Description of a different quantification method for amyloid burden (DPDload) and validation of SPECT/CT in cardiac amyloidosis.

BACKGROUND: Bone tracers such as 99mTc-DPD have shown high sensitivity and specificity in the non-invasive diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). This study aims to validate SPECT/CT and assess the usefulness of uptake quantification (DPDload) in the myocardial tissue as potential information on the amyloid burden. METHODS: In a retrospective analysis of 46 patients with suspected CA, 23 cases with ATTR-CA had two quantification methods conducted to estimate amyloid burden (DPDload) through planar scintigraphic scans and a SPECT/CT. RESULTS: SPECT/CT significantly provided an added value in the patient's diagnosis with CA (P<.05). The estimation of the amyloid burden substantiated that the most affected wall of the LV is the interventricular septum in most cases and the existence of a significant relationship between the Perugini score uptake and the DPDload. CONCLUSIONS: We validate the need for SPECT/CT to complement planar imaging in diagnosing ATTR-CA. For its part, quantifying the amyloid load continues to be a complex area of research. It requires further studies with a larger number of patients to validate a standardized method of amyloid load quantification, both for diagnosis and treatment monitoring.

Evaluation of 177Lu-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors.

BACKGROUND: 177Lu peptide receptor radionuclide therapy (PRRT) is a recently approved therapy in Spain that has been demonstrated to be a well-tolerated therapy for positive somatostatin receptor advanced gastroenteropancreatic neuroendocrine tumors. AIM: To determine the impact of PRRT on quality of life, radiologic and metabolic response, overall survival, prognostic factors and toxicity. METHODS: Thirty-six patients treated with 177Lu-PRRT from 2016 to 2019 were included. The most frequent location of the primary tumor was the gastrointestinal tract (52.8%), pancreas (27.8%), and nongastropancreatic neuroendocrine tumor (11.1%). The liver was the most common site of metastasis (91.7%), followed by distant nodes (50.0%), bone (27.8%), peritoneum (25.0%) and lung (11.1%). Toxicity was evaluated after the administration of each dose. Treatment efficacy was evaluated by two parameters: stable disease and disease progression in response evaluation criteria in solid tumors 1.1 criterion and prognostic factors were tested. RESULTS: From 36 patients, 55.6% were men, with a median age of 61.1 ± 11.8 years. Regarding previous treatments, 55.6% of patients underwent surgery of the primary tumor, 100% of patients were treated with long-acting somatostatin analogues, 66.7% of patients were treated with everolimus, 27.8% of patients were treated with tyrosine kinase inhibitor, and 27.8% of patients were treated with interferon. One patient received radioembolization, three patients received chemoembolization, six patients received chemotherapy. Hematological toxicity was registered in 14 patients (G1-G2: 55.5% and G3: 3.1%). Other events presented were intestinal suboclusion in 4 cases, cholestasis in 2 cases and carcinoid crisis in 1 case. The median follow-up time was 3 years. Currently, 24 patients completed treatment. Nineteen are alive with stable disease, two have disease progression, eight have died, and nine are still receiving treatment. The median overall survival was 12.5 mo (95% confidence interval range: 9.8-15.2), being inversely proportional to toxicity in previous treatments (P < 0.02), tumor grade (P < 0.01) and the presence of bone lesions (P = 0.009) and directly proportional with matching lesion findings between Octreoscan and computed tomography pre-PRRT (P < 0.01), , primary tumor surgery (P = 0.03) and metastasis surgery (P = 0.045). In a multivariate Cox regression analysis, a high Ki67 index (P = 0.003), a mismatch in the lesion findings between Octreoscan and computed tomography pre-PRRT (P < 0.01) and a preceding toxicity in previous treatments (P < 0.05) were risk factors to overall survival. CONCLUSION: Overall survival was inversely proportional to previous toxicity, tumor grade and the presence of bone metastasis and directly proportional to matching lesion findings between Octreoscan and computed tomography pre-PRRT and primary tumor and metastasis surgery.

Advantages and limitations of 18-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography in the diagnosis of infective endocarditis.

INTRODUCTION: The early diagnosis of infective endocarditis (IE) is a medical challenge and a multidisciplinary approach is essential to improve its frequently fatal prognosis. Our goal was to evaluate the usefulness of [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG PET) in the diagnosis of this disease. MATERIALS AND METHODS: We prospectively assessed 43 patients (five female and 38 male) with clinical suspicion of IE between 2014 and 2017. All patients underwent transesophageal echocardiography (TEE) and an 18F-FDG PET scan, and the results were compared. A positive PET finding was defined as increased FDG uptake on cardiac valves or intracardiac devices. RESULTS: Out of 43 patients with suspected IE, the diagnosis was confirmed in 30 cases (79.7%). 18F-FDG PET was positive in 24 patients, with 19 showing FDG uptake on cardiac valves (two native and 17 prosthetic) and five on cardiac devices, being concordant with echocardiographic findings in 11 cases. 18F-FDG PET sensitivity was 80%, specificity 92%, positive predictive value (PPV) 96% and negative predictive value (NPV) 66%. Echocardiography presented sensitivity, specificity, PPV and NPV of 36%, 84%, 84% and 36%, respectively. CONCLUSIONS: 18F-FDG PET proved to be a sensitive technique with a high diagnostic value in patients with prosthetic valves and intracardiac devices and suspected IE. Its utility decreased dramatically in patients with suspected IE on native valves, in which TEE presented higher sensitivity and thus better diagnostic value.

Ocular Biodistribution Studies using Molecular Imaging.

Classical methodologies used in ocular pharmacokinetics studies have difficulties to obtain information about topical and intraocular distribution and clearance of drugs and formulations. This is associated with multiple factors related to ophthalmic physiology, as well as the complexity and invasiveness intrinsic to the sampling. Molecular imaging is a new diagnostic discipline for in vivo imaging, which is emerging and spreading rapidly. Recent developments in molecular imaging techniques, such as positron emission tomography (PET), single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), allow obtaining reliable pharmacokinetic data, which can be translated into improving the permanence of the ophthalmic drugs in its action site, leading to dosage optimisation. They can be used to study either topical or intraocular administration. With these techniques it is possible to obtain real-time visualisation, localisation, characterisation and quantification of the compounds after their administration, all in a reliable, safe and non-invasive way. None of these novel techniques presents simultaneously high sensitivity and specificity, but it is possible to study biological procedures with the information provided when the techniques are combined. With the results obtained, it is possible to assume that molecular imaging techniques are postulated as a resource with great potential for the research and development of new drugs and ophthalmic delivery systems.

Preclinical characterization and clinical evaluation of tacrolimus eye drops.

Severe allergic ocular diseases as atopic keratoconjunctivitis can induce corneal damage due to inflammatory substances released from giant papillae. Tacrolimus eye drops are one of the current therapeutic alternatives for its treatment. This work is aimed at developing and characterizing a 0.03% tacrolimus ophthalmic formulation, which was introduced in three types of vehicles (BBS, PVA and Hyaluronic Acid). For this, we have performed in vitro (stability studies) and in vivo assays (corneal permanence time measured directly by Positron Emission Tomography) of three potential formulations. Next, the best formulation was selected, and its toxicological profile and clinical effectiveness have been evaluated. The biopermanence studies (direct measurements and PET/CT) showed that the formulations with PVA and Hyaluronic Acid present more retention time on the ocular surface of rats than PBS. From the stability study, we have determined that tacrolimus with PVA in cold storage is the best option. Tacrolimus with PVA has shown lower cytotoxicity than cyclosporine at early times. On the other hand, the pilot study performed has shown significant improvements in patients, with no noticeable adverse reactions. Based on stability, biopermanence, safety and clinical effectiveness studies, we concluded that tacrolimus-PVA eye drops are a suitable candidate for its clinical application in inflammatory ophthalmology diseases.

Discrepancy between stress electrocardiographic changes and nuclear myocardial perfusion defects in the prognostic assessment of patients with chest pain.

OBJECTIVES: The aim of the present study was to determine the long-term prognostic value provided by the exercise electrocardiographic (ECG) response to nuclear myocardial perfusion imaging (MPI) in the evaluation of patients with chest pain, focusing on patients with a discrepancy between the two tests. METHODS: A total of 1460 consecutive patients (777 female; 62.6 ± 11.4 years) undergoing exercise myocardial single-photon emission computed tomography (SPECT) were included. The endpoint was the occurrence of acute coronary syndrome, heart failure or cardiac death during follow-up. RESULTS: Ischemic ECG changes were observed during stress testing in 271 patients (18.5%) and 362 patients (24.7%) had positive (abnormal) exercise MPI results. There was a discrepancy between ECG and SPECT findings in 471 patients (32.2%). During the follow-up period (14.0-39.6 months), 224 patients (15.3%) presented cardiac events. The hazard ratios (HR) of ECG and MPI results to predict events were 1.506 (95% CI: 1.113-2.039) and 10.481 (95% CI: 7.799-14.080), respectively. In patients with negative MPI, the ECG response did not predict events (HR 1.214 [95% CI: 0.646-2.282]), the same as in patients with positive MPI (HR 1.203 [95% CI: 0.848-1.705]). Only in hypertensive patients with positive SPECT did the ECG show significant prognostic value (HR 1.937 [95% CI: 1.030-3.642]). In multivariate analysis, positive MPI proved an independent long-term prognostic factor (HR 10.536 [95% CI: 7.759-14.308]), but not ECG (HR 1.356 [95% CI: 0.994-1.850]). CONCLUSION: MPI results (normal vs. abnormal) had strong predictive value and discrepant ECG results had no significant additive prognostic value.

Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer.

Cancer stem cells play an important role in carcinogenesis and resistance to treatment and may lead to metastasis. The isolation of circulating stem cells involves cell sorting based on the presence of cell surface markers. Many surface markers such as CD133, c-Kit, SOX, OCT4 and TWIST have been reported. In the present study, we determined the expression of different stem cell markers and their variation in expression at different stages of the treatment process. Samples of EDTA blood were collected from metastatic colorectal cancer patients, and circulating cancer stem cells were isolated for the analysis of the expression of stem cell markers using RT-PCR. These findings were correlated with the response to therapy. All statistical analyses were performed using the GraphPad Prism 5.03 software. Significant differences were found in the expression levels of the markers CD133, SOX2, OCT4 and TWIST1. No differences were found in c-Kit expression. Correlation in the expression levels of most of the markers was observed. Expression of CD133, OCT4, SOX2 and TWIST1 had a predictive value for colon cancer behavior. Evaluation of this stem cell gene expression panel may be useful for predicting the response during the process of treatment, and the relative easy access to samples facilitates this method. Moreover the correlation between CD133 and TWIST1 expression may be associated with tumor regrowth and metastatic relapse.

"Bulky mass": metastasis of poorly differentiated follicular thyroid carcinoma: a case report.

Poorly differentiated follicular thyroid carcinoma (PDFC) is a tumor of follicular cell origin with intermediate attributes between well-differentiated carcinomas and anaplastic carcinomas. The majority of patients presenting with distant metastases have locally advanced tumors, being lungs and bones the most common sites affected. We present a case of a patient with a painful bulky mass at the left thorax-abdominal wall as an uncommon distant metastasis of a PDFC. After thyroidectomy, a pre-ablative 131I whole-body scan showed distant metastases on the neck, both lungs, and lateral chest-abdominal wall, so the administration of I for thyroid remnant ablation stimulated with RH-TSH was decided.

Gammagrafía de ventilación-perfusión y tomografía computarizada: estudio comparativo en el diagnóstico de la tromboembolia pulmonar / Ventilation perfusion scintigraphy and CT: comparative study in the diagnosis of pulmonary thromboembolism

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Marcadores tumorales de secreción: situación actual / Secretion tumor markers: state of the art

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Proteasas y patología prostática: la catepsina D citosólica / Proteases and prostatic disease: cytosolic cathepsin D

OBJETIVOS: Pretendemos estudiar el comportamiento de la cat-D citosólica, marcador pronóstico ya conocido en cáncer de mama, en la hiperplasia benigna de próstata (HBP) y cáncer de próstata (CaP): su variación en función del volumen glandular, sus relaciones con otros marcadores séricos (PSA, PAP...), con el grado histológico, el estadio tumoral y la supervivencia. MÉTODO: Incluimos 376 pacientes intervenidos por patología prostática en el HCA entre los años 91 y 96. En todas las muestras de tejido prostático obtenidas, se realizó una determinación de Cat-D citosólica según estudio inmunoradiométrico CIS Bio internacional. RESULTADOS: Los valores de cat-D citosólica en HBP oscilaron entre 0,2 y 86,5 pmol/mg con una media de 14,9, observándose mayores valores (p=0,004) conforme el volumen prostático era superior. También en los casos de HBP se encontró una diferencia significativa (p=0,024) entre pacientes portadores y no portadores de sonda vesical, siendo mayor en aquellos. Los valores de Cat-D en CaP oscilar on entre 0,5 y 74 pmol/mg con una media de 18,13, existiendo una diferencia estadísticamente significativa entre medias (p=0,047) con relación a la HBP. También la diferencia fue estadísticamente significativaen el CaP (p=0,04) entre pacientes con y sin sonda. No se observó ninguna relación entre la Cat-D y el resto de los parámetros estudiados. CONCLUSIONES: Al igual que en la mayor parte de la bibliografía revisada, observamos que la catepsina D no se comporta como marcador pronóstico en el cáncer de próstata ni tiene relación alguna con otros marcadores estudiados. El escaso número de muestras tumorales y el corto tiempo de seguimiento podría ser la causa de este resultado (AU)

Tratamiento radical del cáncer de mama / Radical treatment of the breast cancer

Posiblemente, si a lo largo de los 100 años de este siglo XX que termina, nos hubieran encargado este capítulo en diferentes libros de mastología, los criterios expuestos difícilmente hubieran cambiado tanto con otro tema cualquiera. En la primera parte del siglo nos hubiéramos sentido orgullosos de la mastectomía que realizábamos. Por fin podían presentarse resultados satisfactorios en el tratamiento del cáncer de mama con una cirugía radical, que apoyada en la filosofía halstediana, mejoraban incluso, al apoyarla con otras terapéuticas complementarias. Quizas el entusiasmo de esos resultados crecientes y la hegemonía de los principios anatomicistas halstedianos, llevaron la cirugía a su extremo más radical y en la mitad del siglo nos congratulábamos de poder ofertar "más" a nuestras enfermas y llégo la hora de las mastectomías ampliadas. Siempre nos gusto comparar la evolución de la cirugía del cáncer de mama, como de cualquier cirugía oncológica, o tantos criterios no sólo científicos, sino humanos, filosóficos o religiosos, al trayecto de un péndulo, que es este momento llega a su extremo más radical para iniciar su descenso. Y ese descenso de la mano de un mejor conocimiento de la historia natural del cáncer de mama, del inicio de la era biológica y el camino nuevo de la inmunología en las relaciones huesped-tumor, y se apoyó entonces, en lo Fisher llamó su teoría alternativa