A Novel Nomogram to Predict Prognosis of Advanced Hepatocellular Carcinoma Treated with Intensity-Modulated Radiotherapy Plus Anti-PD1.

Purpose: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti-PD1) showed preliminary efficacy in hepatocellular carcinoma (HCC). This study aimed to identify the prognostic factors and construct a nomogram to predict the overall survival (OS) of patients with advanced HCC after treatment with intensity-modulated radiotherapy (IMRT) plus anti-PD1. Patients and Methods: The OS and progression-free survival (PFS) of 102 patients with BCLC stage C HCC was analyzed using the Kaplan-Meier method. Potential independent prognostic factors were determined using univariate and multivariate Cox regression analyses. A nomogram was established to predict prognosis whose accuracy and reliability was verified by a calibration curve and area under the receiver operating characteristic curve (AUROC). Results: The median PFS and OS rates of the 102 patients with advanced HCC were 9.9 months and 14.3 months, respectively. Ninety-three patients were evaluated for efficacy, including five (5.38%) with complete response and 48 (51.61%) with partial response, with an overall response rate of 56.99%. Grade 3 and 4 adverse reactions (AEs) were observed in 32.35% of patients; no grade 5 AEs occurred. Multivariate Cox analysis revealed albumin and alpha-fetoprotein levels, neutrophil counts 3-4 weeks after IMRT initiation, and platelet-to-lymphocyte ratio 3-4 weeks after IMRT initiation to be independent prognostic factors. The nomogram model constructed using these factors had good consistency and accuracy with 1-3 years AUROC of 78.7, 78.6, and 93.5, respectively. Conclusion: IMRT plus anti-PD1 showed promising efficacy and controllable adverse reactions in treating advanced HCC. The nomogram model demonstrated good reliability and clinical applicability.

The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti­PD1) showed preliminary efficacy and manageable safety in HCC. We retrospectively evaluated the efficacy and safety of 102 patients with advanced HCC treated with intensity-modulated radiotherapy (IMRT) plus anti-PD1. The study shows that the combination showed promising efficacy with a median PFS and OS of 9.9 months and 14.3 months, respectively. The adverse reactions were controllable. The novel nomogram model established based on independent prognostic factors including albumin, alpha-fetoprotein, neutrophils count 3­4 weeks after IMRT initiation and platelet-to-lymphocyte ratio 3­4 weeks after IMRT initiation demonstrated good reliability.

Radiotherapy plus anti-PD1 versus radiotherapy for hepatic toxicity in patients with hepatocellular carcinoma.

PURPOSE: In this study, we aimed to compare the radiation-induced hepatic toxicity (RIHT) outcomes of radiotherapy (RT) plus antibodies against programmed cell death protein 1 (anti-PD1) versus RT alone in patients with hepatocellular carcinoma (HCC), evaluate prognostic factors of non-classic radiation-induced liver disease (ncRILD), and establish a nomogram for predicting the probability of ncRILD. PATIENTS AND METHODS: Patients with unresectable HCC treated with RT and anti-PD1 (RT + PD1, n = 30) or RT alone (n = 66) were enrolled retrospectively. Patients (n = 30) in each group were placed in a matched cohort using propensity score matching (PSM). Treatment-related hepatotoxicity was evaluated and analyzed before and after PSM. The prognostic factors affecting ncRILD were identified by univariable logistic analysis and Spearman's rank test in the matched cohort to generate a nomogram. RESULTS: There were no differences in RIHT except for increased aspartate aminotransferase (AST) ≥ grade 1 and increased total bilirubin ≥ grade 1 between the two groups before PSM. After PSM, AST ≥ grade 1 occurred more frequently in the RT + PD1 group (p = 0.020), and there were no significant differences in other hepatotoxicity metrics between the two groups. In the matched cohort, V25, tumor number, age, and prothrombin time (PT) were the optimal prognostic factors for ncRILD modeling. A nomogram revealed a good predictive performance (area under the curve = 0.82). CONCLUSIONS: The incidence of RIHT in patients with HCC treated with RT + PD1 was acceptable and similar to that of RT treatment. The nomogram based on V25, tumor number, age, and PT robustly predicted the probability of ncRILD.

Establishment and validation of a prognostic pomogram in unresectable hepatocellular carcinoma treated with intensity modulated radiotherapy: a real world study.

BACKGROUND: To establish a prognostic model to predict the overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC) treated with intensity modulated radiotherapy (IMRT). METHODS: The unresectable HCC patients treated with IMRT were retrospectively analyzed and randomized into development cohort (n = 237) and validation cohort (n = 103) in a 7:3 ratio. We developed a prognosis model with the multivariate Cox regression analysis in the development cohort to derive the predictive nomogram, which was then validated in the validation cohort. Model performance was evaluated by the c-index, the area under curve(AUC) and the calibration plot. RESULTS: A total of 340 patients were enrolled. Tumor numbers > 3 (HR = 1.69, 95% CI = 1.21-2.37), AFP ≥ 400 ng/ml (HR = 1.52, 95% CI = 1.10-2.10), PLT < 100 × 10^9(HR = 1.7495% CI = 1.11-2.73), ALP > 150U/L (HR = 1.65, 95% CI = 1.15-2.37) and prior surgery (HR = 0.63, 95% CI = 0.43-0.93) were independent prognostic factors. The nomogram based on independent factors was constructed. The c-index for OS prediction was 0.658 (95% CI, 0.647-0.804) and 0.683 (95% CI, 0.580-0.785) in the development and validation cohort, respectively. The nomogram demonstrated good discriminative ability with AUC rates of 0.726, 0.739 and 0.753 at 1-year, 2-year and 3-year models in the development cohort, and 0.715, 0.756 and 0.780 in the validation cohort, respectively. Additionally, good prognostic discrimination of the nomogram is also reflected in stratifying patients into two subgroups with distinct prognosis. CONCLUSIONS: We constructed a prognostic nomogram for predicting the survival of patients with unresectable HCC treated with IMRT.

Non-classic radiation-induced liver disease after intensity-modulated radiotherapy for Child-Pugh grade B patients with locally advanced hepatocellular carcinoma.

BACKGROUND: The incidence of classic radiation-induced liver disease (cRILD) has been significantly reduced. However, non-classic radiation-induced liver disease (ncRILD) remains a major concern following radiotherapy in patients with hepatocellular carcinoma (HCC). This study evaluated the incidence of ncRILD following intensity-modulated radiotherapy (IMRT) for Child-Pugh grade B (CP-B) patients with locally advanced HCC and established a nomogram for predicting ncRILD probability. METHODS: Seventy-five CP-B patients with locally advanced HCC treated with IMRT between September 2014 and July 2021 were included. The max tumor size was 8.39 cm ± 5.06, and the median prescribed dose was 53.24 Gy ± 7.26. Treatment-related hepatotoxicity was evaluated within three months of completing IMRT. A nomogram model was formulated to predict the probability of ncRILD, using univariate and multivariate analysis. RESULTS: Among CP-B patients with locally advanced HCC, ncRILD occurred in 17 (22.7%) patients. Two patients (2.7%) exhibited a transaminase elevation of ≥ G3, fourteen (18.7%) exhibited a Child-Pugh score increase of ≥ 2, and one (1.3%) demonstrated both a transaminase elevation of ≥ G3 and a Child-Pugh score increase of ≥ 2. No cRILD cases were observed. A mean dose to the normal liver of ≥ 15.1 Gy was used as the cutoff for ncRILD. Multivariate analysis revealed that the prothrombin time before IMRT, tumour number, and mean dose to the normal liver were independent risk factors for ncRILD. The nomogram established on the basis of these risk factors displayed exceptional predictive performance (AUC = 0.800, 95% CI 0.674-0.926). CONCLUSIONS: The incidence of ncRILD following IMRT for CP-B patients with locally advanced HCC was acceptable. A nomogram based on prothrombin time before IMRT, tumour number, and mean dose to the normal liver accurately predicted the probability of ncRILD in these patients.

Prognostic value of a nomogram based on peripheral blood immune parameters in unresectable hepatocellular carcinoma after intensity-modulated radiotherapy.

BACKGROUND: For patients with unresectable hepatocellular carcinoma (uHCC), intensity-modulated radiotherapy (IMRT) has become one of the options for clinical local treatment. Immune parameters, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammatory (SII), predict survival in various cancers. This study aimed to determine whether peripheral immune parameters can predict survival in patients with uHCC undergoing IMRT and establish a clinically useful prognostic nomogram for survival prediction. METHODS: The clinical data of 309 HCC patients were retrospectively analyzed and randomly divided into training (n = 216) and validation (n = 93) cohorts. PLR, NLR and SII were collected before and after IMRT. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors affecting survival, which were used to generate a nomogram. RESULTS: The median survival was 16.3 months, and significant increases in PLR, NLR, and SII were observed after IMRT (P < 0.001). High levels of immune parameters were associated with poor prognosis (P < 0.001); enlarged spleen, Barcelona clinic liver cancer stage (B and C), post-SII, and delta-NLR were independent risk factors for survival and were included in the nomogram, which accurately predicted 3- and 5-year survival. The nomogram was well verified in the validation cohort. CONCLUSIONS: High levels of immune parameters are associated with poor prognosis in uHCC patients receiving IMRT. Our nomogram accurately predicts the survival of patients with uHCC receiving IMRT.

Combining stereotactic body radiotherapy with camrelizumab for unresectable hepatocellular carcinoma: a single-arm trial.

PURPOSE: Stereotactic body radiotherapy (SBRT) may have significant immunomodulatory effects that enhance tumor response to immune checkpoint inhibitors. This phase 2 clinical trial was conducted to evaluate the safety and efficacy of combining palliative SBRT with camrelizumab (an anti-PD1 monoclonal antibody) in patients with unresectable hepatocellular carcinoma (uHCC). METHODS: Patients with uHCC, Child-Pugh A/B liver function, and at least one measurable lesion were enrolled between April 2020 and August 2022. Patients were administered 200 mg camrelizumab intravenously from the first day of palliative SBRT and then every 3 weeks. Palliative SBRT was delivered daily over five fractions per week, with a dose range of 30-50 Gy. The primary endpoints were objective response rate (ORR) and safety. This trial was registered at ClinicalTrials.gov (NCT04193696). RESULTS: Twenty-one patients were enrolled; the median radiation dose was 40 Gy, and the median number of cycles of camrelizumab was five. The ORR was 52.4%. After a median follow-up of 19.7 months, the median progression-free and overall survival were 5.8 and 14.2 months, respectively. The overall survival probability was 85.7% at 6 months, 76.2% at 9 months, and 59.9% at 12 months. All grade 3 treatment-related adverse events (TRAEs) occurred in five patients (23.8%) and were manageable. No grade 4/5 TRAEs were observed. CONCLUSION: Palliative SBRT plus camrelizumab showed promising antitumor activity against uHCC. Toxicities were manageable with no unexpected safety issues. This study provides evidence of a new therapeutic method for the treatment of uHCC.

Identification and Validation of a Novel Six-Gene Expression Signature for Predicting Hepatocellular Carcinoma Prognosis.

Background: Hepatocellular carcinoma (HCC) is a highly lethal disease. Effective prognostic tools to guide clinical decision-making for HCC patients are lacking. Objective: We aimed to establish a robust prognostic model based on differentially expressed genes (DEGs) in HCC. Methods: Using datasets from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the International Genome Consortium (ICGC), DEGs between HCC tissues and adjacent normal tissues were identified. Using TCGA dataset as the training cohort, we applied the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analyses to identify a multi-gene expression signature. Proportional hazard assumptions and multicollinearity among covariates were evaluated while building the model. The ICGC cohort was used for validation. The Pearson test was used to evaluate the correlation between tumor mutational burden and risk score. Through single-sample gene set enrichment analysis, we investigated the role of signature genes in the HCC microenvironment. Results: A total of 274 DEGs were identified, and a six-DEG prognostic model was developed. Patients were stratified into low- or high-risk groups based on risk scoring by the model. Kaplan-Meier analysis revealed significant differences in overall survival and progression-free interval. Through univariate and multivariate Cox analyses, the model proved to be an independent prognostic factor compared to other clinic-pathological parameters. Time-dependent receiver operating characteristic curve analysis revealed satisfactory prediction of overall survival, but not progression-free interval. Functional enrichment analysis showed that cancer-related pathways were enriched, while immune infiltration analyses differed between the two risk groups. The risk score did not correlate with levels of PD-1, PD-L1, CTLA4, or tumor mutational burden. Conclusions: We propose a six-gene expression signature that could help to determine HCC patient prognosis. These genes may serve as biomarkers in HCC and support personalized disease management.

TNFAIP3 Interacting Protein 3 Is an Activator of Hippo-YAP Signaling Protecting Against Hepatic Ischemia/Reperfusion Injury.

BACKGROUND AND AIMS: Hepatic ischemia/reperfusion (I/R) injury, a common clinical problem that occurs during liver surgical procedures, causes a large proportion of early graft failure and organ rejection cases. The identification of key regulators of hepatic I/R injury may provide potential strategies to clinically improve the prognosis of liver surgery. Here, we aimed to identify the role of tumor necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) in hepatic I/R injury and further reveal its immanent mechanisms. APPROACH AND RESULTS: In the present study, we found that hepatocyte TNIP3 was markedly up-regulated in livers of both persons and mice subjected to I/R surgery. Hepatocyte-specific Tnip3 overexpression effectively attenuated I/R-induced liver necrosis and inflammation, but improved cell proliferation in mice, whereas TNIP3 ablation largely aggravated liver injury. This inhibitory effect of TNIP3 on hepatic I/R injury was found to be dependent on significant activation of the Hippo-YAP signaling pathway. Mechanistically, TNIP3 was found to directly interact with large tumor suppressor 2 (LATS2) and promote neuronal precursor cell-expressed developmentally down-regulated 4-mediated LATS2 ubiquitination, leading to decreased Yes-associated protein (YAP) phosphorylation at serine 112 and the activated transcription of factors downstream of YAP. Notably, adeno-associated virus delivered TNIP3 expression in the liver substantially blocked I/R injury in mice. CONCLUSIONS: TNIP3 is a regulator of hepatic I/R injury that alleviates cell death and inflammation by assisting ubiquitination and degradation of LATS2 and the resultant YAP activation.TNIP3 represents a promising therapeutic target for hepatic I/R injury to improve the prognosis of liver surgery.

The Role of Arachidonic Acid Metabolism in Myocardial Ischemia-Reperfusion Injury.

Patients with myocardial ischemic diseases or who are undergoing one of various heart treatments, such as open heart surgery, coronary artery bypass grafting, percutaneous coronary artery intervention or drug thrombolysis, face myocardial ischemia-reperfusion injury (MIRI). However, no effective treatment is currently available for MIRI. To improve the prognosis of people with cardiovascular disease, it is important to research the mechanism of MIRI. Arachidonic acid (AA) is one of the focuses of current research. The various metabolic pathways of AA are closely related to the development of cardiovascular disease, and the roles of various metabolites in ischemia-reperfusion injury have gradually been confirmed. AA is mainly metabolized in the cyclooxygenase (COX) pathway, lipoxygenase (LOX) pathway, and cytochrome P450 monooxygenase (CYP) pathway. This paper summarizes the progress of research on these three major AA metabolic pathways with respect to MIRI.

Multifunctional composite hydrogel bolus with combined self-healing, antibacterial and adhesive functions for radiotherapy.

Radiotherapy is a commonly used method for curing cancers that appear on or just below the skin. Because of the dose build-up effect of X-rays, boluses made of various materials such as silica and wax are clinically applied on patients to increase the skin dose for an enhanced therapeutic effect. However, these commercial boluses can't conform well to the skin's surface with some curvature, resulting in radiation dose attenuation/loss at the lesion location. To address this limitation, we have developed a nano-titanium dioxide (nTiO2)-incorporated polyurethane/polyacrylamide (TPU/PAAm) hydrogel with multi-functions for fabricating a desirable bolus. The obtained hydrogel exhibits excellent mechanical, adhesive and self-healing properties and can fit closely to the surface of patients with any 3D curvature, eliminating the air gap which is a common problem for commercial boluses applied on patients. In particular, it is encouraging that when using the bolus made of TPU/PAAm hydrogel, the dose distribution including dose coverage, conformability and homogeneity within the planning target volume (PTV) is far superior to that when using the commercial bolus. A sufficient dose shifts toward the surface of the head model and is located only in the lesion site, demonstrating that TPU-PAAm hydrogel can provide an optimal dose distribution and be clinically effective for treating superficial tumors. Furthermore, nTiO2 particles feature uniform dispersion at the nanometer level in hydrogel after being modified by 2,2-bis(hydroxymethyl)propionic acid (DMPA) based on coordination chemistry, endowing the hydrogel with long-acting antibacterial ability. The good cell affinity of TPU-PAAm hydrogel is also confirmed in this study, further ensuring that the TPU-PAAm hydrogel prepared here is a desirable candidate as a tissue equivalent with the advantages of convenient use and effectiveness in radiotherapy.

Nisin reduces uterine inflammation in rats by modulating concentrations of pro- and anti-inflammatory cytokines.

PROBLEM: The Staphylococcus aureus has been found to be associated with clinical endometritis of cow. The result of oral antibiotic remains poor. Therefore, this study investigates the role of nisin in endometritis. METHOD OF STUDY: The effect of nisin on the growth and cell wall of S aureus were determined in vitro. Besides the blank control group, animals with established post-partum were inoculated with 0.1 mL S aureus intravaginally. Two days post-inoculation, the animals were administered nisin (25 mg/kg), kanamycin (30 mg/kg), and water (model group) for 7 days. On the seventh day, serum and uterine organs were obtained for pro- and anti-inflammatory analysis. The uterine tissue samples were weighed, and histopathological analysis was performed. RESULTS: The results showed that nisin had an inhibitory effect on the growth and cell wall formation of S aureus. Nisin and kanamycin treatment prevented a S aureus-induced decrease in pro-inflammatory cytokines and promoted an increase in the level of serum anti-inflammatory cytokines in the endometrium of these animals. Nisin and kanamycin, significantly decreased (P < 0.05) the endometritis-induced increases in uterine weight, restored endometrial architecture and significantly (P < 0.05) normalized uterine neutrophils to control levels. Additionally, improved levels of B7-2 , IFN-γ, IL-2, and IL-8 were observed when treated with nisin. CONCLUSION: Our findings suggest that nisin compared favorably with kanamycin in endometritis prevention, suggesting that nisin can be used in S aureus-induced endometritis by protecting the uterus from S aureus infection.

Heat Shock Protein 90α-Dependent B-Cell-2-Associated Transcription Factor 1 Promotes Hepatocellular Carcinoma Proliferation by Regulating MYC Proto-Oncogene c-MYC mRNA Stability.

B-cell lymphoma 2 (Bcl-2)-associated transcription factor 1 (Bclaf1) is known to be involved in diverse biological processes, but, to date, there has been no evidence for any functional role of Bclaf1 in hepatocellular carcinoma (HCC) progression. Here, we demonstrate that Bclaf1 is frequently up-regulated in HCC and that Bclaf1 up-regulation is associated with Edmondson grade, lower overall survival rates, and poor prognosis. Overexpression of Bclaf1 in HCC cell lines HepG2 and Huh7 promoted proliferation considerably, whereas Bclaf1 knockdown had the opposite effect. Xenograft tumors grown from Bclaf1 knockdown Huh7 cells had smaller tumor volumes than tumors grown from control cells. Furthermore, our study describes MYC proto-oncogene (c-Myc) as a downstream target of Bclaf1, given that Bclaf1 regulates c-MYC expression posttranscriptionally by its RS domain. To exert this function, Bclaf1 must interact with the molecular chaperone, heat shock protein 90 alpha (Hsp90α). In HCC tissue samples, Hsp90α levels were also increased significantly and Hsp90α-Bclaf1 interaction was enhanced. Bclaf1 interacts with the C-terminal domain of Hsp90α, and this interaction is disrupted by the C-terminal domain inhibitor, novobiocin (NB), resulting in proteasome-dependent degradation of Bclaf1. Moreover, NB-induced disruption of Hsp90α-Bclaf1 interaction dampened the production of mature c-MYC mRNA and attenuated tumor cell growth in vitro and in vivo. Conclusion: Our findings suggest that Bclaf1 affects HCC progression by manipulating c-MYC mRNA stability and that the Hsp90α/Bclaf1/c-Myc axis might be a potential target for therapeutic intervention in HCC.

Bclaf1 promotes angiogenesis by regulating HIF-1α transcription in hepatocellular carcinoma.

The development of hepatocellular carcinomas (HCC) depends on their local microenvironment and the induction of neovascularization is a decisive step in tumor progression, since the growth of solid tumors is limited by nutrient and oxygen supply. Hypoxia is the critical factor that induces transcription of the hypoxia inducible factor-1α (HIF-1α) encoding gene HIF1A and HIF-1α protein accumulation to promote angiogenesis. However, the basis for the transcriptional regulation of HIF1A expression in HCC is still unclear. Here, we show that Bclaf1 levels are highly correlated with HIF-1α levels in HCC tissues, and that knockdown of Bclaf1 in HCC cell lines significantly reduces hypoxia-induced HIF1A expression. Furthermore, we found that Bclaf1 promotes HIF1A transcription via its bZIP domain, leading subsequently to increased transcription of the HIF-1α downstream targets VEGFA, TGFB, and EPO that in turn promote HCC-associated angiogenesis and thus survival and thriving of HCC cells. Moreover, we demonstrate that HIF-1α levels and microvessel density decrease after the shRNA-mediated Bclaf1 knockdown in xenograft tumors. Finally, we found that Bclaf1 levels increase in hypoxia in a HIF-1α dependent manner. Therefore, our study identifies Bclaf1 as a novel positive regulator of HIF-1α in the hypoxic microenvironment, providing new incentives for promoting Bcalf1 as a potential therapeutic target for an anti-HCC strategy.

[Detection of JAK2V617F mutation rate by real-time fluorescent quantitative PCR using allele specific primer and TaqMan-MGB probe for dual inhibiting amplification of wild type alleles].

This study was purposed to develop a real-time PCR assay for sensitive quantification of JAK2V617F allele burden in peripheral blood and to evaluate the clinical value of this method. Both allele-specific mutant reverse primer and wild-type TaqMan-MGB probe were used for dual-inhibiting amplification of wild-type alleles in a real-time PCR, and then the JAK2V617F mutant alleles were amplified specially. The standard curve for quantification of JAK2V617F was established by percentages of JAK2V617F alleles with threshold cycle (Ct) values in a real-time PCR. Furthermore, 89 apparent healthy donors were tested by this method. The results showed that the quantitative lower limit of this method for JAK2V617F was 0.1%, and the intra- and inter-assay average variability for quantifying percentage of JAK2V617F in total DNA was 4.1% and 6.1%, respectively. Two JAK2V617F-positive individuals were identified (the percentage of JAK2V617F alleles were 0.64% and 0.98%, respectively) using this method in blood from 89 apparently healthy donors. It is concluded that the developed method with highly sensitive and reproducible quantification of JAK2V617F mutant burden can be used clinically for diagnosis and evaluation of disease prognosis and efficacy of therapy in patients with myeloproliferative neoplasms. Moreover, this technique can be also used for quantitative detection of variety of single nucleotide mutation.

Cardiopulmonary bypass for thoracic aortic aneurysm: a report on 488 cases.

Our objective was to investigate different cardiopulmonary bypass (CPB) techniques for thoracic aortic aneurysm retrospectively. Four hundred and eighty-eight patients with thoracic aortic aneurysm received surgical treatment. Total CPB was used routinely in 331 cases with ascending aortic aneurysm. When the aneurysm expanded to the aortic arch, brain protection was executed by adopting deep hypothermia circulatory arrest (DHCA) or DHCA combined with retrograde cerebral perfusion (RCP). Selected cerebral perfusion via carotid artery was used in three cases and separated upper and lower body perfusion in five cases. Left heart bypass was adopted for the surgeries of 157 cases with descending aortic aneurysm. In two of the cases, ventricular defibrillation could not be achieved, and then bypass was altered to separated upper and lower body perfusion to acquire satisfactory outcome. In the ascending aortic aneurysm group, DHCA time in the 17 patients was 10-63 minutes (mean 35.58 +/- 18.81 min), and DHCA +/- RCP time in 61 patients was 16-81 minutes (mean 43.43 +/- 17.91 min). Total mortality of aortic aneurysm surgery requiring full CPB was 5.4% (18/331), in which eight patients died in emergency operations. The total mortality of emergency operation was 11.9% (8/67). In the descending aortic aneurysm group, time of left heart bypass was 125.56 +/- 57.28 min, and the total mortality was 7% (11 of 157 patients). Three patients developed postoperative paraplegia. Techniques for extracorporeal circulation for surgery of the aorta are dependent on the nature of the disease and require a flexible approach to meet the specific anatomical challenge. The ability to alter the perfusion circuit to meet unexpected situations should be anticipated and planned for. In this series, we have varied our approach to perfusion techniques as required with acceptable outcome data as compared to the international literature.

[Clinical application of retrograde cerebral perfusion for brain protection during the surgery of ascending aortic aneurysm: 50 cases report].

OBJECTIVE: To assess retrospectively the effects of different protective methods on brain in ascending aortic aneurysm surgery. METHODS: In 65 patients, aneurysm was dissected to the aortic arch or right arch. To protect brain, deep hypothermic circulatory arrest (DHCA) combined with retrograde cerebral perfusion (RCP) through the superior vena cava (n = 50) and simple DHCA (n = 15) were used during the procedure. Blood samples for lactic acid level from the jugular vein were compared in both groups at different phase, and perfusion blood distribution and oxygen content difference between the perfused and returned blood were measured in some RCP patients. RESULTS: The DHCA time was 35.9 +/- 18.8 min (10.0 - 63.0 min) and DHCA + RCP time was 45.5 +/- 17.2 min (16.0 - 81.0 min). The resuscitation time was 7.1 +/- 1.6 h (4.4 - 9.4 h) in DHCA patients and 5.4 +/- 2.2 h (2.0 - 9.0 h) in RCP patients. Operation death was 3/15 in the DHCA group and 1/50 in the RCP patients. Central nervous complication existed in 3/12 of DHCA patients and 1/49 of RCP patients (P < 0.01). The overall survival rate was 96% (RCP) vs 67% (DHCA), central nervous system dysfunction was 20% in DHCA vs 2% in RCP (P < 0.01). The blood lactic acid level increased significantly after reperfusion in DHCA than in RCP. The blood distribution measurement approximated to 20% of the perfused blood returned from arch vessels. Oxygen content between perfused and returned blood showed that oxygen uptake was adequate in the RCP group. CONCLUSIONS: The application of RCP could prolong the safety duration of circulation arrest. Cerebral perfusion may reep the brain cool and flush out particulate and air embolism. Open anastomosis of the aortic arch to the prosthesis can be safely performed. RCP is acceptable for brain protection in clinical practice.

Clinical application of retrograde cerebral perfusion for brain protection during surgery of ascending aortic aneurysm--a report of 50 cases.

This study was designed to discuss the effects on the brain by different protective methods in ascending aortic aneurysm surgery retrospectively. Two hundred seventy-one surgeries of ascending aortic aneurysm have been done in the past 15 years. There were 65 patients with a dissecting aneurysm of the aortic arch or right arch. To protect the brain, deep hypothermic circulatory arrest (DHCA) combined with retrograde cerebral perfusion (RCP) through superior vena cava (N = 50) and simple DHCA (N = 15) were used during the procedure. Blood samples for lactic acid level from the jugular vein were compared in both groups. Perfusion blood distribution and oxygen content difference between the perfused blood and returned blood were measured in 5 and 10 of RCP patients, respectively. The DHCA time was 35.86 +/- 18.81 min (10 approximately 63 min) and DHCA + RCP time was 45.5 +/- 17.21 min (16 approximately 81 min). The resuscitation time was 7.11 +/- 1.59 h (4.4 - 9.4 h) in DHCA versus 5.43 +/- 2.15 h (2 approximately 9 h) in RCP patients. The operation death rate was 3/15 in DHCA group and 1/50 in RCP patients. Central nervous complication occurred in 3/12 of DHCA patients and 1/49 of RCP patients (p < .01). The overall survival rate was 96% (RCP) versus 67% (DHCA); the central nervous system dysfunction was 20% in DHCA versus 2% in RCP (p < .001). The blood lactic acid level increased significantly after reperfusion in DHCA than that in RCP. The measurement of blood distribution indicated that approximately 2Q% of the perfused blood returned from arch vessels. The difference of oxygen content between perfused and returned blood showed that the oxygen uptake was adequate in RCP group. The application of RCP can prolong the safety duration of circulation arrest. Continuous cerebral perfusion may maintain the brain at a cooler temperature and flush out particulate and air emboli while open anastomosis of the aortic arch to the prosthesis can be safely performed. Therefore, RCP is a preferable method for brain protection in our clinical practices.