Dissertations / Theses on the topic 'Biopsija'

Prostatos vėžys yra dažniausia vyrų onkologinė liga JAV, Vakarų Europoje bei Lietuvoje. Dėl senstančios visuomenės ateityje bus nustatoma dar daugiau naujų prostatos vėžio atvejų. Lietuvos vėžio registro duomenimis 1995 – 2005 metais vidutinis metinis prostatos vėžio sergamumo didėjimas - 14,5 proc. per metus. Vyrų sergamumas prostatos vėžiu Lietuvoje 2005 metais siekė 125,9/100000 atvejų, o mirtingumas nuo šios ligos siekė 31/100000 atvejų. Vyrų mirtingumas nuo prostatos vėžio antras pagal dažnį po plaučių vėžio su vėžiu susijusio mirtingumo grupėje. Todėl daugelis tyrėjų pabrėžia, kad norint mažinti mirtingumą, reikia ankstinti prostatos vėžio nustatymo laiką. Pradėta Lietuvos vyrų ankstyvosios prostatos vėžio diagnostikos programa ir dažnas prostatos specifinio antigeno nustatymas lėmė padidėjusį apsilankymų pas urologus skaičių ir padidino prostatos biopsijų kiekį. Norint efektyviai ir optimaliai ištirti šiuos pacientus, reikia daug materialinių išteklių ir laiko.Šio darbo tikslas buvo optimizuoti pacientų su padidėjusia prostatos vėžio rizika ištyrimą ir stebėjimą bei nustatyti ryšį tarp prostatos vėžio rizikos veiksnių ir prostatos vėžio diagnozavimo padidėjusios rizikos grupėje. Darbo uždaviniai: 1. Išanalizuoti prostatos vėžio nustatymo dažnį pirmąja ir kartotinėmis lateralinėmis sekstantinėmis prostatos biopsijomis ir įvertinti jų efektyvumą. 2. Nustatyti amžiaus, rūkymo, alkoholio vartojimo, prostatos vėžio šeiminės anamnezės, viršsvorio ir padidėjusio cholesterolio... [toliau žr. visą tekstą]
Prostate cancer is the most frequent malignant disease in men in United States, Western Europe and in Lithuania. Due to ageing population incidence of prostate cancer will rise even more in the future. Since the year 2003 prostate cancer became the most common form of cancer diagnosed in men in Lithuania (more than 1500 new prostate cancer cases a year). There were 2005 of new prostate cancer cases diagnosed in the year 2005. According to Lithuanian Cancer Registry data during the years 1995-2005 the prevalence of prostate cancer was increasing 14.5 percent annually. Prostate cancer was detected in 24.3 percent of all cancer cases in men in the year 2005 in Lithuania and in 48.3 percent of them disease was detected in the stages I and II. In the year 2005 the prevalence of prostate cancer in Lithuanian men was 125.9 per 100000 population and mortality was 31 per 100000 population. Prostate cancer is a second common form of death after lung cancer in cancer-associated mortality group in Lithuania. Prostate cancer mortality ranged between 19 and 55 per 100000 in Europe and it was 23.2 per 100000 populations in the year 2006 in European Union. Many authors stress that it is important to diagnose prostate cancer in the early stages in order to reduce prostate cancer mortality rate. The aim of the study was to optimize investigation and follow-up of the high prostate cancer risk patients, and to define the relation between prostate cancer risk factors and prostate cancer... [to full text]

Bakteriologinis nudegimo žaizdų tyrimas svarbus nustatant esamus potencialius patogenus, padeda diagnozuoti infekciją, leidžia įvertinti sepsio tikimybę, nustatyti tinkamą laiką žaizdos audinių rekonstrukcijai. Tačiau iki dabar tęsiasi diskusijos, kuris mėginio paėmimo metodas yra optimalus žaizdos mikroflorai arba infekcijai nustatyti. Lietuvoje toks tyrimas iki šiol nebuvo atliktas, o kitų šalių mokslininkų skelbiami rezultatai gana prieštaringi. Atlikto darbo metu tyrėme, kuris bakteriologinio tyrimo metodas (kiekybinis bei pusiau kiekybinis tepinėliai ar biopsija) yra kliniškai vertingiausias žaizdos mikrofloros stebėjimui ligos periodu, infekcijos patvirtinimui atsižvelgiant į klinikinius žaizdos pokyčius. Vienodas bakterijų rūšis tose pačiose žaizdose dažniausiai nustatė biopsija ir pusiau kiekybinis tepinėlis. Šių metodų bendras rezultatų sutapimas buvo labai geras. Abiem metodais nustatomo bakterijų kiekio koreliacija – vidutinė. Tačiau geriausiai rezultatai sutapo žaizdoje esant nedideliam bakterijų kiekiui. Esant klinikiniams žaizdos infekcijos požymiams reikšmingai dažniau bakterijos ir didesnis jų rūšių kiekis nustatytas biopsijos tiriamojoje medžiagoje. Biopsijos metodu reikšmingai dažniau nustatytas labai gausus (>105 KFV) bakterijų kiekis. Nudegimo žaizdų užteršimui bakterijomis stebėti, kai nėra infekcijos požymių, pusiau kiekybinis tepinėlio metodas yra tinkamiausias. Kliniškai nustatytą žaizdos infekciją geriausiai atspindi biopsijos tyrimo rezultatai.
Evaluation of microorganisms in burn wound is important not only in determining potential pathogens present, but also allows diagnosing an infection, evaluating possibility of sepsis, and determining the appropriate time for wound tissue reconstruction. However, there are still many discussions about the optimal wound sample taking method to determine wound microflora or infection, and the opinions about sample taking methods for identification of microorganisms are controversial. We have compared three methods (quantitative swab, semi-quantitative swab, biopsy) and determined significant differences. Similar species of bacteria in the same wounds were most frequently identified by biopsy and the semi-quantitative swab method. The general concordance of the results of these methods was very good. There was a medium correlation of the bacterial amount identified by these methods. However, there was the best concordance of the results in presence of a small amount of bacteria in a wound.In presence of clinical wound infection signs, bacteria and larger number of their species were significantly more frequently identified in the biopsy material. The biopsy method significantly more frequently identified a very large amount (>105 CFU) of bacteria. The semi-quantitative swab method is most appropriate to monitor burn wound contamination with bacteria when there are no infection signs. A clinically determined wound infection was best reflected by the results of biopsy.

Uvod: Implementacija brojnih neuroradioloških modaliteta je značajno uticala na način i efikasnost sprovođenja dijagnostike tumora mozga. Na osnovu neinvazivno dobijenih podataka može se postaviti diferencijalna dijagnoza, ali do sada nije potvrđena nijedna neuroradiološka metoda koja može samostalno i konačno da postavi definitivnu patohistološku (PH) dijagnozu. Stereotaksična biopsija je neurohirurška procedura kojom se, bez bitnog narušavanja integriteta i funkcije moždanog tkiva, može obezbediti reprezentativni uzorak intrakranijalne tumorske promene radi sprovođenja PH i drugih specifičnih analiza, u cilju postavljanja tačne dijagnoze i potom primene adekvatnog lečenja. Cilj: Cilj ove studije je da se utvrditi mogućnost uzorkovanja reprezentativnog tkiva za postavljanje PH dijagnoze uz pomoć stereotaksične biopsije kod pacijenata sa tumorom mozga, kao i da se utvrdi vrsta i učestalost eventualnih komplikacija same procedure i postojanje korelacije između PH nalaza dobijenog stereotaksičnom biopsijom i rezultata sprovedenih neuroradioloških ispitivanja. Materijal i metode: Sprovedeno istraživanje je bilo kliničko, prospektivno, a uzorak je činilo ukupno 50 pacijenata koji su bili hospitalizovani na Klinici za neurohirurgiju KCV zbog dijagnostikovane tumorske promene mozga i postavljene indikacije za stereotaksičnu biopsiju, u periodu od septembra 2016. godine do januara 2018. godine. Svi pacijenti koji su uključeni u studiju su u sklopu sprovedene dijagnostičke obrade imali načinjen magnetno rezonanantni (MRI) pregled glave na osnovu kojeg su se određivale morfološke karakteristike tumora i vršila procena prirode tumorske promene mozga, a kod ukupno 25 pacijenata je dodatno načinjena MR spektroskopija (MRS) dijagnostikovane tumorske promene sa ciljem određivanja biohemijskog profila i dodatne procene i karakterizacije tkiva. Nakon sprovedene detaljne onkološke obrade i adekvatne pripreme, se sprovodila kompjuterizovanom tomografijom (CT) navođena stereotaksična biopsija sa ramom u cilju uzorkovanja adekvatnog tkiva za PH analizu. U toku istraživanja procena uspešnosti uzorkovanja reprezentativnog tkiva se vršila pregledom bioptata od strane patologa, a nakon procedure se kliničkim pregledom i kontrolnim CT pregledom glave utvrđivao stepen komplikacija. Rezultati: Dobijeni rezultati su pokazali da su fokalni neurološki deficit i moždani sindrom bili najčešći klinički simptomi i znaci kod pacijenata kod kojih je indikovana stereotaksična biopsija tumora mozga. Prema MRI nalazu najzastupljenije su bile difuzne tumorske promene sa 36% udela u uzorku, zatim solitarne sa 34% i multifokalne sa 20%, a potom multicentrične tumorske promene koje su predstavljale 10% uzorka. Takođe, na osnovu MRI i MRS nalaza je oko 80% tumora procenjeno kao najverovatnije glijalnog porekla. U 95,9% slučaja je postavljena precizna PH dijagnoza. Nepromenjeno stanje svesti i neurološki nalaz su imali 92% pacijenata nakon biopsije, a kod 3 pacijenta (6%) je došlo do razvoja prolaznog neurološkog deficita, dok je jedan pacijent (2%) razvio trajan neurološki deficit. Ukupan morbiditet vezan za proceduru je stoga 2%, a nije zabeležen ni jedan smrtni slučaj (mortalitet 0%) tokom sprovođenja studije. Zaključak: Stereotaksična biopsija je dokazana i veoma pouzdana procedura sa malim brojem komplikacija i niskom stopom morbiditeta i mortaliteta, kojom se omogućava dobijanje reprezentativnog uzorka tumorskog tkiva za postavljanje sigurne patohistološke dijagnoze. Intraoperativna PH analiza dela uzorka tkiva dodatno poboljšava uspešnost pri uzorkovanju i postavljanju definitivne PH dijagnoze. Savremene neuroradiološke metode imaju visoku specifičnost u razlikovanju biološke prirode tumorskih promena, ali se ne mogu koristi nezavisno od PH analize uzorka tkiva
Introduction: The implementation of numerous neuroradiological techniques has significantly influenced the way and the efficiency in which the diagnosis of brain tumor is established. Based on non-invasive imaging data, a differential diagnosis can be made, but no neuroradiological method has been established so far, which can finally make a definitive diagnosis. Stereotactic biopsy is a neurosurgical procedure that can provide a representative sample of any intracranial tumor in order to performe histopathological and other specific examinations, and to set the exact diagnosis and then apply adequate treatment, but without significantly impairing the integrity and function of brain tissue. Objective: The aim of this study is to determine the diagnostic value of stereotactic biopsy and ability of providing the representative tissue in order to establish a pathohistological diagnosis in patients with brain tumors. Also, the aim is to determine the type and frequency of possible complications of the procedure itself and the correlation between the pathohistological findings obtained and the results of the conducted neuroradiological examinations. Materials and methods: This research was clinical, prospective and included a total of 50 patients who were hospitalized at the Clinical Center of Vojvodina, from September 2016 to January 2018, due to diagnosed brain tumor for which the stereotactic biopsy is indicated. In all patients magnetic resonance (MRI) examination of the head was used to determine morphological characteristics and assesse the nature of the brain tumor tissue, and in a total of 25 patients MR spectroscopy was additionally made with the goal of determining the biochemical profile and additional tissue assessment and characterization. After detailed oncological assessment, completed laboratory and radiological diagnostics, a CT guided framebased stereotactic biopsy was performed for the purpose of sampling tumor tissue for pathohistological analysis. During the research, the success rate of biopsy in providing the representative tissue and establishing the diagnosis was performed by a pathologist, and after the procedure, a clinical and a control head CT examination was used to review the rate of complications. Results: The results obtained showed that focal neurological deficit and psychoorganic syndrome were the most common clinical symptoms and signs in this study. According to MRI, the most common were diffuse brain tumors with 36% of the sample, then solitary with 34% and multifocal with 20%, followed by multicentric tumors representing 10% of the study sample. Also, based on MRI and MRS findings, approximately 80% of tumors are estimated to be most likely of glial origin. In 95.9% of cases, a complete pathohistological (PH) diagnosis was established. The unchanged neurological status was observed in 92% of patients after biopsy, and 3 patients (6%) developed a transient neurological deficit, while only one patient (2%) developed a permanent neurological deficit. The total morbidity associated with the procedure is therefore 2%, and no deaths (mortality 0%) related to the procedure during the study is recorded. Conclusion: Stereotactic biopsy is highly reliable procedure with a small number of complications and a low morbidity and mortality rate, which allows us to acquire the representative sample of brain tumor tissue and to establish a pathohistological diagnosis. Intraoperative PH analysis of acquired tissue samples further enhances the sampling performance and the setting of definitive PH diagnosis. Modern neuroradiological modalities have a high specificity in distinguishing the biological nature of brain tumors, but they still can not be used independently of the pathohistological analysis of the tissue sample.

Darbų apžvalgoje nagrinėjami sergamumo skydliaukės vėžiu pokyčiai Lietuvoje 1978 – 2003 metais bei sergamumo sąsajos su diagnostika. Sergamumas skydliaukės vėžiu Lietuvoje 1978-2003 metais didėjo ir vidutinis metinis pokytis vyrams siekė 4,2% (p<0,0001), o moterims - 6,1% (p<0,0001). Standartizuotas vyrų sergamumo rodiklis padidėjo nuo 0,7 atvejo 100 000 gyventojų 1978 metais iki 2,5 atvejo 100 000 gyventojų 2003 metais, o moterų – atitinkamai nuo 1,5 iki 11,4 atvejo 100 000 gyventojų. Mirtingumas nuo skydliaukės vėžio nagrinėjamu laikotarpiu nepakito. Nustatytas papilinės skydliaukės karcinomos padidėjimas 1978 – 2003 metų laikotarpiu. Didžiausią įtaką susirgimo skaičiaus pokyčiams turėjo skydliaukės vėžio atvejai diagnozuoti ankstyvosiose stadijose. Žymų sergamumo skydliaukės vėžiu padidėjimą 2002-2003 metais Lietuvoje galima susieti su pokyčiais skydliaukės mazgų diagnostikoje, tobulesnių ultragarsinių technologijų panaudojimu bei aktyviu ultragarsu kontroliuojamų aspiracinių biopsijų plona adata pritaikymu klinikinėje praktikoje.
The aim of this study is to analyse changes in thyroid cancer incidence trends in Lithuania during the period of 1978–2003 and the relationship between incidence and diagnostic strategies. Annual percentage changes in the age-standardized rates over this period were 4.2% (p<0.0001) and 6.1% (p<0.0001) for men and women, respectively, for all carcinomas combined. During study period the age-standardized incidence rates increased in males from 0.7 to 2.5 cases per 100000 and in females from 1.5 to 11.4 per 100000. Mortality due to thyroid cancer did not change during the period of 1978–2003. By histopathology, number of papillary thyroid carcinoma cases increased in 1998-2003. Also, there was increase in the number of early stages of thyroid cancer. The increase in thyroid cancer incidence in Lithuania seems to be mainly due to the changes in the management of thyroid nodules and increased usage of ultrasound guided fine needle aspiration biopsy in clinical practice.

Karcinom dojke predstavlja najčešću malignu neoplazmu među ženskom populacijom, a poštedna terapija dojke, preferirani je model lečenja bolesnica u ranom stadijumu bolesti. Smatra se da je optimalna hirurška resekciona margina 2 mm. Opisano je mnogo metoda koje služe za intraoperativnu proveru suficijentnosti resekcione hirurške margine i sve one imaju svoje prednosti i mane. Ciljevi ove studije bili su da se utvrdi, da li postoji statistički značajna razlika u određivanju širine negativne resekcione hirurške margine izražene u milimetrima pri operacijama karcinoma dojke upotrebom palpatorne metode i intraoperativne mobilne radiografije, poređenjem nalaza merenja hiruga sa većim i manjim iskustvom u hirurgiji karcinoma dojke kao i nalaza radiologa u odnosu na patohistološku ex tempore analizu. Istraživanje je sprovedeno kao retrospektivno–prospektivna studija na Klinici za operativnu onkologiju, Instituta za onkologiju Vojvodine i obuhvatilo je 150 bolesnica kod kojih je preoperativno dijagnostikovan karcinom dojke. Kriterijum za uključenje u studiju bilo je izvođenje poštedne operacije dojke sa ili bez disekcije ipsilaterale aksile, dok su iz studije isključene bolesnice kod kojih nije bilo moguće izvesti poštednu operaciju dojke, one sa radiološki potvrđenom diseminovanom bolešću, kao i bolesnice koje su ranije operisane zbog karcinoma iste dojke. Kod svih 150 ekstirpiranih karcinoma dojke urađena je procena širine resekcione hirurške margine intraoperativno palpatornom metodom, zatim na aparatu za mobilnu digitalnu radiografiju, te radiogram analiziran od strane iskusnog i manje iskusnog hiruga u hirurgiji karcinoma dojke, kao i radiologa te upoređen sa nalazom ex tempore patohistološke analize. Definitivna širina resekcione hirurške margine potvrđena je na parafinskim patohistološkim preparatima. Srednja vrednost praćenja bolesnica, postoperativno, iznosila je 100,97 nedelja. Najveći broj bolesnica pripadao je starijoj životnoj dobi (56,67%). Preoperativna lokalizacija klinički nepalpabilnih tumora u dojci urađena je kod 52 (34,67%) bolesnice. Najčešće se tumor prezentovao kao solitarni fokus sa okolnim ognjištima in situ karcinoma (72, 48%), dok je najčešći histološki subtip bio duktalni invazivni karcinom dojke (112 (74,67%)). Najveći broj operacija dojke okarakterisan je kao kvadrantektomija (85 (56,67)), dok je najučestalija operacija aksile bilo određivanje limfnog čvora stražara (119 (79,33%). Analizom rada aparata za mobilnu digitalnu radiografiju došli smo do saznanja da nema statistički značajne razlike u oceni kvaliteta radiograma i širine resekcione hirurške margine merene na aparatu za mobilnu digitalnu radiografiju između iskusnog hirurga i radiologa. Statistički značajna razlika nije uočena ni pri merenju širine resekcione hirurške margine izražene u milimetrima na aparatu za mobilnu digitalnu radiografiju od strane iskusnog hirurga i radiologa u odnosu na ex tempore patohistološku analizu, dok je ista uočena nakon definitivne patohistološke analize. Šansa doresekcije tkiva dojke nakon merenja na aparatu za mobilnu digitalnu radiografiju je 1,4 puta veća nego nakon patohistološke ex tempore analize. Lokalni recidiv javio se kod jedne pacijentkinje tokom perioda praćenja. Ne postoji statistički značajna razlika u određivanju širine resekcione hirurške margine izražene u milimetrima upotrebom aparata za mobilnu digitalnu radiografiju od strane iskusnog hirurga i radiologa u odnosu na patohistološku ex tempore analizu, dok ista postoji nakon analize radiograma od strane manje iskusnog hirurga. Palpatorna metoda se ne može smatrati sigurnom metodom u određivanju širine hirurške resekcione margine. Ne postoji statistički značajna razlika u broju doresekcije tkiva dojke između hirurga sa različitim hirurškim iskustvom.
Breast cancer is the most common malignant neoplasm in the female population, and conservative breast therapy is the preferred treatment model for patients in early stages of the disease. The optimal surgical resection margin, from healthy breast tissue around the primary tumor is 2 mm. Many methods have been described that serve to check the resection margin during breast conservative surgery and all of them have their advantages and disadvantages. The aim of this study was to determine whether there was a statistically significant difference in the determination of the width of the negative resection margin expressed in millimeters in breast cancer surgery using palpatory method and intraoperative mobile specimen radiography, comparing the findings of measuring of surgeons with greater and lesser experience in breast cancer surgery as well as the findings of the radiologist in relation to histopathological ex tempore and definitive histopathological analysis. The study was conducted as a retrospective - prospective study at the Clinic for Operative Oncology, Oncology Institute of Vojvodina and included 150 patients who were preoperatively diagnosed with breast cancer. The criterion for inclusion in the study was the opportunity to perform breast conservative surgery with or without complete axillary lymph node dissection. Patients that were treated with breast amputation, those with radiological confirmed disseminated disease, as well as patients previously operated from cancer were excluded from the study. For all 150 extirpated breast cancers, an estimate of the width of the resection surgical margin was performed intraoperatively with a palpatory method, followed by measuring on device for mobile specimen digital radiography, and a radiogram was analyzed by an experienced and less experienced surgeon in breast cancer surgery, as well as by a radiologist and compared with an ex tempore histopathological analysis. The definitive width of the resection surgical margin was confirmed on histopathological preparations. The mean follow-up, postoperatively, was 100.97 weeks. The majority of patients belonged to the elderly age (56.67%). Preoperative localization of clinically impalpable breast tumors was performed in 52 (34.67%) patients. Most often the tumor was presented as a solitary focus with surrounding foci of in situ cancer (72, 48%), while the most common histological subtype was invasive ductal breast cancer (112 (74.67%)). The majority of breast operations were characterized like quadrantectomy (85 (56.67)), while the most frequent axillary surgery was the determination of the sentinel lymph node (119 (79.33%). No significant difference was observed in the evaluation of radiography quality and the width of the resection surgical margin measured on the mobile digital radiography device between the experienced surgeon and the radiologist. No statistically significant difference was observed in the measurement of the width of the resection surgical margin expressed in millimeters on the mobile digital radiography device by the experienced surgeon and radiologist versus ex tempore histopathological analysis, while the statistical difference was observed after definite histopathological analysis. The chance of breast tissue reexcision after measurement on a mobile digital radiography device is 1.4 times higher than after histopathological ex tempore analysis. Local relapse occurred in one patient during the follow-up period. There is no statistically significant difference in the determination of the width of the resection surgical margin expressed in millimeters using a mobile digital radiography device by an experienced surgeon in breast cancer surgery and radiologist with respect to histopathological ex tempore analysis. However, the statistical difference exists after radiogram analysis by a less experienced surgeon. The palpatory method cannot be considered as a safe method in determining the width of a surgical resection margin. There is no statistically significant difference in the number of breast tissue additional resections between surgeons with different surgical experience.

Le cancer de la prostate est devenu depuis deux décennies le cancer le plus fréquent de l’homme dans le monde et représente la troisième cause de décès par cancer chez l’homme en France. La biopsie de prostate est l’examen de confirmation diagnostique standard de ce cancer. Elle permet, par des prélèvements systématisés ou dirigés vers une cible, l’analyse anatomopathologique du tissu prostatique. Guidée par échographie transrectale, l’objectif de la biopsie est de réaliser une cartographie prostatique avec une série de prélèvements multiples bien distribués dans le volume de la prostate. Cependant, la réalisation de biopsies de prostate présente de nombreuses difficultés pour le clinicien car le geste demande une représentation 3D d’un organe très déformable et mobile. Ainsi l’accès à une cartographie précise des biopsies effectuées a un intérêt pour l’amélioration de la qualité des biopsies, la traçabilité des biopsies et l’apprentissage du geste.En partant de ce constat clinique, l’objectif de cette thèse est la conception d’un système de suivi pour la navigation et le guidage de la biopsie de prostate écho-guidée par voie rectale compatible avec une application clinique. Notre approche se base sur une méthode de recalage 2D-3D rigide, qui met en correspondance une image 2D échographique et un volume échographique de référence acquis en début de procédure. Le recalage 2D-3D d’images échographiques est complexe parce que l’information hors-plan n’est pas présente dans l’image 2D et les images échographiques sont très bruitées. Nous avons développé une méthode, dite hybride, qui consiste en la mise en correspondance de caractéristiques de l’image à partir d’une distance basée sur les intensités de pixels/voxels et sur une proximité euclidienne. La précision et robustesse de l’algorithme ont été évaluées sur des données de 20 patients acquises durant des procédures de biopsies de prostate dans deux centres hospitaliers français. Nous avons montré que l’amélioration de la TRE avant et après recalage est statistiquement significative. Près de 75% des TRE obtenues étaient inférieures à 5mm, qui est le seuil clinique de significativité des tumeurs.Par la suite, nous avons mis en application la méthode de recalage dans le cadre du suivi. Une expérimentation sur fantôme prostatique intégrant une sonde équipée d’un capteur de localisation est réalisée pour déterminer la faisabilité et l’apport en termes de précision pour la navigation pour la biopsie de prostate. Les premiers résultats obtenus par notre méthode de suivi montrent une preuve de concept approfondie pour une application clinique. L’information donnée par le capteur inertiel est difficile à exploiter de manière optimale. De nouvelles expérimentations dans des conditions plus favorables devraient être réalisées. Les premiers résultats du suivi sont malgré tout prometteurs dans l’objectif d’une application clinique.La perspective principale pour la méthode de suivi est son intégration dans la plateforme MIRAS, (commercialisée par Koelis) pour continuer l’évaluation. L’ajustement de la méthode et l’amélioration des temps de calcul sont les deux axes majeurs à approfondir pour faire naı̂tre un premier prototype de guidage temps-réel pour la biopsie de prostate. La collaboration de longue date entre les cliniciens et chercheurs de ce projet est un atout essentiel pour la future validation clinique
Prostate cancer is the most common cancer world-wide for males and the second leading cause of cancer death in France. Prostate biopsy procedures, performed to obtain and analyze tissue samples of the gland, are required for diagnosis. The clinical standard protocol is currently performed under UltraSound (US) control following a systematic protocol. Unfortunately, prostate cancer diagnosis is complicated by the lack of image quality and the low intrinsic contrast between tumor and non-tumor on US images. Conventional biopsies are performed under Transrectal UltraSound (TRUS) guidance. Precisely localizing the biopsy sites is challenging because the gland has a symmetric shape and because the prostate moves and is deformed by the patient motion and the TRUS probe pressure.This work aims at designing a system for navigated prostate biopsies combining a low-cost tracking system and a 2D-3D US registration method. To achieve this objective, our approach is based on hybrid 2D-3D ultrasound (US) rigid registration method for navigated prostate biopsy that enables continuous localization of the biopsy trajectory during the exam.Accuracy and robusteness was evaluated on a significant patient data set recorded in routine uncontrolled conditions from two different hospitals. The results show that 75% of the cases with error less than 5mm, which is clinically acceptable.Thereafter, we developed experiments to evaluate the tracking. The method was tested in a prostate phantom and a probe tracking by a inertial sensor. It was shown that it can do a better localization than and inertial measurement unit. Those first results obtained by our tracking method have established a proof of concept for a future clinical application. We highlighted that the sensor data are complex to exploit in optimal conditions. Additional experiments sould be performed in more realistic conditions.The method adjustment and the computing time-enhancement are the two main approaches to develop to create a first prototype of real-time tracking for navigated prostate biopsy. The long-standing cooperation between clinicians and researchers is an essential asset for a future clinical validation

L'infection par le virus de l'hépatite B est un problème de santé publique avec 250 millions de porteurs chroniques et cela malgré l'existence d'un vaccin préventif. Les traitements actuellement utilisés sont les analogues de nucléos(t)ide et/ou l'interféron a. Bien qu'ils permettent une diminution de la charge virale, ils ne permettent pas d'éradiquer la maladie du fait de la persistance de l'ADNccc, le minichromosome de l'hépatite B. Cet ADN sert de matrice à la transcription virale, et la présence d'une seule copie permet la réactivation de l'infection. En prenant en compte la longue demi-vie des hépatocytes et de la stabilité de l'ADNccc dans leur noyau, un modèle mathématique suggère que de nombreuses années de traitement seraient nécessaires pour éliminer complètement cet ADN du foie des patients infectés chroniquement. Les techniques utilisées en routine pour la quantification de l'ADNccc ne sont pas assez sensibles pour pouvoir détecter des faibles concentrations de cet ADN, notamment dans des biopsies de patients infectés chroniquement et traités à long terme. Il est nécessaire de développer de nouvelles stratégies permettant de cibler directement l'ADNccc afin d'éliminer le virus. Ainsi les travaux de cette thèse reposent sur le développement d'une nouvelle technologie : la Droplet Digital PCR (ddPCR) pour permettre la quantification de l'ADNccc dans les biopsies de patient. Cette technique permet un gain de 2 log au niveau de la sensibilité par rapport à la qPCR, technique utilisée actuellement en routine. Elle nous a ainsi permis de constater la présence de cet ADN chez des patients traités à long terme par des analogues de nucléos(t)ides et même en présence d'interféron. La présence d'ARNpg et les expériences de ChIP ont également confirmé que l'ADNccc était encore transcriptionnellement actif. Ces résultats confirment d'autant plus la nécessité d'élaborer de nouvelles thérapeutiques pour permettre l'inactivation voire l'élimination de l'ADNccc. L'une des stratégies envisagées est le système CRISPR/Cas 9. Ainsi le dernier axe de cette thèse a été de développer ce système dans des modèles d'infection du virus de l'hépatite B. Pour vérifier l'efficacité de ce système sur le VHB, nous avons testé 8 ARN guide différents incorporer via des ribonucléoprotéines dans des cellules HepG2-NTCP. Les résultats préliminaires ont ainsi démontré que ce système pouvait réduire le pool d'ADNccc dans ces cellules et ouvre des perspectives intéressantes pour le développement de nouveaux traitements
Hepatitis B virus {HBV) is a major health problem with 250 million chronic carriers, despite the existence of a preventive vaccine. Currently the treatments used are nucleos{t)ide analogues and / or interferon a. Although they efficiently reach a decrease of the viral load, they do not allow the eradication the disease due to the persistence of the cccDNA, the minichromosome of the hepatitis B. This DNA serves as a template for the viral transcription and only a single copy suffice for the infection rebound. However, the techniques used routinely for the quantification of the cccDNA are not sensitive enough to be able to detect low concentrations of this DNA, in particular in biopsies of patients chronically infected and long term treated. ln addition, it is necessary to develop new strategies to target the cccDNA in order to clear the infection. Thus, my thesis work is based on the development of a new technology: the Droplet Digital PCR {ddPCR) to allow the quantification of cccDNA in patient biopsies. This technique allows a gain of 2 log in sensitivity compared to the qPCR technique currently used in routine. lt allowed us to see the presence of this DNA in long-term treated patients even in the presence of interferon. The presence of pgRNA and ChlP experiments also confirmed that the cccDNA was still transcriptionally active.These results confirm the requirement to develop new therapeutics to allow the inactivation or even the elimination of the cccDNA. One of the strategies envisaged is the CRlSPR / Case 9 system. Thus, the following part of this thesis was to develop this system in hepatitis B virus infection models. To reduce off-target effect we tested 8 different guide RNAs incorporated via ribonucleoproteins into HepG2- NTCP cells. Preliminary results have shown that this system can reduce the pool of cccDNA in these cells and open up the possibilities to test this model on PHH and opens interesting perspectives for the development of new treatments

INTRODUCCIÓN:- La biopsia es el proceso que obtiene y analiza tejidos. La biopsia quirúrgica (BQ) es de elección pero sus complicaciones justifican el uso de técnicas mínimamente invasivas como la BVP. Desde los 90, la nueva tecnología y el trabajo multidisciplinar han hecho de la BVP una técnica rutinaria, fiable y de bajo coste.
HIPÓTESIS Y OBJETIVOS.- La BVP es de elección para confirmar la existencia de lesiones focales del raquis y establecer un diagnóstico exacto de tumor o infección, obteniendo muestra de tejido suficiente en más de un 90% de casos y exacta en más de un 80%.
MATERIAL Y MÉTODO: Este es un estudio retrospectivo de 222 BVP realizadas en un período de 8 años y un seguimiento clínico-radiológico mínimo de un año. Son 119 varones y 103 mujeres (media 58a.) de quienes se obtuvieron datos clínicos, de imagen y patológicos. Se explotaron estadísticamente mediante el sistema SPSS. La técnica reglada de biopsia consistió en selección, consentimiento, uso de tomografía computarizada (TC) como guía, punción coaxial con aguja fina y gruesa, amplia distribución de la muestra y valoración final. Los resultados se distribuyeron en seis grupos de lesiones (metástasis, mieloma, linfoma, otros tumores, infección y otras lesiones), uno de normalidad y uno sin diagnóstico final.
RESULTADOS.- El 75% de lesiones fueron solitarias y el patrón radiológico predominante fue osteolítico. Tan sólo el 23% de las 42 BQ lo fueron para biopsia. Encontramos asociación estadísticamente significativa entre la localización, el aspecto radiográfico y el tipo de lesión. En 95% de muestra macroscópica fue hemática, sin asociación entre el tipo o cantidad de muestra y el resultado final, excepto el "pus" indicativo de discitis. Confirmamos una curva de aprendizaje para la técnica. El 59% de la serie fueron metástasis e infección. El estudio estadístico por grupos de patología mostró una sensibilidad del 95% con un valor predictivo positivo (VPP) de 97% para las metástasis y, respectivamente, del 100% y 95% para el mieloma, del 64% y 100% para el linfoma así como del 82% y 92% para la infección. No hubo complicaciones graves.
DISCUSIÓN.- Se trata de una de las series más amplias estudiadas. La mayoría muestran resultados similares a los nuestros y a la BQ. Coinciden edad, el patrón radiológico y tipo patología confirmándose las múltiples ventajas de la BVP guiada por TC. Se constata la elevada exactitud diagnóstica en metástasis y mieloma con dificultades en infección y linfoma.
CONCLUSION PRINCIPAL.- La BVP es una técnica sencilla, segura, fiable, sensible y reproducible para el diagnóstico de las lesiones focales del raquis. Sus resultados son totalmente aceptables e incluso comparables a los de la cirugía abierta en aquellas lesiones en que está indicado un estudio histológico. La seguridad y los porcentajes en diagnóstico convierten a la BVP en técnica de elección para obtener muestra de tejido e identificar el tipo de lesión en aquella patología que afecta a la columna con mayor frecuencia.
INTRODUCTION. Biopsy is a procedure to obtain tissue specimens for subsequent analysis. Surgical biopsy is the gold standard technique for this purpose, but the associated complication rate justifies the use of less invasive procedures, such as percutaneous vertebral biopsy (PVB). Since the 1990s technological advances and multidisciplinary work have made PVB a reliable, low-cost routine procedure.
HYPOTHESIS AND OBJECTIVES. PVB is the technique of choice to confirm the presence of focal vertebral lesions and to diagnose tumors and infection. Sufficient tissue specimens are obtained in more than 90% of patients and the diagnostic accuracy of the technique is higher than 80%.
MATERIAL AND METHOD. This retrospective study analyzes 222 PBV performed over an 8-year period, with a clinical and radiological follow-up of at least one year in all cases. The series includes 119 men and 103 women with a mean age of 58 years, in whom clinical, radiological and pathological data were obtained. Statistical analysis of the results was done with SPSS software. In all cases the process consisted of patient selection, informed consent, use of CT guidance, coaxial puncture with a fine needle and trephine, wide sample distribution, and data analysis. Patients were divided into six pathological groups (metastasis, myeloma, lymphoma, other tumors, infection and other lesions), a normal tissue group and a group in which a final diagnosis was not established.
RESULTS. The lesion was solitary in 75% of patients and most frequently showed an osteolytic radiologic pattern. Only 23% of the 42 surgical biopsies were performed for biopsy alone. A significant correlation was observed between the pathological group and the location or radiological pattern of the lesion. Among the total, 95% of samples were macroscopically hematic and there was no correlation between the sample appearance or amount of sample and the final diagnosis, except in cases of purulent material which was indicative of discitis. We observed a learning curve for PVB. Metastasis or infection was found in 59% of the patients. We obtained a sufficient sample for histological diagnosis in 93% of cases. The sensitivity of PBV for detecting spinal lesions was 86%, with a positive predictive value of 100%. Among the pathologic groups, the sensitivity and positive predictive value, respectively, of PVB was as follows: 95% and 97% in metastasis, 100% and 100% in myeloma, 64% and 100% in lymphoma and 82% and 92% in infection. No significant complications were observed.
DISCUSSION. This series is one of the largest presented and the diagnostic accuracy of the technique was similar to that of published PVB and surgical biopsy series. Factors such as age, the radiological pattern and the pathologic origin of the lesions also coincided. This study corroborates the multiple advantages of CT-guided spinal biopsy as compared to open surgery. The accuracy for diagnosing metastasis and myeloma was high, although there were some difficulties for diagnosing cases of infection and lymphoma.
PRINCIPAL CONCLUSION. PVB is a safe, easy, readily available, sensitive and reproducible technique for the diagnosis of focal spinal lesions. The results with this technique are acceptable and comparable to those obtained with surgical biopsy for lesions requiring histological study. The safety of the method and its diagnostic accuracy make BVP the procedure of choice for obtaining tissue samples and identifying the most frequent pathologic lesions located in the spine.

El diagnóstico y manejo de nódulos de tiroides requiere habilidad y experiencia por parte de los médicos que participan de la evaluación. La BAAF puede mejorar en gran medida la precisión del diagnóstico, identificar y facilitar un pronto tratamiento de los cánceres de tiroides que de otro modo pueden pasarse por alto. El refinamiento de las técnicas diagnósticas y el énfasis sobre el costo que implican ha originado cambios espectaculares en el estudio del diagnóstico. Por esta razón se ha investigado la validez y fiabilidad de la BAAF, mediante un estudio clínico retrospectivo entre los pacientes con nódulo tiroideo atendidos en el Servicio de Cirugía de Cabeza y Cuello y Máxilo Facial del HNERM de enero a abril de 2004. La utilidad de la BAAF en el diagnóstico etiológico del nódulo tiroideo en el HNERM se correlacionó con los resultados del estudio histológico de los pacientes operados obteniendo una sensibilidad del 94%, una especificidad de 76%, una predictibilidad para casos positivos del 71% y para casos negativos del 95%. La BAAF demostró ser un medio útil para definir el carácter benigno o maligno de un nódulo tiroideo, aunque siempre debe valorarse en el contexto clínico de cada caso en particular.
The diagnosis and handling of thyroid nodules require ability and experience of the doctors who participate in the evaluation. The BAAF could improve the precision of the diagnosis, identifing and facilitating the treatment of the cancers of thyroids that otherwise can be ignored. The refinement of the diagostics techniques and the emphasis on the cost that imply have originated spectacular changes in the study of the diagnosis. Therefore one has investigated the validity and reliability of the BAAF, by means of a retrospective clinical study between the patients with thyroid nodule taken care at the Service of Surgery of Head and Neck of the HNERM from January to April of 2004. The utility of the BAAF in the ethiologic diagnosis of the thyroid nodule in the HNERM was correlated with the results of the histological study of the patients obtaining a sensitivity of 94%, a 76% specificity, a predictability for positive cases of 71% and negative cases of 95%. The BAAF demonstrated to be useful means to define the benign or malignant character of a thyroid nodule, although always it must be valued in the clinical context of each individual case.
Tesis de segunda especialidad

Zielsetzung dieser Arbeit ist die Vorstellung des klinischen Aufbaus und des Arbeitsablaufs eines robotischen Assistenzsystems für bildgeführte Interventionen in einem konventionellen Magnetresonanztomographen (MRT), sowie die Beurteilung der Genauigkeit und der klinischen Erfahrungen bei perkutanen Biopsien in verschieden Körperregionen. Material und Methoden: Das MR- kompatible, servopneumatische robotische Assistenzsystem lässt sich mit dem Patienten in die 60- cm Gantry eines Standard- MR- Scanners fahren. Die Genauigkeit des Systems wurde anhand von Nadelpunktionen (n= 25) in einem Phantommodell ermittelt. Perkutane diagnostische Biopsien wurden bei sechs Patienten durchgeführt. Ergebnisse: Für eine Interventionstiefe zwischen 29 und 95 mm wurde eine 3-DGenauigkeit von 2,2 +/- 0,7 mm (Intervall 0,9- 3,8 mm) bestimmt. Patienten mit einem BMI bis zu ≈30 kg/m2 konnten mit dem System punktiert werden. Die klinischen Arbeitsschritte werden anhand der Fallbeispiele dargestellt. Die mittlere Interventionszeit betrug 44 Minuten (Intervall 36 – 68 Minuten). Zusammenfassung: Die Punktion verschiedener Körperregionen ist mit Hilfe des robotischen Assistenzsystems in einem geschlossenen MRT erfolgreich und sicher möglich. Die Genauigkeit des Systems ist vergleichbar mit anderen Assistenzsystemen in der Literatur und genügt den klinischen Anforderungen. Eine kürzere Interventionszeit ist mittels einer Optimierung der einzelnen Arbeitsschritte möglich.

Receptor epidermalnog faktora rasta (EGFR) pripada porodici receptora protein-tirozin kinaze čija je aktivacija povezana sa proliferacijom malignih, invazijom, inhibicijom apoptoze, tumorskom angiogenezom i metastatskim širenjem stoga ima važnu ulogu u karcinogenezi i tumorskoj progresiji. Aktivirane mutacije se odvijaju oko katalitičkog tirozin kinaza domena. Biopsijski, citološki i hirurški uzorci se koriste u detekciji EGFR mutacija u momentu postavljanja dijagnoze adenokarcinoma ili karcinoma sa komponentom adenokarcinoma, najpouzdanije lančanom reakcijom polimeraze. Činjenica da primena ciljane molekularne terapije tirozin kinaza inhibitorima kod obolelih sa EGFR mutiranim adenokarcinomom pluća poboljšava prognozu bolesti, postoji rezistencija kod pojedinih tipova EGFR mutacija i povezanost histopatološkim i imunohistohemijskim karakteristikama tumora, da je bronhološki uzorak često jedini uzorak u kome je potrebno odrediti i molekularni profil tumora osnovni cilj ove disertacije bio je da se odredi učestalost i tip EGFR mutacija i povezanost sa karakteristikama adenokarcinoma. Da bi se taj cilj realizovao postavljeni su sekundarni ciljevi odnosno da se: izvrši histopatološka reklasifikacija adenokarcinoma pluća na osnovu kriterijuma koje je postavila internacionalna asocijacija za proučavanje carcinoma pluća, američko torakalno društvo i evropsko respiratorno društvo; odredi ekspresija TTF-1 u adenokarcinomu pluća i povezanost sa EGFR mutacionim statusom; odredi učestalost, tip i povezanost EGFR mutacija sa predominantnim tipom adenokarcinoma i utvrdi da li bronhoskopska biopsija može da bude reprezentativni uzorak za određivanje EGFR mutacionog statusa. Histopatološka građa adenokarcinoma pluća u hirurškim uzorcima je heterogenija u odnosu na biopsijske uzorke i ta razlika je statistički značajna (p<0,001). Acinarno predominantni tip je najzastupljeniji u hirurškim i biopsijskim uzorcima bez statistički značajne razlike u raspodeli predominantnih tipova u njima (p=0,65883). Predominantni tip u primarnom tumoru određuje predominantni tip u limfogenim metastazama. EGFR mutacije tipa insercija na egzonu 21 i L858R mutacija na egzonu 20 su detektovane kod tri od 60 (5%) bolesnika u pet od 120 uzoraka (tri hirurška i dva biopsijska uzorka), češće kod žena, starijih od 60 godina, pušača i u solidno predominantnom tipu. Ne postoji statistički značajna razlika u koncentraciji izolovane DNK između EGFR mutiranih i wt EGFR adenokarcinoma u biopsijskim (p=0,132) i hirurškim uzorcima (p=0,641). Procenat invalidnih rezultata prilikom određivanja EGFR mutacionog statusa u je veći u biopsijskim uzorcima u odnosu na hirurške uzorke. Postoji statistički značajna razlika izmeĐu broja TTF-1 pozitivnih i TTF-1 negativnih adenokarcinoma (p<0,001), ali ne i u raspodeli ovih bolesnika prema polovima (p=0,1231), prosečnoj starosti, pušačkim navikama (p=0,6488) i prosečnoj veličini tumora (p=0,21). Postoji pozitivna korelacija između TTF-1 pozitivne ekspresije i EGFR mutacionog statusa stoga TTF-1 pozitivna ekspresija može da bude prediktor pozitivnog EGFR mutacionog statusa. Bronhoskopska biopsija je reprezentativni uzorak za određivanje EGFR mutacionog statusa zato što: većina dijagnostičkih biopsijskih uzoraka ima više od 100 očuvanih tumorskih ćelija, nema razlike u raspodeli predominantnih tipova u odnosu na hirurške uzorke, EGFR mutacije se detektuju u uzorcima sa manje od 100 tumorskih ćelija i manje od 20% volumenske gustine tumorskog tkiva, razlika između koncentracije izolovane DNK u EGFR mutiranim i wt EGFR adenokarcinomima u biopsijskim i hirurškim uzorcima nije statistički značajna (p=0,132 i p=0,641).
Epidermal growth factor receptor (EGFR) belongs to the family of protein-tyrosin kinase family, whose activation is associated with the proliferation of malignant cells, invasion, inhibition of apoptosis, tumor angiogenesis and metastatic spread and thus plays an important role in carcinogenesis and tumor progression. Activated mutations take place around the catalytic tyrosine kinase domain. Biopsy, cytological and surgical specimens are used for the detection of EGFR mutations at the time of diagnosis of adenocarcinoma or carcinoma with an adenocarcinoma component, most reliably using a polymerase chain reaction. The fact that the application of molecular tyrosin kinase inhibitor therapy to patients with EGFR mutated lung adenocarcinoma improves the prognosis of the disease, there is resistance in certain types of EGFR mutations and connection with histopathological and immunohistochemical characteristics of tumor, that the bronchoscopic specimen is often the only specimen in which it is necessary to determine the molecular profile of the tumor, the primary objective of this thesis is to determine the frequency and type of EGFR mutations and their connection with the characteristics of adenocarcinoma. In order to realize this objective, the following secondary objectives have been set: to execute histopathological reclassification of lung adenocarcinoma based on the criteria set by the International Association for the Study of Lung Cancer, the American Thoracic Society and European Respiratory Society; determine the expression of TTF-1 in lung adenocarcinoma and connection with EGFR mutation status; determine the frequency, type and connection of EGFR mutations with predominant type of adenocarcinoma and confirm whether bronchoscopic biopsy may be a representative specimen for the determination of EGFR mutation status. Histopathological material of lung adenocarcinoma in surgical specimens is more heterogeneous in relation to biopsy specimens and such difference is statistically significant (p<0,001). Acinar predominant type is the most common in surgical and biopsy specimens with no statistically significant differences in the distribution of predominant type among them (p=0,65883). The predominant type in the primary tumor determines the predominant type in lymphatic metastases. EGFR mutations in the type of insertions on exon 21 and L858R mutations on exon 20 have been detected in three out of 60 (5%) of patients in five out of 120 specimens (three surgical and two biopsy samples), more often in women older than 60, smokers and in a solid predominant type. There are no statistically significant differences in the concentration of isolated DNA between EGFR mutated and wt EGFR adenocarcinoma in biopsy (p=0,132) and surgical specimens (p=0,641). The percentage of invalid results in determining the EGFR mutation status is higher in biopsy specimens compared to the surgical specimens. There is a statistically significant difference between the number of TTF-1 positive and TTF-1 negative adenocarcinoma (p<0,001), but not in the distribution of these patients according to gender (p=0,1231), average age, smoking habits (p=0,6488) and average tumor size (p-0,21). There is a positive correlation between TTF-1 positive expression and EGFR mutation status and therefore TTF-1 positive expression can be a predictor of positive EGFR mutation status. Bronchoscopic biopsy is a representative sample for the determination of EGFR mutation status because: most diagnostic biopsy specimens have more than 100 preserved tumor cells, there is no difference in the distribution of predominant types in relation to surgical specimens, EGFR mutations are detected in samples with less than 100 tumor cells and less than 20% of volume density of tumor tissue, the difference between the concentration of isolated DNA in EGFR mutated and wt EGFR adenocarcinoma in biopsy and surgical specimens is not statistically significant (p=0,132 and p=0,641).

Orientador: Lineu Cesar Werneck
Contem 33 fots. coladas
Dissertação (mestrado) - Universidade Federal do Parana, Setor de Ciencias da Saude, Programa de Pós-Graduação em Medicina Interna
Resumo: Os vacúolos são formações anormais encontradas nas fibras musculares, podendo ser classificados morfologicamente quanto ao tamanho, número, posição, forma, presença de membranas e se marginados ou não. Os vacúolos marginados, podem ser encontrados em diversas doenças, entre elas a miosite com corpos de inclusão citoplasmática. Esta é caracterizada clinicamente como uma polimiosite crônica tendo na histologia do músculo a presença dos vacúolos marginados, e denominados histologicamente de corpos de inclusão citoplasmáticos, podendo ter filamentos intranucleares e intracitoplasmáticos. Com o objetivo de estudar os vacúolos com aspecto histológico de corpos de inclusão citoplasmática, foram estudados todos os casos entre 1400 biópsias musculares que apresentaram os mesmos, procurando correlacionar com os dados clínicos laboratoriais, afim de verificar a sua especificidade para determinadas doenças. Foram encontrados 16 casos. Dos 16 casos, a idade média foi de 36.0 anos, o início da doença teve a média de 20.5 anos e o tempo de doença de 5.5 anos. Os casos foram classificados conforme a história clínica, hereditariedade, dados laboratoriais, eletrofisiológicos, histoquünicos, imunocitoquímicos e microscopia eletrônica em miosite com corpos de inclusão citoplasmática (4 casos), atrofia muscular espinhal juvenil (6 casos), miopatias distais (3 casos), distrofia de cinturas pélvica e escapular (2 casos) e polineuropatia periférica (1 caso). As enzimas musculares, mais especificamente a creatinoquinase mostrou-se elevada em dez casos. Apenas um caso mostrou moderada redução nas conduções nervosas. A eletromiografia esteve alterada em todos os casos sendo que, em cinco, casos a mesma mostrou sinais de desinervação (ativa e ou crônica), oito foram miopáticos e em dois casos mista (neuromiopática). A biópsia muscular pela histoquímica em cinco casos mostrou histologicamente uma miopatia (ativa e ou crônica); em sete casos, elementos para miopatia e desinervação (misto); em dois casos, desinervação; e em dois casos, miopatia inflamatória. Todos os casos mostravam vacúolos marginados. O estudo imunocitoquímico demonstrou predomínio de linfócitos CD8+ no interstício na maioria dos casos, e ocasionalmente nas regiões perivasculares e no interior das fibras musculares. As miosites por corpos de inclusão citoplasmática tiveram importante aumento de linfócitos CD8+, em relação a outras doenças. A detecção de imunoglobulinas e complemento foram mais evidentes na miosite com corpos de inclusão citoplasmática, embora não demonstre uma diferença marcante, exceto na polineurite em que não teve nenhuma célula ou deposição de imunoglobulina. A microscopia eletrônica demonstrou a presença de filamentos nucleares e dispersos no citoplasma em cinco casos, um caso demontrou a presença de filamentos no núcleo e região subsarcolemal, dois casos mostraram filamentos na região subsarcolemal e citoplasma. Em um caso, os filamentos estavam dispersos no citoplasma e núcleo, sendo que em sete casos não foram observados filamentos intracitoplasmáticos q u intranucleares. Foi concluído que: 1) Os filamentos intracitoplasmáticos e intranucleares não são específicos para uma única entidade; 2) A presença de reação inflamatória auxilia na diferenciação das outras doenças com miosite com corpos de inclusão citoplasmática; 3) A creatinaquinase e eletromiografia não são úteis para diferenciar a miosite com corpos de inclusão citoplasmática das outras entidades; 4) Existe um predomínio de linfócitos T no interstício nas miopatias com corpos de inclusão citoplasmática; 5) Foi notado importante aumento de linfócitos CD8+ no interstício, sugerindo relação com o complexo maior de histocompatibilidade 1 (MCH1); 6) Houve inversão da proporção de linfócitos CD4+/CD8+, sugerindo processo mediado pelo MCH1; 7) As imunoglobulinas e complemento foram detectadas com maior freqüência nas miosites com corpos de inclusão citoplasmática; 8) Os corpos de inclusão citoplasmática ocorrem em diversas entidades, com patogenia e patologia global diferente, sugerindo se tratar de uma reação celular inespecífica, talvez relacionada com tempo de agressão crônica da fibra muscular, tanto nos processos de origem muscular primaria, como de origem neurogênica. VI
Abstract: The vacuoles are abnormal structures of the muscle fibers, who can be morphological classified according the size, number, location, shape, presence of membranes or if they are rimmed. The rimmed vacuoles can be find in several diseases, mainly in the inclusion body myositis. This disease can be presented as chronic polymyositis with rimmed vacuoles in the histology, also called cytoplasmatic inclusion body, with cytoplasmatic or nuclear filaments. With the objectives to study the histopathological aspects of the cytoplasmatic inclusion bodies, we select all the cases who presented rimmed vacuoles among 1400 muscle biopsies, who had the clinical history and laboratory investigation available. We found 16 cases, with mean age of 36.0 years, whose disease started at 20.5 and a mean disease time 5.5 years. The cases where classified regarding the clinical history, hereditary pattern, serum laboratory determinations, electrophysiological tests, histochemical and immunocytochemical analysis and electron microscopic findings in inclusion body myositis (4 cases), juvenile spinal muscular atrophy (6 cases), distal myopathy (3 cases), limb-girdle muscular dystrophy (2 cases) and peripheral neuropathy of unknown etiology (1 case). The serum enzymes, specially the creatinekinases, was increased in ten cases. Only one case had reduced nerve conduction velocity. The electromyography was abnormal in all cases with denervation pattern in five and myopathic pattern in eight and in two cases had a mixed pattern (myopathic and denervation). The muscle biopsy histochemistry had the diagnosis of myopathy (active and chronic) in seven cases, mixed (myopathy and denervation findings) in two cases, denervation in two and inflammatory myopathy in two. All the cases had rimmed vacuoles. The immunocytocheinical analysis showed CD8+ lymphocytes in the interstitial in most cases, occasionally ip the perivascular region and rarely inside the muscle fibers. The inclusion body myositis cases had increased of CD8+ lymphocytes comparing with the other diseases. The immunoglobulins and complement deposition were slight more intense in the inclusion body myositis, comparing with the other diseases. The peripheral neuropathy had no cells or immunoglobulins found any time. The electron microscopy detected filaments in the nucleus and diffusely in the cytoplasm in five cases, one case only in the nucleus and sub-sarcolemmal region, two cases with filaments in the sub-sarcolemmal and cytoplasm. One case had filaments where dispersed in the cytoplasm and nucleus. Seven cases had no filaments found in nucleus or cytoplasm. The following conclusion was drawn: 1) The intracytoplasmic or intranuclear filaments is not specific for only one disease. 2) The inflammatory reaction help in the differentiation of the inclusion body myositis from the other diseases studied. 3) The creatinekinase and electromyography where useless in the differentiation the inclusion body myositis from other diseases. 4) A predominance of T lymphocytes was found in the interstitial tissue in the cases of inclusion body myositis. 5) Was noted an important increased of the CD8+ lymphocytes in the interstitial tissue, suggesting a relationship with the major histocompatibilty 1 complex (MCH1). 6) An inversion of the CD4+/CD8+ lymphocyte's proportion was found , suggesting a mediation by the MCH1. 7) The immunoglobulins and complement deposition were found with major frequency in the inclusion body myositis. 8) The cytoplasmatic inclusion bodies can be found in several diseases with different pathogenesis and pathology, suggesting a non specific cellular reaction, maybe related with the time of the chronic aggression to the muscle tissue, who can be similar in the primary muscle lesion and neurogenic etiology.

La Dystrophie Facio-Scapulo-Humérale (FSHD) est la plus fréquente maladie neuromusculaire chez l'adulte (7 cas pour 100 000 naissances). D'origine autosomique dominante, elle apparait en général durant la seconde décade et se caractérise principalement par une perte de force et une fonte asymétrique des muscles du visage, des épaules et des bras puis progresse au reste du corps. L'analyse du motif répété D4Z4, dont le nombre de répétitions est diminué chez les patients, a mis en évidence la présence d'une phase ouverte de lecture codant pour un facteur de transcription appelé DUX4. Son expression a été retrouvée spécifiquement chez les patients FSHD. Mes travaux de thèse se sont concentrés sur l'étude de DUX4 et son implication dans la physiopathologie de la FSHD. Parce que la FSHD est une maladie progressive, nos analyses ont été faites sur des cultures de cellules et des biopsies f¿tales FSHD1 et Contrôles. Nous avons ainsi mis en évidence pour la première fois que DUX4 est exprimé dès le stade f¿tal et que les dérégulations géniques identifiées chez l'adulte sont également présentent à ce stade. De plus nos expériences semblent montrer que le niveau d'expression de DUX4 entre le f¿tus et l'adulte FSHD est similaire. Enfin, le niveau d'expression de DUX4 est extrêmement restreint (environs 0,5 à 10% des noyaux), mais son effet sur un grand nombre de gènes cibles est lui très fortement prononcé et quantifiable. Des essais de co-cultures ont ainsi mis en évidence que in vivo, DUX4 est à même de diffuser d'un noyau à l'autre au sein d'une fibre musculaire et de diffuser le phénomène pathologique. Nos travaux ouvrent ainsi un nouveau champ d'étude pour la compréhension des mécanismes physiopathologiques conduisant à la FSHD
Facioscapulohumeral muscular dystrophy (FSHD) is inherited in an autosomal dominant pattern and is one of the most common muscular dystrophies (7/100 000). FSHD usually manifests in the second decade of life and includes an asymmetric wasting and weakness of facial, shoulder and arm muscles and is affecting the distal muscles in later stages of the disease. D4Z4 repetitions, which are known to be decreased in FSHD patients, comprise an open reading frame encoding a transcription factor called DUX4 that is only expressed in patients affected by FSHD. My PhD thesis project is aiming to better understanding of the role played by DUX4 in human skeletal muscle in order to elucidate its involvement in the pathophysiology of FSHD. As FSHD is a progressive disease, I studied DUX4 mRNA expression in both primary human fetal muscle cells and in fetal muscle tissue of control subjects and FSHD1 patients. For the first time, we were able to demonstrate DUX4 expression at the fetal stage, and in addition, we showed abnormal expression of various genes that has been reported to be altered in adult FSHD patients. Also, our experiments on fetus and adult FSHD patient cells suggested an equal expression of DUX4 protein. Although DUX4 protein is expressed at a very low level in patients (about 0.5 to 10% of the nuclei), it leads to a strong misexpression of a large number of DUX4 target genes. By performing co-cultures between C2C12 mouse myoblasts and control or FSHD human myoblasts, we demonstrated that expression of toxic DUX4 protein occurs only in a limited number of nuclei in FSHD patient cells. Interestingly, we revealed that the expressed DUX4 protein is able to spread from one nucleus into nearby nuclei within the myotubes and hence transmitting the molecular pathological abnormalities. Our research project will give us new insights into the pathophysiological mechanisms underlying FSHD

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Programa de Pós-Graduação em Ciências Médicas.
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Introdução: O presente trabalho consiste na proposição de um novo arame de marcação para guiar biópsias cirúrgicas em lesões mamárias não palpáveis, bem como sua análise comparativa com o arame de marcação tipo Kopans, o mais utilizado atualmente.

Oralni karcinom je po učestalosti šesta najčešća maligna bolest u svetu čija incidenca varira u različitim geografskim područjima. Predstavlja 5% svih novootkrivenih malignih tumora godišnje i čini 14% svih malignih tumora glave i vrata. Pod oralnim karcinom podrazumevamo planocelularni karcinom obzirom na činjenicu da on čini preko 90% malignih tumora oralne lokalizacije, dok se u manjem procentu javljaju drugi tumori (maligni tumori malih pljuvačnih žlezda, limfomi, mezenhimni tumori). Oralni karcinom podrazumeva karcinome koji se javljaju u sledećim anatomskim regijama: sluznici prednje 2/3 jezika, poda usta, obraza, gingivi gornje i donje vilice, retromolarnom trouglu, kao i sluznici mekog i tvrdog nepca. Najčešća lokalizacija oralnog planocelularnog karcinoma je sluznica pokretnog dela jezika i poda usta. Oralni karcinom se češće javlja kod muškaraca (odnos muškarci:žene je 3:1) verovatno zbog većeg procenta rizičnog ponašanja kod muškaraca. Najčešće se javlja u šestoj i sedmoj deceniji života (medijana je 62 godine) iako se poslednjih godina sve češće javlja kod mlađih od 45 godina. Faktori rizika za oboljevanje su dobro poznati. Na prvom mestu se izdvaja pušenje duvana (značajna je dužina pušenja, da li pacijent puši lulu ili cigaretu, da li žvaće duvan, kao i dužina trajanja apstinencije). Smatra se da je smrtnost kod oralnog karcinoma direktno povezana sa brojem popušenih cigareta na dan. Preko 75% pacijenata sa oralnim karcinomom anamnestički daje podatak o prekomernoj upotrebi alkohola. Postoji sinergističko dejstvo alkohola i cigareta, dugotrajna ekspozicija ovim faktorima rizika dovodi do pojave “polja kancerizacije“, pojave genetske nestabilnosti i razvoja tumora. Kod oralnog planocelulranog karcinoma primećene su hromozomske abnormalnosti koje su rezultat oštećenja DNK i uključuju promene genetskog materijala na hromozomima.Jedna od najčešćih genetskih abnormalnosti kod oralnog planocelularnog karcinoma je mutacija r53 gena koji se nalazi na kratkom kraku hromozoma 17 i predstavlja tumor supresor gen. Planocelularni karcinom nije teško dijagnostikovati kada postane simptomatski. Pacijent se žali na bol, krvavljenje, otalgiju, otežano gutanje, smanjenje pokretljivosti jezika. Neretko je prvi simptom metastatski uvećan limfni čvor na vratu jer bolesnici ne primećuju ili ignorišu oralnu patologiju. Dijagnoza oralnog karcinoma se postavlja na osnovu detaljno uzete anamneze, kliničkog pregleda i patohistološke verifikacije. Oralni planocelularni karcinom se javlja u tri klinike forme: egzofitična, endofitična i infiltrativna. Zlatni standard za dijagnozu oralnog karcinoma je biopsija i patohistološka verifikacija, pri čemu se može primeniti „punch“ biopsija, inciziona biopsija ili eksciziona biopsija kod manjih promena. TNM „staging“ sistem AJCC (American Joint Committee on Cancer) se danas standardno koristi za klinički „staging“ oralnog karcinoma i bazira se na podacima dobijenim kliničkim pregledom i „imaging“ metodama. Sam „staging“ je bitan kako zbog komunikacije među lekarima koji učestvuju u lečenju bolesnika tako i zbog standardizacije prognoze. T stadijum označava veličinu primarnog tumora, N stadijum označava regionalnu nodalnu zahvaćenost dok M stadijum prikazuje prisustvo udaljenih metastaza. Terapija patohistološki dokazanog oralnog karcinoma zahteva multidisciplinarni pristup. Osnova terapije oralnog planocelularnog karcinoma je hirurško lečenje koje podrazumeva ablativno i rekonstruktivno hirurško lečenje. Osnovni princip ablativne hirurgije kod oralnog karcinoma je resekcija primarnog tumora sa najmanje 1cm negativnim hirurškim marginama. Pored ablacije tumora hirurško lečenje podrazumeva i uklanjanje regionalnih limfnih čvorova vrata. Cilj disekcije vrata je da se kod klinički evidentnih metastaza iste uklone (terapijska disekcija) ili da se uklone okultne metastaze koje su klinički neevidentne (elektivna disekcija). Oralni planocelularni karcinom spada u tumore sa visokom stopom smrtnosti, većom nego što je kod limfoma, laringealnog karcinoma, karcinoma testisa i endokrinih karcinoma. Stopa petogodišnjeg preživljavanja je direktno povezana sa veličinom tumora, prisustvom metastaza u regionalnim limfnim čvorovima i prisutvom udaljenih metastaza. Prosečno trogodišnje preživljavanje bolesnika sa oralnim karcinomom je 52% dok je prosečno petogodišnje preživljavanje oko 39% i ove stope se nisu mnogo menjale tokom godina bez obzira na nova saznanja i nove pristupe lečenju oralnog planocelulanog karcinoma. Ciljevi istraživanja su da se utvrdi da li postoji korelacija debljine OPK izmerene kompjuterizovanom tomografijom i svetlosnim mikroskopom, da li dubina invazije OPK i volume tumora mogu biti prediktivni faktor za razvoj regionalnih cervikalnih metastaza kod oralnog planocelularnog karcinoma. Istraživanje je uključilo 65 konsekutivnih bolesnika oba pola lečenih od oralnog karcinoma na Klinici za maksilofacijalnu hirurgiju Kliničkog centra Vojvodine. Dijagnoza oralnog karcinoma je postavljena na osnovu anamneze, kliničkog pregleda i biopsije. U sklopu TNM „staging“-a bolesnika načinjen je pregled glave i vrata i grudnog koša kompjuterizovanom tomografijom (CT) na osnovu kog smo dobili podatak o dimenzijama tumora. Na osnovu kliničkog nalaza i analize CT nalaza planiralo se operativno lečenje u skladu sa bolesnikovim TNM statusom. Postoperatativni patohistoški preparati je pregledan od strane istog patologa. Parametri koji će su određivani su sledeći: 1. Veličina tumora (2 dimenzije) izmerene na osnovu CT pregleda izražene u cm 2. Debljina tumora izmerena na osnovu CT pregleda izražena u cm 3. Veličina tumora (2 dijametra) na makroskopskom preparatu izražena u cm 4. Debljina tumora na mikroskopskom preparatu izmerena svetlosnim mikroskopom izražena u cm 5. Dubina invazije tumora na mikroskopskom preparatu izmerena svetlosnim mikroskopom izražena u mm 6. Volumen tumora koji se izračunavao prema formuli: VT=π/6 x maksimalni dijametar tumora A x minimalni dijametar tumora B x dubina invazije tumora i izražava se u cm³ 7. Broj metastatski izmenjenih limfnih čvorova u disekatu vrata 8. Ukupan broj patohistološki ispitanih limfnih čvorova u disekatu vrata Nakon prikupljanja planiranog materijala urađena je statistička obrada podataka. Statistička analiza podataka je uključila metode deskriptivne statistike (srednja vrednost, standardna devijacija, učestalost), kao i standardne parametrijske i neparametrijske testove za komparacije dve grupe (Studentov T test, Mann–Whitney U test, hikvadrat test). U fazi statističke analize međusobnih uticaja i povezanosti prikupljenih podataka korišćen je Pearsonov test korelacije. Sva testiranja sprovedena su na nivou statističke značajnosti p<0,05. REZULTATI: Istraživanje je obuhvatilo 65 bolesnika, od kojih je 82% bilo muškog pola prosečne starosti 59 godina. 83% bolesnika su se izjašnjavali kao pušači, dok je 69% bolesnika navelo da redovno koristi alkohol. Svim pacijentima je tokom hirurškog lečenja OPK rađena disekcija vrata i to najčeščće selektivna disekcija vrata (91%). Kod 30 bolesnika je utvrđeno postojanje cervikalnih regionalnih metastaza na operativnom preparatu te su bolesnici podeljeni u dve grupe: sa prisustvom i bez prisustva metastaza u limfnim čvorovima vrata. Utvrđeno je da se ove dve grupe statistički značajno razlikuju u dubini invazije tumora i volumenu tumora. Utvrđeno je takođe da postoji statistički značajna korelacija između debljine tumora izmerene CT pregledom i debljine tumora izmerene svetlosnim mikroskopom. Dokazano je da dubina invazije tumora veća od 7mm i zapremina tumora veća od 4cm³ predstavljaju prediktivni faktor za pojavu regionalnih cervikalnih metastaza. ZAKLjUČAK: Na osnovu istraživanja izvedeni su zaključci koji ukazuju na to da postoji statistički značajna korelacija između debljine tumora OPK izmerene CTpregledom i svetlosnim mikroskopom te se debljina tumora izmerena CT pregledom može koristiti za planiranje operativnog zahvata prilikom lečenja OPK. Dubina invazije tumora veća od 7mm i volumen tumora veći od 4 cm³ predstavljaju prediktivni faktor za pojavu nodalnih cervikalnih metastaza te su značajni za određivanje stadijuma bolesti.
Oral cancer is the sixth most common malignant disease in the world which incidence varies based on geographic area. It represents 5% of all newly discovered malignant tumors annually and constitutes 14 % of all malignant tumors of head and neck. Squamous cell carcinoma is considered to be a type of oral cancer because more than 90 % of malignant tumors that occur in oral cavity are squamous cell carcinomas while other tumors (malignant tumor of minor salivary gland, lymphoma, sarcoma) rarely occur. Oral cancer is the cancer found in the following anatomic regions: mucosa of front two-thirds of the tongue, the floor of the mouth, cheeks, upper and lower gingiva, retromolar trigone as well as  mucosa of soft and hard palates. Oral squamous cell carcinoma is most commonly localized in mucous membrane of the movable part of the tongue and floor of the mouth. Men are more affected than women (male to female ratio is 3:1) probably because of men’s riskier behavior. It is most commonly diagnosed in the sixth and seventh decade of life (the median is 62 years old) although it has been diagnosed in patents younger than 45 in recent years. Risk factors of oral squamous cell carcinoma are well known. The major factor is tobacco smoking (the period of smoking is significant, it is also important to consider whether a patient smokes a pipe or cigarette, whether he/she chews tobacco as well as the period of abstinence). The mortality rate is believed to be directly related to the number of cigarettes smoked a day. An excessive use of alcohol has been reported in over 75% of patients with oral cancer. There is a synergistic effect of alcohol and cigarette consumption and long-term exposure to these risk factors results in ‘field of cancerization’, genetic instability and tumor development. Chromosome abnormalities, which are caused by DNA damage and include the change in genetic material of chromosomes, have been reported in patients with oral squamous cell carcinoma. One of the most common genetic abnormalities in patients with oral squamous cell carcinoma is a mutation of р53 gene which is located on a short arm of chromosome 17 and represents a tumor suppressor gene. Oral squamous cell carcinoma is not difficult to diagnose when it becomes symptomatic. The patient complains of pain, bleeding, otalgia, swallowing difficulties, decreased tongue mobility. The first symptom is rarely metastatic lymph node on the neck because patients either do not notice or ignore oral pathology. The oral cancer is diagnosed based on the detailed anamnesis, physical examination and pathohistological verification. The oral squamous cell carcinoma occurs in three clinical forms: exophytic, endophytic and infiltrative form. The gold standard for diagnosis of oral cancer is biopsy and pathohistological verification. However, in case of smaller changes, punch biopsy, incisional and excisional biopsies can also be applied. ТNМ staging system of AJCC (American Joint Committee on Cancer) is nowadays used for clinical staging of oral cancer and it is based on the data acquired by clinical examination and imaging methods. Not only is the staging itself important for communication between the doctors involved in treatment, but it is also important for standardization of prognosis. Т describes the size of primary tumor, N describes regional nodal spread and М describes distant metastasis. The treatment of histopathologically proven oral cancer requires multidisciplinary approach. The main treatment of oral squamous cell carcinoma is surgical treatment which involves ablative and reconstructive surgical treatment. The basic principle of ablative surgery for oral cancer is the resection of primary tumor with at least 1 cm negative surgical margins. Apart from tumor ablation surgical treatment also involves removal of regional lymph nodes on the neck. The aim of neck dissection is to remove clinically evident metastasis (therapeutic dissection) or to remove occult metastasis that are not clinically evident (elective dissection). The oral squamous cell carcinoma is the cancer with high mortality rate. The mortality rate is higher than the mortality rate for lymphoma, laryngeal cancer, testicular cancer and endocrine cancer. The five-year survival rate is directly related to the size of the tumor, presence of metastasis in regional lymph nodes and distant metastasis. The average three-year survival rate of the patients with oral cancer is 52% and the average five-year survival rate is 39%. These rates have not changed a lot over the years regardless of new knowledge and approaches in treatment of oral squamous cell carcinoma. The aims of the study are to determine whether there is a correlation between the depth of invasion of oral squamous cell carcinoma determined by computed tomography and light microscope and whether the invasion depth of OSCC and tumor volume can be predictive factors of development of regional cervical metastases in case of oral squamous cell carcinoma. The study covered 65 consecutive patients of both sexes who received treatment for oral cancer at the Clinic for Maxillofacial Surgery of the Clinical Center of Vojvodina. The diagnosis of oral cancer was established based on the anamnesis, physical examination and biopsies. The TNM ‘staging’ of the cancer involved the examination of the patient’s head and thorax by computed tomography (CT) which enabled us to obtain reliable data about the tumor size. After obtaining clinical findings and CT results, the patients’ treatment was planned based on their TNM status. A postoperative histopathological examination was performed by the same pathologist and the following parameters were determined: 1. Tumor size (2 dimensions) measured by CT and expressed in cm 2. Tumor thickness measured by CT and expressed in cm 3. Tumor size (2 diameters) on microscopic device and expressed in cm 4. Tumor thickness on microscopic device measured by light microscope and expressed in cm 5. Depth of tumor invasion on microscopic device measured by light microscope and expressed in cm 6. Tumor volume calculated based on the following formula: VT=π/6 x maximum tumor diameter А x minimum tumor diameter B x depth of tumor invasion and expressed in cm³ 7. The number of metastatic lymph nodes in the neck dissection 8. Total number of pathohistologically tested lymph nodes in the neck dissection. Upon collecting the planned material, statistical analysis of all data was carried out. The statistical analysis included the methods of descriptive statistics (mean value, standard deviation, frequency) and standard parametric and nonparametric tests for comparison of two groups (Student’s T test, Whitney U test, chi-square test). The Pearson’s Test of Correlation was used in the phase of statistical analysis of interaction effects and correlation of obtained data. All tests were performed at the level of statistical significance of p<0.05. RESULTS: The study covered 65 patients, out of which 82% were male patients aged 59. 83% of patients said they smoked and 69% of patients stated that they consumed alcohol regularly. A neck dissection was performed in all patients during surgical treatment of OSCC and it was selective neck dissection (91%). Cervical regional metastasis was found in 30 patients so they were divided into two groups: the group of patients who had metastasis in the lymph nodes and the group of patients with no metastasis in lymph nodes of the neck. It was determined that there was a statistically significant difference in depth of invasion and tumor volume between these two groups. The statistically significant difference was also determined between the thickness of tumor measured by CT and thickness of tumor measured by light microscope. Moreover, the depth of invasion of tumor greater than 7mm and volume of tumor greater than 4cm³ were proven to represent a predictive factor of development of regional cervical metastasis. The study results show that there is a statistically significant correlation between the thickness of OSCC tumor measured by CT and the thickness measured by light microscope, so the thickness of tumor measured by CT can be used for planning the surgery during the treatment of OSCC. The depth of tumor invasion greater than 7 mm and tumor volume greater than 4 cm³ represent a predictive factor of development of cervical metastasis, which means that they are significant for determining the stage of disease.

Fujimoto et al en 1967 fueron los primeros en describir la detección y caracterización de los nódulos tiroideos en Estados Unidos apartir de entonces varios estudios han sido diseñados con el fin de establecer la validez del ultrasonido en el diagnóstico de las lesiones tiroideas benignas y malignas. Por otra parte, el rápido desarrollo de los equipos de ultrasonido durante los últimos años, con la disponibilidad de los transductores de alta frecuencia de 7 a 13 MHz, ha permitido la detección de las lesiones de tiroides muy pequeñas (2-3 mm). Los nódulos tiroideos no palpables son detectados por este método de estudio en 13-50% en la población general con una edad media de 36 años, planteando la cuestión de la utilización de la aspiración por aguja fina en la caracterización de los nódulos. (1) La Ecografía de la tiroides es una técnica generalizada que se utiliza como primera línea de diagnóstico en la enfermedad de la tiroides. Su utilidad es ampliamente reconocida por la detección y caracterización de la enfermedad tiroidea nodular. Los nódulos tiroideos son comunes en todo el mundo, su prevalencia está aumentando dramáticamente en las zonas con deficiencia de yodo. La gran mayoría de los nódulos son benignos, menos del 5% de ellos malignos. El examen citológico de material obtenido por punción y aspiración con aguja fina (PAAF), debido a su alta sensibilidad y especificidad, es la mejor prueba única para diferenciar entre benignos y malignos (1) En el estudio de los nódulos tiroideos, la evaluación clínica es también muy importante. En particular, como se informó en un reciente consenso, la consistencia firme o dura se asocia con un mayor riesgo de malignidad. Sin embargo, este parámetro clínico es muy subjetivo y depende de la experiencia del examinador. La Elastografía es una nueva técnica dinámica desarrollada y basada en el principio de que las partes más blandas de los tejidos se deforman más fácil que las partes más sólidas al realizar compresión por una fuerza externa. Esta elasticidad puede evaluarse midiendo el grado de distorsión de los tejidos sin embargo ésta técnica aún se sigue estudiando . Las lesiones malignas se asocian a menudo con cambio en las propiedades de un tejido (1).

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As doenças hepáticas são bastante comuns nos animais pecuários e responsáveis por inúmeras perdas econômicas, associadas não apenas à morte como também à diminuição da produção e do rendimento e aos gastos com exames diagnósticos e tratamentos. Em equinos as afecções hepáticas são bastante frequentes, acometendo animais de todas as idades e raças, tanto machos quanto fêmeas. O diagnóstico das afecções hepáticas em animais domésticos é feito por análises bioquímicas, exame radiográfico e ultrassonográfico e exame histopatológico de fragmento do orgão colhido por meio de biópsia hepática. O objetivo com o presente estudo é avaliar as possíveis alterações clínicas e laboratoriais induzidas pela realização da técnica de biópsia hepática percutânea guiada por ultrassom em equinos. Para tanto foram utilizados oito equinos sem raça definida (SRD) adultos, machos ou fêmeas, entre 5 e 10 anos de idade, alocados aleatoriamente em dois grupos experimentais, cada grupo sendo composto por quatro animais. O modelo experimental utilizado foi o “crossing over”, assim os grupos experimentais foram invertidos após um período de descanso de seis meses. Os animais do primeiro grupo, denominado G1, foram submetidos à biópsia hepática, enquanto os animais do grupo denominado G2 serviram como grupo controle, sendo submetidos a todos os procedimentos, exceto à biópsia hepática. Foram realizadas colheitas de sangue e de fluido peritoneal para análise hematimétrica, leucométrica e bioquímica, além de exames físicos diários. As variáveis analisadas não apresentaram diferença estatística entre os grupos Controle e Biópsia, com excessão da coloração do fluido peritoneal que se tornou avermelhado após a biópsia. Conclui-se que a técnica de biópsia ...
Liver diseases are very common in livestock animals and are responsible for numerous economic losses, associated not only with death but also with low production rates and expenses with diagnostic exams and treatments. Hepatic diseases in horses are relatively frequent and it can harm animals of all ages, sex and breeds. The diagnosis of liver affections in domestic animals is made with biochemical analyses, x-ray and ultrasound exams, and histopathological exam of liver fragment obtained by a liver biopsy. The aim of this study was to evaluate the possible clinical and laboratorial changes induced by the percutaneous liver biopsy technique guided by ultrasound in horses. Eight adult horses, male or female, ages ranged from 5 to 10 years, were used in this study. The animals were divided into two experimental groups: control group and biopsy group. Peritoneal fluid and blood samples were collected for hematimetric, leucometric and biochemicanalysis, besides the daily physical exams. The analyzed variables did not differ statistically in between the two groups, regardless the peritoneal fluid color witch became reddish after the biopsy was done. In conclusion, the Tru-cut liver biopsy technique is safe and efficient; its use for diagnoses purposes of hospital routine of liver diseases in horses ...

Orientador: José Corrêa de Lacerda Neto
Banca: Julio Carlos Canola
Banca: Gesiane Ribeiro Leão Ferraz
Resumo: As doenças hepáticas são bastante comuns nos animais pecuários e responsáveis por inúmeras perdas econômicas, associadas não apenas à morte como também à diminuição da produção e do rendimento e aos gastos com exames diagnósticos e tratamentos. Em equinos as afecções hepáticas são bastante frequentes, acometendo animais de todas as idades e raças, tanto machos quanto fêmeas. O diagnóstico das afecções hepáticas em animais domésticos é feito por análises bioquímicas, exame radiográfico e ultrassonográfico e exame histopatológico de fragmento do orgão colhido por meio de biópsia hepática. O objetivo com o presente estudo é avaliar as possíveis alterações clínicas e laboratoriais induzidas pela realização da técnica de biópsia hepática percutânea guiada por ultrassom em equinos. Para tanto foram utilizados oito equinos sem raça definida (SRD) adultos, machos ou fêmeas, entre 5 e 10 anos de idade, alocados aleatoriamente em dois grupos experimentais, cada grupo sendo composto por quatro animais. O modelo experimental utilizado foi o "crossing over", assim os grupos experimentais foram invertidos após um período de descanso de seis meses. Os animais do primeiro grupo, denominado G1, foram submetidos à biópsia hepática, enquanto os animais do grupo denominado G2 serviram como grupo controle, sendo submetidos a todos os procedimentos, exceto à biópsia hepática. Foram realizadas colheitas de sangue e de fluido peritoneal para análise hematimétrica, leucométrica e bioquímica, além de exames físicos diários. As variáveis analisadas não apresentaram diferença estatística entre os grupos Controle e Biópsia, com excessão da coloração do fluido peritoneal que se tornou avermelhado após a biópsia. Conclui-se que a técnica de biópsia ...
Abstract: Liver diseases are very common in livestock animals and are responsible for numerous economic losses, associated not only with death but also with low production rates and expenses with diagnostic exams and treatments. Hepatic diseases in horses are relatively frequent and it can harm animals of all ages, sex and breeds. The diagnosis of liver affections in domestic animals is made with biochemical analyses, x-ray and ultrasound exams, and histopathological exam of liver fragment obtained by a liver biopsy. The aim of this study was to evaluate the possible clinical and laboratorial changes induced by the percutaneous liver biopsy technique guided by ultrasound in horses. Eight adult horses, male or female, ages ranged from 5 to 10 years, were used in this study. The animals were divided into two experimental groups: control group and biopsy group. Peritoneal fluid and blood samples were collected for hematimetric, leucometric and biochemicanalysis, besides the daily physical exams. The analyzed variables did not differ statistically in between the two groups, regardless the peritoneal fluid color witch became reddish after the biopsy was done. In conclusion, the Tru-cut liver biopsy technique is safe and efficient; its use for diagnoses purposes of hospital routine of liver diseases in horses ...
Mestre

El presente trabajo pretende demostrar la utilidad de la Biopsia Punción-Aspiración con Aguja Fina (BAAF o PAAF) de tiroides en el diagnóstico de las condiciones malignas más comunes en nuestro medio mediante la determinación de los niveles de sensibilidad y especificidad frente a las piezas operatorias de tiroides consideradas como el “Gold Standard”. Se admitieron para el estudio todos los pacientes que cumplieron con los criterios de inclusión provenientes de la consulta externa del Servicio de Endocrinología en el periodo señalado, haciendo un total de 401 casos de los cuales el 90% corresponden al sexo femenino entre los 40 y 60 años de edad y 10% al sexo masculino. Los diagnósticos citomorfológicos más frecuentes fueron el carcinoma papilar 32.92%, el bocio adenomatoso 19.20% y la Citología de Tumor Folicular 11.97%. Los datos obtenidos fueron sometidos a análisis estadístico obteniéndose para el carcinoma papilar de tiroides una sensibilidad del 81.7%, una especificidad del 93.8%, un valor predictivo positivo del 87.9% con una exactitud del 89.5%. En el adenoma folicular una sensibilidad del 32%, una especificidad del 83.8%, un valor predictivo positivo del 94.9% y una exactitud del 80.5%. Para el carcinoma Medular presentó una sensibilidad del 70%, especificidad del 100%, valor predictivo positivo del 100%, predictivo negativo del 99.2% y una exactitud del 99.3%. El trabajo también muestra algunas cifras obtenidas para otras condiciones de tipo benigno. Se concluye que la BAAF o PAF de tiroides constituye un método altamente sensible y específico para el diagnóstico del cáncer de tiroides en la consulta de endocrinología del Hospital Edgardo Rebagliati Martins EsSalud. BAAF O PAAF (Biopsia Aspiración con aguja fina) Tipo de biopsia en la cual se utiliza una aguja muy fina y delgada para obtener una muestra de células de una lesión sospechosa con fines diagnósticos.
--- Puncture Biopsy - Fine Needle Aspiration in the diagnosis of thyroid cancer (Unit of thyroid of the Hospital Edgardo Rebagliati Martins in the period of the January 01 from 2001 to December 31 2005) to present work seeks to demonstrate the utility of the puncture biopsy Fine-needle aspiration (FNA or FNA) of thyroid in the diagnosis of malignant conditions more common in our environment through the determination of the levels of sensitivity and specificity compared to surgical specimens of thyroid considered as the "Gold Standard". It is admitted to the study, all patients who met the inclusion criteria from the outpatient Service of Endocrinology in the period indicated, making a total of 401 cases of which 90% correspond to the female sex between the ages of 40 and 60 years of age and 10% male. The diagnosis cytomorphology more frequent were papillary carcinoma 32.92 %, adenomatous goiter 19.20 % and the cytology of follicular tumor 11.97 %. The data obtained were subjected to statistical analysis and obtained for the papillary thyroid carcinoma a sensitivity of 81.7 %, a specificity of 93.8 %, a positive predictive value of 87.9 % with an accuracy of 89.5 %. In the follicular adenoma a sensitivity of 32 %, a specificity of 158 %, a positive predictive value of 94.9 % and an accuracy of 80.5 %. For medullary carcinoma had a sensitivity of 70 %, specificity of 100 %, positive predictive value of 100% , negative predictive of 99.2 % and an accuracy of 99.3 %. The work also shows some of the figures obtained for other conditions of benign. It is concluded that the FNAB or PAF thyroid constitutes a method highly sensitive and specific for the diagnosis of thyroid cancer in the endocrinology clinic of the Hospital Edgardo Rebagliati Martins EsSalud. FNAB OR FNA biopsy (fine needle aspiration) type of biopsy in which a needle is used very fine and thin to obtain a sample of cells from a suspicious lesion for diagnostic purposes.
Tesis

Orientadores : Jesse de Paula Neves Jorge, Anibal Faundes
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Avaliar a correlação entre o diagnóstico histeroscópico e a histologia endometrial torna-se importante, por se tratar de um binômio freqüente e crescente na propedêutica das mulheres na terceira idade, tanto pelo aumento na expectativa de vida, quanto pela maior divulgação da técnica endoscópica. Realizamos validação da histeroscopia como teste diagnóstico, sendo o padrão ouro o resultado da histopatologia, e avaliamos a sua relação com as suas indicações. Foram incluídas no estudo 222 mulheres, nas quais foram realizadas histeroscopias no período de janeiro de 1996 a abril de 2000, no Setor de Endoscopia Ginecológica do Hospital e Maternidade Celso Pierro, da Pontifícia Universidade Católica de Campinas e na clínica privada do pesquisador.Tanto no achado histeroscópico, quanto no exame anatomopatológico, os achados mais freqüentes foram o pólipo endometrial, seguido pelo endométrio atrófico. A sensibilidade do diagnóstico da histeroscopia variou de 62,5% a 100,0%, sendo mais elevada na atrofia endometrial e nos pólipos e mais baixa no endométrio proliferativo e secretor. A especificidade foi alta e oscilou entre 88,6% e 99,5%, sendo mais elevada no câncer endometrial e nos pólipos. As complicações foram raras (1,3%), sendo a reação vagal a mais comum. Achado ultrasonográfico alterado (56,0%) e sangramento uterino anormal (41,0%) foram as principais indicações da histeroscopia. Não encontramos diferenças significativas na sensibilidade e especificidade da histeroscopia, para o diagnóstico de lesões endocavitárias, segundo a indicação do exame. Concluímos que a histeroscopia constitui um bom meio de identificação de lesões endo-uterinas, porém a confirmação histológica é indispensável
Abstract: Evaluating the correlation between hysteroscopy diagnosis and histological endometrial findings has become very important due to their frequent and growing diagnostic use on older women, not only because of the increase in life expectancy but also because of the better understanding of endoscopic techniques. A hysteroscopy validation as a diagnostic test was performed, considering the histological findings as the gold standard, and evaluated its correlation according to its indications. The study consisted of 222 women, on whom hysteroscopy was performed at the Hospital e Maternidade Celso Pierro da Pontifícia Universidade Católica de Campinas - division of gynacological endoscopy, and at the reseacher's private practice during the period of January 1996 to April 2000. The most frequent hysteroscopy and histological findings were endometrial polyps followed by atrophic endometrium. The sensitivity of the hysteroscopy diagnosis varied from 62.5% to 100.0%, being higher for endometrial atrophy and polyps and lower for proliferative and secretory endometrium. The specificity was high and varied between 88.6% and 99.5%, being higher for endometrial cancer and polyps. The complications were rare (1.3%) and the most frequent was vagal reacion. Abnormal ultrasound findings (56.0%) and dysfunctional uterine bleeding (41.0%) were the most common indication for hysterescopy. No significant differences in the hysteroscopy sensitivity and specificity for the diagnosis of endometrial lesion based on the indication, were found. It was therefore concluded that hysteroscopy is a good diagnostic approach for endometrial lesions, however, histological confirmation is indispensable
Mestrado
Tocoginecologia
Mestre em Tocoginecologia

Includes abstract.
Includes bibliographical references.
Prostate cancer is the most common male malignancy amongst black males in South Africa and the second commonest amongst white males (1,2). Prostate biopsy, via the rectum, is an essential part of diagnosing and treating this disease. Traditionally needle biopsies of the prostate were performed blindly by digital palpation of the gland per rectum.

La biopsia pulmonar transbronquial es una técnica broncoscópica indicada en el estudio de las enfermedades pulmonares difusas. Hasta el momento, la técnica diagnóstica utilizada para la obtención de muestras pulmonares de una forma no quirúrgica es la biopsia pulmonar transbronquial con pinza convencional, pero tal y como se detalla en la presente exposición, el rendimiento diagnóstico de esta técnica es limitado y variable. Esta variabilidad es debida, entre otros factores, al pequeño tamaño de las biopsias y a la presencia de artefactos que alteran la calidad de las muestras. La línea de investigación desarrollada tiene como objetivo ampliar las herramientas diagnósticas actualmente disponibles en broncoscopia con la aplicación de una técnica innovadora basada en la utilización de sondas de crioterapia que permiten realizar la biopsia transbronquial de una forma ambulatoria y menos invasiva que otras alternativas actualmente disponibles como la biopsia quirúrgica. Los dos trabajos presentados en esta tesis evalúan la utilización de criosondas para la obtención de parénquima pulmonar como una alternativa diagnóstica a la biopsia pulmonar transbronquial convencional. Ambos estudios se llevaron a cabo en pacientes con sospecha de enfermedad intersticial difusa. En primer lugar, se presentan los resultados de una primera fase prospectiva que ha permitido valorar la viabilidad de la técnica y su aplicación en nuestro medio así como, la descripción de la metodología. En una segunda fase, se analizan los resultados de un ensayo clínico aleatorizado para evaluar el rendimiento diagnóstico del nuevo procedimiento en comparación con la técnica convencional. Los resultados de los trabajos publicados indican que la realización de la biopsia pulmonar transbronquial con criosonda posibilita la mejora en el manejo diagnóstico de los pacientes con determinadas patologías pulmonares, especialmente en el grupo de las enfermedades pulmonares difusas y, actualmente, se ha comenzado a considerar un procedimiento más en el algoritmo diagnóstico de estas enfermedades.
Transbronchial lung biopsy (TBLB) is a bronchoscopic procedure for obtaining material in the diagnosis of diffuse interstitial lung disease. To date, conventional forceps have usually been used to sample tissue in this nonsurgical approach, but the diagnostic yield of TBLB has been limited and variable, as shown by the literature reviewed for this thesis. Variability in the yield of conventional-forceps TBLB can be attributed to the small size of the samples obtained and to the presence of artifacts, among other factors. The line of research presented here aimed to extend the range of bronchoscopic diagnostic tools to include the innovative use of cryoprobes for harvesting tissue. The transbronchial cryobiopsy technique described can be performed as an outpatient procedure and is less invasive than open lung biopsy. Two studies were undertaken to evaluate cryoprobe sampling of the lung parenchyma as an alternative to conventional-forceps TBLB. Both studies were carried out in patients with suspected diffuse interstitial disease. I first present the findings of a prospective study of the cryoprobe technique to assess its viability in a Spanish teaching hospital. In this part of the thesis, the technique is described in detail. Next, I analyze the results of a randomized clinical trial that compared the diagnostic yield of the new cryoprobe procedure to the yield of conventional-forceps TBLB. The studies showed that transbronchial cryobiopsy facilitates the diagnostic process in certain lung conditions, particularly diffuse interstitial lung diseases. When these entities are suspected, transbronchial cryobiopsy is increasingly being included in diagnostic protocols.

La diabetis mellitus és una malaltia d’una crucial importància a nivell mundial per la seva elevada prevalença i augment de la incidència. Una de les seves complicacions més rellevants és el desenvolupament de malaltia renal crònica. La malaltia renal diabètica és la primera causa d’inici de teràpia renal substitutiva en el nostre medi. L’ús de bloquejadors del sistema renina-angiotensina-aldosterona (BSRAA) ha demostrat un efecte beneficiós en els pacients diabètics amb afectació renal lleu, tot i així, aquest benefici a la malaltia renal crònica avançada no és tant clar. Per altra banda, la presència de nefropatia diabètica i nefropatia no-diabètica en el pacient afecte de diabetis i afectació renal, i el valor de la biòpsia renal, han sigut poc estudiats. Estudis recents suggereixen que un percentatge elevat de pacients diabètics amb biòpsia renal estan afectes de nefropatia no-diabètica. L’objectiu de la present tesi és profunditzar en el coneixement i maneig dels pacients diabètics amb malaltia renal des de dos punts de vista: 1) avaluar l’ús de BSRAA en una cohort de pacient diabètics amb malaltia renal crònica avançada i 2) avaluar el paper de la realització de biòpsia renal en els pacients diabètics en quan a diagnòstics histològics, pronòstic renal i supervivència. En quan al primer punt, hem analitzat una cohort de pacients diabètics amb malaltia renal crònica avançada. Vam observar que els que no van rebre tractament amb BSRAA tenien una pitjor funció renal en el moment basal. A més a més, els pacients tractats amb BSRAA no presentaren una major toxicitat ni més progressió de la malaltia renal i no vam evidenciar diferències en el pronòstic renal. En referència al segon punt, vam realitzar dos estudis amb dues cohorts de diabètics amb biòpsia renal en els que vam evidenciar que un important percentatge de diabètics tenen lesions de nefropatia no-diabètica (aproximadament un 60%), essent les més important la nefropatia IgA i la nefroangioesclerosis. Es van identificar els factors predictius de nefropatia no-diabètica en el pacient diabètic afecte d’insuficiència renal: l’edat avançada, la presència de microhematuria, l’absència de retinopatia diabètica i un menor temps de duració de la diabetis mellitus. Per últim, els pacients diabètics amb nefropatia no-diabètica, tenien un millor pronòstic renal i una major supervivència.
La diabetes mellitus es una enfermedad de una crucial importancia a nivel mundial por su elevada prevalencia y aumento de su incidencia. Una de sus complicaciones más relevantes es el desarrollo de enfermedad renal crónica. La enfermedad renal diabética es la primera causa de inicio de terapia renal sustitutiva en nuestro medio. El uso de bloqueadores del sistema renina-angiotensina-aldosterona (BSRAA) ha demostrado un efecto beneficioso en los pacientes diabéticos con afectación renal leve, sin embargo, dicho beneficio en enfermedad renal crónica avanzada no está tan claro. Por otro lado, la presencia de nefropatía diabética y nefropatía no diabética en el paciente afecto de diabetes y afectación renal, y el valor de la biopsia renal, han sido poco estudiados. Estudios recientes sugieren que un porcentaje elevado de pacientes diabéticos con biopsia renal están afectos de nefropatía no diabética. El objetivo de la presente tesis es profundizar en el conocimiento y manejo de los pacientes diabéticos con enfermedad renal desde dos puntos de vista: 1) evaluar el uso de BSRAA en una cohorte de pacientes diabéticos con enfermedad renal crónica avanzada y 2) evaluar el papel de la realización de biopsia renal en los pacientes diabéticos en cuanto a diagnósticos histológicos, pronóstico renal y supervivencia. En cuanto al primer punto, hemos analizado una cohorte de pacientes diabéticos con enfermedad renal crónica avanzada. Observamos que los que no recibieron tratamiento con BSRAA tenían una peor función renal en el momento basal. Además, los pacientes tratados con BSRAA no presentaron mayor toxicidad ni más progresión de la enfermedad renal y no evidenciamos diferencias en el pronóstico renal. En referencia al segundo punto, realizamos dos estudios con dos cohortes de diabéticos con biopsia renal en la que evidenciamos que un importante porcentaje de diabéticos tienen lesiones de nefropatía no-diabética (aproximadamente un 60%), siendo las más importantes la nefropatía IgA y la nefroangioesclerosis. Se identificaron los factores predictivos de nefropatía no-diabética en el paciente diabético afecto de insuficiencia renal: la edad avanzada, la presencia de microhematuria, la ausencia de retinopatía diabética y el menor tiempo de duración de la diabetes mellitus. Por último, los pacientes diabéticos con nefropatía no diabética, tuvieron un mejor pronóstico renal y mayor supervivencia.
Diabetes mellitus is a disease with worldwide importance due to its high prevalence and increased incidence. One of the complications from diabetes is the development of chronic kidney disease. Diabetic kidney disease is the first cause of end-stage chronic kidney disease known in our environment. The use of renin-angiotensin-aldosterone system blockers (RAASB) has shown a beneficial effect in diabetic patients with renal involvement, however, this benefit in advanced chronic kidney disease is not so clear. On the other hand, the role of performing renal biopsy in diabetic patients is an issue with increased importance over the years; since it has been shown that a significant percentage of patients with diabetes and renal disease with kidney biopsy are affected by non-diabetic renal disease. The objective of this thesis was to improve the knowledge and management of patients with diabetes and kidney disease from two points of view: first aim) to evaluate the use of RAASB in a cohort of diabetic patients with advanced chronic kidney disease. Second aim) to evaluate the role of renal biopsy in diabetic patients in terms of histological diagnosis, renal prognosis and survival. Regarding the first aim, we have analyzed a cohort of diabetics with advanced chronic kidney disease. We observed that the patients who did not receive treatment with RAASB had a worse baseline renal function. In addition, patients treated with RAASB did not present more toxicity or more progression of kidney disease than non-treated RAASB patients, and differences in renal prognosis were not observed. In the second aim, we performed two studies with two cohorts of patients with diabetes and kidney biopsy. We showed that an important percentage (approximately 60%) of diabetics have non-diabetic renal disease in the biopsy: IgA nephropathy and nephroangiosclerosis were the most frequent non-diabetic renal disease. Older age, the presence of microhematuria, the absence of diabetic retinopathy and the shorter duration of diabetes mellitus were identified as a risk factors for non-diabetic renal disease. Finally, patients with diabetes and non-diabetic renal disease had a better renal prognosis and survival.

Orientador : Gentil Alves Filho
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Não informado
Abstract: Not informed
Mestrado
Medicina Interna
Doutor em Medicina

El estudio se realizó en 50 pacientes del servicio de Gastroenterología del Hospital Central PNP Luis N. Saenz, con el objetivo de establecer la relación de la prueba de urea en muestras de placa dental y la de biopsia gástrica para la determinación de la presencia del Helicobacter pylori. Se tomaron simultáneamente muestras de placa dental y de biopsias gástricas en el servicio de Gastroenterología a quienes se les indicó endoscopias por el médico tratante obteniéndose muestras del estómago mediante sacabocado y colocadas en caldo urea las que fueron llevadas al laboratorio del hospital. Las muestras de placa dental fueron colocadas directamente en el caldo urea y llevados al laboratorio del la Facultad de Odontología para su incubación a 37 ºC, los resultados fueron leídos a las 24, 48 y 72 horas y registrados en una base de datos. Los resultados de las biopsias gástricas fueron obtenidos del laboratorio de histopatología del Hospital. El análisis de los resultados obtenidos corrobora la hipótesis que existe relación entre la determinación de la prueba de urea positiva en muestras de placa dental con las obtenidas en biopsias gástricas ya que se obtiene un 68% de concordancias de valores tanto positivos como negativos para ambos.
Tesis

Señala que los estudios epidemiológicos muestran una tendencia a la disminución de gastritis asociada a Helicobacter Pylori, lo que induce a sostener que la incidencia relativa de otros tipos de gastritis sería mayor, siendo muy importante realizar un estudio histológico más acucioso para su identificación. En una ficha se recogieron datos de biopsias con diagnóstico de gastritis leves o sin inflamación según el protocolo convencional, luego se aplicó el modificado para identificar las gastropatías reactivas que se pasaron de alto. La evaluación histológica con protocolo modificado identificó gastropatías reactivas en las biopsias gástricas antes diagnosticadas con gastritis leves. Se concluye que el uso del protocolo modificado para evaluación de biopsias gástricas se requiere para identificación de gastropatías Reactivas para el adecuado diagnóstico y tratamiento, por lo que se propone su adopción en las evaluaciones de rutina.
Trabajo académico

El desequilibrio entre la oferta y demanda de órganos para trasplante renal ha obligado en los últimos años a la utilización de donantes marginales. Evaluar estos órganos antes del trasplante exige al anátomo patólogo un conocimiento de los parámetros histológicos más útiles que determinen su viabilidad. Objetivos: Identificar el grado y la frecuencia de glomérulo esclerosis (GE), atrofia tubular (AT), fibrosis intersticial (FI) y estrechamiento vascular (EV) en las biopsias por congelación pretrasplante de riñones de donantes marginales (DM) y no marginales (DNM). Establecer el score de cada biopsia renal según el método semicuantitativo de evaluación y comparar las frecuencias de dichos hallazgos entre DM y DNM. Métodos: Estudio observacional, retrospectivo, transversal y comparativo realizado en el Departamento de Anatomía Patológica del HNERM con 34 biopsias renales en cuña de DM y 23 de DNM, sometidas a estudio por congelación pretrasplante mediante un método semicuantitativo que evaluó el grado de GE, AT, FI y EV. Para el análisis estadístico se utilizó técnicas descriptivas, correlaciones, medianas, modas y rangos. Resultados: DM: AT:88,2%, EV:85,3%, GE:50% y FI:38,2%; DNM: AT y EV:65,2%, GE:34,8% y FI:13%. Grados de severidad: 1 y 2 más frecuentes en DM. Grado 3 sólo en GE y EV en DM y DNM respectivamente. Score: DM: 1 a 6-7 puntos. DNM: 0 a 4-5 puntos. Conclusiones: La atrofia tubular y el estrechamiento vascular son los hallazgos histopatológicos más frecuentes en ambos grupos de donantes, con mayor frecuencia en los DM. Los grados de estos hallazgos son similares en ambos grupos, con una mayor frecuencia de los de mayor severidad en los DM. Finalmente, los scores tienen cierta tendencia a ser mayores en los DM en comparación con los DNM.
Tesis de segunda especialidad

Orientador: Gustavo Antonio de Souza
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A biópsia de fragmento de lesões mamárias não palpáveis vem ganhando espaço como uma alternativa para biópsia cirúrgica com localização préoperatória. Este estudo avaliou o desempenho da biópsia de fragmento guiada por ultra-sonografia, bem como seu impacto no seguimento de pacientes com lesões mamárias suspeitas. Foram realizadas 54 biópsias guiadas por ultrasonografia, sendo que 42 pacientes tem confirmação anatomopatológica e 12 estão em seguimento por imagem. Das 42 pacientes que foram submetidas à localização com exérese da lesão houve concordância dos resultados anatomopatológicos em 41 delas e todas as pacientes em seguimento não apresentaram evolução no período, que variou entre um e três anos. Vinte e três dos 24 casos de neoplasia maligna foram diagnosticados pela biópsia de fragmento. O custo médio da biópsia de fragmento foi avaliado em 942 coeficientes de honorários e o da biópsia cirúrgica em 3.120 coeficientes de honorários. Desta forma, o uso da biópsia de fragmento guiada por ultra-sonografia permite um diagnóstico confiável e econômico das lesões mamárias suspeitas
Abstract: The core needle biopsy for non-palpable breast lesions is an alternative for pre-operative localization and open biopsy. We evaluate the accuracy of USguided large core needle biopsy (LCNB), as well as it's impact on the follow up of these pacients. 54 biopsies were performed, 42 of those had pathology confirmation after open biopsy and 12 of them are on clinical follow-up. In 41 of the 42 pacients who had the lesion excised, the LCNB reached the same results as the open biopsy. All the 12 pacients in follow-up had benign diagnosis in LCNB and non of them showed progression by this time (between 6 months and 2 years of follow-up). 23 of the 24 cases of breast cancer were correctly diagnosed by LCNB. The average cost of the LCNB was 942CH and of the open biopsy 3120CH, therefore, the LCNB is an accurate and cost-effective method for sampling breast lesions when used in a selective fashion
Mestrado
Tocoginecologia
Mestre em Tocoginecologia

Orientadora: Leide Parolin Marinoni
Co-orientador: Sergio Ossamu Ioshii
Dissertação (mestrado) _ Universidade Federal do Parana, Setor de Ciencias da Saude
Resumo: O objetivo deste trabalho foi o de avaliar a aplicabilidade da técnica de imunoperoxidase na localização de imunoglobulinas e complemento nas biópsias de pele de pacientes com dermatoses auto-imunes, processadas de maneira rotineira, ou seja, fixadas em formalina e incluídas em parafina. Foi pesquisada a deposição de imunoglobulinas das classes IgG, IgM e IgA e a fração Q do sistema do complemento em casos de dermatoses bolhosas auto-imunes, lúpus, líquen e vasculite. O estudo foi descritivo e retrospectivo, com a recuperação de material incluído em parafina do arquivo do Serviço de Anatomia Patológica do Hospital de Clínicas da Universidade Federal do Paraná e com a aplicação do método imuno-histoquímico da avidinabiotinaperoxidase. A revelação da coloração foi realizada com a utilização do cromógeno diaminobenzidina. Os resultados foram comparados com os obtidos pela análise com a técnica de imunofluorescência, conforme os dados contidos no livro de registro da Seção de Imunopatologia do Serviço de Anatomia Patológica. Quarenta casos foram analisados quanto ao diagnóstico clínico, histopatológico e achados da imunofluorescência. Os depósitos foram considerados positivos quando mostravam coloração marrom escura, diferente da coloração de fundo, e foram observados quatro locais de deposição: zona da membrana basal, intercelular, subepidérmico e vascular. Obteve-se deposição específica com a técnica da imunoperoxidase em 13 casos (32,5%); em cinco (12,5%), os resultados foram negativos para todas as classes de imunoglobulinas e complemento. Desta forma, obteve-se confirmação diagnostica por este método em 45% dos casos. Pela análise com a imunofluorescência, foram obtidos depósitos específicos em 22 casos (55%) e resultaram negativos os mesmos casos negativos pela imunoperoxidase. Houve concordância de resultados positivos pelos dois métodos em apenas 6 casos (15%). A análise estatística dos resultados evidenciou que as duas técnicas foram comparáveis quanto à deposição de IgG, IgM e C3, porém houve diferença significativa quando pesquisada a deposição de IgA (p=0,00596). Não houve correlação significativa dos resultados em relação aos locais de deposição. Com estes dados, concluiu-se que: a técnica de imunoperoxidase permitiu a identificação de depósitos de imunoglobulinas e complemento nos cortes parafinados; os dois métodos foram comparáveis estatisticamente quanto à deposição de IgG, IgM e C3, porém não de IgA, e que esta técnica pode ser utilizada na avaliação de depósitos imunes na pele quando só se dispõe de material fixado em formalina e incluído em parafina.
Abstract: The aim of this study was to evaluate the feasibility of the immunoperoxidase technique in the localization of immunoglobulins and complement in biopsies o f patients with autoimmune skin diseases routinely processed, which means, fixed in formalin and embedded in paraffin. The deposition of immunoglobulins from IgG, IgM and IgA classes as well as C3 fraction of the complement system was searched for in cases o f autoimmune bullous dermatosis, lupus, lichen and vasculitis. The study was descriptive and retrospective and samples embedded in paraffin were retrieved from the Hospital de Clinicas o f the Universidade Federal do Parana's Histopathology Department and submitted to the immunohistochemical method o f avidin-biotin-peroxidase (ABC). The stain was developed by the utilization o f the chromogen diaminobenzidine. Results were then compared to those obtained by the analysis with the immunofluorescence technique from the records at the immunopathology section o f the Histopathology Department. Forty cases were analyzed in regard to their clinical, histological and immunofluorescent findings. The deposits were considered positive when yielded a dark brown color, different from the background staining and four sites o f deposition were considered: basal membrane zone, intercellular, subepidermal and vascular. There was specific deposition with the immunoperoxidase technique in 13 cases (32.5%) and in five (12.5%) the results were negative to all classes o f IG and C3. Thus, there was diagnostic confirmation by this method in 45% o f all cases. By the immunofluorescence analysis twenty-two (55%) positive results were obtained and there was no deposition in the same 5 cases found negative with the immunoperoxidase technique. There was agreement with the positive results yielded by the two methods in only 6 cases (15%). The statistical analysis showed that both techniques were comparable in relate to the deposition of IgG, IgM and C3 but there was significant difference when analyzed IgA deposits (p=0.00596). There was no significant correlation of the results regarding the localization o f the deposits. With these data it was concluded that: the immunoperoxidase technique allowed the identification o f immunoglobulin and complement deposits in the paraffin sections, the two methods were statistically comparable in regard to the deposition o f IgG, IgM e C3 but not IgA, and that this technique could be used in the evaluation o f immune deposits in the skin when only formalin-fixed, paraffin-embedded tissue is available.

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Universidade Estadual Paulista (UNESP)
As fibras musculares esqueléticas são entidades versáteis, capazes de alterar seus fenótipos de acordo com a demanda energética. Para avaliar os efeitos do exercício de enduro no músculo esquelético, foram utilizados neste estudo 36 equinos da raça Puro Sangue Árabe divididos em dois grupos: treinados e não treinados para enduro. Foram obtidos fragmentos musculares da região profunda do músculo glúteo médio e processados para técnicas histoquímicas e imunoistoquímica, utilizando-se anticorpos específicos contra isoformas de cadeia pesada de miosina (MyHC) lenta e rápida. As fibras identificadas pela histoquímica e imunoistoquímica foram analisadas uma a uma. Determinou-se a porcentagem dos diferentes tipos de fibras musculares, e avaliou-se que, a porcentagem das fibras do tipo IIA foi significativamente mais alta do que a porcentagem das fibras dos tipos I e IIX no grupo não treinado (P<0,05). Em contra partida, a porcentagem das fibras do tipo I foi significativamente mais alta do que a porcentagem das fibras dos tipo IIA e IIX no grupo treinado (P<0,05). Também foram analisados, a média da área de corte transversal e o menor diâmetro da fibra e observou-se que, a média de corte transversal das fibras do tipo IIX foi significativamente maior comparada à média de corte de transversal das fibras dos tipos I e IIA em ambos os grupos. Em conclusão pode-se afirmar que, o exercício de enduro em equinos aumenta a população das fibras de contração lenta, em detrimento da população de fibras de contração rápida
The skeletal muscle fibers are versatile entities capable to change their phonotype according to energy demand. To evaluate the effects of exercise over equine skeletal muscle in this study, 36 Arabian horses divided in 2 groups trained and untrained for endurance were used. The samples was obtained from de deep region of the gluteus medius muscle and processed for histochemistry and immunohistochemistry using specific monoclonal antibodies to selected fast and slow isoforms myosin heavy chain (MyHC). The histochemical and immunohistochemical categorization of the muscle fiber types were compared fiber by fiber. It was analyzed the percentage of different fiber types where, in the untrained group, the percentage of the fiber type IIA was higher significantly than the percentage of fiber types I and IIX (P<0.05). Unlike, the group trained showed a higher proportion of fiber type I than the fiber type IIX (P<0.05). The cross section area and lesser fiber diameter were also analyzed, and showed that, CSA of fiber type IIX was higher significantly than fibers I and IIA (P<0.05) in both groups. In conclusion, endurance exercise in equines increase the population of slow-twitch fibers in detriment of fast-twitch fibers

El valor clínic de la biòpsia selectiva del gangli sentinella (BSGS) en pacients amb melanoma gruixut (Breslow > 4 mm) no ha estat prou estudiada. L'objectiu principal d'quest treball és avaluar si la BSGS augmenta la supervivència en pacients amb melanoma gruixut i com a objectiu secundari, investigar la relació entre la supervivència i l'estat del gangli sentinella (GS). Altres objectius secundaris són identificar quines variables estan associades amb l'afectació de l'GS i analitzar el paper de la dissecció completa dels ganglis limfàtics en pacients amb una BSGS positiva. Es van incloure pacients amb melanomes gruixuts (> 4 mm) registrats en les bases de dades de melanoma dels hospitals participants entre 1997 i 2015. Els pacients van ser aparellats pel mètode de la puntuació de propensió segons el sexe, l'edat, la localització del tumor primari, les característiques histològiques del melanoma, l'any de diagnòstic, l'hospital i la realització de teràpia adjuvant amb interferó. Per identificar els factors associats amb l'afectació del GS, vam realitzar un estudi de cohorts retrospectiu multicèntric que va incloure a tots els pacients amb melanoma gruixut que s'havien sotmès a la BSGS. Per analitzar el paper de la limfadenectomia selectiva (LS) en pacients amb melanoma gruixut i una BSGS positiva, vàrem crear un model multivariat de riscos proporcionals de Cox per a la supervivència específica del melanoma (SEM) i la supervivència lliure de malaltia (SLM) i compararem els pacients que havien rebut LS i els que no. La BSGS enfront de l'observació es va associar amb una millor SLM (raó de risc ajustada [AHR], 0,74; interval de confiança [IC] de el 95%: 0,61-0,90); p = 0.002) i supervivència global (AHR, 0.75; IC 95%, 0,60-0,94; p = 0.013) però no SEM (AHR, 0.84; IC 95%, 0.65-1.08; p = 0,165). Els pacients amb BSGS negativa van tenir una millor SEM als 5 i 10 anys en comparació amb els pacients amb una BSGS positiva (65.4% vs 51.9% i 48.3% vs 38.8%; p = 0.01, respectivament). L'anàlisi de regressió logística va mostrar que l'edat, el subtipus histològic, la ulceració, les satelitosis microscòpiques i la invasió limfovascular es van associar amb l'afectació ganglionar. L'arbre de decisió CHAID (detecció automàtica d'interaccions mitjançant chi-quadrat) va mostrar que la ulceració és el predictor més important deafectació de l'GS. Per als melanomes no ulcerats, els subtipus histològics de melanoma lentigen maligne i altres subtipus poc freqüents es van associar amb una baixa taxa d'afectació de GS (4,3%). No es van observar diferències significatives per SLM i SEM entre els grups als quals s'havia realitzat LS i els que no. L'estat dels ganglis no sentinella en la LS es va associar amb diferències en les taxes de SLM i SEM. En conclusió, la biòpsia SLN es va associar a una millor SLM però no a una millor SEM, en pacients amb melanoma gruixut després de l'ajust per factors pronòstics clàssics. La BSGS és útil per estratificar aquests pacients en diferents grups de risc. Hi ha subgrups de pacients amb melanoma gruixut i una baixa probabilitat d'afectació de l'GS. La LS no ofereix beneficis de supervivència, però proporciona informació pronòstica.
El valor clínico de la biopsia selectiva del ganglio linfático centinela (BSGC) en pacientes con melanoma grueso (Breslow> 4 mm) no ha sido suficientemente estudiada. El objetivo principal del trabajo es evaluar si la biopsia BSGC aumenta la supervivencia en pacientes con melanoma grueso y como objetivo secundario, investigar la relación entre la supervivencia y el estado del ganglio centinela (GC). Otros objetivos secundarios son identificar qué variables están asociadas con la afectación del GC y analizar el papel de la disección completa de ganglios linfáticos en pacientes con una BSGC positiva. Se incluyeron pacientes con melanomas gruesos (> 4 mm) registrados en las bases de datos de melanoma de los hospitales participantes entre 1997 y 2015. Los pacientes fueron emparejados por el método de la puntuación de propensión según el sexo, la edad, la localización del tumor primario, las características histológicas del melanoma, el año de diagnóstico, el hospital y la realización de terapia adyuvante con interferón. Para identificar los factores asociados con la afectación del GC, realizamos un estudio de cohorte retrospectivo multicéntrico que incluyó a todos los pacientes con melanoma grueso que se habían sometido a la BSGC. Para analizar el papel de la linfadenectomía selectiva (LS) en pacientes con melanoma grueso y una BSGC positiva, creamos un modelo multivariado de riesgos proporcionales de Cox para la supervivencia específica del melanoma (SEM) y la supervivencia libre de enfermedad (SLE) y comparamos a los pacientes que habían recibido LS y los que no. La BSGC frente a la observación se asoció con una mejor SLE (razón de riesgo ajustada [AHR], 0,74; intervalo de confianza [IC] del 95%: 0,61-0,90); p = 0.002) y supervivencia global (AHR, 0.75; IC 95%, 0.60-0.94; p = 0.013) pero no SEM (AHR, 0.84; IC 95%, 0.65-1.08; p = 0.165). Los pacientes con BSGC negativa tuvieron una mejor SEM de 5 y 10 años en comparación con los pacientes con BSGC positiva (65.4% vs. 51.9% y 48.3% vs 38.8%; p = 0.01, respectivamente). El análisis de regresión logística mostró que la edad, el subtipo histológico, la ulceración, la satelitosis microscópica y la invasión linfovascular se asociaron con la enfermedad ganglionar. El árbol de decisión CHAID (detección automática de interacciones mediante chi-cuadrado) mostró que la ulceración es el predictor más importante de afectación del GC. Para los melanomas no ulcerados, los subtipos histológicos de melanoma lentigo maligno y otros subtipos poco frecuentes se asociaron con una baja tasa de afectación de GC (4,3%). No se observaron diferencias significativas para SLE y SEM entre los grupos a los que se había realizado LS y los que no. El estado de los ganglios no centinela en la LS se asoció con diferencias en las tasas de SLE y SEM. En conclusión, la biopsia SLN se asoció con una mejor SLE pero no con una mejor SEM en pacientes con melanoma grueso después del ajuste por factores pronósticos clásicos. La BSGC es útil para estratificar a estos pacientes en diferentes grupos de pronóstico. Existen subgrupos de pacientes con melanoma grueso con una baja probabilidad de afectación del GC. La LS no ofrece beneficios de supervivencia, pero proporciona información pronóstica.
The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The main aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. Other secondary objectives include the identification of variables associated with SLN involvement and analyze the role of complete lymph node dissection in patients with a positive SLN biopsy. Patients with thick melanomas (>4 mm) registered in the participating hospitals’ melanoma databases between 1997 and 2015 were included. Patients were matchedinto pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital, and adjuvant interferon therapy. To identify factors associated with SLN involvement in thick melanoma we performed a multicentric retrospective cohort study involving all patients with thick melanoma who had undergone SLN biopsy. To analyze the role of complete lymph node dissection (CLND) in thick melanoma patients with a positive SLN biopsy, we built a multivariate Cox proportional hazards model for melanoma-specific survival (MSS) and diseasefree survival (DFS) and compared patients who had undergone CLND with who had not. The SLN biopsy vs. observation was associated with better DFS (adjusted hazard ratio [AHR], 0.74; 95% confidence interval [CI] 0.61-0.90); p = 0.002) and OS (AHR, 0.75; 95% CI, 0.60-0.94; p = .013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; p = 0.165). SLN-negative patients had better 5- and 10-year MSS compared to SLN-positive patients (65.4% vs. 51.9% and 48.3% vs 38.8%; p = 0.01, respectively). The logistic regression analysis showed that age, histologic subtype, ulceration, microscopic satellitosis, and lymphovascular invasion were associated with nodal disease. The CHAID (Chi-squared Automatic Interaction Detection) decision tree showed ulceration to be the most important predictor of lymphatic involvement. For nonulcerated melanomas, lentigo maligna melanoma and other rare histologic subtypes were associated with a low rate of SLN involvement (4.3%). No significant differences were observed for DFS and MSS between the CLND performed and not-performed groups. Nodal status on CLND was associated with differences in DFS and MSS rates. In conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups. We also identified subgroups of thick melanoma patients with a low likelihood of SLN involvement. CLND does not offer survival benefit, but provides prognostic information.

As doenças do trato digestório nos equinos apresentam altas taxas de morbidade e mortalidade, com diferentes etiologias. Em alguns casos, o emprego da biopsia intestinal se faz necessário para auxílio no diagnóstico dessas enfermidades. No entanto, as técnicas convencionais podem trazer riscos aos pacientes, por serem invasivas, ou não serem elucidativas por apresentarem limitações de acesso a determinados segmentos. O presente estudo teve como objetivo validar uma técnica de biopsia intestinal, intracorpórea, assistida por videolaparoscopia, ainda não descrita na literatura, para coleta de fragmentos de mucosa de jejuno e cólon menor de equinos, que sejam considerados adequados para avaliação histológica. Para tanto, foram utilizados seis equinos machos, da raça Puro Sangue Árabe, com idade de dois anos, sem histórico prévio de doenças do trato digestório, com peso médio de 267 kg. Todos os animais foram submetidos ao mesmo procedimento laparoscópico, instituindo-se apenas jejum alimentar prévio de oito horas. Os equinos foram acompanhados com exame físico e de ultrassonografia abdominal, desde o dia precedente às laparoscopias, até o 15º dia do período pós-operatório, bem como avaliados por meio de hemograma, provas de funções hepática e renal, e análise do líquido peritoneal nos dias 0, 1, 2, 3, 5, 7, 10, 14, 21 e 30. O tempo cirúrgico foi cronometrado, sendo registrado o tempo total, iniciado na criação do primeiro portal de acesso e finalizado ao término da sutura de pele, e os tempos parciais para biopsia de jejuno e cólon menor separadamente, com início na apreensão do segmento intestinal e término quando constatada a polimerização da cola cirúrgica sobre o orifício de acesso da agulha. De cada segmento obtiveram-se dez fragmentos, e posteriormente submetidos à análise histológica. Atribuiu-se escore para cada um deles, sendo considerado 0 fragmentos com qualidade ruim; 1 para qualidade boa e 2 para qualidade ótima. Por sua vez, os considerados viáveis foram somente os que se enquadraram nos escores 1 e 2. Amostras avaliadas como adequadas 11 apresentaram no mínimo 50% dos fragmentos viáveis. A média do tempo total de procedimento foi de 66,50 minutos (± 7,87), enquanto a média do tempo parcial para biopsia de jejuno foi de 14,2 minutos (± 4,3) e a de cólon menor 12,7 minutos (± 5,0). Clinicamente, os animais apresentaram desconforto abdominal nas primeiras 48 horas. Os exames ultrassonográficos do abdômen não revelaram alterações condizentes com peritonite ao longo de todo experimento. Os parâmetros laboratoriais apresentaram apenas características inflamatórias, sendo que o líquido peritoneal permaneceu alterado até o 21º de pós-operatório, havendo normalização de todos os seus valores no 30º dia do estudo. Na inspeção laparoscópica de dois equinos (E2, E4) foi identificada aderência de porção de omento no diafragma. Nas avaliações histológicas de jejuno, uma amostra (E5) de seis foi considerada inadequada, com 5/12 fragmentos viáveis, e em cólon menor, duas (E1, E2) de seis, foram inadequadas, com 4/9 e 5/10 fragmentos viáveis respectivamente. A nova técnica de biopsia intestinal possibilitou a coleta de amostras adequadas de mucosa para análise histológica, de forma segura para os animais, uma vez que as alterações clínicas e laboratoriais foram aquelas relacionadas ao processo inflamatório, compatível com procedimentos laparoscópicos na espécie
Gastrointestinal diseases in horses result in high rates of morbidity and mortality, with different aetiologies. In some cases, an intestinal biopsy is needed to aid in the diagnosis of such diseases. However, the conventional techniques can pose risks to patients for being invasive or for not being elucidating due to having limitations in accessing certain segments. The objective of this study was to validate an intestinal biopsy technique, intracorporeal, assisted by laparoscopy, which has not yet been described in the literature, to collect mucosal fragments from the jejuno and small colon, which might be considered suitable for histological assessment. For such, six male horses were used, Arabian breed, with two years of age, without any records of abdominal diseases, weighing 267 kg in average. All horses were subjected to the same laparoscopic procedure, fasting for eight hours previously to the procedure. All horses were monitored through physical examination and abdominal ultrasonography, from the day previous to laparoscopy, until the 15th postoperative day, as well as hemogram, tests of liver and kidney functions, and analysis of the peritoneal fluid in days 0, 1, 2, 3, 5, 7, 10, 14, 21 and 30. The total laparoscopic procedure time was registered, starting at the moment of the first incision and ending at the moment of the skin closure. The partial times for the jejunal biopsy and small colon biopsy were recorded as well, starting at the grasping of the intestinal segment and ending at the moment of polymerization of the surgical adhesive on the needle access site. From each segment, ten fragments were collected and later subjected to histological analysis. A score was assigned for each one of them, being scored \"0\" fragments of poor quality; \"1\" fragments of good quality and \"2\" fragments of optimal quality. The samples considered viable were only the ones which scored 1 and 2. The samples deemed as adequate showed at least 50% of it fragments to be viable. The average of the surgery total time was of 66,50 minutes (± 7.87), whereas the average of the jejunal biopsy was of 14.2 minutes (± 4.3) and the small colon biopsy time was of 12.7 minutes ( ± 5.0). Clinically, the animals showed mild abdominal 13 discomfort in the first 48 hours. Ultrasonographic examination of the abdomen did not reveal any alterations consistent with peritonitis throughout the entire experiment period. Laboratory parameters presented inflammatory characteristics, and the peritoneal fluid remained altered until the 21th postoperative day, with normalization of all its values on the 30th day of the study. During the laparoscopic inspection of two horses (E2, E4) was identified partial omental adhesion with the diaphragm. In the jejunal histological evaluations, one sample (E5) of six was considered inadequate, with 5/12 viable fragments, and as for the small colon, two (E1, E2) of six were inadequate, with 4/9 and 5/10 viable fragments respectively. The new technique proposed allowed a safe collection of adequate mucosal samples for histological analysis, since clinical and laboratory abnormalities identified were related to the inflammatory process associated to the laparoscopic techniques in horses

Introdução O recurso à biopsia de nervo ou músculo, à electroneuromiografia e a exames analíticos é importante no processo de diagnóstico das patologias do Sistema Nervoso Periférico, nomeadamente miopatias e neuropatias. Tais exames possuem características diferentes e oferecem perspectivas igualmente distintas, muitas vezes decisivas para o correcto diagnóstico destas patologias. Objectivo O objectivo deste trabalho consistiu em saber se os resultados da biopsia de nervo ou músculo se correlacionavam com a hipótese clínica de diagnóstico e/ou com o resultado da electroneuromiografia, num grupo de doentes com patologia do Sistema Nervoso Periférico. Materiais e Métodos Foi realizado um estudo de casos, do qual fizeram parte 18 indivíduos que realizaram biopsia de nervo ou músculo entre os anos de 2003 e 2007, solicitada pelo Hospital Pêro da Covilhã. Os dados foram recolhidos entre Abril e Julho de 2009, através dos processos clínicos em papel e do Sistema de Apoio ao Médico e colocados em bases de dados. O tratamento desses dados foi realizado através dos programas informáticos Microsoft Excel e SPSS Statistics 17.0. Resultados A amostra era maioritariamente do sexo masculino (67%), com idades compreendidas entre os 22 e os 72 anos. Os sinais e sintomas mais evidentes consistiam na força diminuída (72%), nas alterações da sensibilidade (67%) e dos reflexos (39%) e no cansaço (50%). A miopatia era a hipótese de diagnóstico em 78% da amostra. As biopsias e electroneuromiografias mostraram diferentes percentagens de resultados anormais (39% e 92%, respectivamente). A baixa percentagem de biopsias anormais resultou num número baixo de casos (7 em 18) em que o resultado da biopsia coincidiu com a hipótese de diagnóstico. Igualmente baixo foi o número de casos (6 em 13) em que o resultado da biopsia foi coincidente com o resultado da electroneuromiografia. O teste do qui-quadrado, confirmado pelo rácio de verosimilhança (likelihood ratio), para os dados relativos à miopatia não revelou associação estatisticamente significativa entre o resultado da biopsia e a hipótese de diagnóstico. O estudo revelou uma associação estatisticamente significativa entre o resultado da biopsia e o resultado da electroneuromiografia, embora tal associação deva ser interpretada com cuidado. Conclusões Neste grupo de doentes, o resultado da biopsia não mostrou associação estatisticamente significativa com a hipótese de diagnóstico, tendo os resultados da biopsia coincidido com a hipótese de diagnóstico em 7 de 18 doentes. O resultado da biopsia mostrou associação estatisticamente significativa com o resultado da electroneuromiografia, embora os resultados de ambos os exames tenham sido coincidentes em apenas 6 de 13 doentes (3 com miopatia; 3 com neuropatia). Este estudo sugere que a biopsia de nervo ou músculo deve ser vista como meio complementar de diagnóstico da patologia do Sistema Nervoso Periférico, não sendo suficiente por si só para o diagnóstico final.
Introduction The use of nerve or muscle biopsy, electroneuromyography and analytical exams is important for the diagnostic process of the pathology of the Peripheral Nervous System, namely in terms of myopathy and neuropathy. Such exams have different features and provide different perspectives as well, which are often critical to the correct diagnosis of these pathologies. Objective The goal of this thesis consisted of assessing whether nerve or muscle biopsy results correlated with the clinical diagnostic hypothesis and/or with the electroneuromyographical results, as far as the pathology of the Peripheral Nervous System is concerned. Methods A study of cases was conducted, of which 18 individuals took part and in whom a nerve or muscle biopsy was performed between 2003 e 2007, requested by Pêro da Covilhã Hospital. The data were collected between April and June 2009, retrieved from the clinical files and also from the software Sistema de Apoio ao Médico and placed in a specially elaborated database. Processing of data was performed using the Microsoft Excel and SPSS Statistics 17.0 software. Results The sample was mostly male (67%), aged between the 22 and 72 years old. The most obvious signs and symptoms consisted of decreased strength (72%), changes in sensitivity (67%) and reflexes (39%) and fatigue (50%). Myopathy was the diagnostic hypothesis for 78% of the sample patients Biopsies and electroneuromyography exams showed different percentages of anomalies (39% and 92%, respectively). The low percentage of abnormal biopsies resulted in a low number of cases (7 out of 18) in which the biopsy result coincided with the diagnostic hypothesis. The number of cases (6 out of 13) in which the biopsy result coincided with that from the electroneuromyography exam was also low. The chi-square, confirmed by likelihood ratio, as applied to data related to myopathy, did not show a statistically significant association between the biopsy result and the diagnostic hypothesis. The study showed a statistically significant association between the biopsy result and the electroneuromyographical result, although such association needs to be interpreted with caution. Conclusions In this patient group, the biopsy result did not show a statistically significant association with the diagnostic hypothesis, with biopsy results coinciding with the diagnostic hypothesis in 7 out of 18 patients. The biopsy result showed a statistically significant association with the electroneuromyographical result, although the results of both exams were coincident in only 6 out of 13 patients (3 with myopathy; 3 with neuropathy). This study suggests that nerve or muscle biopsy should be seen as a complementary method of diagnosis of the pathology of the Peripheral Nervous System, but is not enough, on its own, for the final diagnosis.

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La biopsia percutánea guiada por tomografía es uno de los métodos principales y más frecuentemente utilizados para el estudio cito-histológico de las lesiones pulmonares, porque nos permite una adecuada caracterización y planificación con respecto a los otros métodos como son la fluoroscopia, ecografía o frente a la resonancia magnética. Sin embargo este procedimiento no está libre de complicaciones. El presente trabajo de tipo retrospectivo descriptivo tiene como objetivo determinar cuales fueron las complicaciones más frecuentes de acuerdo a la experiencia de la Clínica Ricardo Palma, sede central, durante el periodo comprendido del 1º de Enero del 2002 al 31 de julio del 2007. Se estudiaron todas las historias clínicas de aquellos pacientes que fueron remitidos al servicio de radiología intervencionista de la Clínica Ricardo Palma sede central, para que se les practicase una biopsia percutánea por presentar patología pulmonar y que no eran accesibles por otros métodos tales como la broncoscopía, fluoroscopia o ecografía. Las biopsias fueron realizadas con aguja de punción lumbar Nº 18, 20, o 22 , teniendo en cuenta, la localización, profundidad , dimensión, grado de colaboración del paciente, y experiencia del radiólogo y patólogo. Se hallaron 59 casos durante este periodo, 38 fueron varones (64.01%), y 21 fueron mujeres (35.59%) la edad variaba entre 42 y 89 años con una media de 68.4 años. El motivo principal fue el estudio de aquellas imágenes pulmonares sospechosas de malignidad y aquellos casos de infección pulmonar que pese al tratamiento no mostraron mejoría. La mayoría de las lesiones presentaban localización basal y el tamaño de la lesión a estudiar fue mayor de 3cm. Nueve pacientes presentaron complicaciones (15.2%) reportados en los 3 primeros años del procedimiento. La complicación más frecuente fue el neumotórax, hemoptisis y un paciente presentó dolor por 48 horas. Todas las muestras fueron obtenidas el mismo radiólogo que labora en el servicio de radiología intervencionista de la Clínica Ricardo Palma y remitidas a servicio de anatomía patológica quien reportó en todo momento que las muestras remitidas eran de tamaño y volumen suficiente. Concluye que las complicaciones de las biopsias pulmonares más frecuentes son el neumotórax y la hemoptisis observándose que en el presente estudio son operador dependiente, quien para evitarlas requiere de una buena caracterización de la lesión, experiencia del operador, colaboración del paciente y resolución del equipo.
Trabajo académico

El cáncer de mama es la neoplasia más frecuente en la mujer, que cada día se incrementa y afecta cada vez mas a grupos etarios menores y de ahí l a importancia de un método diagnostico rápido sencillo que permita al cirujano seleccionar mejor a sus pacientes, evitar las cirugías innecesarias disminuyendo los gastos que estas conlleven y las horas hombre perdidas y determinar el estudio del cáncer y permitir administrar un tratamiento adecuado de estos pacientes , siendo uno de los beneficios principales de la técnica de aspiración es que sin anestesia se puede llegar a un diagnostico rápido y económico de lesiones mamarias en pacientes ambulatorios siendo importante evaluar cuidadosamente estos beneficios con los posibles riesgos. El “blanco” mas evidente para aspirados , son las lesiones palpables que se abordan con gran facilidad mediante la técnica en la que se emplea aguja fina y permite la obtención de material fino permitiéndole al patólogo la visualización de las estructuras celulares que permitan un adecuado diagnostico de malignidad. En nuestro Hospital se esta realizando este tipo de procedimiento utilizando la técnica con aguja fina y un porta jeringas o manija la cual esta siendo realizada por Anatomos Patólogos entrenados en el procedimiento, abarcando glándulas tiroides y tumores de partes blandas, en contraposición con los Ginecólogos Oncólogos que realizan las aspiraciones en patología mamaria utilizando agujas de 18, y 21 , sin porta jeringa o manija. Como antecedentes se tiene trabajos realizados en este Hospital en patología tiroidea utilizando la técnica de aspiración con aguja fina y manija, los resultados están dentro de los reportados a nivel internacional de falsos positivos, falsos negativos, la efectividad y sensibilidad del proceso, este trabajo permitirá evaluar la sensibilidad y especificidad utilizando la técnica utilizada por Los ginecólogos Oncólogos de esta Institución.
Tesis de segunda especialidad

La patología pleural puede representar hasta un 30% de las interconsultas, a un servicio de neumología, en nuestro medio. (21, 32, 36, 43, 57, 60,62). De ahí la importancia de recordar la fisiología y fisiopatología de esta aún misteriosa membrana que envuelve los pulmones. Así, la pleura consta de dos porciones: la parietal y la visceral. Entre las dos pleuras, existe un espacio que anteriormente se consideraba virtual. En la actualidad, se sabe que este espacio es real, tiene 10 a 20 micras. El volumen del líquido pleural en estado normal es de 0.1 a 0.2 ml/Kg, de peso corporal, es de color claro, inodoro y su concentración proteica varía entre 1 y 1.5 g/100ml. En estado fisiológico, el líquido pleural contiene alrededor de 1,500 células por microlitro con predominio de monocitos (30 – 75 %) y de células mesoteliales (70%), escaso número de linfocitos (2 – 30%), neutrófilos (10%). Rara vez se encuentra polifomorfonucleares. No hay eritrocitos. El pH es alcalino, con una concentración de bicarbonato incrementada en un 20 al 25% con respecto a la plasmática, las concentraciones de cloro y sodio son ligeramente más bajas. Los niveles de potasio y glucosa de líquido pleural y plasma son prácticamente iguales, el de deshidrogenasa láctica (DHL) es inferior a la mitad del valor plasmático.
Tesis de segunda especialidad

La hipótesis del ganglio centinela formula que la diseminación de los tumores sólidos a través del sistema linfático no se produce al azar, sino que sigue un orden o patrón, específico para cada individuo. Si somos capaces de detectar cuál es el primer ganglio receptor, podremos biopsiarlo selectivamente sin tener que llevar a cabo la linfadenectomía regional completa, ya que éste es el ganglio con las máximas probabilidades de albergar una metástasis inicial y, si es negativo, también lo serán el resto de ganglios. El concepto fue propuesto formalmente por R. Cabañas (Cancer 1977) en relación al cáncer de pene. En 1992, D. Morton, cirujano de Santa Mónica, California, aplicó el mismo concepto a la diseminación linfática del melanoma cutáneo y utilizó colorantes quirúrgicos Arch Surg 1992). En 1993 Alex y Krag introdujeron el uso de coloides de tecnecio y de una sonda detectora (Surg Oncol 1993). Giuliano, publicó una primera serie en pacientes con cáncer de mama (Ann Surg 1994). El propio Giuliano describió la posibilidad de re-estadificar gracias a la detección de una frecuencia considerable de micrometátasis en el ganglio centinela (Ann Surg 1995).
HIPÓTESIS: El Ganglio Centinela predice con eficacia el estado de diseminación linfática regional en pacientes con cáncer de mama y, por tanto, su biopsia selectiva puede usarse para ahorrar el vaciado axilar. Además, la técnica permite mejorar la estadificación por reconversión N0 a N1. OBJETIVOS: 1. Comprobar la aplicabilidad de la biopsia del ganglio centinela en Nuestro medio. 2.Plantear la biopsia del ganglio centinela como alternativa a la linfadenectomía axilar convencional 3. Constatar la mejora de la estadificación
POBLACIÓN Y MÉTODOS: se estudiaron 132 pacientes, con edades entre 32 y 86 años (media 60,3).El 26,5% era lesiones no palpables y en el 58% se hizo cirugía conservadora. En estas pacientes se llevó a cabo la biopsia del ganglio centinela mediante la inyección peritumoral de coloides de tecnecio-gelatina, de 2 a 18 horas antes de la intervención. Se realizó linfogammagrafía prequirúrgica, en la que se identificó el ganglio centinela y se marcó el acceso cutáneo directo. Se practicó el vaciado axilar completo .Se calcularon los valores de verdaderos positivos (VP), verdaderos negativos (VN) y falsos negativos (FN) y los parámetros de sensibilidad (S) y valor predictivo negativo (VPN). Se calcularon los intervalos de confianza del 95% para estas proporciones (Diamon Am J Cardiol 1989). Además se llevó a cabo un meta-análisis de acuerdo con las recomendaciones de Irwing (Ann Intern Med 1994).
RESULTADOS: Se biopsiaron 2,0"1,4 ganglios centinela por paciente y 12,6 " 5,1en el resto del vaciado axilar. La tasa de detección del ganglio centinela fue del 96,2%. La localización de los ganglios centinela fue: 73% nivel I, 21% mamaria interna, 6% otros. Se observaron 48 VP, 77VN y 2 FN. La S fue del 96% (IC 85-99) y el VPN del 97,3% (IC 94 -100). Hubo 7 casos de restadificación. En el meta-análisis se identificaron 18 series de más de 50 pacientes, a las que se añadió la nuestra. Se aplicó el modelo de "pooled data analysis"; con 2.569 pacientes, la S fue del 91% (IC 89 - 93). El área bajo la curva SROC fue 0,9967.
CONCLUSIONES: La hipótesis del Ganglio Centinela es válida en pacientes con cáncer de mama; la biopsia del ganglio centinela es predictora de la diseminación linfática. Tomando el vaciado axilar como estándar de referencia, los resultados indican un alto rendimiento diagnóstico. La biopsia del Ganglio Centinela comporta una marcada "Curva de Aprendizaje"y un proceso de validación local. No debe abandonarse la práctica del vaciado axilar convencional en tanto no se cumplan estos requisitos. La Biopsia del Ganglio Centinela constituye un método superior de estadificaciónen pacientes con cáncer de mama, abriendo la posibilidad de llegar a una verdadera microestadificación.
Under the sentinel lymph-node hypothesis, dissemination of tumors through the lymphatic system does not happen randomly, but rather it is an orderly process that is given by a specific pattern of progression for each subject. The sentinel node is the regional lymph-node with the highest probability of harbouring an initial mestastasis. If we detect the first draining node, then it can be selectively excised without the need for a complete lymph node dissection. The sentinel node concept was formally proposed by R. Cabañas (Cancer 1977). In 1992, D. Morton took this concept to the field of the lymphatic spread of cutaneous melanoma, and used for first time a blue dye during surgery for that purpose (Arch Surg 1992). The use of technetium-colloids associated with a surgical gamma probe was introduced by Alex and Krag in 1993 (Surg Oncol 1993). Giuliano, reported the first impact series of sentinel node biopsy in breast cancer patients (Ann Surg 1994). Again, Giuliano stressed the upstaging effect of the technique by an increased detection rate of micrometastases in the sentinel node (Ann Surg 1995).
HYPOTHESIS: The sentinel node can effectively predict lymph-node status in breast cancer patiens, therefore sentinel node biopsy can be used to spare axillary dissection. Furthermore, this technique affords a better staging by a significant Stage I-to-Stage II shift. OBJECTIVES: 1. To test the feasability of sentinel lymph-node biopsy in our own clinical setting. 2.To propose the sentinel node biopsy as an alternative to axillary dissection. 3 To show an increased staging power of the technique.
PATIENTS AND METHODS: included were 132 patients, aged 32 to 86 years (mean 60,3 years) . 26,5% of them presented with non-palpable lesions. In 58% of the patients breast conserving surgery was performed. Sentinel node biopsy was done after peritumoral injection of technetium colloids, 2 to 18 hours before surgery. Presurgical lymphoscintigraphy was always performed. The sentinel node was then identified and a sking marking was done for a direct surgical access. The sentinel node was excised with the aid of a 14 mm gamma probe. A full axillary dissection then ensued .The following values were calculated: true positives (TP), true negatives (TN), and false negatives (FN), as well as sensitivity (S) and negative predictive value (NPV). 95% confidence intervals were also calculated (Diamon Am J Cardiol 1989). A meta-analysis of data reported in english-written literature was done according to the recommendations by Irwing (Ann Intern Med 1994).
RESULTS: 2,0"1,4 sentinel nodes were harvested per patient, as well as 12,6 " 5,1 in the rest of the axillary dissection. Our sentinel node detection rate was 96,2%. Sentinel nodes were located as follows: 73% at level I, 21% at the internal mammary chain, 6% other. The following values were obtained: 48 TP, 77 TN and 2 FN. The S was 96% (CI 85-99) and the NPV 97,3% (CI 94 -100). There were 7 upstaged cases. In the meta-analysis, 18 series were identified containing more than 50 patients each, to which we added our own. A model of "pooled data analysis" was applied. With 2.569 patients, S was 91% (CI 89 - 93). The area under the SROC curve was 0,9967.

CONCLUSIONS: The sentinel node hypothesis applies in breast cancer patients. Sentinel node biopsy is predictive of the lymph-node status. Taking the axillary dissection as the gold standard, our results show a high diagnostic performance of the technique. Sentinel node biopsy is associated with a considerable "learning curve" and needs a local validation process. Axillary dissection must not be abandoned before such goals have been achieved at the local level. Sentinel node biopsy is a superior method for staging in early breast cancer patients, and leads the way for the true patient microstaging

El OBJETIVO principal ha sido analizar la utilidad de la detección radioisotópica y biopsia selectiva del ganglio centinela en pacientes con carcinoma no palpable de mama y comparar los resultados obtenidos en este grupo con los resultados obtenidos en el grupo de pacientes con tumores palpables de mama.

MATERIAL Y MÉTODO
Se ha estudiado 199 pacientes con carcinoma de mama operable a las que se realizó biopsia selectiva del ganglio centinela y linfadenectomía axilar. Se ha dividido la muestra en dos grupos: pacientes con carcinoma no palpable de mama y pacientes con carcinoma palpable de mama.
Para la linfogammagrafía se utilizó 99mTc - nanocoloide de albúmina (111MBq en 1 ml), administrado peritumoralmente, ecoguiada en los tumores no palpables y dirigida mediante palpación en el resto. A partir de los 90 - 120 minutos de la inyección tuvo lugar la adquisición gammagráfica. Se utilizó una fuente plana de Cobalto 57 para delimitar el contorno anatómico de la paciente. Se trabajó con un modelo de sonda EUROPROBER. La cirugía tuvo lugar entre 18-24 h de la linfogammagrafía en las pacientes con tumor palpable y a las 4 h en las pacientes con tumor no palpable. El análisis histopatológico del ganglio centinela se realizó mediante impronta peroperatoria y estudio diferido (Hematoxilina-eosina, inmunohistoquímia de citoqueratinas y estudio mecular). Se analiza: el porcentaje de detección gammagráfica y quirúrgica y la vía de drenaje del ganglio centinela según la palpación del tumor y su localización en la mama; los verdaderos positivos, verdaderos negativos, falsos negativos, la sensibilidad, el valor predictivo negativo, la tasa de falsos negativos y la precisión global de la técnica.
RESULTADOS: Indistintamente de la presentación clínica del tumor, la distribución de las pacientes por edades ha sido muy parecida; no se ha observado diferencias estadísticamente significativas (p > 0,05) en la detección gammagráfica y quirúrgica del ganglio centinela, ni en cuanto a la existencia de drenaje a mamaria interna (p = 0,211). A pesar de ello sí que se ha observado una mayor tendencia a visualizar la presencia de ganglios centinela en la región de la cadena mamaria interna en el grupo de CNPM (11,7%) en relación a las pacientes con lesiones palpables (6,4%). En relación a la prevalencia de afectación metastásica axilar se ha encontrado diferencias estadísticamente significativas (p = 0,019) entre los dos grupos, siendo menor en el grupo de pacientes con lesiones no palpables de mama. Se ha obtenido resultados similares de sensibilidad, valor predictivo negativo y precisión global de la técnica del GC, con valores mayores de 90%, así como una tasa de falsos negativos inferior al 5% en los dos grupos
Conclusiones: La fiabilidad de la técnica es similar en las dos poblaciones estudiadas. La presencia de metástasis "en salto" ha sido similar en los dos grupos, no superando el 3%. Indistintamente de la palpación del tumor, todos los cuadrantes pueden drenar a la axila y a la mamaria interna, predominando sin embargo el axilar. En tumores de localización interna y en tumores no palpables el drenaje a mamaria interna se observa con mayor frecuencia. La detección del ganglio centinela es menor en los tumores de CSE. La quimioterapia primaria parece tener relación en la no detección del ganglio centinela. En un elevado número de pacientes con gammagrafía negativa, la cirugía logra localizar el ganglio centinela, siendo mayor este número en el caso de pacientes con CNPM (60% CNPM vs 43% CPM). La prevalencia de metástasis axilares es menor en las pacientes con lesiones no palpables de mama, siendo estas las que más se benefician de la técnica, evitándose en ellas hasta el 45% de linfadenectomías innecesarias.
LINFOSCINTIGRAPHY and SENTINEL NODE BIOPSY IN NONPALPABLE BREAST CANCER.

OBJECTIVE: The aim of the study was to evaluate the efficay of lymphatic mapping and sentinel node biopsy in nonpalpable breast cancer (NPBC) patients in comparison with palpable breast cancer patients (PBC).
MATERIAL and METHODS: 199 breast cancer patients were studied. Patients were classified into two groups: nonpalpable breast cancer and palpable breast cancer. Following tomorectomy and sentinel node biopsy all patients underwent axillary lymphadenectomy. Lymphoscintigraphy was performed 90-120 minutes after peritumoral injection of 111MBq 99mTc - nanocolloid in 1 ml in PBC (under US guidance in NPBC). Surgery was performed at 18-24 h after lymphoscintigraphy in PBC patients and at 4 h after lymphoscintigraphy in NPBC patients; a gammaprobe was used to localise sentinel node. Hystopathological sentinel node analysis was performed as follows: intrasurgical stydy (citologycal impront) and delayed study (Haematoxylin-eosin, immunohistochemistry of cytokeratin and mecular study). The following parameters were analysed in both groups: scintigraphic and surgical detection rates, true positives, true negatives, sensitivity, predictive negative value, false negative rate and global precision of the technique.
RESULTS: The age of the patients was similar in both groups. Non significant difference was observed (p > 0,05) in lymphoscintigraphy or surgical sentinel node detection. Drainage to internal mamarian chain (p = 0,211) was more frequently seen in NPBC group (11,7%) versus (6,4%) PBC group, but differences were not significant. Metastasic axillary prevalence was lower in NPBC group (p = 0,019). Similar sensityvity, negative predictive value and global precision values (>90%) and false negative rate (< 3%) were found in both groups.
CONCLUSIONS: Technique fiability and was skip metastases rate were similar in both groups. Independly of quadrant location all tumors drained primarly to axillary region. Drainage to internal mamarian chain was more frecuently seen in internal as well as in nonpalpable tumor. Chemotherapy seems to be related with higher non sentinel node detection.

Orientadores: Aarão Mendes Pinto-Neto, Lucia Helena S. da Costa-Paiva
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: O objetivo deste estudo foi o de avaliar a eficácia da histeroscopia associada à biópsia endometrial como método propedêutico em pacientes com sangramento pós-menopausa. Utilizou-se como padrão-ouro o resultado histológico do material obtido através da curetagem uterina fracionada. Foram avaliadas no Centro de Atenção Integral à Saúde da Mulher 453 mulheres que apresentaram sangramento pós-menopausa, com idade superior a 45 anos, com amenorréia no mínimo por 12 meses e que não estavam utilizando terapia de reposição hormonal. Todas as pacientes foram submetidas à histerosçopia ambulatorial com biópsia de endométrio, seguida de curetagem uterina. Os principais diagnósticos histeroscópicos foram os de atrofia endometrial (55,6%), endométrio funcional (24,9%), hiperplasia ...endometrial (12,4%), câncer de endométrio (7,1%), pólipos (38,1%) e miomas (2,6%). Em 1,32% dos casos, a histeroscopia foi inconclusiva devido a dificuldades técnicas. Os dados foram analisados em quatro etapas, sendo que na primeira delas foi efetuado um teste de validação diagnóstica da histeroscopia, com cálculos de sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e estudo das ,razões de verossimilhança para cada diagnóstico histológico. Observaram-se alta sensibilidade e especificidade da histeroscopia para todos os diagnósticos. Em uma segunda etapa, foi feita uma análise para validação diagnóstica da biópsia de endométrio como método propedêutico para a avaliação endometrial. Assim como para a histeroscopia isoladamente, a biópsia de endométrio apresentou uma alta sensibilidade e especificidade para todos os diagnósticos, exceto para o de pólipo endometrial. A comparação entre os valores de sensibilidade e de especificidade da histeroscopia isoladamente e da biópsia de endométrio mostra que a biópsia apresenta, de uma maneira geral, maior segurança diagnóstica, à exceção dos casos de pólipos endometriais. Finalmente, foi realizada uma análise dos dois métodos associados, a qual demonstrou que, quando houve concordância entre os diagnósticos histeroscópicos e os obtidos através da histologia do material da biópsia endometrial, as probabilidades de comprovação das alterações foram maiores, sobretudo nos casos de lesões extremas, como a atrofia e o câncer de endométrio. Concluiu-se que a histeroscopia ambulatorial, associada à biópsia de endométrio, apresenta segurança no diagnóstico do sangramento pósmenopausa, podendo substituir a curetagem uterina evitando os custos de internação ospitalar, além do risco anestésico cirúrgico
Abstract: This study aimed to evaluate the effectiveness of hysteroscopy combined to endometrial biopsy as a propaedeutic method in patients with postmenopausal bleeding. The histological results of the samples obtained through fractionated uterine curettage were utilized as gold standard. A total of 453 women older than 45 years of age, presenting postmenopausal bleeding, am~norrhea for a minimum of 12 months, and not using hormonal replacement therapy were evaluated. Each patient was submitted to an outpatient hysteroscopy with an endometrial biopsy, followed by a uterine curettage. 'The main hysteroscopic diagnoses found were, endometrial atrophy (55.6%), functional endometrium (24.9%), endometrial hyperplasia (12.4%), endometrium cancer (7.1 %), polyps (38.1 %) and myoméls (2.6%). The hysteroscopy was inconclusive in 1.34% of the cases due tp technical difficulties. The data were analyzed in four stages. In the first of them, a diagnostic validation test of the hysteroscopy was performed by calculating sensitivity, specificity, positive predictive value, negative predictive value, and studying the likelihood reasons for each histological diagnosis. High sensitivity and specificity were observed in the hysteroscopy of each diagnosis. In a second stage, an analysis was performed for the diagnostic validation of the. endometrial biopsy as a propaedeutic method for the endometrial evaluation. Like hysteroscopy alone, the endometrial biopsy presented high sensitivity and specificity for ali diagnoses, except for the endometrial polyp one. The comparison between the sensitivity and specificity values of hysteroscopy alone and the endometrial biopsy ones normally shows that biopsies present higher diagnosis certainty, except for endometrial polyp cases. Finally, an analysis of the two methods combined was performed showing that whenever concordance was found between the hysteroscopic diagnoses and the ones obtained through a histology of the endometrial biopsy samples, the probability of the confirmation of changes was greater, especially in the cases of extreme lesions like atrophy and endometrial cancer. Therefore, we conclude that the outpatient hysteroscopy combined to an endometrial biopsy presents a diagnosis certainty of postmenopausal bleeding, and can substitute uterine curettage, avoiding hospitalization costs and the risk of surgical anesthesia
Doutorado
Doutor em Tocoginecologia

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OBJECTIVE: Evaluating the kit-Bh performance in carrying out of breast biopsies. METHODS: They were randomly selected a sample of 30 patients with breast cancer undergoing mastectomy, based on the results of a pilot study from February 2008 to April 2010. They were excluded women with had not palpable, stone-hard consistency tumors, previous surgical manipulation or that contains liquid. Using the helicoid biopsy Kit (kit Bh) and an equipment Core biopsy with cannula and needle and 14 gauge respectively, it was collected a fragment of sound equipment in the area and in tumors in each specimen, totaling 120 fragments for histological study. For data analysis, it was defined a 95% confidence level and used the SPSS-13 version, the Kappa index and the parametric Student t test. RESULTS: Mean age of patients was 51.6 years (? 11.1 years). The infiltrating ductal carcinoma showed a higher incidence, 26 cases (86.7%). The Core biopsy had a sensitivity of 93.3%, specificity of 100% and accuracy 96.7%, while the helicoid biopsy had a sensitivity of 96.7%, specificity of 100% and accuracy 98.3%. By comparing the histology of tumors and the fragments of biopsies, there was high degree of agreement in diagnoses (kappa of 0.93 with p <0.05) CONCLUSION: Both devices provided the histological diagnosis of lesions with high accuracy. Results of this study showed that the helicoid biopsy is a reliable alternative in 22 the preoperative diagnosis of breast lesions. Further studies in vivo better will define the role of Kit Bh in the diagnosis of these lesions
OBJETIVO: avaliar o desempenho do Kit Bh na realiza??o de biopsias mam?rias. M?TODOS: de fevereiro de 2008 a abril de 2010, com base nos resultados de um estudo piloto, selecionou-se aleatoriamente uma amostra composta de 30 pacientes portadoras de c?ncer de mama submetidas a mastectomia. Exclu?ram-se as mulheres portadoras de tumor que tivesse consist?ncia p?trea, n?o palp?vel, com manipula??o cir?rgica pr?via ou que contivesse l?quido. Utilizando-se o Kit de biopsia helic?ide ( Kit Bh ) e um equipamentos de Core biopsy com c?nula e agulha de 14 gauge respectivamente, coletou-se um fragmento por equipamento em ?rea s? e nos tumores, em cada pe?a cir?rgica, totalizando 120 fragmentos para estudo histol?gico. Para a an?lise dos dados definiu-se um n?vel de confian?a de 95% e utilizou-se o software SPSS-vers?o 13, o ?ndice de concord?ncia Kappa e o teste param?trico t de Student. RESULTADOS: a m?dia das idades das pacientes foi de 51,6 anos (? 11,1 anos). O Carcinoma ductal infiltrante apresentou maior incid?ncia, 26 casos (86,7%). A Core biopsy apresentou sensibilidade de 93,3%, especificidade de 100% e acur?cia de 96,7%, enquanto a Biopsia helic?ide teve sensibilidade de 96,7%, especificidade de 100% e acur?cia de 98,3%. Na compara??o entre a histologia dos tumores e dos fragmentos de biopsias houve alto grau de concord?ncia nos diagn?sticos ( Kappa igual a 0,93 com p<0,05) CONCLUS?ES: ambos os equipamentos proporcionaram o diagn?stico histol?gico das les?es com alta acur?cia.Os resultados deste estudo demonstraram que a biopsia helic?ide ? uma alternativa confi?vel no diagnostico pr?-operat?rio de les?es mam?rias. Estudos mais aprofundados in vivo, definir?o melhor o papel do Kit Bh no diagn?stico dessas les?es

Objetives. To evaluate the clinical, epidemiological and endoscopic characteristics of the Helicobacter pylori (Hp) negative peptic ulcer disease. Methods. In this cross sectional study we included 651 patients diagnosed of peptic ulcer disease between January 2000 and December 2005. The diagnosis of Hp infection was established by histology. Clinical and epidemiological characteristics of patients with and without Hp infection were compared. Results. Males prevailed (69%). Hp negative ulcers were older (57,73 +/- 19,44 years old vs 50,26 +/- 18, 64 years old, P < 0.001). Clinical characteristics did not differ among both groups. Duodenal ulcer prevailed in Hp positive patients (56,5%) and gastric ulcer in Hp negative patients (53,5%). Multiple ulcers and intestinal metaplasia were more frequently found in Hp negative cases [9.3% vs 4.5 % (P = 0,015) and 34.5% vs 22.1% (P = 0,001), respectively]. Conclusion. Hp negative peptic ulcer disease is found in older patients, with a higher frequency of gastric ulcers, multiple lesions and intestinal metaplasia.
Revisión por pares

Sinais clínicos de dispepsia são frequentemente observados em pequenos animais, recomendando-se nesses pacientes a pesquisa de Helicobacter sp., pois esse agente pode estar associado com a ocorrência desses distúrbios. Há poucos relatos de isolamento dessa bactéria em animais no Brasil. Portanto, o objetivo do estudo foi investigar a presença de Helicobacter sp. em pacientes com indicação de endoscopia digestiva alta, atendidos no Hospital de Clínicas Veterinárias da Universidade Federal do Rio Grande do Sul, empregando os métodos diagnósticos mais comumente adotados para sua detecção. Foram colhidos fragmentos de biópsia gástrica de um total de 30 cães e gatos submetidos à endoscopia, que não faziam uso de medicação antimicrobiana e inibidores de bomba de prótons no período mínimo de quatro semanas anteriores à coleta. Os fragmentos foram submetidos ao teste rápido da ureia (URT), colorações histológicas (H&E, Warthin Starry-WS), imunohistoquímica (IHQ), semi-nested PCR, tendo como alvo o gene 16SrRNA e cultura. Foram considerados positivos para Helicobacter sp. os pacientes que apresentaram resultado positivo em pelo menos dois métodos diagnósticos. Em apenas três animais foram detectadas lesões macroscópicas durante a endoscopia e 17 apresentaram lesões histopatológicas na mucosa do estômago. O URT foi positivo em 25 amostras e Helicobacter foi isolado de oito animais. Lâminas coradas por H&E e WS monstraram bactérias com morfologia compatível em 20 e 26 amostras, respectivamente. As técnicas de IHQ e semi-nested PCR resultaram positivas em 27 e 28 amostras, respectivamente. Ao todo, 28 pacientes foram considerados positivos, sendo que IHQ e semi-nested PCR detectaram 96,4% e 100% desses, respectivamente. Dessa forma, conclui-se que ambas as técnicas podem ser recomendadas para a detecção de Helicobacter em pequenos animais. A presença de Helicobacter sp. pode ter causado os sinais gastrintestinais apresentados por cães e gatos incluídos no estudo, porém em muitos pacientes sintomáticos houve presença da bactéria na ausência de lesões microscópicas detectáveis.
Dyspepsia signs are frequently observed in small animals. In these patients, Helicobacter sp. investigation is recommended, since this pathogen may be associated with the occurrence of this kind of disorders. In Brazil there are few reports of Helicobacter sp. detection in small animals. Therefore, the aim of the study was to investigate the presence of Helicobacter sp. by the most common methods adopted for diagnosis in patients referred for upper endoscopy at the Veterinary Hospital of the Federal University of Rio Grande do Sul. Thirty patients, which had not been using any antimicrobial drugs and proton pump inhibitors for at least four weeks prior the endoscopy, were selected for this study. The biopsy fragments were submitted to rapid urea test (URT), histological staining (H&E, Warthin Starry- WS), immunohistochemistry (IHC), semi-nested PCR targeting the 16S rRNA gene and culture. Patients that tested positive in at least two diagnostic methods were considered positive for Helicobacter sp. Macroscopic lesions were detected in only three animals during endoscopy, and seventeen had histopathological lesions in the stomach mucous. The URT resulted in 25 positive samples, while Helicobacter sp. was isolated from only eight patients. Histological staining (H&E and WS) showed bacteria with typical morphology in 20 and 26 samples, respectively. The IHC and semi-nested PCR were positive in 27 and 28 samples, respectively. A total of 28 patients were considered positive; among them IHC and semi-nested PCR resulted positive in 96.4% and 100%, respectively. In conclusion, both techniques can be recommended for Helicobacter sp. detection in small animals. Helicobacter infection may have been the cause of gastrointestinal signs detected in patients; however many symptomatic animals without microscopic lesions were also diagnosed positive.