OBJETIVO: Determinar la eficacia de dos dosis de radioyodo para la ablación del remanente tiroideo en pacientes con Cáncer Diferenciado de Tiroides que presentan metástasis ganglionar locoregional. METODOLOGÍA: El estudio fue de diseño experimental del tipo muestreo aleatorio simple. La muestra estuvo conformada por 40 pacientes con el diagnóstico de Cáncer diferenciado de tiroides con evidencia de metástasis ganglionar locoregional. Los pacientes fueron inscritos y randomizados en dos grupos, el grupo experimental (3700 MBq I-131) y grupo control (5550 MBq I-131). En relación a nuestro estudio la medición de la eficacia fue un rastreo corporal total con I-131 negativo, porcentaje de captación a las 24 horas < 0,5 % y tiroglobulina sérica < 2 ng/ml. RESULTADOS: Cuando se definió el éxito la ablación, solamente con el rastreo corporal con I-131 negativo, no se encontraron diferencias entre el grupo de estudio(100 %, P=0.31) y el grupo control (94,4 %, para un P>0.05). Cuando se consideró el rastreo corporal total con I-131 más el valor de corte de la tiroglobulina sérica <2 ng/ml, si hubo diferencia significativa en la tasa de éxito de la ablación entre el grupo de estudio y el grupo control (P=0,006). CONCLUSIÓN: La eficacia de la ablación del remanente tiroideo usando dosis de 3700 MBq es similar al de 5550 MBq de radioyodo en pacientes con cáncer diferenciado de tiroides que presentan metástasis ganglionar locoregional.

Intra-arterial or percutaneous locoregional therapies (LRT) are often employed to maintain potential liver transplant (LT) recipients with hepatocellular carcinoma (HCC) within T2/Milan criteria. Predictors of survival when LRT is used as destination therapy in those who are either ineligible or unwilling for LT remain poorly defined. We evaluated predictors of 3-year survival with destination LRT in a population of cirrhotic patients diagnosed with HCC, presenting within T2 criteria, and either ineligible or unwilling for LT. The cohort surviving 3 years had a significantly lower model for end-stage liver disease (MELD) score at HCC diagnosis (9.7 vs. 11.4, P= 0.037) and MELD following initial locoregional therapy (10.7 vs. 13.3, P= 0.008) compared to those not surviving three years despite similar demographic, tumor, and treatment variables. LRT as destination therapy results in modest intermediate term survival, with liver function at presentation and immediately following initiation of LRT predicting intermediate survival with this approach.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23566号 / 医博第4780号 / 新制||医||1054(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 武藤 学, 教授 佐藤 俊哉, 教授 羽賀 博典 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Submitted by Simone Souza (simonecgsouza@hotmail.com) on 2018-05-15T13:49:55Z No. of bitstreams: 1 DISS_2015_Daiane Cristina Winter.pdf: 535766 bytes, checksum: f5395d3952e03a361e7e71fb8aa3084b (MD5) / Approved for entry into archive by Jordan (jordanbiblio@gmail.com) on 2018-05-24T16:39:31Z (GMT) No. of bitstreams: 1 DISS_2015_Daiane Cristina Winter.pdf: 535766 bytes, checksum: f5395d3952e03a361e7e71fb8aa3084b (MD5) / Made available in DSpace on 2018-05-24T16:39:31Z (GMT). No. of bitstreams: 1 DISS_2015_Daiane Cristina Winter.pdf: 535766 bytes, checksum: f5395d3952e03a361e7e71fb8aa3084b (MD5) Previous issue date: 2015-03-06 / CAPES / A anestesia epidural é uma técnica anestésica locorregional que proporciona analgesia e relaxamento muscular na região retroumbilical. A associação de opioides com os anestésicos locais contribui para o aumento da intensidade e prolongamento da analgesia, ocorrendo bloqueio sensitivo e motor imediato, melhorando a recuperação no período pós-operatório. Objetivou-se avaliar comparativamente no trans- e pós-operatório, os efeitos cardiorrespiratórios e a analgesia proporcionada pelo tramadol, ropivacaína ou sua associação, pela via epidural, bem como o requerimento anestésico do isoflurano no trans-operatório, em cadelas submetidas à ovariosalpingohisterectomia eletiva. Este estudo foi realizado com 24 fêmeas da espécie canina, pré-medicadas com clorpromazina (0,5mg/Kg IV), anestesiadas com propofol (à efeito) e isoflurano, e distribuídas aleatoriamente em três grupos, nas quais foi utilizado pela via epidural 2mg/Kg de tramadol (GT), 1,5mg/Kg de ropivacaína (GR) ou sua associação (GTR) nas doses citadas anteriormente. Em momentos pré-definidos, dos períodos pré, trans- e pós-operatório, foram analisadas variáveis cardiorrespiratórias e a analgesia por um período de até 420 minutos após a anestesia epidural. Pode-se verificar analgesia de aproximadamente 105, 217 e 382 minutos, no GR, no GT e no GTR respectivamente, e ausência de depressão cardiovascular e respiratória. Os fármacos utilizados neste estudo podem ser considerados seguros e eficientes para a técnica cirúrgica em questão devido à estabilidade cardiorrespiratória e analgesia trans-operatória, porém, a associação de ropivacaína e tramadol promoveu maior redução no anestésico inalatório e melhor analgesia no período pós-operatório. / Epidural anesthesia is a locoregional anesthetic technique that provides analgesia and muscle relaxation in retroumbilical region. The combination of opioids and local anesthetics contributes to increasing the intensity and prolongation of analgesia occurring immediately motor and sensory block, improving recovery after surgery. The aim was to comparatively evaluate the trans- and postoperative cardiorespiratory effects and analgesia provided by tramadol, ropivacaine or its association, epidural, and the anesthetic requirement of isoflurane during surgery, in canines undergoing elective ovariohysterectomy. This study was performed with 24 female canine species, pre-medicated with chlorpromazine (0.5mg/kg IV), anesthetized with propofol (the effect) and isoflurane and randomly divided into three groups, which was employed in epidural 2mg/kg tramadol (GT), 1.5mg/kg ropivacaine (GR) or their association (GTR) in the above-mentioned doses. In pre-defined times, the periods before, during and postoperative, cardiorespiratory variables and analgesia were analyzed for a period of up to 420 minutes after epidural anesthesia. Analgesia was observed of approximately 105, 217 and 382 minutes, in GR, in GT and GTR respectively, and there was nor cardiovascular neither respiratory depression. The drugs tested in this study can be considered safe and effective in the surgical technique in question due to cardiorespiratory stability and trans-operative analgesia, however, the combination of ropivacaine and tramadol promoted greater reduction in inhaled anesthetic and better analgesia in the postoperative period.

Small Intestinal Neuroendocrine Tumors (SI-NETs) are indolent neoplasms with an increasing annual incidence of approximately 1/100 000 people. They are often diagnosed at a late stage, restricting treatment efficacy. The aim of this thesis was to investigate clinical aspects of patients with advanced and/or disseminated disease with regard to clinical signs and management of abdominal fibrosis, the role of locoregional surgery and liver transplantation, as well as the ex vivo sensitivity of tumor samples to cytotoxic and targeted agents. Additionally, novel serum biomarkers for the diagnosis and prognosis of SI-NETs were investigated. In Paper I, abdominal fibrosis induced by serotonin and other cytokines from tumor cells, was associated with clinically significant symptoms of intestinal ischemia and/or obstructive uropathy, and was linked to advanced disease. Prompt recognition and minimally invasive intervention with superior mesenteric vein stenting and/or percutaneous nephrostomy and J stent treatment were effective in disease palliation. Paper II challenged the role of prophylactic, upfront locoregional surgery in Stage IV, which conferred no survival advantage in asymptomatic SI-NET patients. The option of delayed surgery as needed seemed to be comparable in all the outcomes examined, whilst also offering the advantage of fewer re-operations for intestinal obstruction in patients with already disseminated disease. Paper III confirmed that most young patients (&lt;65 years) with SI-NET and liver metastases had a favorable survival with standardized multimodality treatment and that survival figures reported after liver transplantation for NETs do not surpass these figures. In Paper IV, 145 biomarkers were analyzed in blood serum using two different multiplex proximity assays. Subsequent ELISA and immunohistochemical analyses identified DcR3, TFF3 and midkine as novel serum biomarkers for SI-NETs. In Paper V, SI-NET samples were profiled with respect to sensitivity ex vivo to a panel of standard chemotherapeutics and targeted agents using a short-term total cell kill assay. SI-NETs exhibited variable but generally intermediate sensitivity ex vivo compared with other cancer diagnoses, calling for individualized selection of therapy.

Este estudo teve por objetivo investigar os efeitos analgésicos trans e pós-operatórios da administração epidural da ropivacaína associada à morfina e/ou xilazina em cadelas submetidas a mastectomia unilateral total. Poucos são os relatos na literatura sobre uso de epidural mastectomia radical. Foram utilizadas 23 cadelas, pre-medicadas com acepromazina (0,02 mg/kg IM) e morfina (0,3 mg/kg IM) , e anestesiadas com propofol e posteriormente isofluorano associado à anestesia epidural com um dos três tratamentos: grupo RM (n=7), ropivacaína com morfina (0,75 e 0,1 mg/kg respectivamente); grupo RX (n=8), ropivacaína com xilazina (0,75 e 0,1 mg/kg respectivamente); e grupo RMX (n=7), ropivacaína associada à morfina e xilazina nas mesmas doses. O volume padronizado final dos tratamentos epidurais foi de 0,35 mL/kg ao serem diluídos com solução salina. Foram avaliados parâmetros cardiovasculares e respiratórios em seis momentos: Basal (durante a anestesia inalatória, antes da anestesia epidural), pós-epidural (30 minutos após tratamento epidural), T1, T2 e T3 (durante incisão da pele e divulsão do tecido dos terços caudal, médio e cranial da cadeia mamária, respectivamente) e T4 (rafia). Os escores de dor (escalas de Glasgow e EAVID) e necessidade de resgates analgésicos no pós-operatório foram avaliados durante 24 horas Houve menor requerimento de isofluorano nos animais dos grupos RX (1,1±0,2% em T3 e T4) e RMX (0,9 a 1,0±0,2% em T2, T3 e T4) versus o RM (1,3±0,2%). Nos grupos RX e RMX, houve diminuição da frequência cardíaca (RX no pós-epidural e em RMX no pós-epidural e T3) quando comparada com o basal mas não houve variações das pressões arteriais intra-grupo nem entre os grupos. O resgate pós-operatório foi necessário em 85,7%, 14,3% e 25,0% dos animais dos grupos RX, RM e RMX respectivamente. Os escores de dor foram menores nas primeiras quatro horas de pós-operatório no grupo RMX versus RX. Os animais do grupo RX demoraram mais para se manter em posição quadrupedal que o grupo RM (335 ± 82 versus 113 ± 69 minutos respectivamente) e teve maiores tempos de bloqueio motor (299 ± 90 versus 195 ± 37 minutos respectivamente). Quando administrados por via epidural, os três tratamentos fornecem analgesia trans-operatória aceitável para cadelas submetidas à mastectomia unilateral total, com mínimos efeitos cardiovasculares. A analgesia pós-operatória é mais prolongada nos protocolos de anestesia que têm morfina na sua composição (RM e RMX). Os protocolos com xilazina podem reduzir o requerimento de isofluorano, mas podem retardar o tempo de deambulação das cadelas. / This study aimed to investigate the intra and postoperative analgesic effects of epidural administration of ropivacaine combined with morphine and/or xylazine in bitches undergoing total unilateral mastectomy. There are few reports in the literature on the use of epidural in radical mastectomy. Twenty-three bitches were pre-medicated with acepromazine (0.02 mg/kg IM) and morphine (0.3 mg/kg IM) and anesthetized with propofol and isoflurane associated with epidural anesthesia with one of three treatments: RM group (n = 7), ropivacaine with morphine (0.75 and 0.1 mg/kg respectively); RX group (n = 8), ropivacaine with xylazine (0.75 and 0.1 mg/kg respectively); and RMX group (n = 7), ropivacaine combined with morphine and xylazine at the same doses. The final standarized volume of the epidural treatments was 0.35 mL/kg when diluted with saline solution. Cardiovascular and respiratory parameters were evaluated in six moments: Basal (during inhalational anesthesia, before epidural anesthesia), post-epidural (30 minutes after epidural treatment), T1, T2 and T3 (skin incision and divulsion of the caudal, middle and cranial thirds of the mammary chain, respectively) and T4 (raffia). Pain scores (Glasgow scales and EAVIDs) and the need for postoperative analgesic rescues were evaluated for 24 hours The intraoperative requirement for isofliurane was lower in the RX (1.1±0.2% in T3 and T4) and RMX (0.9 to 1.0±0.2% in T2, T3 and T4) groups versus RM group (1.3±0.2%). Heart rate decreased bellow baseline in the RX and RMX groups, (post-epidural in RX group and post-epidural and T3 in RMX group) when compared to baseline but there was no significant change in blood pressure within any group or among groups. Postoperative analgesic rescue was necessary in 85.7%, 14.3% and 25.0% of the animals of the RX, RM and RMX groups, respectively. Pain scores were significantly lower from 1 to 4 hours postoperatively in the RMX versus RX group. Time to standing was longer in the RX group than the RM group (335 ± 82 versus 113 ± 69 minutes, respectively) and duration of motor block was also longer in the RX compared to the RM group (299 ± 90 versus 195 ± 37 minutes respectively). When administered epidurally, all three treatments provide acceptable intraoperative analgesia for bitches undergoing total unilateral mastectomy with minimal cardiovascular adverse effects. Postoperative analgesia is longer in protocols containing morphine (RM and RMX groups). Protocols containing xylazine may reduce the intraoperative requirement of isoflurane, but may prolong the time until ambulation of the dogs.

Este estudo teve por objetivo investigar os efeitos analgésicos trans e pós-operatórios da administração epidural da ropivacaína associada à morfina e/ou xilazina em cadelas submetidas a mastectomia unilateral total. Poucos são os relatos na literatura sobre uso de epidural mastectomia radical. Foram utilizadas 23 cadelas, pre-medicadas com acepromazina (0,02 mg/kg IM) e morfina (0,3 mg/kg IM) , e anestesiadas com propofol e posteriormente isofluorano associado à anestesia epidural com um dos três tratamentos: grupo RM (n=7), ropivacaína com morfina (0,75 e 0,1 mg/kg respectivamente); grupo RX (n=8), ropivacaína com xilazina (0,75 e 0,1 mg/kg respectivamente); e grupo RMX (n=7), ropivacaína associada à morfina e xilazina nas mesmas doses. O volume padronizado final dos tratamentos epidurais foi de 0,35 mL/kg ao serem diluídos com solução salina. Foram avaliados parâmetros cardiovasculares e respiratórios em seis momentos: Basal (durante a anestesia inalatória, antes da anestesia epidural), pós-epidural (30 minutos após tratamento epidural), T1, T2 e T3 (durante incisão da pele e divulsão do tecido dos terços caudal, médio e cranial da cadeia mamária, respectivamente) e T4 (rafia). Os escores de dor (escalas de Glasgow e EAVID) e necessidade de resgates analgésicos no pós-operatório foram avaliados durante 24 horas Houve menor requerimento de isofluorano nos animais dos grupos RX (1,1±0,2% em T3 e T4) e RMX (0,9 a 1,0±0,2% em T2, T3 e T4) versus o RM (1,3±0,2%). Nos grupos RX e RMX, houve diminuição da frequência cardíaca (RX no pós-epidural e em RMX no pós-epidural e T3) quando comparada com o basal mas não houve variações das pressões arteriais intra-grupo nem entre os grupos. O resgate pós-operatório foi necessário em 85,7%, 14,3% e 25,0% dos animais dos grupos RX, RM e RMX respectivamente. Os escores de dor foram menores nas primeiras quatro horas de pós-operatório no grupo RMX versus RX. Os animais do grupo RX demoraram mais para se manter em posição quadrupedal que o grupo RM (335 ± 82 versus 113 ± 69 minutos respectivamente) e teve maiores tempos de bloqueio motor (299 ± 90 versus 195 ± 37 minutos respectivamente). Quando administrados por via epidural, os três tratamentos fornecem analgesia trans-operatória aceitável para cadelas submetidas à mastectomia unilateral total, com mínimos efeitos cardiovasculares. A analgesia pós-operatória é mais prolongada nos protocolos de anestesia que têm morfina na sua composição (RM e RMX). Os protocolos com xilazina podem reduzir o requerimento de isofluorano, mas podem retardar o tempo de deambulação das cadelas. / This study aimed to investigate the intra and postoperative analgesic effects of epidural administration of ropivacaine combined with morphine and/or xylazine in bitches undergoing total unilateral mastectomy. There are few reports in the literature on the use of epidural in radical mastectomy. Twenty-three bitches were pre-medicated with acepromazine (0.02 mg/kg IM) and morphine (0.3 mg/kg IM) and anesthetized with propofol and isoflurane associated with epidural anesthesia with one of three treatments: RM group (n = 7), ropivacaine with morphine (0.75 and 0.1 mg/kg respectively); RX group (n = 8), ropivacaine with xylazine (0.75 and 0.1 mg/kg respectively); and RMX group (n = 7), ropivacaine combined with morphine and xylazine at the same doses. The final standarized volume of the epidural treatments was 0.35 mL/kg when diluted with saline solution. Cardiovascular and respiratory parameters were evaluated in six moments: Basal (during inhalational anesthesia, before epidural anesthesia), post-epidural (30 minutes after epidural treatment), T1, T2 and T3 (skin incision and divulsion of the caudal, middle and cranial thirds of the mammary chain, respectively) and T4 (raffia). Pain scores (Glasgow scales and EAVIDs) and the need for postoperative analgesic rescues were evaluated for 24 hours The intraoperative requirement for isofliurane was lower in the RX (1.1±0.2% in T3 and T4) and RMX (0.9 to 1.0±0.2% in T2, T3 and T4) groups versus RM group (1.3±0.2%). Heart rate decreased bellow baseline in the RX and RMX groups, (post-epidural in RX group and post-epidural and T3 in RMX group) when compared to baseline but there was no significant change in blood pressure within any group or among groups. Postoperative analgesic rescue was necessary in 85.7%, 14.3% and 25.0% of the animals of the RX, RM and RMX groups, respectively. Pain scores were significantly lower from 1 to 4 hours postoperatively in the RMX versus RX group. Time to standing was longer in the RX group than the RM group (335 ± 82 versus 113 ± 69 minutes, respectively) and duration of motor block was also longer in the RX compared to the RM group (299 ± 90 versus 195 ± 37 minutes respectively). When administered epidurally, all three treatments provide acceptable intraoperative analgesia for bitches undergoing total unilateral mastectomy with minimal cardiovascular adverse effects. Postoperative analgesia is longer in protocols containing morphine (RM and RMX groups). Protocols containing xylazine may reduce the intraoperative requirement of isoflurane, but may prolong the time until ambulation of the dogs.

Este estudo teve por objetivo investigar os efeitos analgésicos trans e pós-operatórios da administração epidural da ropivacaína associada à morfina e/ou xilazina em cadelas submetidas a mastectomia unilateral total. Poucos são os relatos na literatura sobre uso de epidural mastectomia radical. Foram utilizadas 23 cadelas, pre-medicadas com acepromazina (0,02 mg/kg IM) e morfina (0,3 mg/kg IM) , e anestesiadas com propofol e posteriormente isofluorano associado à anestesia epidural com um dos três tratamentos: grupo RM (n=7), ropivacaína com morfina (0,75 e 0,1 mg/kg respectivamente); grupo RX (n=8), ropivacaína com xilazina (0,75 e 0,1 mg/kg respectivamente); e grupo RMX (n=7), ropivacaína associada à morfina e xilazina nas mesmas doses. O volume padronizado final dos tratamentos epidurais foi de 0,35 mL/kg ao serem diluídos com solução salina. Foram avaliados parâmetros cardiovasculares e respiratórios em seis momentos: Basal (durante a anestesia inalatória, antes da anestesia epidural), pós-epidural (30 minutos após tratamento epidural), T1, T2 e T3 (durante incisão da pele e divulsão do tecido dos terços caudal, médio e cranial da cadeia mamária, respectivamente) e T4 (rafia). Os escores de dor (escalas de Glasgow e EAVID) e necessidade de resgates analgésicos no pós-operatório foram avaliados durante 24 horas Houve menor requerimento de isofluorano nos animais dos grupos RX (1,1±0,2% em T3 e T4) e RMX (0,9 a 1,0±0,2% em T2, T3 e T4) versus o RM (1,3±0,2%). Nos grupos RX e RMX, houve diminuição da frequência cardíaca (RX no pós-epidural e em RMX no pós-epidural e T3) quando comparada com o basal mas não houve variações das pressões arteriais intra-grupo nem entre os grupos. O resgate pós-operatório foi necessário em 85,7%, 14,3% e 25,0% dos animais dos grupos RX, RM e RMX respectivamente. Os escores de dor foram menores nas primeiras quatro horas de pós-operatório no grupo RMX versus RX. Os animais do grupo RX demoraram mais para se manter em posição quadrupedal que o grupo RM (335 ± 82 versus 113 ± 69 minutos respectivamente) e teve maiores tempos de bloqueio motor (299 ± 90 versus 195 ± 37 minutos respectivamente). Quando administrados por via epidural, os três tratamentos fornecem analgesia trans-operatória aceitável para cadelas submetidas à mastectomia unilateral total, com mínimos efeitos cardiovasculares. A analgesia pós-operatória é mais prolongada nos protocolos de anestesia que têm morfina na sua composição (RM e RMX). Os protocolos com xilazina podem reduzir o requerimento de isofluorano, mas podem retardar o tempo de deambulação das cadelas. / This study aimed to investigate the intra and postoperative analgesic effects of epidural administration of ropivacaine combined with morphine and/or xylazine in bitches undergoing total unilateral mastectomy. There are few reports in the literature on the use of epidural in radical mastectomy. Twenty-three bitches were pre-medicated with acepromazine (0.02 mg/kg IM) and morphine (0.3 mg/kg IM) and anesthetized with propofol and isoflurane associated with epidural anesthesia with one of three treatments: RM group (n = 7), ropivacaine with morphine (0.75 and 0.1 mg/kg respectively); RX group (n = 8), ropivacaine with xylazine (0.75 and 0.1 mg/kg respectively); and RMX group (n = 7), ropivacaine combined with morphine and xylazine at the same doses. The final standarized volume of the epidural treatments was 0.35 mL/kg when diluted with saline solution. Cardiovascular and respiratory parameters were evaluated in six moments: Basal (during inhalational anesthesia, before epidural anesthesia), post-epidural (30 minutes after epidural treatment), T1, T2 and T3 (skin incision and divulsion of the caudal, middle and cranial thirds of the mammary chain, respectively) and T4 (raffia). Pain scores (Glasgow scales and EAVIDs) and the need for postoperative analgesic rescues were evaluated for 24 hours The intraoperative requirement for isofliurane was lower in the RX (1.1±0.2% in T3 and T4) and RMX (0.9 to 1.0±0.2% in T2, T3 and T4) groups versus RM group (1.3±0.2%). Heart rate decreased bellow baseline in the RX and RMX groups, (post-epidural in RX group and post-epidural and T3 in RMX group) when compared to baseline but there was no significant change in blood pressure within any group or among groups. Postoperative analgesic rescue was necessary in 85.7%, 14.3% and 25.0% of the animals of the RX, RM and RMX groups, respectively. Pain scores were significantly lower from 1 to 4 hours postoperatively in the RMX versus RX group. Time to standing was longer in the RX group than the RM group (335 ± 82 versus 113 ± 69 minutes, respectively) and duration of motor block was also longer in the RX compared to the RM group (299 ± 90 versus 195 ± 37 minutes respectively). When administered epidurally, all three treatments provide acceptable intraoperative analgesia for bitches undergoing total unilateral mastectomy with minimal cardiovascular adverse effects. Postoperative analgesia is longer in protocols containing morphine (RM and RMX groups). Protocols containing xylazine may reduce the intraoperative requirement of isoflurane, but may prolong the time until ambulation of the dogs.