Background The composition of the lung preservation solution used in lung graft procurement has been considered the key to minimize lung injury during the period of ischemia. Low-potassium dextran glucose （LPDG）, an...Background The composition of the lung preservation solution used in lung graft procurement has been considered the key to minimize lung injury during the period of ischemia. Low-potassium dextran glucose （LPDG）, an extracellular-type solution, has been adopted by most lung transplantation centers, due to the experimental and clinical evidences that LPDG is superior to intracellular-type solutions. Ulinastatin has been shown to attenuate ischemia-reperfusion （I/R） injury in various organs in animals. We supposed that the addition of ulinastatin to LPDG as a flushing solution, would further ameliorate I/R lung injury than LPDG solution alone.Methods Twelve male New Zealand white rabbits were randomly divided into 2 groups. Using an alternative in situ lung I/R model, the left lung in the control group was supplied and preserved with LPDG solution for 120 minutes. In the study group 50 000 U/kg of ulinastatin was added to the LPDG solution for lung preservation. Then re-ventilation and reperfusion of the left lung were performed for 90 minutes. Blood gas analysis （PaO2, PaCO2）, mean pulmonary artery pressure （MPAP） and serum TNF-α level were measured intermittently. The pulmonary water index （D/W）, tissue myeloperoxidase （MPO） activity, tissue malondialdehyde （MDA） content and morphologic changes were analyzed.Results The study group showed significantly higher PaO2 and lower MPAP at the end of reperfusion. Serum TNF-α level, left lung tissue MPO and MDA in the study group were significantly lower than those in the control group. D/W and pathologic evaluation were also remarkably different between the two groups.Conclusions This study indicated that better lung preservation could be achieved with the use of an ulinastatin modified LPDG solution. Ulinastatin further attenuated lung I/R injury, at least partly by reducing oxidative reactions,inhibiting the release of inflammatory factors and neutrophils immigration.展开更多
According to the main international clinical guidelines,the recommended treatment for locally-advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery.However,doubts have been raised about the appro...According to the main international clinical guidelines,the recommended treatment for locally-advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery.However,doubts have been raised about the appropriate definition of clinical complete response(cCR)after neoadjuvant therapy and the role of surgery in patients who achieve a cCR.Surgical resection is associated with significant morbidity and decreased quality of life(QoL),which is especially relevant given the favourable prognosis in this patient subset. Accordingly, therehas been a growing interest in alternative approaches with less morbidity,including the organ-preserving watch and wait strategy, in which surgery isomitted in patients who have achieved a cCR. These patients are managed with aspecific follow-up protocol to ensure adequate cancer control, including the earlyidentification of recurrent disease. However, there are several open questionsabout this strategy, including patient selection, the clinical and radiologicalcriteria to accurately determine cCR, the duration of neoadjuvant treatment, therole of dose intensification (chemotherapy and/or radiotherapy), optimal followupprotocols, and the future perspectives of this approach. In the present review,we summarize the available evidence on the watch and wait strategy in thisclinical scenario, including ongoing clinical trials, QoL in these patients, and thecontroversies surrounding this treatment approach.展开更多
Longstanding research describes the mechanisms whereby the restoration of blood flow and reoxygenation(reperfusion) aggravates the ischaemic injury caused by a period of anoxia to a donor liver. This phenomenon, calle...Longstanding research describes the mechanisms whereby the restoration of blood flow and reoxygenation(reperfusion) aggravates the ischaemic injury caused by a period of anoxia to a donor liver. This phenomenon, called ischaemia-reperfusion injury(IRI), leads to parenchymal cell death,microcirculatory failure, and inflammatory immune response. Clinically, IRI is the main factor responsible for the occurrence of posttransplant graft dysfunction and ischaemic-type biliary lesions. While extended criteria donor livers are more vulnerable to IRI, their utilisation is required to address the shortfall in donor organs. Thus, the mitigation of IRI should drive the setting of a new benchmark for marginal organ preservation. Herein, strategies incorporating different modalities of machine perfusion of the liver to alleviate IRI are discussed in conjunction with advantages and disadvantages of individual protocols.Techniques leading to reperfusion of the liver during machine perfusion(in situ normothermic regional perfusion and ex situ normothermic machine perfusion)may mitigate IRI by shortening the ischaemic period of the organs. This benefit potentially escalates from the minimum level, obtained following just partial alleviation of the ischaemic period, to the maximum level, which can be potentially achieved with ischaemia-free organ transplantation. Techniques that do not lead to reperfusion of the liver during machine perfusion(hypothermic,subnormothermic, and controlled-oxygenated rewarming) optimise mitochondrial oxidative function and replenish cellular energy stores, thereby lowering reactive oxygen species production as well as the activation ofdownstream inflammatory pathways during reperfusion. Further mechanistic insights into IRI may guide the development of donor-specific protocols of machine perfusion on the basis of the limitations of individual categories of extended criteria donor organs.展开更多
文摘Background The composition of the lung preservation solution used in lung graft procurement has been considered the key to minimize lung injury during the period of ischemia. Low-potassium dextran glucose （LPDG）, an extracellular-type solution, has been adopted by most lung transplantation centers, due to the experimental and clinical evidences that LPDG is superior to intracellular-type solutions. Ulinastatin has been shown to attenuate ischemia-reperfusion （I/R） injury in various organs in animals. We supposed that the addition of ulinastatin to LPDG as a flushing solution, would further ameliorate I/R lung injury than LPDG solution alone.Methods Twelve male New Zealand white rabbits were randomly divided into 2 groups. Using an alternative in situ lung I/R model, the left lung in the control group was supplied and preserved with LPDG solution for 120 minutes. In the study group 50 000 U/kg of ulinastatin was added to the LPDG solution for lung preservation. Then re-ventilation and reperfusion of the left lung were performed for 90 minutes. Blood gas analysis （PaO2, PaCO2）, mean pulmonary artery pressure （MPAP） and serum TNF-α level were measured intermittently. The pulmonary water index （D/W）, tissue myeloperoxidase （MPO） activity, tissue malondialdehyde （MDA） content and morphologic changes were analyzed.Results The study group showed significantly higher PaO2 and lower MPAP at the end of reperfusion. Serum TNF-α level, left lung tissue MPO and MDA in the study group were significantly lower than those in the control group. D/W and pathologic evaluation were also remarkably different between the two groups.Conclusions This study indicated that better lung preservation could be achieved with the use of an ulinastatin modified LPDG solution. Ulinastatin further attenuated lung I/R injury, at least partly by reducing oxidative reactions,inhibiting the release of inflammatory factors and neutrophils immigration.
文摘According to the main international clinical guidelines,the recommended treatment for locally-advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery.However,doubts have been raised about the appropriate definition of clinical complete response(cCR)after neoadjuvant therapy and the role of surgery in patients who achieve a cCR.Surgical resection is associated with significant morbidity and decreased quality of life(QoL),which is especially relevant given the favourable prognosis in this patient subset. Accordingly, therehas been a growing interest in alternative approaches with less morbidity,including the organ-preserving watch and wait strategy, in which surgery isomitted in patients who have achieved a cCR. These patients are managed with aspecific follow-up protocol to ensure adequate cancer control, including the earlyidentification of recurrent disease. However, there are several open questionsabout this strategy, including patient selection, the clinical and radiologicalcriteria to accurately determine cCR, the duration of neoadjuvant treatment, therole of dose intensification (chemotherapy and/or radiotherapy), optimal followupprotocols, and the future perspectives of this approach. In the present review,we summarize the available evidence on the watch and wait strategy in thisclinical scenario, including ongoing clinical trials, QoL in these patients, and thecontroversies surrounding this treatment approach.
基金supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham
文摘Longstanding research describes the mechanisms whereby the restoration of blood flow and reoxygenation(reperfusion) aggravates the ischaemic injury caused by a period of anoxia to a donor liver. This phenomenon, called ischaemia-reperfusion injury(IRI), leads to parenchymal cell death,microcirculatory failure, and inflammatory immune response. Clinically, IRI is the main factor responsible for the occurrence of posttransplant graft dysfunction and ischaemic-type biliary lesions. While extended criteria donor livers are more vulnerable to IRI, their utilisation is required to address the shortfall in donor organs. Thus, the mitigation of IRI should drive the setting of a new benchmark for marginal organ preservation. Herein, strategies incorporating different modalities of machine perfusion of the liver to alleviate IRI are discussed in conjunction with advantages and disadvantages of individual protocols.Techniques leading to reperfusion of the liver during machine perfusion(in situ normothermic regional perfusion and ex situ normothermic machine perfusion)may mitigate IRI by shortening the ischaemic period of the organs. This benefit potentially escalates from the minimum level, obtained following just partial alleviation of the ischaemic period, to the maximum level, which can be potentially achieved with ischaemia-free organ transplantation. Techniques that do not lead to reperfusion of the liver during machine perfusion(hypothermic,subnormothermic, and controlled-oxygenated rewarming) optimise mitochondrial oxidative function and replenish cellular energy stores, thereby lowering reactive oxygen species production as well as the activation ofdownstream inflammatory pathways during reperfusion. Further mechanistic insights into IRI may guide the development of donor-specific protocols of machine perfusion on the basis of the limitations of individual categories of extended criteria donor organs.
