ABSTRACT
In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization.
Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.
Subject(s)
Colorectal Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Brazil , Combined Modality Therapy , Embolization, Therapeutic , HumansABSTRACT
Ischemic preconditioning (IPC) may be useful in attenuating the hepatic ischemia reperfusion (IR) syndrome by means of improving cell resistance to anoxia and reoxygenation and preventing cell death. Since there are insufficient data available regarding the chronology of preconditioning effects, we investigated the role of IPC, to test the hypothesis that liver protection would occur during the early and intermediate phases of the reperfusion period. Wistar rats (n = 72) were randomly assigned into six experimental groups, 12 animals each. A 40-min ischemia to the left lateral and median liver lobes was induced by selective hepatic pedicle clamping followed by 30 min or 240 min of reperfusion (IR30 and IR240). IPC groups (IPC30 and IPC240) underwent a 10 min of ischemia followed by 10 min of reperfusion preceding the definitive 40-min ischemic period. Sham-operated animals were followed for 30 and 240 min. Hepatic enzymes and histological evaluation were performed after the reperfusion period. Hepatic ischemia-reperfusion (IR30 and IR240) induced marked increases in liver enzymes levels after 30 min and particularly after 240 min. IPC effectively attenuated those enzymatic increases. Microvesicular steatosis was observed after 30 min, but not 240 min, of reperfusion in both IPC and IR livers. Necrosis was detected in 66.7% of IR240 and only in 8.3% of IPC240. Both hepatocyte and sinusoidal apoptosis were markedly attenuated by IPC. We conclude that IPC provided protection against hepatic ischemia reperfusion injury in early and intermediate phases of the reperfusion period, reducing hepatic enzymatic leakage and ameliorating hepatic apoptosis and necrosis.
