Nódulos tireoidianos são um problema clínico comum, com prevalência de 1 a 76% a depender do método de avaliação e da população estudada. Cerca de 7 a 15% deles são malignos, podendo corresponder ao Carcinoma Papilífero (CPT), Carcinoma Folicular (CFT), Carcinoma Medular (CMT) ou Carcinoma Anaplásico. Estudos epidemiológicos recentes mostram um aumento de incidência do câncer de tireoide (CT), sobretudo devido ao CPT. Na avaliação etiológica do nódulo tireoidiano, são utilizados principalmente a ultrassonografia e a análise citológica por punção aspirativa com agulha fina (PAAF). Os resultados citológicos em nosso meio são reportados de acordo com o Sistema Bethesda, onde cada categoria (I a VI) tem seu risco de malignidade estimado e a conduta clínica recomendada. O objetivo deste estudo foi avaliar a efetividade da citologia de nódulos tireoidianos em um grupo populacional na região nordeste do estado de São Paulo, correspondente ao DRS VIII: quantificar os resultados pertencentes a cada categoria Bethesda e correlacionar com achados de tireoidectomia; calcular a prevalência do CT na amostra estudada; calcular o tempo entre a citologia e a cirurgia e verificar diferenças entre os tipos de assistência à saúde. Foram coletados dados de identificação, resultados de citologia dos nódulos e anatomopatológico das tireoidectomias do ano de 2014 nos três laboratórios de patologia do município de Franca, responsáveis por uma ampla cobertura local e regional, o que resultou numa amostra de 597 pacientes, 803 nódulos avaliados e 127 cirurgias. Dos 597 pacientes, 229 (38,3%) realizaram a PAAF utilizando o SUS, 312 (52,3%) a Saúde Suplementar (SS) e 56 (9,4%) foram exames particulares; 215 nódulos (26,7%) tiveram tamanho desconhecido e dos 588 nódulos com tamanho conhecido, o tamanho médio foi 1,8 cm (1,8 ± 1,2). Os resultados da citologia foram: Bethesda I 135 (16,8%); Bethesda II 475 (59,2%); Bethesda III 107 (13,3%); Bethesda IV 32 (4%); Bethesda V 20 (2,5%); Bethesda VI 34 (4,2%). Dos nódulos avaliados, 65,9% tiveram citologia B II, B V e B VI e 34,1% tiveram citologias B I, B III e B IV. Foram realizadas 127 tireoidectomias em 125 pacientes. De 210 nódulos operados, foi possível fazer a correlação entre a citologia e o laudo antomopatológico em 162 deles. Foram identificadas diferenças entre os sistemas público e privado na avaliação e tratamento da doença nodular tireoidiana na amostra. O tempo entre a citologia e cirurgia, o tamanho dos nódulos avaliados pela PAAF e dos nódulos operados foi maior em pacientes tratados pelo SUS. O principal motivo desta diferença seria a dificuldade de acesso a consultas especializadas, exames diagnósticos e cirurgias no SUS. A prevalência de CT na amostra foi 9,2% (55/597: 51 CPT, 3 CFT minimamente invasivos e 1 CMT), semelhante à descrita na literatura. 16/55 (29%) dos pacientes com CT, tiveram CPT menores que 1 cm. A citologia teve sensibilidade de 95%, especificidade de 50% e acurácia de 67,8% na detecção do CT. Este estudo confirmou que a citologia é um bom teste de triagem para CT em suas categorias B II, B V e B VI. Porém, existe grande limitação de desempenho da citologia nas categorias B I, B III e B IV, o que reforça a necessidade de combinação de testes diagnósticos como a US e os testes moleculares. / Thyroid nodules are a common clinical problem, with prevalence of 1 to 76% depending on the method of evaluation and the population studied. About 7 to 15% of them are malignant, and may correspond to Papillary Thyroid Carcinoma (PTC), Follicular Thyroid Carcinoma (FTC), Medullary Thyroid Carcinoma (MTC) or Anaplastic Carcinoma. Recent epidemiological studies have shown an increasing incidence of thyroid cancer (TC), mainly due to PTC. Ultrasound scanning and cytological analysis by fine needle aspiration (FNA) are used for the etiologic evaluation of thyroid nodules. In Brazil, cytological results are reported according to the Bethesda System, which estimates the risk of malignancy of each category (I to VI) and recommends the clinical management. The objectives of this study were to evaluate the effectiveness of FNA of thyroid nodules in a population group from the northeastern region of the state of São Paulo corresponding to DRS VIII; to quantify the results for each Bethesda category and to correlate them with thyroidectomy findings; to calculate the prevalence of TC in the sample studied, to calculate the time between cytology and surgery and to determine differences between the types of health care. Identification data, nodule cytology and anatomopathological diagnosis of thyroidectomies performed in 2014 were collected from three pathology laboratories in the city of Franca, responsible for a wide local and regional coverage, which resulted in a sample of 597 patients, 803 nodules evaluated and 127 surgeries. Taking all the 597 patients into consideration, 229 (38.3%) were submitted to FNA using the Unified Health System (SUS), 312 (52.3%) using the supplementary health (SS) and 56 (9.4%) were private examinations; 215 nodules (26.7%) were of unknown size and the mean size of 588 nodules of known size was 1.8 cm (1.8 ± 1.2). The results of FNA were Bethesda I 135 (16.8%); Bethesda II 475 (59.2%); Bethesda III 107 (13.3%); Bethesda IV 32 (4%); Bethesda V 20 (2.5%); Bethesda VI 34 (4.2%). Of the nodules evaluated, 65.9% had cytology B II, B V and B VI and 34.1% had cytologies B I, B III and B IV. A total of 127 thyroidectomies were performed in 125 patients. For 162 of the 210 operated nodules it was possible to correlate the cytology and anatomopathological results. Differences between the public and private systems were identified in the evaluation and treatment of thyroid nodular disease in the sample. The time between cytology and surgery, the size of the nodules assessed by FNA and the operated nodules were higher for the SUS cases. The main reason for this difference could be the difficulty in accessing specialized consultations, diagnostic exams and surgeries in SUS. The prevalence of TC in the sample was 9.2% (55/597: 51 PTC, 3 minimally invasive FTC and 1 MTC), similar to that described in the literature. 16/55 (29%) of TC patients had PTC less than 1 cm. Cytology showed 95% sensitivity, 50% specificity and 67.8% accuracy for the detection of TC. This study confirmed that cytology is a good screening test for CT in its B II, B V and B VI categories. However, the performance of cytology is greatly limited in categories B I, B III and B IV, supporting the need for a combination of diagnostic tests such as US and molecular tests.

Nódulos tireoidianos são um problema clínico comum, com prevalência de 1 a 76% a depender do método de avaliação e da população estudada. Cerca de 7 a 15% deles são malignos, podendo corresponder ao Carcinoma Papilífero (CPT), Carcinoma Folicular (CFT), Carcinoma Medular (CMT) ou Carcinoma Anaplásico. Estudos epidemiológicos recentes mostram um aumento de incidência do câncer de tireoide (CT), sobretudo devido ao CPT. Na avaliação etiológica do nódulo tireoidiano, são utilizados principalmente a ultrassonografia e a análise citológica por punção aspirativa com agulha fina (PAAF). Os resultados citológicos em nosso meio são reportados de acordo com o Sistema Bethesda, onde cada categoria (I a VI) tem seu risco de malignidade estimado e a conduta clínica recomendada. O objetivo deste estudo foi avaliar a efetividade da citologia de nódulos tireoidianos em um grupo populacional na região nordeste do estado de São Paulo, correspondente ao DRS VIII: quantificar os resultados pertencentes a cada categoria Bethesda e correlacionar com achados de tireoidectomia; calcular a prevalência do CT na amostra estudada; calcular o tempo entre a citologia e a cirurgia e verificar diferenças entre os tipos de assistência à saúde. Foram coletados dados de identificação, resultados de citologia dos nódulos e anatomopatológico das tireoidectomias do ano de 2014 nos três laboratórios de patologia do município de Franca, responsáveis por uma ampla cobertura local e regional, o que resultou numa amostra de 597 pacientes, 803 nódulos avaliados e 127 cirurgias. Dos 597 pacientes, 229 (38,3%) realizaram a PAAF utilizando o SUS, 312 (52,3%) a Saúde Suplementar (SS) e 56 (9,4%) foram exames particulares; 215 nódulos (26,7%) tiveram tamanho desconhecido e dos 588 nódulos com tamanho conhecido, o tamanho médio foi 1,8 cm (1,8 ± 1,2). Os resultados da citologia foram: Bethesda I 135 (16,8%); Bethesda II 475 (59,2%); Bethesda III 107 (13,3%); Bethesda IV 32 (4%); Bethesda V 20 (2,5%); Bethesda VI 34 (4,2%). Dos nódulos avaliados, 65,9% tiveram citologia B II, B V e B VI e 34,1% tiveram citologias B I, B III e B IV. Foram realizadas 127 tireoidectomias em 125 pacientes. De 210 nódulos operados, foi possível fazer a correlação entre a citologia e o laudo antomopatológico em 162 deles. Foram identificadas diferenças entre os sistemas público e privado na avaliação e tratamento da doença nodular tireoidiana na amostra. O tempo entre a citologia e cirurgia, o tamanho dos nódulos avaliados pela PAAF e dos nódulos operados foi maior em pacientes tratados pelo SUS. O principal motivo desta diferença seria a dificuldade de acesso a consultas especializadas, exames diagnósticos e cirurgias no SUS. A prevalência de CT na amostra foi 9,2% (55/597: 51 CPT, 3 CFT minimamente invasivos e 1 CMT), semelhante à descrita na literatura. 16/55 (29%) dos pacientes com CT, tiveram CPT menores que 1 cm. A citologia teve sensibilidade de 95%, especificidade de 50% e acurácia de 67,8% na detecção do CT. Este estudo confirmou que a citologia é um bom teste de triagem para CT em suas categorias B II, B V e B VI. Porém, existe grande limitação de desempenho da citologia nas categorias B I, B III e B IV, o que reforça a necessidade de combinação de testes diagnósticos como a US e os testes moleculares. / Thyroid nodules are a common clinical problem, with prevalence of 1 to 76% depending on the method of evaluation and the population studied. About 7 to 15% of them are malignant, and may correspond to Papillary Thyroid Carcinoma (PTC), Follicular Thyroid Carcinoma (FTC), Medullary Thyroid Carcinoma (MTC) or Anaplastic Carcinoma. Recent epidemiological studies have shown an increasing incidence of thyroid cancer (TC), mainly due to PTC. Ultrasound scanning and cytological analysis by fine needle aspiration (FNA) are used for the etiologic evaluation of thyroid nodules. In Brazil, cytological results are reported according to the Bethesda System, which estimates the risk of malignancy of each category (I to VI) and recommends the clinical management. The objectives of this study were to evaluate the effectiveness of FNA of thyroid nodules in a population group from the northeastern region of the state of São Paulo corresponding to DRS VIII; to quantify the results for each Bethesda category and to correlate them with thyroidectomy findings; to calculate the prevalence of TC in the sample studied, to calculate the time between cytology and surgery and to determine differences between the types of health care. Identification data, nodule cytology and anatomopathological diagnosis of thyroidectomies performed in 2014 were collected from three pathology laboratories in the city of Franca, responsible for a wide local and regional coverage, which resulted in a sample of 597 patients, 803 nodules evaluated and 127 surgeries. Taking all the 597 patients into consideration, 229 (38.3%) were submitted to FNA using the Unified Health System (SUS), 312 (52.3%) using the supplementary health (SS) and 56 (9.4%) were private examinations; 215 nodules (26.7%) were of unknown size and the mean size of 588 nodules of known size was 1.8 cm (1.8 ± 1.2). The results of FNA were Bethesda I 135 (16.8%); Bethesda II 475 (59.2%); Bethesda III 107 (13.3%); Bethesda IV 32 (4%); Bethesda V 20 (2.5%); Bethesda VI 34 (4.2%). Of the nodules evaluated, 65.9% had cytology B II, B V and B VI and 34.1% had cytologies B I, B III and B IV. A total of 127 thyroidectomies were performed in 125 patients. For 162 of the 210 operated nodules it was possible to correlate the cytology and anatomopathological results. Differences between the public and private systems were identified in the evaluation and treatment of thyroid nodular disease in the sample. The time between cytology and surgery, the size of the nodules assessed by FNA and the operated nodules were higher for the SUS cases. The main reason for this difference could be the difficulty in accessing specialized consultations, diagnostic exams and surgeries in SUS. The prevalence of TC in the sample was 9.2% (55/597: 51 PTC, 3 minimally invasive FTC and 1 MTC), similar to that described in the literature. 16/55 (29%) of TC patients had PTC less than 1 cm. Cytology showed 95% sensitivity, 50% specificity and 67.8% accuracy for the detection of TC. This study confirmed that cytology is a good screening test for CT in its B II, B V and B VI categories. However, the performance of cytology is greatly limited in categories B I, B III and B IV, supporting the need for a combination of diagnostic tests such as US and molecular tests.

No description available.

Σκοπός της παρούσας διδακτορικής διατριβής είναι η ανάπτυξη ενός ολοκληρωμένου συστήματος υποστήριξης της διάγνωσης (Decision Support System - DSS) με χρήση μεθόδων εξόρυξης δεδομένων για την ταξινόμηση επιχρισμάτων βιοψίας με λεπτή βελόνα (Fine Needle Aspiration - FNA). Δύο κατηγορίες επιλέχθηκαν για τα δείγματα FNA: καλοήθεια και κακοήθεια. Το σύστημα αυτό αποτελείται από τις ακόλουθες βαθμίδες: 1) συλλογής δεδομένων, 2) επιλογής δεδομένων, 3) εύρεσης κατάλληλων χαρακτηριστικών, 4) εφαρμογής ταξινόμησης με χρήση μεθόδων εξόρυξης δεδομένων. Επίσης, βασικός στόχος της παρούσας διδακτορικής διατριβής ήταν η βελτίωση της ορθής ταξινόμησης των ύποπτων επιχρισμάτων (suspicious), για τα οποία είναι γνωστή η αδυναμία της μεθόδου FNA να τα ταξινομήσει. Το σύστημα εκπαιδεύτηκε και ελέγχθηκε σε σχέση με το δείγμα για το οποίο είχαμε ιστολογικές επιβεβαιώσεις (ground truth). Για περιπτώσεις οι οποίες χαρακτηρίστηκαν ως μη κακοήθεις από την FNA, και για τις οποίες δεν είχαμε ιστολογικές επιβεβαιώσεις, το δείγμα προέκυψε από την συνεκτίμηση και άλλων κλινικών, εργαστηριακών και απεικονιστικών εξετάσεων. Στα πλαίσια της παρούσας διδακτορικής διατριβής συλλέχθηκαν εξετάσεις FNA θυρεοειδούς από το Εργαστήριο Παθολογοανατομίας του Α’ Τμήματος Παθολογίας της Ιατρικής Σχολής του Πανεπιστημίου Αθηνών. Δεδομένου ότι το εν λόγω εργαστήριο λειτουργεί και σαν κέντρο αναφοράς, σημαντικός αριθμός των δειγμάτων εστάλησαν εκεί και από άλλα Εργαστήρια Παθολογοανατομίας για επανέλεγχο. Το αρχειακό υλικό ήταν πολύ καλά ταξινομημένο σε χρονολογική σειρά αλλά ήταν σε έντυπη μορφή. Αρχικά πραγματοποιήθηκε η ανάλυση απαιτήσεων για τη δομή και το σχεδιασμό της βάσης δεδομένων. Με βάση τα στοιχεία από την τεκμηριωμένη διάγνωση σχεδιάστηκε και αναπτύχθηκε προηγμένο σύστημα για την κωδικοποίηση και αρχικοποίηση των δεδομένων. Με τη βοήθεια του σχεδιασμού και ανάλυσης απαιτήσεων αναπτύχθηκε και υλοποιήθηκε η βάση δεδομένων στην οποία αποθηκεύτηκαν τα δεδομένα προς επεξεργασία. Παράλληλα, με το σχεδιασμό της βάσης έγινε και η προεργασία για το σχεδιασμό και την ανάλυση απαιτήσεων του γραφικού περιβάλλοντος εισαγωγής στοιχείων. Λαμβάνοντας υπόψη ότι το σύστημα θα μπορούσε να χρησιμοποιηθεί και πέρα από τα πλαίσια της παρούσας διδακτορικής διατριβής λήφθηκε μέριμνα ώστε να παρέχεται ένα φιλικό και ευέλικτο προς το χρήστη περιβάλλον. Σύμφωνα με τη μεθοδολογία προσέγγισης η οποία ακολουθήθηκε προηγήθηκε στατιστική ανάλυση των 9.102 συλλεχθέντων δειγμάτων FNA ως προς τα κυτταρολογικά χαρακτηριστικά τους και τις διαγνώσεις. Οι κυτταρολογικές διαγνώσεις των συγκεκριμένων δειγμάτων συσχετίστηκαν με τις ιστολογικές διαγνώσεις, στοχεύοντας στον υπολογισμό της πιθανής επίδρασης και συμβολής κάθε κυτταρολογικού χαρακτηριστικού σε μια ορθή ή ψευδή κυτταρολογική διάγνωση, έτσι ώστε να προσδιοριστούν οι πιθανές πηγές λανθασμένης διάγνωσης. Τα δείγματα τα οποία περιείχαν μόνο αίμα ή πολύ λίγα θυλακειώδη κύτταρα χωρίς κολλοειδές θεωρήθηκαν ανεπαρκή για τη διάγνωση. Οι βιοψίες εκτελέσθηκαν είτε στο Α’ τμήμα του Πανεπιστημίου Αθηνών (οι περισσότερες από τις περιπτώσεις με ψηλαφητούς όζους) είτε αλλού (κυρίως κάτω από την καθοδήγηση του κέντρου αναφοράς). Τα δείγματα επιστρωμένα σε πλακάκια, στάλθηκαν στο κέντρο αναφοράς από διάφορα νοσοκομεία, με διαφορετικά πρωτόκολλα σχετικά με τα κριτήρια εκτέλεσης βιοψίας FNA σε θυρεοειδή. Μετεγχειρητικές ιστολογικές επαληθεύσεις ήταν διαθέσιμες για 266 ασθενείς (κακοήθειες και μη). Το χαμηλό ποσοστό ιστολογικών επαληθεύσεων οφείλεται στην ετερογενή προέλευση των ασθενών και στην έλλειψη ολοκληρωμένης παρακολούθησης και επανελέγχου των ασθενών. Για την αξιολόγηση των δεδομένων χρησιμοποιήθηκαν περιγραφικά στατιστικά μεγέθη όπως, μέση τιμή, τυπική απόκλιση, ποσοστά, μέγιστο και ελάχιστο. Έγιναν επίσης και χ2 δοκιμές επιπέδου σημαντικότητας διαφόρων παραμέτρων για να ελεγχθεί η πιθανή συσχέτιση ή η ανεξαρτησία. Για τη συσχέτιση των κυτταρολογικών και των ιστολογικών διαγνώσεων και την αξιολόγηση των εργαστηριακών ευρημάτων, πέραν των περιγραφικών στατιστικών μεγεθών χρησιμοποιήθηκαν και υπολογισμοί της ευαισθησίας, της ειδικότητας, της συνολικής ακρίβειας, της αρνητικής και θετικής αξίας πρόβλεψης (negative and positive predictive value). Προκειμένου να καθοριστεί εάν μια κατηγορία ασθενειών συσχετίζεται ή όχι με συγκεκριμένες κυτταρολογικές παραμέτρους εφαρμόστηκε μέθοδος ελέγχου στατιστικής σημαντικότητας σε επίπεδο 5% (p < 0,05). Η διαδικασία ακολουθήθηκε για κάθε κατηγορία ασθενειών ή συνδυασμό τους και για κάθε παράμετρο των κυτταρολογικών και αρχιτεκτονικών στοιχείων της κυτταρολογικής διάγνωσης. Τα αποτελέσματα της στατιστικής ανάλυσης επέτρεψαν το διαχωρισμό των δεδομένων σε καλοήθη, κακοήθη, νεοπλασματικά, ύποπτα για κακοήθεια και οριακά με χαρακτηριστικά γνωρίσματα μεταξύ ενός καλοήθους και ενός νεοπλασματικού. Στην συνέχεια αναπτύχθηκε σύστημα υποστήριξης της διάγνωσης χρησιμοποιώντας εξειδικευμένες μεθόδους εξόρυξης δεδομένων. Το σύστημα αποτελείται από τέσσερις βαθμίδες. Η πρώτη βαθμίδα αυτού του συστήματος είναι το περιβάλλον Συλλογής Δεδομένων στην οποία τα δεδομένα αποθηκεύονται στη βάση δεδομένων. Η Δεύτερη Βαθμίδα αυτού του συστήματος αφορά στην Επιλογή Δεδομένων. Σύμφωνα με την καταγραφή των απαιτήσεων, την εισαγωγή και τη ψηφιοποίηση των στοιχείων, δημιουργήθηκαν 111 χαρακτηριστικά για κάθε ασθενή (record). Τα περισσότερα χαρακτηριστικά είχαν τιμές δυαδικού τύπου, αποτυπώνοντας την ύπαρξη ή μη του κάθε χαρακτηριστικού, ενώ κάποιες άλλες είχαν τιμές τύπων αριθμών ή αλφαριθμητικών χαρακτήρων. Από τα 111 χαρακτηριστικά επιλέχθηκαν 60 χαρακτηριστικά τα οποία περιγράφουν τη δομή των επιχρισμάτων ενώ δημιουργήθηκαν άλλα 7 χαρακτηριστικά τα οποία αφορούσαν στην ομαδοποίηση άλλων χαρακτηριστικών. Η Τρίτη Βαθμίδα του συστήματος αφορά στην εύρεση των Κατάλληλων Χαρακτηριστικών. Λόγω του αρχικά υψηλού αριθμού χαρακτηριστικών παραμέτρων (67 ανά περίπτωση), ήταν απαραίτητο να εξαλειφθούν οι χαρακτηριστικές παράμετροι που συσχετίζονταν γραμμικά ή δεν είχαν καμία διαγνωστική πληροφορία. H μέθοδος επιλογής χαρακτηριστικών εφαρμόστηκε πριν από την ταξινόμηση, με γνώμονα την ανεύρεση ενός υποσυνόλου των χαρακτηριστικών παραμέτρων που βελτιστοποιούν σε ακρίβεια τη διαδικασία ταξινόμησης. Εφαρμόστηκε η τεχνική επιπλέουσας πρόσθιας ακολουθιακά μεταβαλλόμενης επιλογής (SFFS). Ο αριθμός των δειγμάτων που χρησιμοποιήθηκαν είναι 2.036 (1.886 καλοήθειες και 150 κακοήθειες). Εξ αυτών, όλες οι κακοήθειες είναι ιστολογικά επιβεβαιωμένες. Επίσης, 140 καλοήθειες είναι ιστολογικά επιβεβαιωμένες με επάρκεια υλικού. Οι υπόλοιπες 1.726 καλοήθειες είναι επιβεβαιωμένες με συνεκτίμηση κλινικών, εργαστηριακών και απεικονιστικών ιατρικών εξετάσεων (υπέρηχοι κ.λπ.). Από τα 2.036 δείγματα, το 25% χρησιμοποιήθηκε για την επιλογή χαρακτηριστικών παραμέτρων, δηλαδή 37 περιπτώσεις κακοήθειας (Malignant) και 472 περιπτώσεις καλοήθειας (Non Malignant). Από την εφαρμογή της τεχνικής (SFFS) επιλέχθηκαν τελικά 12 χαρακτηριστικά ως βέλτιστα για την ταξινόμηση των δεδομένων FNA σε καλοήθη και κακοήθη. Η Τέταρτη βαθμίδα επεξεργασίας είναι η Εφαρμογής Ταξινόμησης με χρήση Μεθόδων Εξόρυξης Δεδομένων ή Ταξινομητής. Για το σκοπό αυτό, επιλέχθηκε να εφαρμοστεί μια πληθώρα αξιόπιστων, καλά επιβεβαιωμένων και σύγχρονων μεθόδων εξόρυξης δεδομένων. Το σύστημα εκπαιδεύτηκε και ελέγχθηκε σε σχέση με το δείγμα για το οποίο είχαμε ιστολογικές επιβεβαιώσεις (ground truth). Η ανεξάρτητη εφαρμογή τεσσάρων αξιόπιστων μεθόδων, Δέντρων Αποφάσεων (Decision Trees), Τεχνιτών Νευρωνικών Δικτύων (Artificial Neural Network), Μηχανών Στήριξης Διανυσμάτων (Support Vector Machine), και Κ - κοντινότερου γείτονα (k-NN), έδωσε αποτελέσματα συγκρίσιμα με αυτά της FNA μεθόδου. Περαιτέρω βελτίωση των αποτελεσμάτων επιτεύχθηκε με την εφαρμογή της μεθόδου πλειοψηφικού κανόνα (Majority Vote - CMV) συνδυάζοντας τα αποτελέσματα από την εφαρμογή των τριών καλύτερων αλγορίθμων, ήτοι των Νευρωνικών Δικτύων, Μηχανών Στήριξης Διανυσμάτων και Κ - κοντινότερου γείτονα. Η τροποποιημένη μέθοδος τεχνητών αυτοάνοσων συστημάτων (Artificial Immune Systems – AIS) χρησιμοποιήθηκε για πρώτη φορά στην ταξινόμηση και παρουσίασε ιδιαίτερα βελτιωμένα αποτελέσματα στην ταξινόμηση των επιχρισμάτων τα οποία χαρακτηρίζονται ύποπτα (suspicious) από τους ειδικούς και αποτελούν το αδύναμο σημείο της μεθόδου FNA. Αυτές οι περιπτώσεις υπόνοιας αποτελούν ένα πολύ δύσκολο κομμάτι για τη διάκριση μεταξύ των καλοηθειών και των κακοηθειών, ακόμα και για τους πλέον ειδικούς. Επειδή όλα τα περιστατικά που χαρακτηρίζονται από την βιοψία FNA ως υπόνοιες αντιμετωπίζονται κλινικά σαν κακοήθειες, η εφαρμογή των αλγοριθμικών μεθόδων βελτιώνει αισθητά τη διαχείριση αυτών των περιπτώσεων μειώνοντας τον αριθμό των άσκοπων χειρουργικών επεμβάσεων θυρεοειδεκτομών. / The Aim of present thesis is the development of an integrated system for supporting diagnosis (Decision Support System - DSS) using for categorizing FNA biopsy smears. Two categories were selected for the FNA smears: malignant and nonmalignant. The system is constituted by the following stages of 1) data collection, 2) data selection 3) choice of suitable clinical and cytological features, 4) application of data mining method for the categorization of FNA biopsy smears. Furthermore a fundamental objective of the doctoral thesis was the improvement of suspect smears (suspicious) categorization, for the latter FNA Biopsy has a known restriction. The system had been trained and checked in relation to the sample that histologic evaluation existed (ground truth). For smears that characterized as nonmalignant by FNA and histological data we’re not available, complementary clinical, laboratory and imaging evaluations took into account in order to create the sample. Τhe smears that were available in this thesis, were collected from FNA biopsies in Pathologoanatomy Laboratory, A’ Pathology Department, Medical School of Athens University. Given that the above referred laboratory is a reference center, an important number of FNA smears were sent to it from other laboratories for cross check. The examination files were sorted in chronological order, but there were in paper forms. The requirements for the formation and the design of database system were collected. Based on the material of the diagnosis an improved system was designed and developed for data initialization and coding. The database was developed based on the design and analysis of requirements; in this database data were stored for further investigation. Analysis of the graphical user interface design was performed in parallel to the database design. Taking into account that the system might be used after the completion of thesis, the graphical user interface was designed in order to be user friendly and flexible environment. According to the methodological approach that was followed, the various cytological characteristic of 9102 FNA smears aspired among 2000-2004 was analyzed statistically. The cytological reports cross correlated with histological diagnoses, aiming to calculate the effect or contribution of each cytological characteristic to a false or true cytological diagnosis and to find the possible sources of erroneous diagnosis. The smears that have blood or a few follicular cells without colloid were characterized as insufficient for further diagnosis. The aspiration was performed either in Α’ department of Athens University (most of the cases with palpable nodules) or elsewhere (mainly under guidance of the reference center). The acquired smears being send to the reference center from various hospitals with different protocols concerning criteria to perform a thyroid FNA. Histological reports were available for 266 patients. The small number of histological verifications was due to the heterogeneity and the lack of patients files. For evaluating of data, descriptive statistic values were used like mean, standard deviation, percentage, maximum and minimum. In addition to that χ2 tests of significance were performed in order to check possible correlation or independence. For correlating cytological and histological diagnosis and evaluating laboratory findings, apart from the descriptive statistic parameters also calculated sensitivity, specificity, total accuracy, negative predictive value and positive predictive value. Method of statistical significance in the level of 5% (p < 0,05) was applied in order to specify if a disease was correlated to a cytological parameter. Those checks were performed for each disease category in correlation to any cytological parameter. Statistical analysis divided the smears into nonmalignant, malignant, neoplasms, suspicious for malignancy and borderline. A diagnosis support system was implemented using data mining methods. The system is consisted of four stages. The First stage of the system is the Data Collection environment, which stores the data to the database. The Second stage of this system concerns the Selection of Data. User requirements concluded that 111 characteristics are needed to describe each patient (record). Most of them have binary values, presenting existence and not existence, other have alphanumeric and number values. Among them 60 were selected and 7 more are produced from grouping other characteristics. The final analysis reveals that 67 characteristics of the smears are capable for describing the structure of smears in general. The Third stage of system concerns the Selection of Best Characteristics. Due to the high number of attributes (67 per case), it was essential to eliminate the characteristics that are connected linearly or do not bring diagnostics information. The choice of characteristics applied before the classification, having the aim of discovering a subset of characteristics that optimizes the process of classification. The technique of Sequential Float Forward Search (SFFS) was applied. The number of patients that used was 2,036 (1886 non malignancies and 150 malignancies). Among them all malignancies were histologically confirmed. In addition to that 140 no malignancies were histologically confirmed in correlation to evaluation of clinics, laboratorial and medical image actions (ultrasounds etc.). Among 2.036 smears the 25% used for characteristics selection, 37 smears of Malignant and smears of Non Malignant. The Sequential Float Forward Search (SFFS) Technique, choose the best 12 elements that they reveal high performance to FNA data categorization. The Fourth stage is the Application of Classification using Data Mining Methods or in other words data mining method. For this aim a set of reliable, well confirmed but also modern methods applied. In addition to that the system was trained and was checked using the sample with histological verifications (ground truth). The independent application of four reliable methods, Decision Trees, Artificial Neural Network, Support Vector Machine, and k-NN, resulting to comparable outcomes concerning those of FNA. However, further improvement was achieved with the application of Majority (Majority Vote - CMV) using of previous results of three algorithms Artificial Neural Network, Support Vector Machine, and k-NN. The modified Artificial Immune System (AIS) was applied for first time. AIS presents particularly improved results for the categorization of smears, which are characterised “suspicious” by the experts and is a known weakness of FNA method. These cases constitute a very difficult part for the discrimination among non-malignant and malignant, even for a specialist. Since all these cases are faced clinically using FNA as malignancies, the application of an improved algorithmic method improves accordingly the management of these cases by decreasing the number of useless surgical thyroid operations.