Systemic haemodynamic, renal perfusion and renal oxygenation responses to changes in inspired oxygen fraction during total intravenous or volatile anaesthesia.

BACKGROUND: Anaesthesia-induced changes in renal perfusion are dependent on the choice of anaesthetic agent. However, the effects of varying inspired oxygen fraction (FiO2) on renal perfusion and oxygenation during TIVA (propofol + fentanyl) or volatile anaesthesia (VA; isoflurane) are unknown. METHODS: In 16 Merino ewes, we surgically implanted a renal artery flow probe and laser-Doppler and oxygen-sensing probes in the renal medulla and cortex. We compared the systemic and renal effects of graded alterations in FiO2 (0.21, 0.40, 0.60, and 1.0) during TIVA or VA and compared the changes with those in the non-anaesthetised state. RESULTS: Compared with the non-anaesthetised state, TIVA and VA decreased renal blood flow (-50% vs -75%), renal oxygen delivery (-50% vs -80%), and renal cortical (-40% vs -60%) and medullary perfusion (-50% vs -75%). At an FiO2 of 0.21, both anaesthetic regimens induced similar reductions in cortical (-58 vs -65%) and medullary (-37% vs -38%) oxygenation. At higher concentrations of FiO2, renal blood flow and renal tissue perfusion were not changed, but intrarenal oxygenation improved similarly under TIVA and VA. In particular, at an FiO2 of ≥0.40 and ≤0.60, cortical and medullary oxygen tension were similar to the non-anaesthetised state. CONCLUSIONS: Irrespective of FiO2, TIVA decreased renal and intrarenal perfusion less than VA, but at low FiO2 concentrations both led to equivalent reductions in renal cortical and medullary oxygenation. However, with FiO2 between 0.40 and 0.60 during TIVA or VA, both cortical and medullary oxygenation was maintained at normal physiological levels.

30-Day Outcomes Post Veno-Arterial Extra Corporeal Membrane Oxygenation (VA-ECMO) After Cardiac Surgery and Predictors of Survival.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is sometimes needed for post-cardiotomy cardiogenic shock (PCCS). There is little data regarding outcomes in the Australian context, particularly in a non-cardiac transplant centre. Our aim was to report on 30-day outcomes after patients with PCCS treated with VA-ECMO in an Australian non-cardiac transplant tertiary centre, and to determine risk factors for non-survival in this population. METHODS: A retrospective analysis was performed on all adults treated with VA-ECMO for PCCS between August 2001 and September 2016 at our centre. Univariate analysis with adjustment for multiplicity identified risk factors for non-survival. Area under the receiver operating characteristics (AUROC) method was used to assess their predictive value. RESULTS: We identified 64 patients out of 5,502 open-heart surgery cases of which three patients did not meet inclusion criteria. Mean (SD) age was 63 (14) years. Survival to hospital discharge or 30 days post VA-ECMO occurred in 27/61 (44%) patients. VA-ECMO was able to be weaned in 44/61 patients (72%); 54/61 patients (89%) had at least one major complication. Prior to VA-ECMO initiation, no statistically significant differences between survivors and non-survivors could be determined. After VA-ECMO initiation, only 24-hour nadir lactate and 48-hour nadir lactate levels were significantly different between survivors and non-survivors (1.50 mmol/L vs 3.20 mmol/L p=0.001; and 1.20 mmol/L vs. 1.90 mmol/L p=0.001 respectively). For mortality prediction, 24- and 48-hour nadir lactate levels had AUROCs of 0.775 and 0.782, respectively. CONCLUSIONS: VA-ECMO is associated with acceptable survival rates but significant morbidity. Nadir lactate levels in the first 24 and 48 hours after VA-ECMO initiation may be useful in predicting early survival.

Renal perfusion, oxygenation, and sympathetic nerve activity during volatile or intravenous general anaesthesia in sheep.

BACKGROUND: Global and intra-renal perfusion and oxygenation may be affected by the choice of anaesthetic. We compared the effects of isoflurane with those of propofol and fentanyl on renal blood flow (RBF) and intra-renal perfusion and oxygenation, and assessed how these were associated with renal sympathetic nerve activity (RSNA). METHODS: A renal artery flow probe and laser Doppler and oxygen-sensing probes were surgically implanted in the renal medulla and cortex in 20 Merino ewes. RSNA was measured in 12 additional ewes. We compared the effects of volatile or i.v. anaesthesia on global RBF, renal oxygen delivery (RDO2), intra-renal perfusion, and RSNA with the non-anaesthetised state on postoperative day 3 as control reference. RESULTS: Compared with a non-anaesthetised state, volatile anaesthesia reduced global RBF [-76 (82-68)%], RDO2 [-76 (83-71)%], and cortical [-68 (74-54)%] and medullary [-76 (84-72)%] perfusion. I.V. anaesthesia reduced RBF [-55 (67-38)%], RDO2 [-55 (65-44)%], and cortical [-27 (45-6)%] and medullary [-35 (48-30)%] perfusion, but to a lesser extent than volatile anaesthesia. Renal PO2 was not influenced by anaesthesia, whilst RSNA was elevated during volatile, but not during i.v. anaesthesia. CONCLUSIONS: Volatile and i.v. general anaesthesia markedly reduced global RBF, RDO2, and regional kidney perfusion. These effects were greater with volatile anaesthesia, and were paralleled by an increase in RSNA. Our findings suggest a neurogenic modulatory effect of anaesthetics on renal perfusion and oxygenation.

Simultaneous analysis of the gene expression profiles of cancer and stromal cells in endometrial cancer.

To address the role of cancer-stroma interactions, we performed gene expression profiling of both cancer and stroma, using matching samples of endometrial cancer (EC), and analyzed the relationship between the gene expression pattern and prognosis in EC. Sixty EC cases were included in this study (38 nonrecurrent and 22 recurrent). Cancer and stroma were separated by performing laser capture microdissection, and microarray analysis was performed separately on cancer and stromal cells. Genes related with progression-free survival (PFS) in cancer and stroma were analyzed using the Cox regression model, and we established a formula, based on the gene expression pattern of cancer and stroma, to predict recurrence using logistic regression. We estimated the accuracy of the formula using the 0.632 method. All cases were classified based on the 79 selected genes of cancer and stroma related to PFS, based on unsupervised clustering. A total of 143 genes in cancer, and 79 genes in stroma were significantly related with PFS. The estimated area under the curve of receiver operating characteristics curve in cancer and stroma to predict recurrence were 0.800 and 0.758, respectively. Based on the 79 genes of cancer, the 22 recurrent cases were divided into two groups, which generally correlated with the histological grade. In contrast, based on the 79 genes of stroma, the 22 recurrent cases displayed homogeneous gene expression, unrelated to the histological grade. We conclude that gene expression profiles of cancer and stroma can predict the recurrence of EC and stromal that gene expression does not depend on the cancer grade.

The origin of stroma surrounding epithelial ovarian cancer cells.

Cancer stroma is thought to play an important role in tumor behavior, including invasion or metastasis and response to therapy. Cancer stroma is generally thought either to be non-neoplastic cells, including tissue-marrow or bone-marrow-derived fibroblasts, or to originate in epithelial mesenchymal transition of cancer cells. In this study, we evaluated the status of the p53 gene in both the cancer cells and the cancer stroma in epithelial ovarian cancer (EOC) to elucidate the origin of the stroma. Samples from 16 EOC patients were included in this study. Tumor cells and adjacent nontumor stromal cells were microdissected and DNA was extracted separately. We analyzed p53 sequences (exons 5-8) of both cancer and stromal tissues in all cases. Furthermore, we examined p53 protein expression in all cases. Mutations in p53 were detected in 9 of the 16 EOCs: in 8 of these cases, the mutations were detected only in cancer cells. In 1 case, the same mutation (R248Q) was detected in both cancer and stromal tissues, and p53 protein expression was detected in both the cancer cells and the cancer stroma. Most cancer stroma in EOC is thought to originate from non-neoplastic cells, but some parts of the cancer stroma might originate from cancer cells.

Role of circulating free alu DNA in endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is the most common cancer of the female genital tract. However, no screening method for EC has been established yet. In this study, we evaluated the cell-free DNA in EC. METHODS: Fifteen healthy individuals, 9 with benign gynecologic diseases, and 53 with ECs were included in this study. Alu sequences in free DNA fragments were used as surrogate markers, and cell-free DNA density was measured by quantitative real-time polymerase chain reaction. RESULTS: The cell-free DNA levels in ECs tended to be higher than in benign condition (healthy individuals + benign gynecologic diseases, n = 24; P = 0.095). There was no significant difference in cell-free DNA among stage or histological grade of EC, and no significant change in cell-free DNA before and after operation (P = 0.25): Moreover, in 19 ECs, cell-free DNA decreased after operation, however, in 6 ECs, cell-free DNA did not decrease. Three ECs recurred, and cell-free DNA did not decrease in these cases. CONCLUSIONS: Measurement of cell-free DNA is not useful for EC screening; however, the change of cell-free DNA in a patient may be a prognostic biomarker of EC.