Joan Duch

Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study

BACKGROUND Patients with idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) may develop neurodegenerative conditions associated with substantia nigra dysfunction such as Parkinsons disease. In patients with Parkinsons disease, ¹²³I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (¹²³I-FP-CIT) SPECT detects striatal dopamine dysfunction resulting from nigral pathology whereas transcranial sonography (TCS) shows increased substantia nigra echogenic size, even before parkinsonism is clinically evident. We postulated that these neuroimaging changes could occur in a proportion of IRBD individuals who might then be at increased risk for development of a neurodegenerative disorder associated with substantia nigra dysfunction. METHODS In our prospective study, we identified patients with IRBD from individuals referred to our sleep disorders centre in Barcelona, Spain. At baseline, we assessed dopamine transporter [corrected] uptake by use of ¹²³I-FP-CIT SPECT, and estimated echogenicity of the substantia nigra by use of TCS. After a follow-up of 2·5 years, participants were clinically assessed to establish whether they had developed neurodegenerative syndromes. Data were compared with those of matched healthy controls. FINDINGS 43 individuals with IRBD agreed to participate in the study. We found reduced ¹²³I-FP-CIT binding in the striatum (p=0·045) in 17 (40%) of 43 participants compared with 18 controls, and substantia nigra hyperechogenicity in 14 (36%) of 39 participants with IRBD, compared with 16 (11%) of 149 controls (p=0·0002). Tracer uptake reduction was more pronounced in the putamen than it was in the caudate nucleus. 27 (63%) participants had reduced ¹²³I-FP-CIT binding or substantia nigra hyperechogenicity at baseline. Eight (30%) of these participants developed a neurodegenerative disorder (five Parkinsons disease, two dementia with Lewy bodies, and one multiple system atrophy). Individuals with normal neuroimaging results remained disease-free. Sensitivity of combined ¹²³I-FP-CIT SPECT and TCS to predict conversion to synucleinopathy after 2·5 years was 100% and specificity was 55%. INTERPRETATION In patients with IRBD, ¹²³I-FP-CIT SPECT and TCS can detect subclinical changes much the same as those typically seen in patients with early Parkinsons disease. Decreased striatal ¹²³I-FP-CIT binding and substantia nigra hyperechogenicity might be useful markers to identify individuals at increased risk for development of synucleinopathies. FUNDING None.

Preoperative Staging of Large Primary Breast Cancer With [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Compared With Conventional Imaging Procedures

PURPOSE To evaluate the utility of positron emission tomography (PET) and [(18)F]fluorodeoxyglucose in the initial staging of large primary breast tumors. PATIENTS AND METHODS This prospective study was approved by the ethics committee, and all patients gave their informed consent before enrollment. Sixty consecutive patients with large (> 3 cm) primary breast cancer diagnosed by clinical examination and breast magnetic resonance imaging (MRI) were entered onto the study. The mean age was 57 +/- 13 years. Chest computed tomography (CT), liver ultrasonography, bone scan, and PET/CT were performed in all patients. All findings were histologically confirmed, and/or at least 1 year of follow-up was required. Correlation between parameters was calculated using Pearsons correlation coefficient. P < .05 was considered statistically significant. RESULTS Primary tumor was identified by both PET/CT and MRI in all patients. Multifocal and/or multicentric tumors were found in 19 patients by MRI. Axillary lymph node metastases were found in 20 of 52 patients. Extra-axillary metastatic lymph nodes were also found in three patients. One patient showed an infiltrated lymph node in the contralateral axilla. The sensitivity and specificity for PET/CT to detect axillary lymph nodes metastases were 70% and 100%, respectively. PET/CT diagnosed all extra-axillary lymph nodes. The overall sensitivity and specificity of PET/CT in detecting distant metastases were 100% and 98%, respectively; whereas the sensitivity and specificity of conventional imaging were 60% and 83%, respectively. PET led to a change in the initial staging in 42% of patients. CONCLUSION PET/CT underestimates locoregional lymph node staging in large primary breast cancer patients. PET/CT is a valuable tool to discard unsuspected extra-axillary lymph nodes and distant metastases.

Clinical relevance of sentinel lymph nodes in the internal mammary chain in breast cancer patients

PurposeDespite the widespread use of sentinel lymph node (SLN) biopsy in breast cancer patients, some controversy exists about the correct management of extra-axillary nodes, especially those located in the internal mammary chain. The aim of this study was to evaluate the incidence of SLNs in this region, calculate the lymphoscintigraphic and surgical detection rates and evaluate the clinical impact on staging and therapeutic decisions.MethodsThe study involved 383 consecutive women diagnosed with early breast cancer with T1 or T2 tumours. Eight patients had a bilateral tumour, which brought the total to 391 lesions. Lymphoscintigraphy was performed on the day before surgery by injection of 99mTc-labelled nanocolloid. The injection site was subdermal (68 patients), peritumoural (107 patients) or intratumoural (216 patients). During surgery a gamma probe was used to guide the surgeon and the SLNs were removed. SLNs were analysed by a conventional pathological study and processed for H&E examination and immunohistochemistry.ResultsLymphoscintigraphy detected at least one SLN in 369 out of the 391 procedures (94.4%). SLNs were found in the axillary chain in 367 cases and in the internal mammary chain in 55. In two of these 55 cases (3.6%), the SLN was the only one detected. There was no drainage to the internal mammary chain in any case of subdermal injection but such drainage was found in 15.9% of cases with peritumoural injection and 17.6% of those with intratumoural injection. Compared with tumours located in the outer quadrants, a higher percentage of tumours located in the inner quadrants showed drainage to the internal mammary chain (p<0.001). A total of 42 SLNs in the internal mammary chain could be removed in 32 patients without appreciable morbidity. In 20 cases both axillary and internal mammary SLNs were negative, in four both were positive, and in five axillary SLNs were positive and internal mammary SLNs were negative. More interestingly, in the remaining patient with both axillary and internal mammary SLNs, the axillary SLN was negative while malignant cells were found in the internal mammary region. In the evaluation of the clinical impact of internal mammary SLN biopsy, we found that staging was modified from pN1a to pN1c in four patients and, more importantly, from pN0 to pN0(i+) in one patient. The change in stage led to a modification of the postoperative treatment plan with respect to radiotherapy and systemic therapy.ConclusionEvaluation of the SLNs in the internal mammary chain provides more accurate staging of breast cancer patients. If internal mammary sampling is not performed, patients can be understaged. This technique can offer a better indication of those patients who will benefit from selective treatment options like radiotherapy to this region or systemic therapy.

Evaluación de la respuesta terapéutica y PET-TAC: ¿realmente sólo importa el tamaño?

El criterio de evaluación de la respuesta al tratamiento de las neoplasias sólidas continúa siendo un tema controvertido. Desde los primeros intentos de estandarización de Moertel y sus colaboradores basados en la exploración fı́sica y la radiologı́a simple, se han ido proponiendo diversos modelos influidos principalmente por los avances tecnológicos en el diagnóstico por la imagen. En 1981 la Organización Mundial de la Salud (OMS) publicó los primeros criterios de respuesta tumoral principalmente dirigidos a ensayos clı́nicos. Se introdujeron conceptos de evaluación global del crecimiento tumoral tales como la comparación de la suma de medidas bidimensionales de las lesiones con respecto a estudios basales y la categorización de la respuesta como completa, parcial, enfermedad estable y progresión (tabla 1). Posteriormente diversos grupos de trabajo y laboratorios farmacéuticos modificaron estos criterios para acomodarlos a las nuevas tecnologı́as. Los Response Evaluation Criteria in Solid Tumors (RECIST) fueron publicados en el año 2000 en respuesta a las limitaciones de los de la OMS. Estos criterios ya se basaban en el TAC y la RM, especificando el número de lesiones que habı́a que valorar, diferenciando entre )lesiones diana* y )no diana*, implementando la medida unidimensional del diámetro máximo del tumor y diferenciando entre lesiones )medibles* y )no medibles*. Redefinı́an asimismo las categorı́as de respuesta al tratamiento. Cabe destacar la prácticamente nula referencia a conceptos de respuesta no morfológica basada en el PET. De manera prácticamente paralela al RECIST se propusieron los criterios de respuesta terapéutica de la European Organization for Research and Treatment of Cancer (EORTC), muy dirigidos a la radioterapia. En ellos ya se reconocı́a que la respuesta metabólica subclı́nica observada precozmente por PET (con o sin correlación morfológica) podı́a ser importante. Los tumores podı́an progresar no sólo por aumento de tamño, sino también por incrementos en los valores de standarized uptake value (SUV). Para valorar esta respuesta, no obstante, era esencial una metodologı́a estricta y reproducible en cuanto a la práctica e interpretación de los estudios.

Drenaje bilateral en cadena mamaria interna en la detección del ganglio centinela en un tumor de mama

Presentamos el caso de una paciente de 64 anos con una neoplasia de mama localizada en el cuadrante inferior externo derecho. La linfogammagrafia se llevo a cabo el dia previo a la cirugia mediante la inyeccion intratumoral de 111 MBq de 99mTc-nanocoloide (fi g. 1), que mostro drenaje a las regiones axilar derecha y mamaria interna de ambos lados. La mayoria de los estudios han refl ejado que los tumores localizados en los cuadrantes internos presentan un mayor porcentaje de drenaje en esta zona respecto al resto de las localizaciones1-3. En nuestro caso, presentamos a una paciente con un tumor en el cuadrante inferior externo de la mama derecha con drenaje a la region mamaria interna. Ademas, este caso tambien demuestra que pueden existir vasos linfaticos que comuniquen las dos regiones mamarias internas, lo que explicaria el drenaje bilateral visualizado en las imagenes gammagrafi cas.