Dissertations / Theses on the topic 'Pneumonectomy'

A utilização das ressecções pulmonares em cães e gatos, quer sejam por lobectomia ou pneumonectomia, é realizada no intuito de cura ou paliação de processos broncopulmonares sempre que os meios conservadores de tratamento clínico sejam considerados ineficientes. Tendo em vista as significativas modificações que a pneumonectomia acarreta, novos estudos experimentais devem ser feitos para elucidar as vantagens desta intervenção cirúrgica, bem como aplicá-la com a devida segurança. O presente estudo tem como objetivo avaliar as alterações eletrocardiográficas e as alterações histopatológicas no pulmão esquerdo de cães submetidos à pneumonectomia direita. Foram utilizados dez cães, machos ou fêmeas, adultos, sem raça definida e pesando entre dez e trinta quilos. Foram avaliados os parâmetros clínicos do animal diariamente, as alterações em todas as derivações do eletrocardiograma e realizado estudo morfométrico de pulmão esquerdo bem como descrição das principais alterações histopatológicas. Foram descritos tópicos importantes da técnica cirúrgica que colaboram na prevenção de intercorrências trans e pós-operatórias. Todos os animais apresentaram boa evolução pós-operatória. Quanto à análise eletrocardiográfica, apenas um animal apresentou alteração de relevância clínica, sendo a ausência de alterações, a maioria dos casos. Presenciamos um caso de Complexos Ventriculares Prematuros decorrente à parada cardiorrespiratória revertida com sucesso. Verificamos diminuição da amplitude dos Complexos QRS nos primeiros 14 dias, retornado após 60 dias de pós-operatório. Quanto à descrição histopatológica, foram presenciados processos de hiperinsuflação ou alterações parenquimatosas não expressivas. Na análise morfométrica,as artérias intra-acinares indicaram aumento significante da porcentagem de espessura após pneumonectomia direita. As artérias com diâmetro 0-50 &micro;m apresentaram os maiores valores tanto nos períodos pré e pós-operatório, mas a taxa de aumento (%) foi mais evidente nas artérias com diâmetro maior de 100 &micro;m.<br>The intention of the use of pulmonary resections in dogs and cats, either lobectomy or pneumonectomy, is the cure or palliation of bronchopulmonary processes whenever the conservative clinical treatment means are considered ineffective. Bearing in mind the significant alterations that the pneumonectomy causes, new experimental studies must be done to elucidate the advantages of this surgical intervention, as well as perform it without any risk. The aim of the current study is to evaluate both the eletrocardiographical and the histopathological alterations in the lungs of dogs that were undergone a right pneumonectomy. Ten either male or female adult mongrel dogs weighing between ten and thirty kilos were investigated. The clinical parameters of the animals and the alterations in every eletrocardiogram derivation were evaluated day after day, and a left lung morphometrical study and the description of the main histopathological alterations were made, as well. Important topics of the surgical technique that contribute to prevent the trans and post-operative complications were described. All the animals presented a good post-operative outcome. As for the eletrocardiographical analysis, few of them were of clinical significance and in most cases there were no alterations. We observed a premature ventricular complex case resulted from a cardiorrespiratory arrest that was reverted to successfully. We found out decrease of QRS Complex Amplitude on the 0-14 days, and it returned to normal after sixty post-operative days. As for histopathological description, neither significant hiperinsuflation processes nor parenquimatous alterations were practically observed. In the morphometric analysis, the intra-acinar arteries showed, a significant increase of the thickness percentage after right pneumonectomy. The arteries with diameter 0-50&micro;m presented the most values either period pre or post-operative, but increase rate (%) was more evident in the greater than 100 &micro;m diameter arteries.

Introducción En el tratamiento quirúrgico del cáncer pulmonar la neumonectomía es un procedimiento esporádico y clásicamente relacionado con mayor morbimortalidad respecto a otro tipo de resecciones. El objetivo de este estudio fue evaluar en este tipo de pacientes, los factores pronósticos relacionados a la morbilidad y mortalidad. Pacientes y Métodos Se desarrolló un estudio retrospectivo, observacional, descriptivo, de 380 pacientes consecutivos, intervenidos en el servicio de cirugía torácica del Hospital Vall d´Hebron entre 1993 y 2013. Se aplicaron pruebas tanto de asociación entre variables, como univariante y multivariante para supervivencia y tiempo libre de enfermedad. Resultados Fueron mayor la prevalencia de pacientes hombres, resecciones derechas y las de tipo convencional, la media de edad fue 61 años. Las complicaciones postoperatorias se presentaron en un 24.2% y la mortalidad peroperatoria y subsecuente fue de 5% y 62% respectivamente. La estirpe más habitual fue Carcinoma Escamoso (56.6 %), y el estadio oncológico IIIA, mayormente en tumores T2, con una media de compromiso N2 de 34.6%. El 55.7% recibió neoadyuvancia y el 57.3% adyuvancia. Se encontraron los siguientes factores de riesgo en función del riesgo de recidiva y muerte: edad superior a 70 años, antecedente de arritmia, neumonectomía derecha, afectación N2, presencia durante el ingreso de distres, infarto al miocardio o necesidad de ventilación mecánica, estadios oncológicos avanzados, y la utilización de adyuvancia. Conclusiones Consideramos que existen factores pre y transoperatorios que influyen tanto en la evolución peroperatoria como en la posterior; impactando directamente en la supervivencia y el tiempo libre de enfermedad y deben ser tomados en cuenta por el equipo médico quirúrgico.<br>Introduction In the surgical treatment of lung cancer pneumonectomy is a procedure typically sporadic and related to higher morbidity and mortality compared to other resections. The aim of this study was to evaluate in these patients, the prognostic factors related to morbidity and mortality. Patients and Methods A retrospective, observational, descriptive study, with 380 consecutive patients who underwent surgery in the thoracic surgery unit at the Hospital Vall d'Hebron between 1993 and 2013. Both tests of association between variables were applied, such as univariate and multivariate survival and disease-free time. Results They were the highest prevalence of male patients, right resections and conventional type, the mean age was 61 years. Postoperative complications occurred in 24.2% and perioperative and subsequent mortality was 5% and 62% respectively. The most common tumor type was Squamous Cell Carcinoma (56.6%), and cancer stage IIIA, mostly in T2 tumors, with an average of 34.6% N2 commitment. Received neoadjuvant 55.7% and 57.3% adjuvant. The following risk factors depending on the risk of recurrence and death were found: over 70 years of age, history of arrhythmia, right pneumonectomy, N2 disease, presence of distress during admission, myocardial infarction or need for mechanical ventilation, advanced cancer stages, and the use of adjuvant. Conclusions We believe that there are pre- and intraoperative factors that influence both perioperative evolution and the back; directly impacting the survival and disease-free time and they must be taken into account by the surgical medical team.

Male and female Sprague-Dawley rats matched for litter and body weight, were subjected to left pneumonectomy and sham operations at four weeks of age. Three weeks following surgery, rats were sacrificed, and somatic and lung growth, pressure-volume curves, biochemical, and morphometric parameters were measured. Females weighed 48% less than males at the end of the experiment. Somatic growth of neither sex was effected by pneumonectomy. Following pneumonectomy, lung weight and lung volume increased significantly and matched that of both lungs of the sham-operated group in both sexes. The absolute amount of DNA and protein content also increased but was significantly less than that of both lungs of shams. Since females weighed less, absolute lung weight, lung volume, DNA and protein content increased more in males but specific parameters (i. e. values/ 100 g body weight) increased significantly less compared to females. This occurred because specific lung weight and volume decreased with increasing body weight. Mean linear intercept and mean chord length of alveoli were increased. Alveolar surface area increased by 51% in males and 31% in females, and matched that of both lungs of shams in males but not in females. The total number of alveoli increased 15% and 18% in males and females respectively and was significantly less compared to both lungs of shams in both sexes. After pneumonectomy, the post-caval lobe increased in volume 70% and 73% in males and females respectively as compared to a 60% and 47% increase in total lung volume. The mean linear intercept and mean chord length of alveoli increased less in the upper and lower lobes compared to the middle and post-caval lobes in males as well as in females. The number of alveoli per unit volume decreased more in middle and post-caval lobes compared to the upper and lower lobes in both sexes. In sham-operated male rats the upper and lower lobes had a smaller mean linear intercept and mean chord length of alveoli compared to the post-caval lobe. Postpneumonectomy, loss of elastic lung recoil at mid-volumes was observed in females. It was inferred that compensatory response following pneumonectomy was in general similar in males and females. While there was an evidence of alveolar multiplication, simple dilation of airspaces occurred and this was the dominant effect especially in females. In certain aspects (weight, volume) compensatory growth was complete but in most (DNA. protein, morphometry) was not. Male and female differences could not account for differing results in the literature concerning completeness or otherwise of lung compensatory growth.<br>Medicine, Faculty of<br>Pathology and Laboratory Medicine, Department of<br>Graduate

INTRODUÇÃO: A pneumonectomia está associada à alta mortalidade e alto índice de complicações. Entre estas, o edema pulmonar pós-pneumonectomia é uma das mais graves, podendo chegar a 100% de mortalidade. Pouco se sabe acerca dos fatores etiológicos desta doença, bem como sua associação a um processo inflamatório ou estresse oxidativo. O objetivo deste estudo foi analisar os efeitos agudos da pneumonectomia esquerda sobre o pulmão remanescente de ratos quanto à avaliação funcional por gasometria e avaliação histológica por formação de edema, infiltrado inflamatório, estresse oxidativo e reatividade vascular. MÉTODOS: Trinta e um ratos Wistar foram submetidos ao estudo. Vinte e um foram submetidos à pneumonectomia esquerda, sendo sacrificados em 48 horas (11 animais) e 72 horas (10 animais). Como controle do tratamento, 10 ratos foram submetidos à operação sham, sendo 5 sacrificados em 48 horas e 5 em 72 horas. A avaliação funcional foi realizada por meio de coleta de sangue arterial, gasometria e análise da relação pO2/FiO2. A análise histológica consistiu da avaliação dos seguintes parâmetros: (1) grau de edema perivascular; (2) presença de infiltrado inflamatório obtido por meio da densidade de neutrófilos; (3) expressão tecidual imunoistoquímica da Óxido Nítrico Sintase (NOS) para a avaliação do estresse oxidativo e (4) do grau de reatividade vascular, medido por meio da relação luz parede (lumen/wall ratio). Na avaliação do estresse oxidativo, foram analisadas a isoformas induzida e endotelial da NOS (iNOS e eNOS). Além destes parâmetros, o edema pulmonar foi avaliado por meio do ganho de massa pulmonar proporcional, denominado de Índice Pulmonar (IP) e da relação do peso úmido e do peso seco (Razão U/S). A análise estatística foi realizada por meio do teste ANOVA. RESULTADOS: Não houve diferença entre os grupos quanto à relação pO2/FiO2. Quanto à análise histológica, houve diferença quanto ao edema perivascular, infiltrado inflamatório, imunoexpressão de iNOS e eNOS e reatividade vascular. Houve interação entre a pneumonectomia e o sacrifício mais tardio, com maior índice de edema perivascular neste grupo (p=0,0274). Houve menor densidade de neutrófilos nos animais submetidos à pneumonectomia tanto em 48 como 72 horas (p=0,0168). Não houve diferença na imunoexpressão tecidual de iNOS entre os animais submetidos à pneumonectomia e seus respectivos grupos controle, mas houve diminuição no grupos de 72 horas (p=0,0212). A análise imunoistoquímica da eNOS evidenciou maior expressão nos animais submetidos à pneumonectomia (p=0,0208). Quanto ao grau de reatividade vascular, houve menor razão L/P nos grupos sacrificados após 72 horas (p=0,0107), sugerindo maior vasoconstrição nestes grupos. Embora tenha havido maior ganho de massa pulmonar nos dois grupos de animais submetidos à pneumonectomia (p=0,0033), a Razão U/S não mostrou diferença entre os grupos. CONCLUSÕES: A pneumonectomia esquerda em ratos não causou alterações funcionais, mas causou alterações histológicas. Quanto a estas alterações, não foram de natureza inflamatória e nem relacionadas ao estresse oxidativo. Foram caracterizadas por edema perivascular e vasoconstrição, observados após 72 horas da operação.<br>INTRODUCTION: Pneumonectomy is associated with high mortality and complication rates. Of these complications, post-pneumonectomy pulmonary edema is one of the most severe with a mortality rate that can reach 100%. Little is known about the etiological factors involved in this process and its association with inflammatory process or oxidative stress. The objective of this study was to analyze the acute effects of left pneumonectomy on the remaining lung of rats based on functional assessment by blood gas analysis and on histological assessment by edema formation, inflammatory infiltrate, oxidative stress and vascular reactivity. METHODS: Thirty one Wistar rats were included in the study. Twenty one underwent left pneumonectomy and were sacrificed in 48 hours (11 animals) and 72 hours (10 animals). Ten rats underwent sham procedure for control and five were sacrificed in 48 hours and five in 72 hours. Functional assessment was conducted by arterial blood gas and pO2/FiO2 ratio analyses. Histological analysis consisted of the assessment of the following parameters: (1) degree of perivascular edema; (2) presence of inflammatory infiltrate suggested by neutrophil density; (3) immunohistochemical expression of Nitric Oxide Synthase (NOS) in tissues to assess oxidative stress and (4) the degree of vascular reactivity measured by lumen/wall ratio (L/W ratio). For the assessment of oxidative stress, induced and endothelial isoforms of NOS (iNOS and eNOS) were analyzed. In addition to these parameters, pulmonary edema was assessed by means of proportional pulmonary mass gain, called Pulmonary Ratio (PR) and of the wet/dry weight ratio (W/D Ratio). The statistical analysis was conducted using the ANOVA test. RESULTS: The histological analysis showed difference regarding perivascular edema, inflammatory infiltrate, immunoexpression of iNOS and eNOS and vascular reactivity. The rate of perivascular edema was higher in animals submitted to pneumonectomy and sacrificed after 72 hours (p=0.0274). Neutrophil density was lower in animals submitted to pneumonectomy for those sacrificed after 48 and 72 hours alike (p=0.0168). There was no difference in the immunoexpression of iNOS in tissues between animals submitted to pneumonectomy and control groups, but such immunoexpression was reduced in both 72-hour groups (p=0.0212). The immunohistochemical analysis of eNOS evidenced a higher expression in animals submitted to pneumonectomy (p=0.0208). As concerns the degree of vascular reactivity, there was a lower W/D ratio in the groups sacrificed after 72 hours (p=0.0107), suggesting greater vasoconstriction in these groups. There was no difference between the groups as to the pO2/FiO2 ratio. Although the two groups submitted to pneumonectomy had greater gain of mass (p=0.0033), there was no difference in the W/D ratio between the groups. CONCLUSIONS: Left pneumonectomy in rats did not cause functional alterations but caused histological alterations that were neither of inflammatory nature nor related to oxidative stress. The alterations included perivascular edema and vasoconstriction observed after 72 hours of the procedure.

Objetivos: Comparar dois modelos de hipertensão pulmonar (monocrotalina isoladamente e pneumonectomia com monocrotalina) em relação à gravidade hemodinâmica, estrutura das artérias pulmonares, marcadores inflamatórios - interleucina-1 (IL-1) e fator de crescimento derivado de plaquetas (PDGF) - e sobrevida em 45 dias. Métodos: Total de 80 animais analisados em 2 protocolos de estudo: análise estrutural e análise de sobrevida. Foram divididos em 4 grupos [controle (C), monocrotalina (M), Pneumonectomia com monocrotalina (PM) e pneumonectomia (P)]. Após 28 dias, os animais foram cateterizados, sendo obtidos os valores hemodinâmicos. Após foram sacrificados, sendo obtidos os tecidos cardíaco e pulmonar. O ventrículo direito (VD) foi dissecado do septo interventricular e a relação do seu peso sobre o peso do ventrículo esquerdo (VE+S) com o septo foi obtida como índice de hipertrofia de VD. No tecido pulmonar foram realizadas as análises histológicas (área da camada média das artérias pulmonares) e dosados os peptídeos IL-1 e PDGF através da técnica de ELISA. Para o estudo de sobrevida os animais foram observados por 45 dias. Resultados: Os grupos M e PM apresentaram hipertensão pulmonar em relação aos demais. Houve aumento significativo da relação VD/VE+S no grupo PM em relação aos demais. Não houve diferença significativa entre os grupos M e PM na área da camada média das artérias pulmonares, nas dosagem de IL-1 e PDGF e na sobrevida. Conclusões: Com os resultados obtidos não podemos afirmar que o modelo de pneumonectomia com monocrotalina é superior ao modelo de monocrotalina<br>Objectives: To compare two models of pulmonary hypertension (monocrotaline and pneumonectomy with monocrotaline alone) in relation to the hemodynamic severity, structure of the pulmonary arteries, inflammatory markers - interleukin-1 (IL-1) factor and platelet-derived growth factor (PDGF) - and survival at 45 days. Methods: Total of 80 animals were analyzed in two study protocols: structural analysis and survival analysis. They were divided into four groups [control (C), monocrotaline (M), Pneumonectomy with monocrotaline (PM) and pneumonectomy (P)]. After 28 days, the animals were catheterized, and the hemodynamic values obtained. Then, they were euthanized and obtained the heart and lung tissues. The right ventricle (RV) was dissected from the interventricular septum and the ratio of its weight on the weight of the left ventricle (LV + S) with the septum was obtained as an index of RV hypertrophy. In lung tissue histological analyzes were performed (area of the middle layer of the pulmonary arteries) and the peptides IL-1 and PDGF measured by ELISA. To the survival study , the animals were observed for 45 days. Results: The groups M and PM show pulmonary hypertension in relation to the others. A significant increase in the RV / LV + S was observed in PM in relation to M, and M and PM in relation to the others. There was no significant difference between groups M and PM in the medial layer of pulmonary arteries, the dose of IL-1 and PDGF, and survival

L'objectif était d'étudier le remodelage vasculaire pulmonaire après pneumonectomie droite (PN) chez le rat, et d'explorer in vitro les mécanismes impliqués sur des cellules humaines soumises à un shear stress. Chez les patients, l'objectif était de déterminer l'incidence de dysfonctionnement ventriculaire droite (VD) précoce après résection pulmonaire majeure, évaluée par le strain longitudinal de la paroi latérale du VD (RVLW).Soixante rats mâles Sprague-Dawley ont subi soit une PN droite ou une chirurgie sham. Dix rats par groupe ont été sacrifiés au 3ème, 7ème et 28ème jours postopératoires (J3, J7, J28). Les altérations cardio-pulmonaires ont été étudiées par des analyses échocardiographiques, hémodynamiques et histologiques. Un antagoniste compétitif du récepteur β du facteur de croissance dérivé des plaquettes (PDGFR- β), appelé inhibiteur A4, a été administré entre J0 et J28 chez dix rats en prévention de l’HTP. In vitro, le shear stress a été reproduit à l'aide d'un système FlexCell ™ Tension. Un étirement cyclique pathologique (allongement de 18%) a été appliqué sur des cellules endothéliales pulmonaires (P-ECs) humaines pour évaluer l'impact sur la croissance des cellules musculaires lisses artérielles pulmonaires (PA-SMCs). Une étude prospective a été menée au CHU de Montpellier (France). Tous les patients opérés d’une chirurgie de résection pulmonaire majeure, sans hypertension pulmonaire ni dysfonction VD préexistante, étaient éligibles. Une échocardiographie standardisée (GE® Vivid iq ™) a été réalisée en préopératoire puis aux jours 1, 2 et 3 postopératoires par le même examinateur. Le critère d'évaluation était la survenue d'une dysfonction VD définie par un RVLW longitudinal strain supérieur à -15%. La pression artérielle pulmonaire (PAP) moyenne a progressivement augmenté dans le groupe PN pour atteindre 35 ±7 mmHg à J28 vs 18 ±4 (sham) (P=0.001), de même que la proportion d'artères pulmonaires distales muscularisées, 83 ±1% vs 5 ±1 respectivement (P&lt;0.001), liée à une prolifération in situ de PA-SMC. La surface télé-diastolique du VD et l'épaisseur de la paroi latérale VD étaient doublées dans le groupe PN à J28. La fraction d'éjection du ventricule gauche était diminuée à J7 et J28 tandis que la fonction systolique VD était préservée. In vitro, la croissance des PA-SMCs humaines était significativement plus élevée avec le milieu de culture des P-ECs « stretchées » vs « non stretchées ». Cela a permis de mettre en évidence le rôle du shear stress sur la fonction paracrine de la P-EC. Le PDGF était le principal facteur de croissance impliqué. Chez le rat, un traitement par antagoniste du PDGFR-β a diminué la PAP systolique après PN, de 69 ±10 (PN) à 46 ±6 mmHg (PN+A4) (P=0.0005), et l'indice d'hypertrophie du VD de 0.52 ±0.09 à 0.42 ±0.06 respectivement (P=0.004). Entre Février 2017 et Juillet 2018, 110 patients ont été inclus, 92 ont été analysés, âge moyen 65 ±10 ans, 59% d'hommes, BPCO dans 41% des cas, 74 lobectomie (80%), 8 pneumonectomie (9%), 6 bilobectomie (7%). Le RVLW longitudinal strain s’altérait dans les trois premiers jours chez 55% des patients (IC 0.44—0.66), passant de -20 ±7% (J0) à -16 ±6 (J3) (P=0.002). Le strain des segments de la RVLW (basal, moyen et apex) était altéré de manière homogène. Un TAPSE altéré a été observé chez 15% des patients, préférentiellement après pneumonectomie ou bilobectomie qu'après lobectomie (P=0.04). Une HTP survenait chez 11% des patients. CONCLUSIONS: Chez le rat, la pneumonectomie droite a conduit à une HTP liée à une forte muscularisation des artères pulmonaires distales et associait un remodelage sélectif du VD. In vitro, le shear stress a modifié le contrôle paracrine des P-ECs sur la croissance des PA-SMCs. L'inhibitionsélective du PDGFR-β pourrait être une cible thérapeutique. Après chirurgie de résection pulmonaire majeure, le RVLW strain a montré un dysfonction précoce du VD chez environ 50% des patients<br>The objective was to investigate the consequences of right pneumonectomy (PN) on the pulmonary vascular bed in rats, and to explore in vitro the involved mechanisms in human cells. In patients, the objective was to determine the incidence of right ventricular (RV) dysfunction during the first three days after major pulmonary resection surgery, assessed by the RV lateral wall (RVLW) longitudinal strain, a new marker of RV function.Sixty Sprague-Dawley male rats randomly underwent either a right PN or sham surgery. Ten rats per group were sacrificed on postoperative days 3, 7 and 28 (D3, D7, D28). Cardiopulmonary alterations were investigated by echocardiographic, hemodynamic and histological analyses. A competitive antagonist of the platelet-derived growth factor (PDGF)-receptor β (named A4 inhibitor) was administered between D0 and D28 in ten rats to prevent PH development. In vitro, the shear stress was reproduced using a FlexCell™ Tension system. A pathological cyclic stretch (18% elongation) was applied on cultured human pulmonary endothelial cells (P-ECs) to investigate the impact on pulmonary artery smooth muscle cell (PA-SMC) growth. Growth factors were dosed in P-ECs using qRT-PCR. A prospective study was conducted in the Montpellier University Hospital (France). All patients undergoing a major pulmonary resection surgery, without pre-existing PH or RV dysfunction, were eligible. A standardized echocardiography (GE® Vivid iq™) was performed preoperatively and then on postoperative days 1, 2 and 3 by the same examiner. The endpoint was the occurrence of a RV dysfunction, defined by a RV lateral wall (RVLW) longitudinal strain greater than -15%.Mean pulmonary arterial pressure (mPAP) gradually increased in the PN group to reach 35 ±7 mmHg on D28 vs 18 ±4 in sham (P = 0.001), likewise the proportion of muscularized distal pulmonary arteries, 83 ±1% vs 5 ± 1 respectively (P &lt; 0.001), related to in situ PA-SMC proliferation. The RV enddiastolic area and RV lateral wall thickness were doubled in the PN group on D28. The left ventricle ejection fraction decreased on D7 and D28 while the RV systolic function was maintained. In vitro, the human PA-SMC growth was significantly greater when seeded with stretched vs non stretched P-EC media, highlighting the role of shear stress on the P-EC paracrine function. The qRT PCR highlighted that the PDGF was the main growth factor involved. In rats, a treatment by PDGFR-β antagonist decreased the systolic PAP after pneumonectomy, from 69 ±10 (PN) to 46 ±6 mmHg (PN+A4) (P = 0.0005), and the RV hypertrophy index from 0.52 ± 0.09 to 0.42 ± 0.06 respectively (P = 0.004). Between February 2017 and July 2018, 110 patients were included, 92 were analyzed, mean age 65 ±10 years, 59% male, COPD in 41% of cases, 74 lobectomy (80%), 8 pneumonectomy (9%), 6 bilobectomy (7%). In the early postoperative period, the RVLW longitudinal strain was altered in 55% of patients (CI 0.44—0.66), and dropped from -20 ±7% (D0) to -16 ±6 (D3) (P = 0.002). The longitudinal strain of the RVLW segments (basal, middle and apex) was homogeneously altered. An altered TAPSE (less than 17 mm) was observed in 15% of patients, preferentially after pneumonectomy or bilobectomy than after lobectomy (P = 0.04). Pulmonary hypertension (defined by systolic PAP &gt;35 mmHg) occurred in 11% of patients, and the systolic PAP increased from 19 ±9 (D0) to 21 ±11 (D3) mmHg (P = 0.006). CONCLUSIONS: In rats, right pneumonectomy led to PH related to high muscularisation of distal pulmonary arteries, and was associated with a selective RV remodeling. In vitro, the shear stress related to high blood flow altered the pulmonary endothelial paracrine control of SMC growth. Selective PDGFR-β inhibition could be a therapeutic target. After major pulmonary resection surgery, the RVLW longitudinal strain showed an early RV dysfunction in approximately 50% of patients

Introduzione Il Mesotelioma Pleurico Maligno (MPM) è un tumore primitivo della pleura raro ma estremamente aggressivo, con un’incidenza di circa 2000 – 3000 casi annui negli Stati Uniti. La sopravvivenza mediana dal momento della diagnosi è di circa 4-16 mesi, con meno del 5% di pazienti vivi a 5 anni. Il trattamento chemioterapico di scelta prevede la combinazione del cisplatino con il pemetrexed, che ha dimostrato un incremento della sopravvivenza di circa 3 mesi rispetto ai precedenti schemi chemioterapici. Attualmente il trattamento di scelta per i pazienti in stadio iniziale, candidabili ad intervento chirurgico, è il trattamento multimodale con l’associazione di chemioterapia, radioterapia e resezione chirurgica (pleuropneumonectomia extrapleurica o pleurectomia/decorticazione). Ad oggi non è ancora ben chiaro l’impatto della terapia multimodale e del tipo di trattamento chirurgico sulla sopravvivenza. Attualmente c’è una controversia su quale sia il migliore trattamento chirurgico per i pazienti con MPM. La pleurectomia decorticazione (P/D) presenta gli stessi risultati in termini di sopravvivenza globale rispetto alla pleuropneumonectomia extrapleurica (EPP) con una mortalità e morbidità postoperatoria minori, mantenendo l’intento citoriduttivo nel contesto di un trattamento multimodale. Lo scopo del nostro studio, chiamato PASS (Pleural Mesothelioma Strategy Study), è quello di valutare l’impatto della chirurgia nei pazienti con MPM, dopo aver analizzato i fattori prognostici favorevoli per la sopravvivenza, validati in due casistiche retrospettive indipendenti. Lo studio PASS è uno studio randomizzato controllato di fase III che si propone di confrontare la sola chemioterapia versus l’associazione di chemioterapia preoperatoria seguita dalla pleurectomia decorticazione nei pazienti portatori di mesotelioma pleurico maligno con malattia stabile e resecabile. Per disegnare lo studio e garantire che ai pazienti fosse offerto un trattamento adeguato e sicuro in termini di risultati a breve termine e a distanza, sono stati prima analizzati i soggetti con MPM, diagnosticati e trattati o con terapia medica o con chirurgia presso sei centri italiani di Chirurgia Toracica tra il 1982 e il 2012 (Spedali Civili Brescia, Ospedale Maggiore della Carità Novara, Ospedale San Luigi Orbassano (Torino), Ospedale Policlinico Milano, IRCCS San Martino Genova, Fondazione IRCCS Istituto Nazionale dei Tumori Milano), analizzando i fattori prognostici preoperatori ed intraoperatori e mettendo a confronto i risultati a distanza della terapia medica (palliativa e chemioterapia) e della chirurgia inserita nel contesto della terapia trimodale, confrontando in maniera specifica i risultati della extrapleuropneumonectomia e della pleurectomia decorticazione in termini di mortalità e morbidità postoperatoria e di risultati a lungo termine. I fattori prognostici sono inoltre stati analizzati e rivalidati in una serie indipendente contemporanea di pazienti trattati con chemioterapia a base di cisplatino e pemetrexed al Memorial Sloan Kettering Cancer Center. Dopo di che è stato condotto uno studio pilota per valutare la fattibilità e la sicurezza del trattamento chemioterapico neoadiuvante seguito da pleurectomie/decorticazione, che è utilizzato nello studio prospettico PASS. Materiali e metodi Nel periodo compreso tra il Settembre 1982 ed il Settembre 2012 sono stati analizzati retrospettivamente 1365 pazienti consecutivi con diagnosi istologica di mesotelioma pleurico maligno (MPM) che sono stati sottoposti a biopsia pleurica a cielo aperto o toracoscopica presso sei strutture italiane di Chirurgia Toracica. Inoltre è stata condotta un’analisi retrospettiva dei dati clinici di pazienti con diagnosi istologica di mesotelioma pleurico maligno che furono esaminati e trattati con chemioterapia secondo lo schema cisplatino e pemetrexed al Memorial Sloan Kettering Cancer Center (MSKCC) tra il Gennaio 2000 ed il Dicembre 2013. I pazienti con mesotelioma peritoneale, i pazienti trattati presso altri centri, ed i pazienti persi al follow up furono esclusi dall’analisi. In quanto mancano dati sulla fattibilità e sulla tollerabilità del trattamento chemioterapico neoadiuvante seguito da pleurectomia/decorticazione, prima di cominciare lo studio PASS, dal Settembre 2012 ad Agosto 2014 i pazienti sottoposti a chemioterapia neoadiuvante secondo lo schema cisplatino e pemetrexed seguita da pleurectomia decorticazione presso la Struttura Complessa di Chirurgia Toracica dell’istituto Nazionale dei Tumori furono valutati prospetticamente, analizzando i risultati postoperatori, in termini di morbidità e mortalità, ed i risultati a distanza. Dopo aver analizzato i dati retrospettivi e valutato la sicurezza del regime terapeutico proposto, lo studio PASS, studio prospettico randomizzato multicentrico di fase III, è stato aperto e la fase di arruolamento è tutt’ora aperta. Saranno inclusi nello studio 120 pazienti con mesotelioma pleurico maligno, in stadio clinico T1-3 N0-1, che al termine del trattamento chemioterapico standard con 4 cicli di cisplatino e pemetrexed presenteranno una malattia in regressione e/o stabile o localmente avanzata ma ancora resecabile. Previo consenso informato per la partecipazione allo studio, questi pazienti verranno randomizzati in due gruppi: braccio chirurgico e braccio di controllo. È stato inoltre creato un registro prospettico europeo per i pazienti portatori di mesotelioma trattati chirurgicamente ma non arruolati in nessuno studio prospettico chirurgico, al fine di ottenere un numero maggiore di risultati circa l’impatto della chirurgia sui risultati a distanza. Risultati Un totale di 1365 pazienti consecutivi furono inclusi nell’analisi retrospettiva italiana multicentrica. La maggior parte dei pazienti erano di sesso maschile (68.1%) e la variante istologica più frequente fu quella epiteliomorfa (57.9%). Cinquecento tre pazienti furono sottoposti ad intervento chirurgico resettivo di Pleurectomia/Decorticazione, P/D (n=202) o di PleuroPneumonectomia Extrapleurica, EPP (n=301). La mortalità a 30 e 90 giorni fu del 2.6% e 6% dopo P/D, e del 4.1% e 6.9% dopo EPP, rispettivamente. Fu osservata una differenza statisticamente significativa nel tasso di complicanze postoperatorie, più elevato dopo EPP (p<0.001). Al momento dell’analisi, la durata del follow up fu di 6.7 anni (intervallo 0.1-14.8 anni). Duecento trenta (17.7%) pazienti erano vivi al momento dell’analisi. Cinquecento ventidue (40.3%) pazienti morirono entro il primo anno dalla diagnosi. La sopravvivenza mediana dell’intera populazione in studio fu di 14.5 mesi (95%IC 13.5-15.2 mesi). La sopravvivenza mediana dei pazienti sottoposti a intervento chirurgico e terapia adiuvante fu significativamente più lunga rispetto ai pazienti sottoposti a sola chemioterapia: 19.8 mesi vs. 11.7 mesi. I pazienti sottoposti a P/D mostrarono una sopravvivenza mediana di 20.5 mesi (intervallo 18.2-23.1 mesi) ed una sopravvivenza a 2 e 5 anni del 40% (95%CI 0.32-0.48) e del 10% (95%CI 0.06-0.16). I pazienti sottoposti ad EPP ebbero una sopravvivenza mediana di 18.8 mesi (intervallo 17.2-20.9 mesi), e un tasso di sopravvivenza a 2 e 5 anni del 37% (95%CI 0.31-0.42) e del 12% (95%CI 0.07-0.17). Analizzando i 3 gruppi di pazienti prima e dopo l’introduzione del pemetrexed come agente chemioterapico standard di prima linea per il trattamento del mesotelioma, ci fu un miglioramenteo della sopravvivenza in tutti e tre i gruppi. In base all’analisi multivariate l’età, la variante istologica e il trattamento chirurgico furono confermati come fattori prognostici indipendenti associati con la sopravvivenza. I pazienti con un’età inferiore ai 70 anni, e con un mesotelioma epiteliomorfo, trattati con chemioterapia dimostrarono la miglior sopravvivenza sia nel gruppo non chirugico che in quello chirurgico. Quando l’impatto della chirurgia sulla sopravvivenza fu valutato solo nel sottogruppo di pazienti con prognosi migliore (pazienti di età inferiore ai 70 anni, con meostelioma epiteliomorfo, sottoposti a chemioterapia; n=313) il gruppo P/D ha dimostrato la miglior sopravvivenza (24.6 mesi, 95%CI: 20.5-29.0), seguito dal gruppo EPP (20.9 mesi, 95%CI: 17.6-23.4 months) e dai pazienti non chirurgici (18.6 months, 95%CI: 16.2-24.9). Comunque la differenza in termini di sopravvivenza non fu statisticamente significativa (p-value=0.596) In seguito sono poi stati analizzati 413 pazienti con MPM trattati al MSKCC tra Gennaio 2000 e Dicembre 2013; 191 pazienti furono inclusi nello studio. Il follow up medio fu di 13.2 mesi, 14 pazienti erano ancora in vita all’ultimo follow up, e la sopravvivenza mediana fu di 13.4 mesi. All’analisi multivariata, solo la variante istologica, la conta piastrinica e le condizioni generali furono fattori prognostici indipendenti per la sopravvivenza. I pazienti che ebbero un beneficio clinico in termini sintomatologici o radiologici dalla chemioterapia mostrarono una sopravvivenza mediana di 16.8 mesi (95% CI 14.8 – 20.1) ed un tasso di sopravvivenza ad un anno del 70% rispetto ai pazienti che non ebbero nessun beneficio clinico dalla chemioterapia, con una sopravvivenza mediana di 6.5 mesi (95% CI 5.4 – 8.5) e un tasso di sopravvivenza ad un anno del 22%. I pazienti che ricevettero più di una linea di chemioterapia mostrarono una migliore sopravvivenza rispetto ad i pazienti che ricevettero una sola linea chemioterapica con una sopravvivenza mediana di 14.2 mesi (95% CI 12.1 – 16.8) vs 8.7 mesi (95% CI 6.6 – 11.0) ed un tasso di sopravvivenza ad un anno del 60% vs 37%, rispettivamente. Tra i pazienti che dimostrarono un beneficio dalla chemioterapia di prima linea (n=99), 60 (61%) ricevettero una seconda linea di chemioterapia. I pazienti che vennero trattati con radioterapia a dosaggi curativi (n=25) mostrarono un significativo miglioramento della sopravvivenza (p=0.013) rispetto ai pazienti trattati con sola chemioterapia: sopravvivenza mediana di 17.1 mesi (95% CI 14.8 – 30.6) vs 10.4 mesi (95% CI 8.6 – 12.6). I pazienti in buone condizioni generali mostrarono una risposta clinica nel 64% dei casi rispetto al 36% dei pazienti con condizioni generali scadute (p=0.001). Il 63% dei pazienti con mesotelioma epiteliomorfo ed il 45% dei pazienti con mesotelioma sarcomatoide mostrarono un miglioramento clinico dopo la prima linea di chemioterapia e ricevettero più di due cicli di trattamento (p=0.012). Un aumentato numero di linfociti (> 1.4 K/mcL) fu associato con un miglioramento clinico nei pazienti sottoposti a chemioterapia (p=0.010): 67% dei pazienti con linfociti > 1.4 K/mcL vs 46% dei pazienti con linfociti < 1.4 K/mcL mostrarono una risposta clinica alla chemioterapia e ricevettero più di due cicli di chemioterapia. Prima di cominciare l’arruolamento dello studio PASS, lo studio pilota arruolò sedici pazienti consecutivi trattati chirurgicamente tra Settembre 2012 e Agosto 2014 presso l’Istituto Nazionale dei Tumori. Tutti i pazienti vennero sottoposti a chemioterapia neoadiuvante: pemetrexed e cisplatino in 14 pazienti, carboplatino e pemetrexed in 1 paziente e pemetrexed come monoterapia in 1 paziente. I pazienti ricevettero in media 4 cicli di chemioterapia (intervallo 3-8), e poi vennero sottoposti ad intervento di pleurectomia/decorticazione. Non ci fu nessuna mortalità postoperatoria e la morbidità postoperatoria fu del 37%. La sopravvivenza mediana della popolazione in esame fu di 22.8 mesi (95% CI 19.4 -26.1), con una sopravvivenza ad 1 e 3 anni del 93% e del 51% rispettivamente. All’ultimo follow up 4 pazienti erano deceduti per mesotelioma, 12 pazienti erano ancora viventi con un follow up medio di 11 mesi (range 4 – 22 mesi). Tra i 12 pazienti ancora vivi, 3 erano liberi da malattia a 10, 11 e 15 mesi dall’intervento. I restanti 9 pazienti recidivarono con un intervallo libero di malattia di circa 6 mesi: sei pazienti presentarono una recidiva locale a livello pleurico, e 3 pazienti presentarono una recidiva a distanza a livello osseo (n=2) e a livello gengivale (n=1). Lo studio PASS ha cominciato l’arruolamento a Dicembre 2013, al Febbraio 2015 sono stati valutati 20 pazienti e ne sono stati arruolati 12 nello studio. Sei pazienti sono stati sottoposti a chemioterapia e P/D e sei pazienti a sola chemioterapia e sono attualmente seguiti con regolare follow up. Il registro europeo del mesotelioma, basato su pazienti non arruolati in studi prospettici sul trattamento chirurgico, si avvale di una raccolta retrospettiva di dati di circa 3000 casi. Inoltre 11 centri hanno deciso di prendere parte al registro del mesotelioma compilando i dati in maniera prospettica. Conclusioni Alla luce dei dati emersi dalla nostra analisi possiamo concludere che il mesotelioma pleurico maligno continua a rappresentare una sfida per il chirurgo toracico in quanto il trattamento migliore non è ancora stato definito e quindi la scelta su quale trattamento adottare spesso è legata all’esperienza individuale e alle valutazioni soggettive del chirurgo e dell’oncologo. I fattori prognostici di sopravvivenza confermati dal nostro studio includono l’età (solo nello studio italiano multicentrico), le condizioni cliniche generali, la conta piastrinica, ma soprattutto l’istotipo. Questi fattori sono stati validati anche nei soli pazienti trattati con il pemetrexed in combinazione con il platino. Questo studio è stato, inoltre, il primo a valutare fattori prognostici di risposta clinica alla chemioterapia: buone condizioni generali, la variante epiteliomorfa ed un elevata conta linfocitaria sono correlati ad una miglior risposta alla chemioterapia. Il disegno retrospettivo della prima parte del progetto con la conseguente variabilità dei sistemi stadiativi e dei trattamenti nel corso degli anni ha reso difficile esprimere un parere definitivo circa il ruolo della chirurgia e della terapia multimodale nel trattamento del mesotelioma pleurico maligno. Sicuramente oltre ad i limiti della chirurgia nel trattamento del mesotelioma pleurico maligno, ad oggi non c’è un trattamento sistemico efficace nel controllare la neoplasia. Lo studio pilota ha evidenziato come la chemioterapia preoperatoria, secondo lo schema cisplatino pemetrexed, nei pazienti con mesotelioma è fattibile senza un incremento del rischio di morbidità o mortalità postoperatoria dopo pleurectomia / decorticazione. Per queste ragioni, lo studio prospettico randomizzato di fase III PASS ed il registro prospettico sono le risposte alla mancanza di dati prospettici che ci permetteranno di analizzare il reale impatto dei diversi trattamenti, ed il ruolo dei nuovi fattori prognostici emersi in questi ultimi anni, come il SUVmax alla PET e la misura volumetrica del tumore.<br>Background Malignant pleural mesothelioma (MPM) is a rare and aggressive disease with approximately 2500 newly diagnosed cases each year in USA and about 5000 in Western Europe. Median survival is 6 to 9 months from the diagnosis, and 6-month, 1 and 5-year overall survival are 55%, 33%, and 5%, respectively. Chemotherapy alone for advanced stages, or in combination with surgery and/or radiotherapy for resectable disease, is the mainstay of treatment. Surgery with pleurectomy / decortication (P/D) or extrapleural pneumonectomy (EPP) can be an option for selected patients with resectable malignant pleural mesothelioma (MPM). Since 2003, the combination of pemetrexed and cisplatin has been the standard first-line treatment based on the results of a phase III trial showing almost a 3 month improvement in median survival over treatment with cisplatin alone. Various prognostic factors for survival in MPM have been described. Previous prognostic scoring systems for MPM included patients managed surgically and predated the use of pemetrexed. The most significant prognostic factor remains histology: epithelioid mesothelioma is the subtype with the best prognosis. The aim of this study was to investigate the impact of pleurectomy decortication on the outcome of patients with MPM. A randomized phase III multicenter controlled trial, called PASS trial was established to compare neoadjuvant chemotherapy followed by pleurectomy decortication versus chemotherapy alone. Also, a European Registry was created to collect data on surgical patients with mesothelioma not enrolled in any trials. Before enrolling patients in the PASS trial, we analyzed prognostic factors in a retrospective cohort of patients treated with chemotherapy or surgical resection and in a contemporary cohort of patients with unresectable MPM who received pemetrexed-based chemotherapy. Moreover a pilot study was conducted to evaluate the feasibility and the safety of the naodjuvant chemotherapy followed by pleurectomy/decortication. Methods We retrospectively reviewed data from 1365 consecutive patients with histologically proven MPM, treated from 1982 to 2012 in six Italian Institutions (Spedali Civili Brescia, Ospedale Maggiore della Carità Novara, San Luigi Hospital Orbassano (Torino), Policlinico hospital Milan, IRCCS San Martino Genova, Fondazione IRCCS Istituto Nazionale dei Tumori Milan). Patients received chemotherapy alone (n=172) or best supportive care (n=690) or surgical treatment (n=503), by either P/D (n=202) or EPP (n=301) with or without chemotherapy. Then a single institution analysis included MPM patients managed non-surgically from 2000-2013 at Memorial Sloan Kettering Cancer Center (MSKCC). Variables correlated with overall survival (OS) included sex, performance status (PS), asbestos exposure, tumor laterality, histology, clinical stage, initial PET maximum Standardized Uptake Value (SUVmax), hemoglobin, platelet, lymphocyte, white cell (WBC) and neutrophil counts, treatment type, and clinical benefit from treatment. The pilot study included patients receiving induction pemetrexed-based chemotherapy, followed by pleuectomy decortication from September 2012 and August 2014. Postoperative morbidity and mortality and OS were analyzed. The PASS trial is a multicentric randomized trial with 2 arms. Patients were randomized at the end of the chemotherapy in 2 groups: follow up group and surgical group (pleurectomy/decortication). OS was analyzed by Kaplan-Meier method, and significance (p<0.05) of prognostic factors was analyzed by log-rank test and Cox regression. Results: After a median follow-up of 6.7 years (range 1.1-14.8), 230 (16.8%) patients were alive in the Italian retrospective study; median survival for patients who received palliative treatment or chemotherapy alone, P/D and EPP were 11.7 (95%CI: 10.5-12.5), 20.5 (95%CI: 18.2-23.1), and 18.8 (95%CI: 17.2-20.9) months, respectively. The 30 day mortality was 2.6% after P/D and 4.1% after EPP (p=0.401). According to multivariate analysis (n=1227) age < 70, epithelial histology and chemotherapy were independent favourable prognostic factors. In the subset of 313 (25.5%) patients with all favourable prognostic factors median survival was 18.6 months after medical therapy alone, 24.6 months after P/D, and 20.9 months after EPP (p=0.596). In the MSKCC contemporary series191 patients were included: median age 71 years (range 46-90), 147 (77%) male, 128 (67%) epithelioid tumors, 157 (82%) stage III-IV. Median OS for all patients was 13.4 months. By univariate analysis, histology (p<0.001), platelet count (≤450,000 vs >450,000 p<0.001), initial PS (0-1 versus ≥ 2), SUVmax (> or ≤8.1, p=0.037), and lymphocyte counts (p=0.019) were associated with OS. By multivariable analysis, only histology, platelet count and PS were independent prognostic factors. Epithelioid histology, PS and elevated lymphocyte count at diagnosis were significantly associated with clinical benefit from first-line chemotherapy. Patients who experienced clinical benefit from chemotherapy had a better median OS of 16.8 months (95% CI 14.8 – 20.1) and 1-year survival rate of 70% compared to patients who did not demonstrate clinical benefit, with a median OS of 6.5 months (95% CI 5.4 – 8.5) and 1-year survival rate of 22%. In the pilot study 16 patients were included and treated at the Fondazione IRCCS istituto Nazionale dei Tumori. All patients received neoadjuvant chemotherapy: cisplatin and pemetrexed (n=14), carboplatin and pemetrexed (n=1) or pemetrexed alone (n=1). Median number of chemotherapy cycles was 4 (range 3-8), followed by pleurectomy and decortication. Postoperative mortality was nil and the morbidity was 37%. The median OS was 22.8 months (95% CI 19.4 -26.1), with 1 and 3-year survival of 93% and 51%, respectively. During the follow up 4 paients died for mesothelioma, 12 patints were still live with a median follow up of 11 months (range 4 – 22 months). Among the 12 patients still alive, 3 were free of disease at 10, 11 and 15 months from the surgery. The remaining 9 patients recurred with a median interval of 6 months: 6 presented with a pleural local recurrence and 3 with a distant recurrence with bone metastasis (n=2) and gengival metastasis (n=1). Pass trial started in Secember 2013, until February 2015 20 patients had been evaluated and 12 were enrolled. Six patients underwent chemotherapy followed by pleurectomy decortication and 6 patients were treated with only chemotherapy and all of them are still under regular follow up. The European registry of mesothelioma, based on patients not involved in prospective studies on surgical treatment for mesothelioma, collected 3000 cases retrospectively and 11 centers so far are collecting data prospectively. Conclusions Our retrospective data from the Italian study suggest that patients with good prognostic factors had a similar survival whether they received medical therapy only, P/D or EPP. The modest benefit observed after surgery over medical treatment requires further investigation. Our results also confirm the significance of elements of the CALGB and EORTC prognostic scoring systems, identify factors associated with clinical benefit from chemotherapy, and emphasize the impact of histology and clinical benefit of chemotherapy on outcomes. A large multicenter randomized trial, testing P/D after induction chemotherapy versus chemotherapy alone in MPM patients with good prognostic factors, and a prospective European registry on surgical patients with mesothelioma are the best way to assess the real impact of the surgical treatment on survival.

Objetivo: Analisar os principais achados do tratamento cirúrgico das malformações congênitas pulmonares em um serviço de cirurgia torácica pediátrica. Métodos: Foram revisados cinqüenta e dois prontuários de pacientes com diagnóstico anatomopatológico de malformações congênitas pulmonares que foram submetidos à ressecção pulmonar, no período de janeiro de 1997 a dezembro de 2006. Deste total, 39 casos eram de pacientes menores de 12 anos. Quatro casos foram excluídos, por prontuário incompleto. Resultados: Dos 35 pacientes estudados, a média de idade foi de 31 meses com predominância do sexo masculino (n=21). Os achados anatomopatológicos foram: enfisema lobar congênito (n=13), seqüestro pulmonar (n=8), malformação adenomatóide cística (n=14), malformação arterio-venosa (n=1). A ressecção mais comum foi a lobectomia inferior esquerda (25,71%), seguida pela lobectomia superior esquerda (22,85%). A lobectomia superior direita foi realizada em 5 casos (14,28%), a lobectomia média em 2 casos (5,71%) e a lobectomia inferior direita em 3 pacientes (8,57%). Em 8 pacientes foram realizadas diferentes tipos de segmentectomias (22,85%). Trinta e quatro pacientes (97,14%) foram submetidos a drenagem pleural fechada. O tempo médio de permanência do dreno torácico foi de 3,9 dias. Dez pacientes (28,5%) apresentaram complicações pós-operatórias. Não houve óbitos nesta série. Conclusões: A ressecção pulmonar para o tratamento das malformações pulmonares é um procedimento seguro, que em serviço de referência para doenças pulmonares, apresenta pouca morbidade e nenhuma mortalidade.<br>Objectives: Analyze the main findings of the surgical treatment of congenital lung malformations from a pediatric thoracic surgery service. Methods: We reviewed the medical charts of fifty-two patients with anatomopathologic diagnosis of congenital lung malformations who were submitted to pulmonary resection from January 1997 to December 2006. Overall, thirty-nine patients were under 12 years-old. Four patients were excluded due to incomplete clinical data. Results: The mean age of the thirty-five patients was 31 months with predominance of males (n=21). The anatomopathologic findings were: adenomatoid cystic malformation (n=14), congenital lobar emphysema (n=13), pulmonary sequestration (n=8) and arteriovenous pulmonary malformation (n=1). The most common lung resection was the left lower lobectomy (25.71%) followed by left upper lobectomy (22.8%). Right upper lobectomy was performed in 5 cases (14.28%), middle lobectomy in 2 cases (5.71%) and right inferior lobectomy in three cases (8.57%). Eight patients were submitted to different segmentectomies (22.85%). Chest tubes were left in thirty-four patients (97.14%) for 1 to 9 days (average, 3.9 days). Ten patients had at least one post operative complication (28,5%). There was no death in this series. Conclusion: Pulmonary resection for the treatment of congenital lung malformation is a safe procedure, which in a reference pediatric thoracic surgery service presents low morbidity and no mortality.

UVOD: Drenaža grudnog ko&scaron;a nakon resekcija pluća je osnovni grudno hirur&scaron;ki postupak, koji omogućuje pro&scaron;irenje (reekspanziju) pluća iz kolabiranog stanja, evakuaciju vazduha, krvi i izliva iz pleuralnog prostora i potpomognuta je primenom aspiracije na drenove (sukciona ili aspiraciona drenaža). Iako je drenaža&nbsp; svakodnevna grudno hirur&scaron;ka procedura, postupak sa drenovima je zasnovan prvenstveno na iskustvu, a manje na osnovu naučnih studija. Pri mirnom disanju inspiratorni pritisak u pleuralnom prostoru je prosečno - 8 cm H2O, a ekspiratorni - 4 cm H2O. Pri forsiranom disanju pritisci mogu dostići - 50 cm H2O i +70 cm H2O. Na osnovu tih fiziolo&scaron;kih podataka, većina hirurga primenjuje aspiraciju od - 10 do - 40 cm H2O. Koncepta pleuralnog deficita - disproporcije volumena preostalog plućnog tkiva i zapremine grudnog ko&scaron;a doveo je do razvoja tehničkih postupaka za postizanje nove fiziolo&scaron;ke ravnoteže u pleuralnom prostoru i razmatranja rutinske primene podvodne (pasivne) drenaže nakon resekcija pluća. Pritisak na zdravstvenu službu za smanjenje tro&scaron;kova i skraćenje postoperativne hospitalizacije uz mogućnost rane mobilizacije pacijenta čine podvodnu drenažu zanimljivom alternativom tradicionalno prihvaćenoj aktivnoj aspiraciji na drenove.&nbsp; CILJ: Da se utvrdi da li aplikacija aktivne aspiracije na drenove nakon lobektomije pluća u poređenju da podvodnom drenažom ima povoljno terapijsko dejstvo na postizanje i održavanje reekspanzije pluća; Da se kvantitativno uporede različiti modovi aktivne aspiracije preko drenova; Da se uporedi dužina hospitalizacije i pojava hirur&scaron;kih i nehirur&scaron;kih komplikacija između grupa ispitanika kod kojih se primenjuje podvodna (pasivna) drenaža i aspiracija preko drenova. METODOLOGIJA: Prospektivna studija bez randomizacije obuhvatila je 301 ispitanika kojima je načinjena lobektomija pluća zbog karcinoma pluća na Klinici za grudnu hirurgiju Instituta za plućne bolesti Vojvodine u Sremskoj Kamenici u periodu od 01.01.2008. - 28.02.2010. godine. Beleženi su i analizirani podaci o preoperativnom stanju: plućnoj funkciji, prethodno primljenoj neoadjuvantnoj hemioterapiji i pridruženim bolestima. Analizirani su hirur&scaron;ki operativni podaci o postojanju buloznog emfizema, adhezija u pleuralnom prostoru, anatomskoj vrsti lobektomije, dodatnim hirur&scaron;kim procedurama i postojanju gubitka vazduha na kraju operacije. Analizirani su postoperativni podaci o secernaciji na drenove tokom prva 24 h i ukupno, trajanju gubitka vazduha na drenove u danima, ukupnom trajanju drenaže, ukupnom trajanju hospitalizacije, pojavi produženog gubitka vazduha na dren definisanog kao gubitak duže od 7 dana, potrebi za redrenažom grudnog ko&scaron;a (broj drenova upotrebljenih za redrenažu), kompletnost reekspanzije pluća pre vađenja drenova, pojavi drugih hirur&scaron;kih komplikacija, pojavi op&scaron;tih medicinskih komplikacija i pojavi kasnih komplikacija &ndash; vi&scaron;e od 30 dana nakon operacije ili nakon otpusta. Prvu grupu ispitanika sačinjavaju pacijenti kojima je načinjena lobektomija pluća, nakon čega je aplikovana aspiracija od -20 cm vodenog stuba do klemovanja i vađenja drenova. Drugu grupu ispitanika sačinjavaju pacijenti kojima je aplikovana aspiracija od -20 cm vodenog stuba na dan operacije i zatim -10 cm vodenog stuba do klemovanja i vađenja drenova. Treću grupu ispitanika sačinjavaju pacijenti kojima je načinjena lobektomija pluća, nakon čega je aplikovana aspiracija od -20 cm vodenog stuba na dan operacije i zatim podvodna drenaža do klemovanja i vađenja drenova. Četvrtu grupu ispitanika sačinjavaju pacijenti kojima je načinjena lobektomija pluća, nakon čega je aplikovana aspiracija od -20 cm vodenog stuba na dan operacije i zatim dnevna procena i modifikacija na sledeći način: aspiracija od -20 cm vodenog stuba do postizanja reekspanzije pluća, zatim postepeno smanjenje aspiracije po nahođenju operatera do klemovanja i vađenja drenova. REZULTATI: Između grupa ispitanika ne postoji statistički značajna razlika po starosti (p=0,77),&nbsp; parametrima plućne funkcije: vrednost FEV1 (p=0,6316), vrednost ITGV (p=0,6202), vrednost TLC (p=0,6922) i za vrednost RV ne postoji razlika (p=0,6552). Razlika ne postoji između grupa ni u učestalosti pridruženih bolesti (p=0,4522). Grupe su međusobno homogene po preoperativnim parametrima. Snižen FEV1 u ukupnoj populaciji pacijenata nije uticao na pojavu produženog gubitka vazduha (P=0,571), kao ni povi&scaron;enje ITGV (P=0,22), RV (p=0,912), niti vrednost TLC (0,521). Upoređene su međusobno osnovne vrste lobektomija: desna gornja, leva gornja, desna donja, leva donja, srednja lobektomija, kao i donja i gornja bilobektomija desno. Kako je učestalost svake pojedinačne lobektomije u 4 grupe ispitanika mali da bi se uporedile iste lobektomije između grupa, poređenje je moguće samo između anatomski različitih lobektomija kumulativno u svim grupama. Razlika u pojavi produženog gubitka vazduha između različitih lobektomija postoji, ali nije dostigla statističku značajnost (p=0,061). Međutim, kada se analizira svaka lobektomija pojedinačno, uočava se da desna donja bilobektomija ima značajno veću učestalost produženog gubitka vazduha u odnosu na sve ostale lobektomije zajedno (P=0,009). Razlika u dužini drenaže kod&nbsp; različitih lobektomija je dostigla statistički značaj (p=0,0356), kao i u ukupnoj dužini hospitalizacije (p=0,0007). Dodatak resekcije perikarda, grudnog zida ili dijafragme, klinasta resekcija susednog režnja ili sleeve resekcija bronha kao dodatne procedure nisu uticali na pojavu produženog gubitka vazduha (p=0,58). Podaci o učestalosti adhezija u ispitivanoj populaciji pacijenata i njihovom uticaju na pojavu produženog gubitka vazduha daju granične vrednosti. I ovde je broj pacijenata u svakoj pojedinačnoj kategoriji adhezija (postojanje adhezija na skali od 0-3) mali da bi testiranje povezanosti sa produženim gubitkom vazduha moglo dostići statističku značajnost - razlika postoji, ali nije značajna (p=0,065). Radi povećanja statističke snage je izvedeno testiranje za podelu ima ili nema adhezija. Razlika postoji, ali ni ovim testiranjem nije dostignuta statistički značajna razlika (p=0,057). Postojanje buloznog emfizema takođe dovodi do povećanja učestalosti produženog gubitka vazduha, ali ni ovde razlika nije značajna (p=0,063).&nbsp; Primena hemoterapije pre operacije nije dovela do statistički značajne razlike u pojavi produženog gubitka vazduha (p=0,0623) i ukupnoj stopi komplikacija (p=0,088), kao ni dužine hospitalizacije (p=0,2), iako razlika postoji i paradoksalno rezultat je bolji kod pacijenata koji su primili hemioterapiju, &scaron;to može ukazivati na uticaj selekcije pacijenata za operaciju. Između 4 grupe ispitanika nije uočena razlika u potrebi za redrenažom grudnog ko&scaron;a (p=0,101), potrebi za povećanjem nivoa aktivne aspiracije (p=0,326), ukupnoj pojavi komplikacija (p=0,087) i pojavi produženog gubitka vazduha (P=0,323). Razlika postoji i visoko je značajna u dužini trajanja drenaže (p=0,001) i dužini hospitalizacije (P=0,000). Broj drenova (1 ili 2 drena postavljena intraoperativno) nije uticao na pojavu produženog gubitka vazduha (p=0,279), ali je značajno kraća hospitalizacija kod pacijenata sa jednim drenom (p=0,0001). Logistička regresiona analiza je pokazala da je samo donja bilobektomija značajno uticala na pojavu produženog gubitka vazduha na dren, dok nije nađen uticaj aktivne aspiracije na drenove, prisustva adhezija, buloznog emfizema, sniženih vrednosti FEV1, primene redukcije pleuralnog prostora (space reducing), broja drenova i dodatne operacije (resekcije). ZAKLJUČAK: Sprovedenim istraživanjem utvrđeno je da primena aktivne aspiracije na drenove ne pokazuje razliku u odnosu na podvodnu drenažu u postizanju i održavanju reekspanzije pluća nakon lobektomije. Aktivna aspiracija ne utiče na pojavu produženog gubitka vazduha na drenove definisanog kao gubitak vazduha duže od 7 dana, ali utiče na produženje ukupnog trajanja drenaže i hospitalizacije. Nivo aktivne aspiracije ili primena dnevnih modifikacija nivoa aspiracije ne utiče na rezultate lečenja.&nbsp; U ovom istraživanju preoperativna plućna funkcija, kao ni preoperativna hemoterapija ne utiču na pojavu produženog gubitka vazduha na drenove. Desna donja bilobektomija u odnosu na sve druge lobektomije dovodi do če&scaron;će pojave produženog gubitka vazduha, produžene drenaže i hospitalizacije. Dodatne resekcije okolnih tkiva u sklopu lobektomije ili primena redukcije pleuralnog prostora ne utiču na pojavu produženog gubitka vazduha. Intraoperativni nalaz adhezija u pleuri i buloznog emfizema pluća povećavaju rizik produženog gubitka vazduha, ali je taj uticaj na granici statističke značajnosti. Primena jednog drena nakon lobektomije umesto dva ne utiče na pojavu produženog gubitka vazduha, ali utiče na skraćenje drenaže i hospitalizacije. U multivarijatnoj analizi samo je donja bilobektomija značajno uticala na pojavu produženog gubitka vazduha na dren, dok nije nađen uticaj aktivne aspiracije na drenove, prisustva adhezija, buloznog emfizema, sniženih vrednosti FEV1, primene redukcije pleuralnog, broja drenova i dodatne resekcije okolnih tkiva.<br>INTRODUCTION: The drainage of the thorax after pulmonary resection is a basic thoracic surgery procedure which enables reexpansion after lung collapse and the evacuation of air, blood and effusion from the pleural cavity. It is supported by the use of drainage aspiration (suction or aspiration drainage). Although drainage is an everyday procedure in thoracic surgery, the use of drains is based mainly on specialist experience and less on scientific research. During calm breathing the inspiratory pressure in the pleural cavity is &ndash; 8cm H2O on average, while the expiratory pressure is &ndash; 4cm H2O. During forced breathing the pressures can reach up to &ndash; 50 cm H2O and + 70 cm H2O. Based on this physiological data, most surgeons apply the aspiration from &ndash; 10 to &ndash; 40 cm H2O. The concept of pleural deficit (the disproportion of the volume of the remaining pulmonary tissue and the volume of the thorax) has attributed to development of new technical procedures in order to achieve a new physiological balance in the pleural cavity. It has also brought upon the consideration of routine underwater seal drainage after pulmonary resection. Underwater seal drainage represents an interesting alternative to the traditional active drainage aspiration, especially considering the need to reduce medical expenses and shorten the postoperative hospitalization period. AIM: To determine whether active drainage aspiration after pulmonary lobectomy has a favorable therapeutic effect on achieving and maintaining pulmonary reexpansion in comparison with underwater seal drainage; to quantitatively compare the different modes of active drainage aspiration; to compare hospitalization duration and surgical and non-surgical complication with groups of patients on whom either underwater seal drainage or aspiration drainage was applied. METHODOLOGY: The prospective study without randomization has covered 301 patients on whom pulmonary lobectomy was performed due to lung carcinoma at the Thoracic Surgery Clinic of the Institute of Pulmonary Diseases of Vojvodina from 1st January 2008 to 28th February 2010. The data collected in the pre-operative state included: pulmonary function, previous neoadjuvant chemotherapy and comorbidities. In the research, surgical operative data and postoperative data were analyzed. Surgical operative data included information about the bullous emphysema, adhesion in the pleural cavity, anatomic type of lobectomy, additional surgical procedures and air leak after surgery. Postoperative data involved information about amount of fluid on drainage during the first 24 hours and in total, air leak duration in days, total drainage period, overall hospitalization period, prolonged air leak defined as leak longer than 7 days, the need for redrainage of thorax (number of tubes used for redrainage), completeness of pulmonary reexpansion before the end of drainage, other surgical complications, comorbidities and late complications (after more than 30 days following the surgery or release). The first group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of &ndash; 20 cm H2O was applied before clamping and tube extraction. The second group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of &ndash; 20 cm H2O was applied on surgery day and again &ndash; 10 cm H2O before clamping and tube extraction. The third group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of &ndash; 20 cm H2O was applied on surgery day and underwater seal drainage was applied before clamping and tube extraction. The fourth group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of &ndash; 20 cm H2O was applied on surgery day, and then daily monitored and modified in such a way that an aspiration of &ndash; 20 cm H2O was applied until pulmonary reexpansion and then gradually lowered according to individual surgery experience before clamping and tube extraction. RESULTS: There is no significant statistical difference between groups of patients in: age (p=0.77), FEV1 (p=0.6316), ITGV (p=0.6202), TLC (p=0.6922) and RV (p=0.6552) and comorbidities (p=0.4522). The groups are homogenous in pre-operative parameters. Lowered FEV1 among all patients did not affect prolonged air leak (p=0.571), nor the increase in values of ITGV (p=0.22), RV (p=0.912) and TLC (p=0.5211). The lobectomies that were compared were: upper right, upper left, lower right, lower left, middle, as well as upper and lower right bilobectomy. The comparison was implemented only on anatomically different lobectomies cumulatively among groups, due to the low occurrence of each type of lobectomy in groups. The difference in prolonged air leak does exist, but is not statistically significant (p=0.061). Prolonged air leak has a significantly higher occurrence in lower right bilobectomies (p=0.009). Drainage duration and hospitalization period variations in different kinds of lobectomy are statistically significant (p=0.0356 and p=0.0007, respectively). Additional pericardial, thoracic or diaphragm resection, wedge resection of the neighboring lobe, or sleeve bronchial resection did not affect prolonged air leak (p=0.58). The research has established that the occurrence of adhesion (on a scale 0-3) in patients and bulous emphysema attribute to prolonged air leak (p=0.065 and p=0.063, respectively).&nbsp; Comparison between patients with and without adhesions revealed similar result. Difference exists, but it is not statistically significant (p=0,057).&nbsp; Pre-operative chemotherapy had no statistical significance on prolonged air leak (p=0.0623), total rate of complications (p=0.088), nor hospitalization period (p=0.2). Paradoxically, the treatment was in favor of those patients who had taken pre-operative chemotherapy, which could be due to the selection of patients for surgery.&nbsp; Among the four groups, there was no difference in need for thoracic redrainage (p=0.101), need for increase in level of active aspiration (p=0.326), overall complication occurrence (p=0.087) and prolonged air leak occurrence (p=0.323). There is a statistically significant difference in drainage duration (p=0.001) and hospitalization period (p=0.000). The number of tubes (1 or 2 tubes set intraoperatively) did not affect prolonged air leak occurrence (p=0.279). The hospitalization period in patients with one tube set intraoperatively is significantly shorter (p=0.0001). Logistic regression analysis has shown that only lower bilobectomy had a significant impact on prolonged air leak, unlike active drainage aspiration, the presence of adhesions, bullous emphysema or lowered FEV1 values, pleural cavity space reducing, number of tubes and resection. CONCLUSION: The research has shown: Active drainage aspiration has no difference in effect in achieving and maintaining pulmonary reexpansion after lobectomy when compared to underwater seal drainage; Active drainage aspiration does not affect prolonged air leak, defined as air leak longer than 7 days; Active drainage aspiration has an impact on the overall drainage duration and hospitalization period; The level of active drainage aspiration and daily modification of the mentioned do not affect treatment results; Preoperative pulmonary function does not affect prolonged air leak occurrence; Preoperative chemotherapy does not affect prolonged air leak occurrence; Prolonged air leak and drainage and hospitalization period occur most often in lower right bilobectomies; Nor additional resections nor pleural cavity reduction affect prolonged air leak occurrence; The presence of pleural adhesions and bullous emphysema rarely attribute to the increase of prolonged air leak occurrence; The number of tubes implemented intraoperatively does not affect prolonged air leak occurrence, but it shortens drainage and hospitalization periods; By multivariate analysis, that only lower bilobectomy has a significant impact on prolonged air leak, unlike active drainage aspiration, the presence of adhesions, bulous emphysema or lowered FEV1 values, pleural cavity space reducing, number of tubes and resection.

Introduzione La pneumonectomia su modello animale potrebbe essere un’utile piattaforma di studio per approfondire i meccanismi della risposta compensatoria al danno polmonare. Scopo dello studio è determinare la presenza di variazioni morfologiche e di espressione del trascrittoma dopo pneumonectomia. Materiali e metodi Undici suini sono stati sottoposti a pneumonectomia sinistra. Sono stati eseguiti prelievi sito-specifici intraoperatori su polmone sinistro e successivamente confrontati con prelievi sito-specifici su polmone destro dopo eutanasia a 60 giorni. I prelievi degli animali con decorso regolare sono stati sottoposti a RNA-sequencing e successiva analisi computazionale per valutare il peso funzionale del singolo gene o di clusters di geni. Risultati Un animale è stato escluso per insorgenza di ernia diaframmatica. In 7/10 è stata riscontrata apertura della pleura mediastinica con parziale erniazione del polmone controlaterale e shift mediastinico. L’istologia ha mostrato dilatazione degli spazi aerei, rottura dei setti interalveolari, lieve infiammazione, assenza di fibrosi, stiramento radiale dei bronchi e riduzione del letto capillare. L’analisi di bulk RNA-sequencing ha identificato 553 geni espressi in modo differenziale (DEG)(P<0,001) tra pre e post-pneumonectomia. I primi 10 DEG up-regolati: Edn1, Areg, Havcr2, Gadd45g, Depp1, Cldn4, Atf3, Myc, Gadd45b, Socs3; i primi 10 geni down-regolati: Obscn, Cdkn2b, ENSSSCG00000015738, Prrt2, Amer1, Flrt3, Efnb2, Tox3, Znf793, Znf365. Tra i DEG è stata riscontrata una predominanza di geni specifici dei macrofagi. L’analisi di gene ontology basata su DAVID ha mostrato un significativo arricchimento della "via di segnalazione apoptotica estrinseca"(FDR q=7,60x10 -3), della via di “Risposta all’insulina”(FDR q=7,60x10 -3) ed un arricchimento di geni “Regolatori negativi del segnale DDX58/IFIH1”(FDR q=7.50x10 -4). Conclusioni Il presente studio conferma la presenza di variazioni macroscopiche e microscopiche fenotipiche dopo pneumonectomia. L’RNA sequencing e lo studio di genomica traslazionale hanno mostrato l’esistenza di geni singoli e di network di geni disregolati dopo pneumonectomia, prevalentemente in determinate popolazioni cellulari.<br>Introduction Pneumonectomy on animal model could be useful to investigate mechanisms of the compensatory response to lung damage. Aim of the study is to determine the presence of morphological and transcriptome expression changes after pneumonectomy. Materials and methods Eleven pigs underwent left pneumonectomy. Intraoperative site-specific samples were performed on the left lung and subsequently compared with site-specific samples on the right lung after euthanasia at 60 days. The samples of the animals with a uneventful course were subjected to RNA-sequencing and subsequent computational analysis to evaluate the functional weight of the single gene or of clusters of genes. Results One animal was excluded for diaphragmatic hernia. In 7/10 mediastinal pleura was interrupted with partial herniation of the remaining lung and mediastinal shift. Histology showed dilation of the air spaces, rupture of the interalveolar septa, mild inflammation, absence of fibrosis, radial stretching of the bronchi and reduction of the capillary bed. Bulk RNA-sequencing analysis identified 553 differentially expressed genes (DEG) (P <0.001) between pre and post-pneumonectomy state. The top 10 up-regulated DEGs: Edn1, Areg, Havcr2, Gadd45g, Depp1, Cldn4, Atf3, Myc, Gadd45b, Socs3; the top 10 down-regulated genes: Obscn, Cdkn2b, ENSSSCG00000015738, Prrt2, Amer1, Flrt3, Efnb2, Tox3, Znf793, Znf365. A predominance of macrophage-specific genes was found among the DEGs. The DAVID-based gene ontology analysis showed a significant enrichment of the "extrinsic apoptotic signaling pathway" (FDR q = 7.60x10 -3), of the "Insulin response" pathway (FDR q = 7.60x10 - 3) and of “DDX58 / IFIH1 negative regulators” genes (FDR q = 7.50x10 -4). Conclusions The present study confirms the presence of macroscopic and microscopic phenotypic variations after pneumonectomy. This translational genomics study showed the existence of individual genes and networks of genes which resulted disregulated after pneumonectomy, mainly in certain cell populations.

Introdução: O transplante pulmonar tem sido limitado pela escassez de doadores cadavéricos adequados. O transplante pulmonar lobar, utilizando doadores vivos, apresenta-se como uma alternativa para minimizar a mortalidade em lista de espera. Entretanto, este procedimento coloca dois indivíduos saudáveis sob os riscos de uma lobectomia em benefício de um receptor. Objetivo: Avaliar as complicações cirúrgicas no pós-operatório imediato (0-30 dias) de 32 doadores vivos de lobos pulmonares para transplante e a função pulmonar após 30 dias. Métodos: Entre setembro de 1999 e maio de 2005 foram realizadas lobectomias em 32 doadores saudáveis para transplante pulmonar em 16 receptores. Os prontuários médicos destes doadores foram analisados retrospectivamente para verificar a incidência de complicações pós-operatórias e as alterações da função pulmonar pré e pós a lobectomia. Resultados : Vinte doadores (62,5%) não apresentaram complicações. Entre aqueles que apresentaram alguma complicação (n=12) o derrame pleural foi mais freqüente, ocorrendo em 5 deles (15,6%). Três doadores (9,3%) necessitaram de transfusão de sangue e, em dois casos (6,25%), foi necessária nova intervenção cirúrgica por hemotórax. Um doador apresentou pneumotórax após a retirada do dreno de tórax e houve um caso de infecção respiratória. Ocorreram duas complicações intra-operatórias (6,25%): em um doador foi realizada broncoplastia do lobo médio; em outro, foi necessária a ressecção da língula. Não houve mortalidade cirúrgica nesta série. As provas de função pulmonar do pós-operatório demonstraram uma redução média de 17,0% no VEF1 (P<000,1), em comparação com os valores verificados antes da cirurgia. Conclusão: Não houve mortalidade cirúrgica nos primeiros 30 dias após a lobectomia para transplante pulmonar utilizando doadores vivos e os riscos operatórios associados com a lobectomia do doador são semelhantes àqueles observados nas ressecções pulmonares usuais. Um cuidadoso preparo préoperatório é necessário para reduzir a incidência de complicações dos doadores vivos em transplante pulmonar.<br>Introduction: Lung transplantation has been limited by shortage of suitable cadaveric lung donors. Pulmonary lobe transplantation from living donors has been presented as an alternative in order to minimize the waiting list mortality. However, this procedure places two healthy donors to the risks of a lobectomy in benefit of one recipient. Objective: To evaluate the complications of 32 living-donors of pulmonary lobes for transplantation. Methods: From September 1999 to May 2005, lobectomies were performed in 32 healthy donors for lung transplantation in 16 recipients. The medical records of these donors were retrospectively analyzed in order to examine the incidence of postoperative complications and the changes in pulmonary function prior and after lobectomy. Results: Twenty donors (62,5%) had no complications. Among the complications, the most frequent was the pleural effusion, occurring in five donors (15,6%). Red blood cell transfusion was required in 3 donors (9,3%) and two of them had to undergo surgery due to post-operative hemothorax. One donor had a pneumothorax following chest tube withdrawal, and an other developed pneumonia. There were two intraoperative complications (6,25%): one donor had a broncoplasty of the right middle lobe bronchus; the other had a lingular resection. There was no surgical mortality in this study. The postoperative pulmonary function tests demonstrated an average of reduction in 17% in FEV1 (P<000.1), when compared to the preoperative values. Conclusion: There has been no perioperative mortality after lobectomy for living lobar lung transplantation. The perioperative risks associated with donor lobectomy are similar to those seen with standard lung resections. Careful preoperative workup is necessary to reduce the incidence of complications of the living donors for lung transplantation.

Le but de ce travail a été d’étudier la diffusion métastatique à la fois lymphatique et hématogène, par la détection d’une dissémination tumorale occulte, et par l’étude du rôle d’EPO/EPO-R et de VEGF-C/VEGFR-3. L’utilisation d’un panel d’ARNm marqueurs pour la mise en évidence de cellules tumorales occultes en RT-PCR quantitative dans les ganglions médiastinaux a été validée. Avec le même outil, des cellules tumorales circulantes dans la veine pulmonaire de patients opérés ont été détectées dans 30% des cas, sans relation avec la survie ou la réponse à la chimiothérapie. La coexpression de VEGF-C/VEGFR-3 a été retrouvée dans 39% des cas, associée à la prolifération tumorale, à l’envahissement ganglionnaire et à un risque de rechute élevé. Dans les ganglions métastatiques, la coexpression VEGF-C/VEGFR-3 était de 71%. Enfin, l’expression d’EPO/EPO-R par les cellules tumorales était un facteur pronostique péjoratif indépendant chez les patients opérés<br>The purpose of this work was to study the lymphatic as well as hematogeneous metastatic diffusion, by detecting occult tumour cells, and by studying the role of EPO/EPOR and VEGF-C/VEGFR-3. The diagnosis of mediastinal lymph node occult tumor cells using real-time RT-PCR for the detection of a panel of mRNA markers has been validated. By using the same tool, circulating tumour cells have been detected in 30% patients who undergone curative surgery; we failed to find any correlation with survival and response to chemotherapy. VEGF-C/VEGFR-3 expression in tumor cells was investigated in both primitive tumor and metastatic lymp nodes; a coexpression of these factors was observed in 39% of the tumors, and was associated with a high proliferation rate, high risk of lymph node metastasis, and poor survival. VEGF-C/VEGFR-3 were coexpressed in 71% of metastatic tumour cells. Finally, EPO/EPO-R coexpression in tumour cell is an independent poor prognostic factor in patientsundergoing surgery

Objetivo: Analisar o impacto das co-morbidades no desempenho pós-operatório de lobectomia por carcinoma brônquico. Pacientes e Métodos: Entre Janeiro de 1998 e Dezembro de 2004, foram estudados retrospectivamente 493 pacientes submetidos à lobectomia por carcinoma brônquico, dentre os quais 305 preencheram os critérios de inclusão. Todos os pacientes foram submetidos à lobectomias com técnica cirúrgica semelhante. Foi realizada análise das co-morbidades de forma a categorizar os pacientes nas escalas de Torrington-Henderson (PORT) e de Charlson, estabelecendo-se assim grupos de risco para complicações e óbito. Resultados: a mortalidade operatória foi 2,9% e o índice de complicações de 44%. O escape aéreo prolongado foi a complicação mais freqüente (20.6%). A análise univariada mostrou que sexo, idade, tabagismo, terapia neoadjuvante e diabetes apresentaram impacto significativo na incidência de complicações. O índice de massa corporal (23,8 ± 4,4), o VEF1 (74,1±24%), bem como a relação VEF1/CVF (0,65 ± 0,1) foram fatores preditivos da ocorrência de complicações. Ambas as escalas de Charlson e PORT foram eficazes na identificação de grupos de risco e na relação com a morbi-mortalidade (p=0,001 e p<0,001). A análise multivariada identificou que o IMC e o índice de Charlson foram os principais determinantes de complicações, enquanto que o escape aéreo prolongado foi o principal fator envolvido na mortalidade (p=0,01). Conclusão: Valores reduzidos de VEF1, VEF1/CVF e IMC baixo, assim como graus 3-4 de Charlson, e 3 de PORT estão associados a maior número de complicações após lobectomias por carcinoma brônquico. Nesta amostra, o escape aéreo persistente esteve fortemente associado à mortalidade.<br>Objetive: To analyze the impact of comorbidities on the postoperative outcome of patients who underwent lobectomy for lung cancer. Patients and Methods: From January 1998 to December 2004, records of 493 lobectomies for lung cancer were reviewed and 305 met the inclusion criteria. All resections were carried out by the same team using the same surgical technique. The co-morbidity analysis was done in a way that all the patients could be categorized both on the Torrington-Henderson scale (PORT) and the Charlson comorbidity index to identify the highest risk patients as well as the factors involved in morbidity and mortality. Univariate and multivariate analyses were performed to define the impact of comorbidities on the postoperative outcome. Results: the operative mortality was 2.9% and complication rate was 44 %. The univariate analysis showed that gender, age, diabetes, smoking and neoadjuvant chemotherapy had no impact on morbidity. Conversely, BMI (23.8 ± 4), FEV1 (74.1±24%) and FEV1/CVF (0.65 ± 0,1) were predictors of complications (p<0.05). The PORT scale and the Charlson index were both useful to identify the patients at risk and their relationship with morbidity and mortality. The logistic regression showed that BMI (p=0.03) and the Charlson index (p=0.01) were the only significant variables involved in postoperative complications. In this study, prolonged air leak was a factor associated in mortality (p=0.01). Conclusions: low preoperative FEV1, FEV1/FVC, BMI and grades 3-4 on the Charlson and grade 3 on PORT scale were associated to higher postoperative complications. Persistent air leak was a strong predictor of postoperative mortality.

Melhor sincronia entre os compartimentos da caixa torácica tem sido identificada como um dos fatores para a redução da dispnéia e aumento da capacidade de exercício após a cirurgia de redução de volume pulmonar (CRVP).Para elucidar os efeitos da CRVP nas variações de volume da caixa torácica em repouso e durante exercício, seis pacientes (VEF1% 26,5 ± 5,5 e VR 224,6 ± 30,2%) foram avaliados antes CRVP, 1 e 3 meses após a cirurgia. Provas de função pulmonar e teste de caminhada de 6 minutos, mudanças de volume da caixa torácica pulmonar (RCp), caixa torácica abdominal (RCa) e abdome (AB) foram registradas pela Pletismografia Opto-Eletrônica (POE) em repouso e durante um teste de exercício incremental em esteira. Após a CRVP, todos os valores espirométricos, os volumes pulmonares, escores de dispnéia e teste de caminhada de 6 minutos melhoraram significativamente. Antes da cirurgia, volume expiratório final da caixa torácica tendeu a diminuir no início do exercício e aumentar depois. Por outro lado, após a cirurgia, o aumento do volume expiratório final foi significativa a partir de 1 mph para a velocidade máxima, o que foi totalmente devido as mudanças de volume do abdômen. O sincronismo entre PCR e AB também melhorou em 1 e 3 meses após o CRVP (p <0,001, p <0,05, respectivamente). Em conclusão, em pacientes com DPOC grave LVRS modifica a ação da musculatura abdominal expiratória e melhora a sincronização entre a caixa torácica pulmonar e o abdome. Estas melhorias são associadas e, possivelmente, explicam o aumento da capacidade de exercício e da diminuição da dispnéia.<br>Better-synchronized chest wall displacement has been identified as one of the factors for the reduction of dyspnea and increase in exercise capacity after Lung Volume Reduction Surgery (LVRS). To elucidate the effects of LVRS on chest wall volume variations at rest and during exercise six patients (FEV1 26.5±5.5 % and RV 224.6±30.2 %) were studied before LVRS, 1 and 3 months after the surgery. Pulmonary function test and 6-min walking test, volume changes of the pulmonary rib cage (RCp), abdominal rib cage and abdomen (AB) were recorded by Opto-Electronic-Plethysmography (OEP) at rest and during an incremental test on a treadmill. After LVRS, all spirometric and lung volume values, dyspnea scores and 6-minute walking distance significantly improved. Before surgery, end-expiratory volume of the chest wall tended to decrease at the onset of exercise and to increase thereafter. Conversely, after surgery, the increase of end-expiratory volume was significant from 1 mph to the maximum speed and it was totally due to the abdomen. The synchronism between RCp and AB also improved at 1 and 3 month after LVRS (p<0.001,p<0.05, respectively). In conclusion, in severe COPD patients LVRS determines a different action of the abdominal expiratory muscles and a better synchronization between the pulmonary rib cage and abdominal displacement. These improvements are associated to and possibly explain the increased exercise capacity and decreased dyspnea.

Os autores apresentam os resultados obtidos no desenvolvimento de um modelo experimental de fístula brônquica e na comparação de diferentes formas de proteção no modelo de fístula brônquica desenvolvido. Para isso, foram utilizados ratos submetidos a pneumonectomia esquerda e o coto brônquico protegido com músculo intercostal ou gordura pericárdica pediculados. Os resultados demonstraram ser possível o desenvolvimento de um modelo de fístula brônquica em ratos com 65% de confiança e que não há diferença estatística (p>0,05) entre tecidos utilizados na proteção brônquica, desde que sejam pediculados.<br>The authors present the resulte obtained after the development of an experimental model of bronchíal fistula and the comparison among different forms of post-pneumonectomy bronchial fistula protection. In order to achieve 'ha',were used rats that undergone left pneumonectomy whose bronchial stump was protected with either pedided muscle or pedicled fat. The results showed that it was possible to develop a bronchial fistula model with 65% of certainty and there was no slatistical difference (p>0,05) among the tissues used for bronchial protection, once they were pedicled.

碩士<br>國防醫學院<br>生理學研究所<br>96<br>Pneumonectomy (PnX) still remains a challenging surgical intervention. It causes major anatomical changes that must have an extensive effect on spatial distribution of ventilation (VA) and perfusion (Q) in the lung. Turning and positioning of critical ill patient are well-accepted routine nursing activities. There has a clinical report that patients of life-threatening hypoxemia occurring during postpneumonectomy edema (PPE) successfully managed with lateral decubitus (LD), with the remaining lung placed uppermost. However, the mechanism remains unclear. Our study uses fluorescent microspheres (FMS) technique to measure the spatial distribution of regional VA and Q post left PnX and on left and right LD. According to the FMS we may tell how the LD improves oxygenation. Pulmonary Q and VA were analyzed with intravenous and inhaled FMS (15 and 1 micro meter) in piglets (23.4 ± 1.9 kg) studied in baseline – supine (BS), postPnX – supine (PS), postPnX – RLD (PR) and postPnX – LLD (PL) four conditions. Using the multiple inert gas elimination technique (MIGET), we determined the distribution of VA/Q ratio in whole lung. Lungs were dried and sectioned into approximately 431 ± 36 pieces (about 1.7 cm3) per animal. Fluorescence was read on a spectrophotometer. Signals were analyzed after corrected for pieces weight and normalized to mean VA and mean Q. According to the results, arterial O2 pressure (PaO2) was decreased post left PnX, and both VA and Q became bimodal distribution, and both of them moved to high VA/Q region. Base on FMS data, we found Q had huge redistribution and its spatial distribution become more heterogeneous. Q moved to dorsal and central part while VA moved to ventral and peripheral part of the remaining lung. The coefficient of correlation (R value) between VA and Q decreased significantly in PS. After turning to LLD posture, both VA and Q became one peak distribution, and was centered at VA/Q – ratio = 1 region. The R value between VA and Q significantly increased from 0.13 ± 0.03 to 0.50 ± 0.20, and PaO2 also improved from 148.6 ± 18.6 to 200.9 ± 14.1 mmHg in PL. In conclusion, VA and Q become mismatching as a result of Q redistribution post PnX, and PaO2 also decreased. LLD posture can make the spatial distribution of Q becomes homogenous, and it also can less the compression of heat and abdomen to the lung, and the functional residual capacity also increases significantly that could improve the ventilation. Therefore, LLD posture can increase PaO2 significantly through the improvement of VA/Q – matching.

碩士<br>國防醫學院<br>生理學研究所<br>103<br>Pulmonary arterial hypertension (PAH) is characterized by abnormal increase in pulmonary arteries (PAs) resistance and right ventricular (RV) hypertrophy. 7, 8-Dihydroxyflavone (7, 8-DHF) is a neuroprotective effect, and that has anti-inflammatory and antioxidant activities. However, whether 7,8-DHF improves the PAH remains unknown. Therefore, the aim of this study was to investigate whether 7, 8-DHF has beneficial effect on pneumonectomy and monocrotaline (P/M)-induced PAH in rats. The PAH model was established in rats injected with monocrotaline (60 mg/kg) at Day 7 after pneumonectomy. The PAH rats were treated intraperitoneally with vehicle or 7, 8- DHF (20 and 40 mg/kg/2 day, respectively) from Day 14 to Day 35 after pneumonectomy. We found that therapeutic administration with 7,8-DHF attenuated the development of PAH, as shown by lower values for RV systolic pressure and hypertrophy, and histopathological change of vascular remodeling of PAs including vascular wall thickening. The decreased endothelial nitric oxide synthase (eNOS), increased inducible NOS, endothelin-1(ET-1) level and ETA receptor (ETAR), and overproduction of superoxide observed in the lung of PAH rats, were marklly decreased by 7,8-DHF. PAH also induced glycogen synthase kinase-3β(GSK3β) phosphorylation in pulmonary artery smooth muscle cell and β-catenin, accompanied by ERK 1/2 phosphorylation of the lung, which was inhibited by 7,8-DHF. In addition 7,8-DHF increased H0-1(heme oxygenase-1,HO-1) and Nrf2 (nuclear factor erythroid-2-related factor, Nrf2)expression. In conclusion, we demonstrate for the first time that treatment with 7,8DHF exerts a beneficial effect in P/M induced PAH through inhibition GSK3β/β-catenin but enhancement of Nrf2/HO-1induction attenuated PAH