Segmentation of gliomas in 18F-fluorocholine PET/CT. A multiapproach study. / Segmentación de gliomas con PET/TC con 18F-fluorocolina. Estudio multiaproximación.

AIM: Our aim was two-fold, to study the interobserver agreement in tumour segmentation and to search for a reliable methodology to segment gliomas using 18F-fluorocholine PET/CT. METHODS: 25 patients with glioma, from a prospective and non-randomized study (Functional and Metabolic Glioma Analysis), were included.Interobserver variability in tumour segmentation was assessed using fixed thresholds. Different strategies were used to segment the tumours. First, a semi-automatic tumour segmentation was performed, selecting the best SUVmax-% threshold for each lesion. Next we determined a variable SUVmax-% depending on the SUVmax. Finally a segmentation using a fixed SUVmax threshold was performed. To do so, a sampling of 10 regions of interest (ROI of 2.8cm2) located in the normal brain was performed. The upper value of the sample mean SUVmax±3 SD was used as cut-off. All procedures were tested and classified as effective or not for tumour segmentation by two observer's consensus. RESULTS: In the pilot segmentation, the mean±SD of SUVmax, SUVmean and optimal SUVmax-% threshold were: 3.64±1.77, 1.32±0.57 and 21.32±8.39, respectively. Optimal SUVmax-% threshold showed a significant association with the SUVmax (Pearson=-0.653, p=.002). However, the linear regression model for the total sample was not good, that supported the division in two homogeneous groups, defining two formulas for predicting the optimal SUVmax-% threshold. As to the third procedure, the obtained value for the mean SUVmax background+3 SD was 0.33. This value allowed segmenting correctly a significant fraction of tumours, although not all. CONCLUSION: A great interobserver variability in the tumour segmentation was found. None of the methods was able to segment correctly all the gliomas, probably explained by the wide tumour heterogeneity on 18F-fluorocholine PET/CT.

Global heterogeneity assessed with 18F-FDG PET/CT. Relation with biological variables and prognosis in locally advanced breast cancer. / Medidas de heterogeneidad global y esfericidad con 18F-FDG PET/TC en el cáncer de mama: relación con la biología tumoral, valor predictivo y pronóstico.

AIM: To analyze the relationship between measurements of global heterogeneity, obtained from 18F-FDG PET/CT, with biological variables, and their predictive and prognostic role in patients with locally advanced breast cancer (LABC). MATERIAL AND METHODS: 68 patients from a multicenter and prospective study, with LABC and a baseline 18F-FDG PET/CT were included. Immunohistochemical profile [estrogen receptors (ER) and progesterone receptors (PR), expression of the HER-2 oncogene, Ki-67 proliferation index and tumor histological grade], response to neoadjuvant chemotherapy (NC), overall survival (OS) and disease-free survival (DFS) were obtained as clinical variables. Three-dimensional segmentation of the lesions, providing SUV, volumetric [metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] and global heterogeneity variables [coefficient of variation (COV) and SUVmean/SUVmax ratio], as well as sphericity was performed. The correlation between the results obtained with the immunohistochemical profile, the response to NC and survival was also analyzed. RESULTS: Of the patients included, 62 received NC. Only 18 responded. 13 patients relapsed and 11 died during follow-up. ER negative tumors had a lower COV (p=0.018) as well as those with high Ki-67 (p=0.001) and high risk phenotype (p=0.033) compared to the rest. No PET variable showed association with the response to NC nor OS. There was an inverse relationship between sphericity with DFS (p=0.041), so, for every tenth that sphericity increases, the risk of recurrence decreases by 37%. CONCLUSIONS: Breast tumors in our LABC dataset behaved as homogeneous and spherical lesions. Larger volumes were associated with a lower sphericity. Global heterogeneity variables and sphericity do not seem to have a predictive role in response to NC nor in OS. More spherical tumors with less variation in gray intensity between voxels showed a lower risk of recurrence.

Predictive and prognostic potential of volume-based metabolic variables obtained by a baseline 18F-FDG PET/CT in breast cancer with neoadjuvant chemotherapy indication. / Papel predictivo y pronóstico de las variables volumétricas metabólicas obtenidas en la 18F-FDG PET/TC en el cáncer de mama con indicación de quimioterapia neoadyuvante.

AIM: To investigate the usefulness of metabolic variables using 18F-FDG PET/CT in the prediction of neoadjuvant chemotherapy (NC) response and the prognosis in locally advanced breast cancer (LABC). MATERIAL AND METHODS: Prospective study including 67 patients with LABC, NC indication and a baseline 18F-FDG PET/CT. After breast tumor segmentation, SUV variables (SUVmax, SUVmean and SUVpeak) and volume-based variables, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were obtained. Tumors were grouped into molecular phenotypes, and classified as responders or non-responders after completion of NC. Disease-free status (DFs), disease-free survival (DFS), and overall survival (OS) were assessed. A univariate and multivariate analysis was performed to study the potential of all variables to predict DFs, DFS, and OS. RESULTS: Fourteen patients were classified as responders. Median±SD of DFS and OS was 43±15 and 46±13 months, respectively. SUV and TLG showed a significant correlation (p<0.005) with the histological response, with higher values in responders compared to non-responders. MTV and TLG showed a significant association with DFs (p=0.015 and p=0.038 respectively). Median, mean and SD of MTV and TLG for patients with DFs were: 8.90, 13.73, 15.10 and 33.78, and 90.54 and 144.64, respectively. Median, mean and SD of MTV and TLG for patients with non-DFs were: 16.72, 29.70 and 31.09 and 90.89, 210.98 and 382.80, respectively. No significant relationships were observed with SUV variables and DFs. Volume-based variables were significantly associated with OS and DFS, although in multivariate analysis only MTV was related to OS. No SUV variables showed an association with the prognosis. CONCLUSION: Volume-based metabolic variables obtained with 18F-FDG PET/CT, unlike SUV based variables, were good predictors of both neoadjuvant chemotherapy response and prognosis.

18F-FDG PET/CT as predictor of tumour biology and prognosis in epithelial ovarian carcinoma. / PET/TC con 18F-FDG como predictor de la biología tumoral y del pronóstico en el cáncer epitelial ovárico.

OBJECTIVE: To investigate the relationship between maximum standardised uptake value (SUVmax) of ovarian lesions and histopathology subtypes, and their involvement in the response and prognosis of patients with epithelial ovarian carcinoma (EOC). MATERIAL AND METHODS: A retrospective analysis of 31 patients with EOC and 18F-FDG-PET/CT before treatment, including an assessment of the SUVmax of ovarian lesion. Histopathological diagnosis and follow-up was performed. A study was made on the relationship between the SUVmax and histological type (type I and II) and tumour stage, as well as the role of various parameters (SUVmax, histology, stage) on the patient outcomes (complete response [CR], overall survival [OS], disease-free survival [DFS], and disease-free [DF] status, at 12 and 24 months). RESULTS: The medium SUVmax in type I lesions was lower than in type II (6.3 and 9.3, respectively; P=.03). A 7.1 cut-off was set for SUVmax in order to identify type II EOC (sensitivity: 77.8%, specificity: 69.2%; AUC=0.748; P=.02). No significant relationship was found between tumour stage and SUVmax. CR was more common in early stages; relative risk (RR) of 1.64; P=.003, as well as in type I tumours and a lower SUVmax. Tumour stage was decisive in DFS (P=.04), LE24m (0.07) and OS (P=.08). Longer DFS and a higher percentage of DF 24m were observed in type I tumours (RR: 1.32; P=.26). CONCLUSIONS: SUVmax was related to EOC histology, so could predict the response and prognosis of these patients. No association was found between glycolytic activity of the primary tumor with the response and prognosis.

Aplicación de la técnica de árboles de clasificación y regresión en la valoración ecográfica de los nódulos tiroideos / Using Classification and Regression Trees in the ultrasound evaluation of thyroid nodules

Objetivo: Evaluar la capacidad de los árboles de clasificación y regresión (CART) en la valoración ecográfica de los nódulos tiroideos malignos. Materiales y métodos: Se realizaron 404 punciones aspiración con aguja fina (PAAF) a 384 pacientes. De los nódulos analizados, se registraron las características ecográficas (localización, tamano, morfología, contorno, consistencia, ecoestructura, ecogenicidad, calcificaciones y vascularización) y los resultados de la elastografía. Se aplicó el CART para investigar la relación entre los hallazgos ecográficos, la elastografía y el cáncer de tiroides. Resultados: El análisis CART determinó que la realización de una elastografía no aporta datos relevantes y que las zonas homogéneas pueden clasificar a los nódulos tiroideos en: 1.ª zona) caracterizada por ausencia de áreas de degeneración coloide e hipoecogenicidad asociada a malignidad; 2.ª zona) diferenciada por presencia de áreas de degeneración coloide combinada con ausencia de microcalcificaciones, constituyendo un indicador fiable de benignidad de los nódulos tiroideos; y 3.ª zona) la ausencia de hipoecogenicidad y una lesión menos alta que ancha deparan un indicador fiable de benignidad. El árbol de clasificación alcanzó una sensibilidad del 87,5% y un valor predictivo negativo del 98,8%. Discusión: El CART muestra una elevada capacidad de predicción de los nódulos malignos frente a otras técnicas lineales. Conclusión: La utilización de los árboles de clasificación provee una herramienta simple para la toma de decisión clínica con el objeto de reducir las PAAF innecesarias, con una elevada sensibilidad.

Objective: To evaluate the use of Classification and Regression Trees (CART) in the ultrasound evaluation of malignant thyroid nodules. Materials and methods: A study was performed on 404 fine needle aspirates (FNA), with biopsies being performed on 384. The information collected about the thyroid nodules was: ultrasound features (location, size, morphology, contour, consistency, echo-structure, echogenicity, calcification, and vascularisation) and elastography results. The CART technique was used to investigate the relationship between ultrasound findings and the thyroid cancer. Results: The CART analysis showed that elastography does not provide any relevant data, and that the homogeneous areas could classified the thyroid nodules into: 1st area) characterised by the absence of colloid degeneration areas and a hypo-echogenicity associated with malignancy; 2nd area) differentiated by the presence of colloid degeneration areas combined with absence of microcalcifications, constituting a reliable indicator of benign thyroid nodules; and a 3rd area) the absence of hypo-echogenicity and a lesion wider than it is long that provides a reliable indicator of being benign. The optimum tree produced a sensitivity of 87.5% and negative predictive value of 98.8%. Discussion: The CART technique demonstrated a high predictive capacity for malignant nodules compared to other linear techniques. Conclusion: The use of classification trees provides us with a simple tool for clinical decision making, in order to reduce unnecessary FNA biopsies, as well as achieving a high sensitivity.

Utility of 18F-FDG-PET/CT in patients suspected of paraneoplastic neurological syndrome: importance of risk classification.

PURPOSE: To assess the diagnostic impact of 18F-FDG-PET/CT in patients suspected of paraneoplastic neurological syndrome (PNS) based on our own pre-test risk classification (PRC). METHODS: A multicenter retrospective longitudinal study was conducted from 2006 to 2014. We designed a seven-point scoring system using the clinical syndrome characteristics [classical (CS) and non-classical syndromes (NCS)] and its location (central, peripheral, in the neuromuscular junction or combined), onconeural antibodies and tumor markers. Patients were classified as low (score 0-2), intermediate (3-4) and high (5-7) pre-test risk of PNS. FDG-PET/CT was classified as negative or positive. Final diagnosis according Graus' criteria (definite, possible or no PNS) was established. Relations between clinical and metabolic variables with the final diagnosis were studied. RESULTS: 73 patients were included, with a follow-up time of 33 months. Eleven (15 %) patients were finally diagnosed with neoplasm (8 invasive cancers). Ultimately, 13 (18 %) and 24 (33 %) subjects were diagnosed as definite or possible PNS. All the patients with final diagnosis of neoplasm had a CS (p = 0.005). PET/CT was helpful to diagnose 6/8 (75 %) invasive cancers. PET/CT findings were associated with the final diagnosis of neoplasm (p = 0.003) and the diagnosis of PNS attending to Graus' criteria (p = 0.019). PRC showed significant association with the final diagnosis of neoplasm and PET/CT results. A majority of patients (10/11) diagnosed of neoplasm had intermediate/high-risk. CONCLUSIONS: Our PRC seems to be a valid tool to select candidates for PET/CT imaging in this setting. PET/CT detected malignancy in a significant proportion of patients with invasive cancer.

[(18)F-FDG PET/CT in the evaluation of patients suspected of paraneoplastic neurological syndrome]. / PET/TC con (18)F-FDG en la valoración de pacientes con sospecha de síndrome paraneoplásico neurológico.

OBJECTIVE: This study aimed to determine the diagnostic impact of (18)F-FDG PET/CT based on the clinical features of paraneoplastic neurological syndrome (PNS). MATERIAL AND METHODS: Multicenter retrospective and longitudinal study of patients with suspicion of PNS. The clinical picture was classified into classic (CS) and non-classic syndrome (NCS). After the follow-up, the definitive or possible diagnosis of PNS was established. The pictures that did not match any of the previous criteria were categorized as non-classifiable. The state of the onco-neural antibodies was studied. The PET/CT was classified as positive or negative for the detection of malignancy. The relationship between PET/CT findings and the final diagnosis was determined. The differences between variables (Pearson test X(2)) and the relationship between the results of the PET/CT and the final diagnosis were analyzed. RESULTS: A total of 64 patients were analyzed, classifying 30% as CS and 42% as NCS. After the follow-up, 20% and 16% of subjects were diagnosed as possible and definitive PNS, respectively. Positive onco-neural antibodies were found in 13% of the patients. A definitive diagnosis of PNS was associated with a positive PET/CT (P=.08). A significant relation between antibodies expression and final diagnosis of neoplasia (P=.04) was demonstrated. The PET/CT correctly localized malignancy in 5/7 cases of invasive cancer. CONCLUSIONS: The PET/CT showed a higher percentage of positive results in patients with definitive diagnosis of PNS. Despite the low prevalence of malignancy in our series, the PET/CT detected malignancy in a significant proportion of patients with invasive cancer.

[Validation of segmentation techniques for positron emission tomography using ex-vivo images of oncological surgical specimens]. / Validación de técnicas de segmentación para la tomografía por emisión de positrones mediante imágenes ex-vivo de piezas quirúrgicas oncológicas.

OBJECTIVE: To design a novel ex-vivo acquisition technique to establish a common framework to validate different segmentation techniques for oncological PET images. To evaluate several automatic segmentation algorithms on this set of images. MATERIAL AND METHODS: In 15 patients with cancer, ex-vivo PET studies of surgical specimens removed during surgery were performed after injection of (18)F-FDG. Images were acquired in two scanners: a clinical PET/CT and a high-resolution PET scanner. Real tumor volume was determined in each patient, and a reference image was generated for segmentation of each tumor. Images were segmented with 12 automatic algorithms and with a standard method for PET (relative threshold at 42%) and results were evaluated by quantitative parameters. RESULTS: It has been possible to demonstrate by segmentation of PET images of surgical specimens that on high resolution PET images, 8 out of 12 evaluated segmentation techniques outperformed the standard method, whose value is 42%. However, none of the algorithms outperformed the standard method when applied on images from the clinical PET/CT. Due to the great interest of this set of PET images, all studies have been published on the Internet in order to provide a common framework for validation and comparison of different segmentation techniques. CONCLUSIONS: We have proposed a novel technique to validate segmentation techniques for oncological PET images, acquiring ex-vivo PET studies of surgical specimens. We have demonstrated the usefulness of this set of PET images by evaluating several automatic segmentation algorithms.

[Lung hot spot as pitfall in PET-CT interpretation: focal lung uptake of 18F-fluorodeoxyglucose]. / Foco pulmonar facticio con (18)F-FDG: posible error en la interpretación de la PET-CT.

(18)F-FDG PET-CT has become an essential tool in oncology patient management. The normal distribution of the FDG and the possible artifacts (pitfalls), including those from CT-based attenuation correction, have already been described in several reviews. However, only a few cases of FDG focal lung uptake have been reported recently. We present two cases of oncology patients during a routine follow-up with this type of pitfall, without morphological correlation in the CT scan. We repeated the study in one of them, which made it possible to verify normalization of the hyperuptake, orienting us towards a possible pitfall.

[Hydatid disease in the Department of Health #2 of the Valencian Community (Spain)]. / Casos de hidatidosis en el Departamento de Salud 2 de la Comunidad Valenciana.

Hydatidosis is one of the most important zoonotic parasitic diseases of Mediterranean and South American countries where they constitute a significant health problem. Its diagnosis is realized essentially by image techniques and its treatment continues being eminently surgical. During the period 2000-2005, we reviewed clinical records of diagnosed and treated cases of hydatidosis carried out at the Department of Health 2 of the Valencia Community, Spain. Thirty three cases were evaluated of which we describe demographic, radiological, clinical, analytic, therapeutical and evolutionary data. We discuss the peculiarities found in them: thirty two cases were of hepatic location, essentially right, 48.5% unique cysts, five casual finding, 88.87% were diagnosed by ultrasonographic technique and in 2/3 of the cases the serology was positive. In addition, 52.17% of the twenty three cases treated surgically cured without recurrence and a 15.15% recurred without subsequent healing. Studies will require long-term monitoring of patients evolution.

Solitary focus in the liver in a thyroid cancer patient after a whole body scan with 131 iodine.

A 51-year-old woman diagnosed with follicular variant of papillary thyroid carcinoma underwent a total thyroidectomy followed four weeks later by an ablative dose of 3.7 GBq of 131I. A whole body scan 5 days after ablation showed an intense uptake within the thyroid bed and a focal uptake located in the right lung base or liver dome. Computed tomography examination revealed a hypodense hepatic node in segment VII resembling a liver metastasis. Histological examination after ultrasound-guided fine-needle aspiration characterized the lesion as a liver abscess. The abscess regressed after antibiotic therapy. Liver metastases from papillary thyroid carcinoma are uncommon. On the other hand, false positive findings of 131I whole body scans have been described. A focal hepatic uptake might represent a metastasis (rare in papillary carcinomas) or be related to other causes (cysts, inflammation or infection, non-thyroidal neoplasms, etc.).

[Incidence and mortality due to cancer in Navarre, 1998-2002. Trends in the last 30 years]. / Incidencia y mortalidad por cáncer en Navarra, 1998-2002. Evolución en los últimos 30 años.

Between 1998-2002, 16,952 new cases of cancer were registered in Navarre. In men, the most frequently diagnosed cancers were in the following order: prostate, lung, colon and rectum, bladder and stomach, which accounted for 63.2%. In women, the sites were breast, colon and rectum, corpus uteri, stomach and ovary, which accounted for 57.6% of the cases. In the same period, 1998-2002, 4,127 men and 2,470 women died from cancer. Sixty percent of all deaths due to malign tumours in men were due to cancer of the lung, prostate, colon and rectum, stomach and bladder. In women this was due to cancers of colon and rectum, breast, stomach, pancreas and lung, which accounted for 49% of the cases. In men in Navarre there has been an increase in the incidence rates of cancer of the prostate, kidney and non-Hodgkin lymphoma. Avoidable cancers such as those related to smoking (lung, oral cavity and pharynx or pancreas) continue to rise, and represent a greater global risk of dying from cancer in the latest period studied than in the decades of the 1970s and 1980s. From 1995 up to the present, mortality due to cancer has moved from occupying the second place to become the first cause of death among men in Navarre. The global risk of death due to cancer in men is now equal to the first period studied, 1975-1977. Amongst women the global risk of death due to cancer fell by 25% between 1975 and 2002, basically at the cost of breast and stomach cancer. Tumours related to smoking increased both in mortality and in incidence and appear as a significant health problem amongst women in Navarre. Breast cancer has increased in incidence, with lower mortality figures than those of the first period 1975-1977. Invasive cancer of the cervix remains at very low rates in comparison with many European countries, including Spain. In both sexes colorectal and skin cancer has increased, while the incidence and mortality of stomach cancer continues to fall.

[Bone scintigraphy in Erdheim-Chester disease]. / Gammagrafía ósea en la enfermedad de Erdheim-Chester.

Erdheim-Chester disease (ECD) is a rare disorder with fewer than 80 cases reported in the world. It consists of a non-Langerhans' cell histiocytosis that usually presents as pain due to bone involvement; however, the prognosis is marked by extraskeletal involvement. Although the final diagnosis needs an anatomophatologic study (normally through a bone biopsy), radiologic and scintigraphic findings are quasi pathognomonic. In this work, we report 2 ECD cases and their respective bone scans showing typical findings described in the literature. We found bilateral and symmetrical increased uptake of diaphyses and metaphyses of long bones, mainly in lower limbs. The mid-diaphyses and the epiphyses (partially in the first case) as well as the axial skeleton are spared.

[Pathological anatomy of organ transplantation]. / Anatomía patológica del trasplante de órganos.

We review some morphological aspects shared by all allografts. The main points are: 1) The expression of antigens of histocompatibility, essentially DR, allows the diagnosis of acute rejection with a significant specificity; 2) A lesion similar to "Quilty" effect may be seen in other allografts, and it is the first manifestation of an acute rejection; 3) Fine-needle aspiration biopsy may help in the follow-up of kidney transplant but has been demonstrated ineffective in other transplants; 4) The morphology of rejection is different according to the type of immunosuppressive therapy; 5) The basic lesions of chronic rejection are vascular, but chronic rejection may be diagnosed without vessels in the biopsy specimen, by the degree of atrophy of the parenchyma; 6) For the characterization of lymphomas in transplanted patients is necessary study the clonality of tumor cells, the gene rearrangement and the lymphoid subset; 7) Molecular Pathology may help in the early diagnosis of viral infections after transplantation.

[Iliac-ureteral fistula as a complication of multimodal treatment of bladder carcinoma]. / Fístula iliaco-ureteral como complicación del tratamiento multidisciplinar de carcinoma vesical.

We report on a patient who developed a fistula between the primitive left iliac artery and left ureter following combined treatment with systemic chemotherapy, local radiotherapy and surgery with ureteric diversion and ileal bladder. The role of each of the factors involved in this uncommon complication is discussed.

[Histopathological features of carcinomas of the bladder treated with radiotherapy. Anatomo-clinical correlation]. / Características histopatológicas de los carcinomas de vejiga tratados con radioterapia. Correlación anatomoclínica.

We evaluated the effects of radiotherapy (total dose 6,100 rads; 1,500 intraoperative and 4,600 external irradiation) on urothelial carcinomas in 16 patients. Tumor response and the histopathological changes were evaluated. All but one of the patients were men. Mean patient age was 58 years. The urothelial tumors were graded from I-III according to the histological features and degree of invasion. Two were classed as grade I, 6 grade II and 8 grade III. The post-irradiation cystectomy specimens revealed no tumor cells in 9 cases (56%); 2 grade II and 7 grade III tumors. All cystectomy specimens revealed histopathological changes following radiotherapy: edema and congestion (16 cases), squamous metaplasia (11 cases), multinucleated giant cells (7 cases), fibroblast proliferation (6 cases), dystrophic calcification (4 cases), macrophages with lipids (3 cases) and osseous formation (1 case). The mean patient follow-up was 18 months. Four patients died (3 from the tumor). Mean patient survival was 12 months. The foregoing findings indicate that radiotherapy appears to be more effective in destroying the more undifferentiated and deeper urothelial carcinoma.