La résection hépatique est le seul traitement curatif des tumeurs malignes du foie et l’insuffisance hépatique est la première cause de morbi-mortalité après hépatectomie. L’amélioration du traitement des tumeurs du foie inclut le dévelopement de statégies capables de prévenir ou de traiter cette complication. Sur une série prospective récente de 232 hépatectomies (avec 0,8 % de mortalité à 3 mois) pour métastases hépatiques de cancer colorectal (MHCCR), une insuffisance hépatique était présente dans 7 % des cas d’hépatectomies majeures et était le facteur de plus mauvais pronostic pour la survie à 2 ans. Notre objectif a été d’évaluer de nouvelles approches thérapeutiques pour leur capacité à corriger l’insuffisance hépatique post-opératoire après hépatectomie élargie pour MHCCR. Un moyen mécanique de modulation pneumatique de l’hémodynamique portale et un moyen pharmacologique d’utilisation d’un facteur de survie des hépatocytes, la protéine recombinante HIP/PAP, ont été testés respectivement chez le porc et le rat. Nous montrons qu‘après hépatectomie (PHX) de 70 % sur foie normal, l’injection systémique de protéine HIP/PAP en péri-opératoire stimulait la régénération hépatique et améliorait la fonction hépatique chez le rat. En présence de MHCCR en place depuis 7 jours, la protéine HIP/PAP n’aggravait pas la maladie métastatique, et semblait au contraire diminuer la croissance tumorale après hépatectomie. In vitro, HIP/PAP n’augmentait pas la croissance tumorale de lignées cellulaires transformées dérivées de cancer du colon. Chez le porc, une sténose portale pneumatique pendant et après PHX majeure laissant en place moins de 0,5% du poids corporel entraînait une diminution de la pression portale intra-hépatique sans modifier le débit comparé au groupe sans anneau. Cette modulation de la pression était associée à une diminution significative de la bilirubine sérique et des lésions histologiques du foie restant au 7ème jour après chirurgie. Au total, il serait possible grâce à la protéine HIP/PAP et à l’anneau portal de corriger l’insuffisance hépatique post-hépatectomie en protégeant les cellules du foie de la mort et du stress secondaires aux modifications hémodynamiques et biochimiques. La question de leur association pour diminuer l’incidence de l’insuffisance hépatique reste entière. / Liver resection is the only curative treatment of tumoral liver malignancies and post-operative liver insufficiency is the 1st cause of post-operative mortality. Tumor liver treatment improvements must be associated to innovatives methods to prevent and cure this complication. On a recent prospective study including 232 hepatectomies (with a 3-month post-operative mortality of 0.8 %) for colorectal liver metastases (CRLM), post-operative liver insufficiency was present after 7 % of major hepatectomies and was the worst 2-year survival prognostic factor. To prevent this complication, we have evaluated a perioperative systemic injection of a recombinant anti-oxydant protein (HIP/PAP) before a major hepatectomy for CRLM in rats. In vitro then in model of implanted CLRM since 7 days, we have showed that HIP/PAP did not increased tumoral growth. After 70 % hepatectomy, perioperative systemic HIP/PAP injection improved liver function. After 70 % hepatectomy, HIP/PAP seemed decrease tumoral growth of implanted CRLM. On pig, we have assessed the consequences of a portal vein stenosis with pneumatic ring during and after a major hepatectomy that conserved a liver volume < 0.5 % of body weight. With this method, we have showed that the portal stenosis decreased intra-hepatic portal pressure wihout modify the portal flow by comparison with pigs without ring. This device was associated with a significant diminution of bilirubin plasmatic concentration and liver remnant histological lesions at sacrifice on post-operative day 7. Overall, chemical and physical methods and moreover their combination should allowed to decrease post-operative liver insufficicency.

No Brasil a principal causa de hipertensão portal é a esquistossomose mansônica na sua forma hepato-esplênica, classificada como pré-sinusoidal. Esta doença adquire grande importância epidemiológica, por acometer indivíduos jovens, com função hepática preservada, e por atingir uma grande parcela da população (cerca de 1 milhão de indivíduos). Destes, cerca de 12 a 52% irão apresentar hemorragia digestiva por ruptura de varizes de esôfago. Não existe até o momento nenhum tratamento que se estabeleça como de consenso para esta enfermidade, porém há uma preferência dos autores para o tratamento cirúrgico e, no Brasil, esta recai sobre a desconexão ázigo-portal e esplenectomia geralmente associada a escleroterapia endoscópica das varizes no pós-operatório. Não estão bem estabelecidas as alterações hemodinâmicas portais decorrentes do tratamento cirúrgico da hipertensão portal e sua influência no resultado deste tratamento. Com o objetivo de avaliar o impacto imediato da desconexão ázigo-portal e esplenectomia (DAPE) na pressão portal e os resultados do tratamento cirúrgico da hipertensão portal no que se refere à recidiva hemorrágica e ao calibre das varizes de esôfago, foram estudados 19 pacientes portadores de esquistossomose hepato-esplênica e hipertensão portal com história de hemorragia digestiva alta por ruptura de varizes esofágicas, com idade média de 37,9 anos. Durante a cirurgia foi avaliada a pressão portal, no início e no final do procedimento através da cateterização da veia porta por cateter de polietileno introduzido por veia jejunal. Todos os pacientes foram submetidos à endoscopia no pré e pós-operatório para avaliar a variação do calibre das varizes esofágicas. Os pacientes foram acompanhados ambulatorialmente e o tempo médio de seguimento foi de 26 meses. Como resultado obteve-se uma queda na pressão portal média de 31,3% após a DAPE (p=0,0001). No acompanhamento pós-operatório houve redução significativa do calibre das varizes esofágicas quando comparadas com a avaliação pré-operatória (p < 0,05). Apenas um paciente (8,3%) apresentou, durante o acompanhamento, recidiva hemorrágica porém, esta foi decorrente de úlcera gástrica e não de varizes esofágicas. Por fim chegou-se à conclusão de que a desconexão ázigo-portal e esplenectomia promoveu queda imediata na pressão portal, com conseqüente diminuição do calibre das varizes esofágicas, tendo sido eficaz no tratamento da hipertensão portal destes pacientes / The main cause of portal hypertension in Brazil is the hepato-splenic form of mansonic schistosomiasis, which is classified as pre-sinusoidal. It acquires major epidemiological importance because it occurs in young individuals and affects a huge parcel of the population (around 1 million people), 12 to 52% of whom will present digestive hemorrhage due to rupture of esophageal varices. There is no consensus treatment for this disease up to the moment, but there is a predilection for the surgical approach. In Brazil, the most employed technique is the esophagogastric devascularization with splenectomy (EGDS), generally associated to late postoperative endoscopical sclerotherapy of the esophageal varices. The hemodynamic alterations in the portal flow resulting from the surgery and their possible influences on the outcome are not well established. With the aim of evaluating the immediate impact of the EGDS upon the portal pressure as well as the results of the surgical treatment on the digestive hemorrhage recurrence and the caliber of the esophageal varices, 19 patients (11males, aged between 18 and 61 years) with hepato-splenic schistosomiasis, presenting portal hypertension and previous episodes of digestive hemorrhage were studied. None of the patients had received any treatment prior to the surgery. The portal pressure was assessed at the beginning and the end of the EGDS through catheterization of the portal vein with a polyethylene catheter introduced through a branch of a jejunal vein. All the patients were submitted to digestive endoscopy before and after the surgery (2 months), in order to classify the caliber of the esophageal varices according to Palmer\'s classification. They also entered the continuous program of endoscopical evaluation and sclerotherapy. The mean clinical follow up period was 26 months. Our results showed that the portal pressure had diminished in all the patients, with a mean decrease of 31.3% after the EGDS. In the postoperative follow up (1 month), the esophageal varices showed a statistically significant reduction in their calibers, when compared to the pre-surgical measurements (p=0.004). Only one patient presented digestive hemorrhage during the follow up period, but it was due to gastric ulcer and not to rupture of esophageal varices. These results have demonstrated that the EGDS promotes an immediate decrease in the portal pressure and a reduction in the caliber of the esophageal varices, thus contributing to the good results of this technique. With the association of EGDS and sclerotherapy of the esophageal varices, no hemorrhagic episodes were observed in this series, during the study

No Brasil a principal causa de hipertensão portal é a esquistossomose mansônica na sua forma hepato-esplênica, classificada como pré-sinusoidal. Esta doença adquire grande importância epidemiológica, por acometer indivíduos jovens, com função hepática preservada, e por atingir uma grande parcela da população (cerca de 1 milhão de indivíduos). Destes, cerca de 12 a 52% irão apresentar hemorragia digestiva por ruptura de varizes de esôfago. Não existe até o momento nenhum tratamento que se estabeleça como de consenso para esta enfermidade, porém há uma preferência dos autores para o tratamento cirúrgico e, no Brasil, esta recai sobre a desconexão ázigo-portal e esplenectomia geralmente associada a escleroterapia endoscópica das varizes no pós-operatório. Não estão bem estabelecidas as alterações hemodinâmicas portais decorrentes do tratamento cirúrgico da hipertensão portal e sua influência no resultado deste tratamento. Com o objetivo de avaliar o impacto imediato da desconexão ázigo-portal e esplenectomia (DAPE) na pressão portal e os resultados do tratamento cirúrgico da hipertensão portal no que se refere à recidiva hemorrágica e ao calibre das varizes de esôfago, foram estudados 19 pacientes portadores de esquistossomose hepato-esplênica e hipertensão portal com história de hemorragia digestiva alta por ruptura de varizes esofágicas, com idade média de 37,9 anos. Durante a cirurgia foi avaliada a pressão portal, no início e no final do procedimento através da cateterização da veia porta por cateter de polietileno introduzido por veia jejunal. Todos os pacientes foram submetidos à endoscopia no pré e pós-operatório para avaliar a variação do calibre das varizes esofágicas. Os pacientes foram acompanhados ambulatorialmente e o tempo médio de seguimento foi de 26 meses. Como resultado obteve-se uma queda na pressão portal média de 31,3% após a DAPE (p=0,0001). No acompanhamento pós-operatório houve redução significativa do calibre das varizes esofágicas quando comparadas com a avaliação pré-operatória (p < 0,05). Apenas um paciente (8,3%) apresentou, durante o acompanhamento, recidiva hemorrágica porém, esta foi decorrente de úlcera gástrica e não de varizes esofágicas. Por fim chegou-se à conclusão de que a desconexão ázigo-portal e esplenectomia promoveu queda imediata na pressão portal, com conseqüente diminuição do calibre das varizes esofágicas, tendo sido eficaz no tratamento da hipertensão portal destes pacientes / The main cause of portal hypertension in Brazil is the hepato-splenic form of mansonic schistosomiasis, which is classified as pre-sinusoidal. It acquires major epidemiological importance because it occurs in young individuals and affects a huge parcel of the population (around 1 million people), 12 to 52% of whom will present digestive hemorrhage due to rupture of esophageal varices. There is no consensus treatment for this disease up to the moment, but there is a predilection for the surgical approach. In Brazil, the most employed technique is the esophagogastric devascularization with splenectomy (EGDS), generally associated to late postoperative endoscopical sclerotherapy of the esophageal varices. The hemodynamic alterations in the portal flow resulting from the surgery and their possible influences on the outcome are not well established. With the aim of evaluating the immediate impact of the EGDS upon the portal pressure as well as the results of the surgical treatment on the digestive hemorrhage recurrence and the caliber of the esophageal varices, 19 patients (11males, aged between 18 and 61 years) with hepato-splenic schistosomiasis, presenting portal hypertension and previous episodes of digestive hemorrhage were studied. None of the patients had received any treatment prior to the surgery. The portal pressure was assessed at the beginning and the end of the EGDS through catheterization of the portal vein with a polyethylene catheter introduced through a branch of a jejunal vein. All the patients were submitted to digestive endoscopy before and after the surgery (2 months), in order to classify the caliber of the esophageal varices according to Palmer\'s classification. They also entered the continuous program of endoscopical evaluation and sclerotherapy. The mean clinical follow up period was 26 months. Our results showed that the portal pressure had diminished in all the patients, with a mean decrease of 31.3% after the EGDS. In the postoperative follow up (1 month), the esophageal varices showed a statistically significant reduction in their calibers, when compared to the pre-surgical measurements (p=0.004). Only one patient presented digestive hemorrhage during the follow up period, but it was due to gastric ulcer and not to rupture of esophageal varices. These results have demonstrated that the EGDS promotes an immediate decrease in the portal pressure and a reduction in the caliber of the esophageal varices, thus contributing to the good results of this technique. With the association of EGDS and sclerotherapy of the esophageal varices, no hemorrhagic episodes were observed in this series, during the study