging and in 4 post-radiotherapy biochemical recurrence. Every infradiaphragmatic uptake (n: 24) showed accumulative pattern, with percentage increase of +9.1% (χ20.97), all of them depicted on early imaging. As for 12 supradiaphragmantic uptake, 8 of them showed clearance pattern with percentage decrease: −13.0% (χ20.95). Accumulative pattern showed in 4 of them with percentage increase +13.0% (χ2 0.96), thus being assessed as invasive/malignant. Every bone uptake (n: 18) showed accumulative pattern, with percentage increase: +17.1% (χ20.95), all of them depicted on 1 hour imaging. CONCLUSIONS: As for prostate assessment is concerned, dual point at 0 min/1 hour proved to be the best procedure. As for supradiaphragmatic lymph-nodes detection, dual point with 1/2 hours performed best. As for infradiaphragmatic and bone involvement, as well as for inconclusive findings, the 2 hour imaging increased our diagnostic confidence

Utilidad de la PET con 68Ga-DOTATOC en la búsqueda del tumor primario en pacientes con metástasis hepáticas de origen neuroendocrino. A propósito de un caso / Diagnostic value of 68Ga-DOTATOC PET in the localization of primary tumor in patients with liver metastases of neuroendocrine origin but unknown primary. About a case

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Standardization of acquisition protocols using PET/CT with 18F-Choline in prostate cancer. / Estandarización de los protocolos de adquisición mediante PET/TC con 18F-Colina en el cáncer de próstata.

AIM: To standardize acquisition protocols for 18F-Choline PET/CT to prevent from urine interference, to determine the best time point for the whole-body study, and to assess whether "dual point" acquisition allows for differentiating malignant vs. benign lesions. METHODS: One hundred consecutive patients with prostate cancer were prospectively studied. Immediately after 18F-Choline injection, a pelvis study was acquired, and a whole-body was subsequently obtained 1 and 2 hours p.i. Mean SUVmax was obtained in regions and for every sequential imaging. Mean analysis (χ2) and SUV percentage change (2/1 hours; 1 hours/0 min) were obtained. Metabolic pattern dynamics were assessed: accumulative vs. clearance. Patient follow-up after therapy and directed classification whenever ethically possible were performed. RESULTS: Fifty-three prostate foci, without disturbing urinary activity was ever found on early images. Accumulative pattern in 42, with percentage increase was: 0 min/1 hour: +16.7% (χ20.94); 1/2 hours: +10,0% (χ2 0.83). Clearance pattern in 11, with percentage decrease: 0 min/1 hour: -21.4% (χ20.91): -7.7% (χ20.85), corresponding in 7 to initial staging and in 4 post-radiotherapy biochemical recurrence. Every infradiaphragmatic uptake (n: 24) showed accumulative pattern, with percentage increase of +9.1% (χ20.97), all of them depicted on early imaging. As for 12 supradiaphragmantic uptake, 8 of them showed clearance pattern with percentage decrease: -13.0% (χ20.95). Accumulative pattern showed in 4 of them with percentage increase +13.0% (χ2 0.96), thus being assessed as invasive/malignant. Every bone uptake (n: 18) showed accumulative pattern, with percentage increase: +17.1% (χ20.95), all of them depicted on 1 hour imaging. CONCLUSIONS: As for prostate assessment is concerned, dual point at 0 min/1 hour proved to be the best procedure. As for supradiaphragmatic lymph-nodes detection, dual point with 1/2 hours performed best. As for infradiaphragmatic and bone involvement, as well as for inconclusive findings, the 2 hour imaging increased our diagnostic confidence.

Value of 18F-Choline PET/MRI hybrid technique on the therapeutic approach for patients with prostate cancer treated with prostatectomy and rising prostate specific antigen levels below 1 ng/ml. / Impacto de la tecnología híbrida PET/RM con 18F-colina en la estrategia terapéutica de los pacientes con cáncer de próstata tratados con prostatectomía que presentan elevación del antígeno prostático específico inferior a 1 ng/ml.

OBJECTIVE: To assess the detection rate of 18F-Choline PET/MRI and subsequent changes in therapy approach for patients with prostate cancer treated by prostatectomy and with rising levels of PSA <1 ng/ml. METHODS: Prospective study with our first 36 patients with prostatectomy for prostate cancer and rising levels of PSA, who were referred for an 18F-Choline PET/MRI study. A dual-phase study was acquired after intravenous administration of 185±10% MBq of 18F-Choline: 1) early imaging (immediately after tracer administration) of prostate area (emission PET/Multiparametric MRI). 2) whole-body imaging 1 h after tracer injection (emission PET/MRI: T1, T2, STIR, diffusion). The therapy approach for patients was decided upon the Oncology Committee consensus based on 18F-Choline PET/MRI findings. RESULTS: Twenty out of 36 patients (55.6%) were positive for the 18F-Choline PET/MRI study: 8 (22.2%) within the prostatectomy bed, 7 (19.4%) with infradiaphragmatic lymph nodes, 4 (11.1%) with local recurrence and infradiaphragmatic lymph nodes, and 1 (2.8%) with bone metastasis. Sixteen out of the 36 patients (44.4%) were negative for the 18F-Choline PET/MRI study. 18F-Choline PET/MRI findings had an impact on the therapy approach to follow: 15 patients (41.6%) showed oligometastatic disease which was treated by imaging-guided radiotherapy, 5 (13.9%) with multiple metastatic disease were treated by androgen deprivation therapy, 16 (44.4%) negative were under active surveillance. CONCLUSION: Hybrid 18F-Choline PET/MRI procedure showed a high detection rate for recurrence in prostate cancer patients treated with prostatectomy and rising PSA levels <1 ng/ml, and 18F-Choline PET/MRI findings resulted in a better tailored therapy approach delivered to our patients.

Heterogeneity of functional outcomes in patients with bipolar disorder: a cluster-analytic approach.

OBJECTIVE: The aim was to examine the heterogeneity of psychosocial outcomes in euthymic bipolar disorder (BD) patients and analyse the potential influence of distinct variables on functioning. METHOD: Using a hierarchical cluster exploratory analysis, 143 euthymic patients with diagnosis of BD were grouped according to their functional performance based on domains scores of the Functioning Assessment Short Test (FAST). The resulting groups were compared on sociodemographic, clinical and neurocognitive variables to find factors associated with each functional cluster. RESULTS: Patients were grouped in three functional profiles: patients with good functioning in all the FAST areas, patients with an intermediate profile showing great difficulties in the occupational domain and milder difficulties in most of the rest domains, and a third group with serious difficulties in almost all functional areas. Both functionally impaired groups were characterized by higher subthreshold symptoms (depressive and manic) and higher unemployment rates. The most functionally impaired group also showed lower scores on some measures of processing speed. CONCLUSION: Two of three functional profiles showed some kind of impairment which was associated with subsyndromal symptoms and cognitive performance. These patterns should be taken into consideration to develop more individualized interventions to restore, or improve, psychosocial outcomes.

Psychometric properties of the well-being index (WHO-5) spanish version in a sample of euthymic patients with bipolar disorder.

BACKGROUND: The concept of well-being which focuses on positive emotions has received increased research attention. However, a consensus definition of this term is lacking. The Well-Being Index scale (WHO-5) is a generic, self-report scale that contains five Likert-type items to evaluate psychological well-being. This construct may provide a relevant outcome in bipolar disorder (BD) research and care beyond the rating of mood symptoms. Thus, in the current study, the psychometric properties of the WHO-5 Spanish version were assessed in a sample of euthymic patients with BD. METHODS: Patients with BD- I and BD-II and healthy controls completed the Well-Being Index (WHO-5) together with an assessment of depressive (Hamilton Depression Rating Scale-17; HAM-D) and manic symptoms (Young Mania Rating Scale; YMRS); and a measure of psychosocial functioning (Functioning Assessment Short Test; FAST). Internal consistency reliability was measured through Cronbach's alpha. Test-retest reliability was calculated comparing the WHO-5 total score at baseline and after 10 days of the first administration. To assess the structure of the scale, a principal component analysis (PCA) was carried out. Correlations between the WHO-5, HAM-D, YMRS and FAST were calculated. Finally, a t-test for independent samples was applied to compare the WHO-5 total score in the patient and control groups. RESULTS: A total of 104 patients with BD and 40 healthy controls were included in this study. A Chronbach's alpha of 0.83 indicated acceptable internal consistency. A paired sample t-test revealed no significant differences between WHO-5 total score at baseline and at follow-up (tn = - 0.72; df = 15; p = 0.48). The PCA provided a single factor solution that accounted for 59.74% of the variation in WHO-5. Test-retest reliability was high (r = 0.83; p < 0.001). Moderate negative correlations were observed between the WHO-5 total score, the FAST (r = - 0.46.; p < 0.001) and the HAM-D (r = - 0.68; p < 0.001), but not with the YMRS (r = - 0.07; p = 0.42). Finally, significant differences were found when comparing the WHO-5 total score between patient and healthy controls (t = 5.1; df = 147; p < 0.001). LIMITATIONS: some limitations include the lack of a comparator scale to test for validity construct and the small sample size in the test-retest reliability CONCLUSIONS: The WHO-5 shows an acceptable reliability index and measures a unitary construct in a Spanish population of euthymic patients with BD.

Social cognition in bipolar disorder: Focus on emotional intelligence.

BACKGROUND: The present study aims to characterize emotional intelligence (EI) variability in a sample of euthymic bipolar disorder (BD) patients through the Mayer- Salovey-Caruso Emotional Intelligence Test (MSCEIT). METHOD: A total of 134 euthymic BD outpatients were recruited and divided into three groups according to the total Emotional Intelligence Quotient (EIQ) score of the MSCEIT, following a statistical criterion of scores 1.5SDs above/below the normative group mean, as follows: a low performance (LP) group (EIQ <85), a normal performance (NP) group (85≤EIQ≤115), and a high performance (HP) group (EIQ >115). Afterwards, main sociodemographic, clinical, functional and neurocognitive variables were compared between the groups. RESULTS: Three groups were identified: 1) LP group (n=16, 12%), 2) NP group (n=93, 69%) and 3) HP group (n=25, 19%). There were significant differences between the groups in premorbid intelligence quotient (IQ) (p=0.010), axis II comorbidity (p=0.008), subthreshold depressive symptoms (p=0.027), general functioning (p=0.013) and in four specific functional domains: autonomy, occupation, interpersonal relations and leisure time. Significant differences in neurocognitive performance were found between groups with the LP group showing the lowest attainments. LIMITATIONS: The cross-sectional design of the study. CONCLUSION: Our results suggest that EI variability among BD patients, assessed through MSCEIT, is lower than expected. EI could be associated with premorbid IQ, subthreshold depressive symptoms, neurocognitive performance and general functioning. The identification of different profiles of SC may help guide specific interventions for distinct patient subgroups aimed at improving social cognition, neurocognitive performance and psychosocial functioning.

High cognitive reserve in bipolar disorders as a moderator of neurocognitive impairment.

BACKGROUND: Cognitive reserve (CR) reflects the capacity of the brain to endure neuropathology, minimize clinical manifestations and successfully complete cognitive tasks. The present study aims to determine whether high CR may constitute a moderator of cognitive functioning in bipolar disorder (BD). METHODS: 102 patients with BD and 32 healthy controls were enrolled. All patients met DSM-IV criteria for I or II BD and were euthymic (YMRS≤6 and HDRS≤8) during a 6-month period. All participants were tested with a comprehensive neuropsychological battery, and a Cerebral Reserve Score (CRS) was estimated. Subjects with a CRS below the group median were classified as having low CR, whereas participants with a CRS above the median value were considered to have high CR. RESULTS: Participants with BD with high CR displayed a better performance in measures of attention (digits forward: F=4.554, p=0.039); phonemic and semantic verbal fluency (FAS: F=9.328, p=0.004; and Animal Naming: F=8.532, p=0.006); and verbal memory (short cued recall of California Verbal Learning Test: F=4.236, p=0.046), after multivariable adjustment for potential confounders, including number of admissions and prior psychotic symptoms. LIMITATIONS: The cross-sectional design of the study does not allow the establishment of causal inferences. Additionally, the small size of the sample may have limited some results. CONCLUSIONS: High cognitive reserve may therefore be a valuable construct to explore for predicting neurocognitive performance in patients with BD regarding premorbid status.

ZEB1 and TCF4 reciprocally modulate their transcriptional activities to regulate Wnt target gene expression.

The canonical Wnt pathway (TCF4/ß-catenin) has important roles during normal differentiation and in disease. Some Wnt functions depend on signaling gradients requiring the pathway to be tightly regulated. A key Wnt target is the transcription factor ZEB1 whose expression by cancer cells promotes tumor invasiveness by repressing the expression of epithelial specification markers and activating mesenchymal genes, including a number of Wnt targets such as LAMC2 and uPA. The ability of ZEB1 to activate/repress its target genes depends on its recruitment of corepressors (CtBP, BRG1) or coactivators (p300) although conditions under which ZEB1 binds these cofactors are not elucidated. Here, we show that TCF4 and ZEB1 reciprocally modulate each other's transcriptional activity: ZEB1 enhances TCF4/ß-catenin-mediated transcription and, in turn, Wnt signaling switches ZEB1 from a repressor into an activator. In colorectal cancer (CRC) cells with active Wnt signaling, ZEB1 enhances transcriptional activation of LAMC2 and uPA by TCF4/ß-catenin. However, in CRC cells with inactive Wnt, ZEB1 represses both genes. Reciprocal modulation of ZEB1 and TCF4 activities involves their binding to DNA and mutual interaction. Wnt signaling turns ZEB1 into an activator by replacing binding of CtBP/BRG1 in favor of p300. Using a mouse model of Wnt-induced intestinal tumorigenesis, we found that downregulation of ZEB1 reduces the expression of LAMC2 in vivo. These results identify a mechanism through which Wnt and ZEB1 transcriptional activities are modulated, offering new approaches in cancer therapy.