Routine utilization of machine perfusion in liver transplantation:Ready for prime time?

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.

Hemoperfusion and continuous veno-venous hemodiafiltration for eliminating chlorfenapyr in poisoning patients

Chlorfenapyr is a liposoluble insecticide belonging to the pyrrole family.Chlorfenapyr is activated when the N-ethoxymethyl side chain breaks,forming a toxic metabolite,which uncouples oxidative phosphorylation in the mitochondria,inhibits the production of adenosine triphosphate (ATP),and leads to the death of cells and targe organisms.[1] Symptoms of chlorfenapyr poisoning in patients are mild and atypical in the early stage,especially in patients receiving low dose exposure;however,such cases are rare and may be ignored by physicians,often leading to delayed treatment.[2,3].

Evaluation of the blood flow in common hepatic tumors by multi-slice spiral CT whole-liver perfusion imaging

Objective To study the characteristics of blood flow in common hepatic tumors by 256-slice spiral CT wholeliver perfusion imaging.Methods Seventy-one patients with hepatic tumors were examined retrospectively by256-slice spiral CT whole-liver perfusion.Among them,twenty-seven cases were of primary hepatic cancer,twen-

Machine perfusion and the prevention of ischemic type biliary lesions following liver transplant:What is the evidence?

The widespread uptake of different machine perfusion(MP)strategies for liver transplant has been driven by an effort to minimize graft injury.Damage to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary drainage.This problem continues to trouble clinicians,and may have catastrophic consequences for the graft and patient.Ischemic injury,as a result of compromised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft failure.However,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial compromise.Both the warm and cold ischemic period duration appear to influence the onset of ITBL.All of the commonly used MP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of ITBL.As clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to consider.In this review,the evidence for the three commonly used MP strategies(abdominal normothermic regional perfusion[A-NRP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[NMP])for ITBL prevention has been critically reviewed.Inconsistencies with ITBL definitions used in trials,coupled with variations in techniques of MP,make interpretation challenging.Overall,the evidence suggests that both HOPE and A-NRP prevent ITBL in donated after circulatory death grafts compared to cold storage.The evidence for ITBL prevention in donor after brain death grafts with any MP technique is weak.

Cardiovascular outcomes and mortality after abnormal myocardial perfusion scans in the elderly:a retrospective study at a tertiary care institution

While the diagnostic and prognostic utility of single photon emission computed tomography(SPECT)myocardial perfusion scan(MPS)has been well established,[1,2]there is a paucity of literature evaluating SPECT MPS in elderly populations.Specifically,it is unclear whether the prognostic value of MPS diminishes as patients get older.We conducted this study to evaluate the role of SPECT MPS in risk-stratifying a large sample of elderly patients with or without known coronary artery disease(CAD)and hypothesized that abnormal MPS in patients over 75 years would be associated with a greater risk of all-cause mortality and major adverse cardiac events.

In vivo solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during in vivo lung perfusion of FOLFOX

In vivo lung perfusion(IVLP)is a novel isolated lung technique developed to enable the local,in situ administration of high-dose chemotherapy to treat metastatic lung cancer.Combination therapy using folinic acid(FOL),5-fluorouracil(F),and oxaliplatin(OX)(FOLFOX)is routinely employed to treat several types of solid tumours in various tissues.However,F is characterized by large interpatient variability with respect to plasma concentration,which necessitates close monitoring during treatments using of this compound.Since plasma drug concentrations often do not reflect tissue drug concentrations,it is essential to utilize sample-preparation methods specifically suited to monitoring drug levels in target organs.In this work,in vivo solid-phase microextraction(in vivo SPME)is proposed as an effective tool for quantitative therapeutic drug monitoring of FOLFOX in porcine lungs during pre-clinical IVLP and intravenous(IV)trials.The concomitant extraction of other endogenous and exogenous small molecules from the lung and their detection via liquid chromatography coupled to high resolution mass spectrometry(LC-HRMS)enabled an assessment of FOLFOX's impact on the metabolomic profile of the lung and revealed the metabolic pathways associated with the route of administration(IVLP vs.IV)and the therapy itself.This study also shows that the immediate instrumental analysis of metabolomic samples is ideal,as long-term storage at80℃ results in changes in the metabolite content in the sample extracts.

Whole-brain CT Perfusion at Admission and During Delayed Time-window Detects the Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage

Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage.Methods Eighty patients underwent CTP at admission and during DCITW.The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group,and comparisons were also made between admission and DCITW within each group.The qualitative color-coded perfusion maps were recorded.Finally,the relationship between CTP parameters and DCI was assessed by receiver operating characteristic(ROC)analyses.Results With the exception of cerebral blood volume(P=0.295,admission;P=0.682,DCITW),there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW.In the DCI group,the extreme parameters were significantly different between admission and DCITW.The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps.For the detection of DCI,mean transit time to the center of the impulse response function(Tmax)at admission and mean time to start(TTS)during DCITW had the largest area under curve(AUC),0.698 and 0.789,respectively.Conclusion Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW.The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.

Intraoperative pancreas stump perfusion assessment during pancreaticoduodenectomy:A systematic scoping review

BACKGROUND Post-operative pancreatic fistula(POPF)is the primary cause of morbidity following pancreaticoduodenectomy.Rates of POPF have remained high despite well known risk factors.The theory that hypoperfusion of the pancreatic stump leads to anastomotic failure has recently gained interest.AIM To define the published literature with regards to intraoperative pancreas perfusion assessment and its correlation with POPF.METHODS A systematic search of available literature was performed in November 2022.Data extracted included study characteristics,method of assessment of pancreas stump perfusion,POPF and other post-pancreatic surgery specific complications.RESULTS Five eligible studies comprised two prospective non-randomised studies and three case reports,total 156 patients.Four studies used indocyanine green fluorescence angiography to assess the pancreatic stump,with the remaining study assessing pancreas perfusion by visual inspection of arterial bleeding of the pancreatic stump.There was significant heterogeneity in the definition of POPF.Studies had a combined POPF rate of 12%;intraoperative perfusion assessment revealed hypoperfusion was present in 39%of patients who developed POPF.The rate of POPF was 11%in patients with no evidence of hypoperfusion and 13%in those with evidence of hypoperfusion,suggesting that not all hypoperfusion gives rise to POPF and further analysis is required to analyse if there is a clinically relevant cut off.Significant variance in practice was seen in the pancreatic stump management once hypoperfusion was identified.CONCLUSION The current published evidence around pancreas perfusion during pancreaticoduodenectomy is of poor quality.It does not support a causative link between hypoperfusion and POPF.Further well-designed prospective studies are required to investigate this.

Computed tomography perfusion in differentiating portal hypertension: A correlation study with hepatic venous pressure gradient

BACKGROUND Hepatic venous pressure gradient(HVPG)is the gold standard for diagnosis of portal hypertension(PH),invasiveness and potential risks in the process of measurement limited its widespread use.AIM To investigate the correlation of computed tomography(CT)perfusion parameters with HVPG in PH,and quantitatively assess the blood supply changes in liver and spleen parenchyma before and after transjugular intrahepatic portosystemic shunt(TIPS).METHODS Twenty-four PH related gastrointestinal bleeding patients were recruited in this study,and all patients were performed perfusion CT before and after TIPS surgery within 2 wk.Quantitative parameters of CT perfusion,including liver blood volume(LBV),liver blood flow(LBF),hepatic arterial fraction(HAF),spleen blood volume(SBV)and spleen blood flow(SBF),were measured and compared before and after TIPS,and the quantitative parameters between clinically significant PH(CSPH)and non-CSPH(NCSPH)group were also compared.Then the correlation of CT perfusion parameters with HVPG were analyzed,with statistical significance as P<0.05.RESULTS For all 24 PH patients after TIPS,CT perfusion parameters demonstrated decreased LBV, increased HAF, SBV and SBF, with no statistical difference in LBF. Compared withNCSPH, CSPH showed higher HAF, with no difference in other CT perfusion parameters. HAFbefore TIPS showed positive correlation with HVPG (r = 0.530, P = 0.008), while no correlation wasfound in other CT perfusion parameters with HVPG and Child-Pugh scores.CONCLUSIONHAF, an index of CT perfusion, was positive correlation with HVPG, and higher in CSPH thanNCSPH before TIPS. While increased HAF, SBF and SBV, and decreased LBV, were found afterTIPS, which accommodates a potential non-invasive imaging tool for evaluation of PH.

Progress of mechanical perfusion in split liver transplantation

Split liver transplantation is an essential means which expand the donor pool currently and the two livers obtained after splitting are marginal donor livers.The adoption of Static Cold Storage during allocation and preservation leads to a higher cold ischemia time,thus increasing the occurrence of related postoperative complications,which limits the further development of split-liver transplantation.Mechanical perfusion as a complement to split liver transplantation can minimize the damage to the marginal donor liver during preservation and reduce the occurrence of ischemia-reperfusion.At present,mechanical perfusion has achieved better efficacy in other types of marginal donor liver transplantation such as DCD,elderly donor liver,fatty liver,and so on.In recent years,mechanical perfusion has also shown great potential for application in split-liver transplantation,and limited clinical studies have shown outstanding therapeutic effects.Therefore,this paper will summarize the research progress and mechanisms related to the application of mechanical perfusion in split liver transplantation in order to promote the application of mechanical perfusion in split liver transplantation and reduce the damage of the organ during preservation.

Effects of cytoreductive surgery combined with hyperthermic perfusion chemotherapy on prognosis of patients with advanced gallbladder cancer

BACKGROUND Gallbladder cancer(GC)is a common malignant tumor and one of the leading causes of cancer-related death worldwide.It is typically highly invasive,difficult to detect in the early stages,and has poor treatment outcomes,resulting in high mortality rates.The available treatment options for GC are relatively limited.One emerging treatment modality is hyperthermic intraperitoneal chemotherapy(HIPEC).HIPEC involves delivering heated chemotherapy directly into the abdominal cavity.It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions,aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.AIM To determine the effects of cytoreductive surgery(CRS)combined with HIPEC on the short-term prognosis of patients with advanced GC.METHODS Data from 80 patients treated at the Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed.The control group comprised 44 patients treated with CRS,and the research group comprised 36 patients treated with CRS combined RESULTS The baseline data of the research and control groups were similar(P>0.05).Six days after surgery,the alanine aminotransferase,aspartate aminotransferase,total bilirubin,and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups(P<0.05).However,the values did not differ between the two groups six days postoperatively(P>0.05).Similarly,the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups(P<0.05),but they did not differ between the groups six days postoperatively(P>0.05).Furthermore,the research group had fewer postoperative adverse reactions than the control group(P=0.027).Finally,a multivariate Cox analysis identified the tumor stage,distant metastasis,and the treatment plan as independent factors affecting prognosis(P<0.05).The three-year survival rate in the study group was higher than that in the control group(P=0.002).CONCLUSION CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.

Role of pulmonary perfusion magnetic resonance imaging for the diagnosis of pulmonary hypertension:A review

Among five types of pulmonary hypertension,chronic thromboembolic pulmonary hypertension(CTEPH)is the only curable form,but prompt and accurate diagnosis can be challenging.Computed tomography and nuclear medicine-based techniques are standard imaging modalities to non-invasively diagnose CTEPH,however these are limited by radiation exposure,subjective qualitative bias,and lack of cardiac functional assessment.This review aims to assess the methodology,diagnostic accuracy of pulmonary perfusion imaging in the current literature and discuss its advantages,limitations and future research scope.

Efficacy of continuous arterial perfusion chemotherapy combined with transarterial chemoembolization regional arterial thermal perfusion in the treatment of pancreatic cancer with liver metastases

Background:The aim of the study was to investigate the efficacy of continuous transcatheter arterial infusion chemotherapy combined with transarterial chemoembolization(TACE)for the treatment of advanced pancreatic cancer with liver metastasis.Methods:Sixty patients with advanced pancreatic cancer and liver metastases were enrolled in this study.In the treatment group,31patients underwent continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial thermal perfusion,whereas 29 patients included in the control group received intravenous chemotherapy with gemcitabine and S-1.All patients received maintenance chemotherapy with S-1 after 4 cycles of the study regimen.Treatment efficacy,quality of life,survival,and toxicity were evaluated.Results:Efficacy was better in the treatment group than in the control group,as reflected by the objective remission,partial remission,and disease progression rates(all P<0.05).The Eastern Cooperative Oncology Group and Numerical Rating Scale pain scores were also higher in the treatment group(both P<0.05).In survival analysis,the 1-year overall survival rates in the treatment and control groups were64.516%and 10.345%,respectively,whereas the median overall survival times were 16 and 6 months,respectively(both P<0.05).The6-month progression-free survival rates in the treatment and control groups were 77.419%and 13.790%,respectively,and the median progression-free survival times were 12 and 3 months,respectively(both P<0.05).The rates of hematological and nonhematological toxicological adverse effects were also lower in the treatment group(both P<0.05).Although the rate of liver dysfunction was higher in the treatment group,this finding had no adverse effects on prognosis.Conclusions:Continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial perfusion chemotherapy resulted in better efficacy and safety outcomes in patients with pancreatic cancer and liver metastasis,suggesting its utility as a reference method for the clinical treatment of advanced pancreatic cancer.

输入动脉选择对CT Perfusion 3.0软件包肺灌注成像的影响

目的:探讨输入动脉的选择对CT Perfusion 3.0软件包肺灌注成像的影响。方法:健康新西兰白兔2只,非离子型对比剂优维显5ml,对比剂的注射流率分别为0.1、0.3、0.5和0.8ml/s。所得数据传输到工作站,经Perfusion 3.0软件包以三种不同的灌注成像方案处理。结果:以主动脉为输入动脉的体部肿瘤方案组所计算的血容量(BV)、血流量(BF)分别与以肺动脉为输入动脉组和肝脏肿瘤方案组所得数值间差异存在显著性意义(t=4.376、t=2.779);以肺动脉为输入动脉组和肝脏肿瘤方案组所得数值组间差异无显著性意义(t=1.5)。结论:应用CT Perfusion 3.0软件包,选择不同的输入动脉会对肺灌注成像结果产生影响,其实际应用有待进一步研究。

Plasma perfusion治疗对HBV相关性肝衰竭患者T淋巴细胞亚群及炎性因子表达水平影响的相关性分析

目的:探讨血浆灌流(PP)治疗对肝衰竭患者循环血中T淋巴细胞亚群及炎性因子水平表达的影响及临床意义。方法:以112例肝衰竭患者作为治疗组,选取同期HBsAg(-)的健康体检者25例为对照组,检测在PP治疗前后循环血中CD4+T、CD8+T及炎性因子中的肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-10、γ-干扰素(IFN-γ)的水平表达。结果:治疗组患者在采用PP治疗后,TBIL、ALT、PTA、CRP的表达水平较治疗前明显下降(P<0.05)。治疗组患者采用PP治疗前,CD4+T、CD8+T水平较对照组低表达,CD4+T/CD8+T比值高表达,差异有统计学意义(P<0.05)。治疗组患者在PP治疗后,CD4+T、CD8+T水平较治疗前明显上调,CD4+T/CD8+T比值明显下调,差异有统计学意义(P<0.05);CD4+T、CD8+T水平较对照组明显下调,CD4+T/CD8+T比值明显上调,差异有统计学意义(P<0.05)。治疗组患者在PP治疗前,TNF-α、IFN-γ、IL-6、IL-10水平较对照组明显上调,差异有统计学意义(P<0.05);治疗组患者在PP治疗后TNF-α、IFN-γ、IL-6、IL-10水平较治疗前明显下调,差异有统计学意义(P<0.05);治疗组患者在PP治疗后TNF-α、IFN-γ、IL-6、IL-10水平较对照组明显上调,差异有统计学意义(P<0.05)。结论:PP治疗肝衰竭患者可显著调控循环血中T淋巴细胞亚群的失衡状态,调节紊乱的炎性因子水平,促进肝功能复常,提高肝衰竭患者存活率。

Chemotherapy with laparoscope-assisted continuous circulatory hyperthermic intraperitoneal perfusion for malignant ascites

AIM:To investigate the procedure, feasibility and effects of laparoscopeassisted continuous circulatory hyperthermic intraperitoneal perfusion chemotherapy (CHIPC) in treatment of malignant ascites induced by peritoneal carcinomatosis from gastric cancers. METHODS: From August 2006 to March 2008, the laparoscopic approach was used to perform CHIPC on 16 patients with malignant ascites induced by gastric cancer or postoperative intraperitoneal seeding. Each patient underwent CHIPC three times after laparoscopeassisted perfusion catheters placing. The first session was completed in operative room under general anesthesia, 5% glucose solution was selected as perfusion liquid, and 1500 mg 5 fluorouracil (5FU) and 200 mg oxaliplatin were added in the perfusion solution. The second andthird sessions were performed in intensive care unit, 0.9% sodium chloride solution was selected as perfusion liquid, and 1500 mg 5FU was added in the perfusion solution alone. CHIPC was performed for 90 min at a velocity of 450600 mL/min and an in flow temperature of 43 ± 0.2℃.RESULTS: The intraoperative course was uneventful in all cases, and the mean operative period for laparoscopeassisted perfusion catheters placing was 80 min for each case. No postoperative deaths or complications related to laparoscopeassisted CHIPC occurred in this study. Clinically complete remission of ascites and related symptoms were achieved in 14 patients, and partial remission was achieved in 2 patients. During the followup, 13 patients died 29 mo after CHIPC, with a median survival time of 5 mo. Two patients with partial remission suffered from port site seeding and tumor metastasis,and died 2 and 3 mo after treatment. Three patients who are still alive today survived 4, 6 and 7 mo, respectively. The Karnofsky marks of patients (5090) increased significantly (P < 0.01) and the general status improved after CHIPC. Thus satisfactory clinical efficacy has been achieved in these patients treated by laparoscopic CHIPC. CONCLUSION: Laparoscopeassisted CHIPC is a safe, feasible and effective procedure in the treatment of debilitating malignant ascites induced by unresectable gastric cancers.

Quantification of angiogenesis by CT perfusion imaging in liver tumor of rabbit

BACKGROUND:Tumor angiogenesis is essential for primary and metastatic tumor growth.Computed tomography perfusion(CTP)is a new imaging method,made possible by the recent development of fast CT scanners and improved data analysis techniques,which allows measurement of the physiologic and hemodynamic properties of tissue vasculature.This study aimed to evaluate CTP in the quantification of angiogenesis and to assess the relationship between tissue perfusion parameters and microvascular density(MVD)and vascular endothelial growth factor(VEGF),attempting to detect the physiologic properties of angiogenesis.METHODS:Sixteen rabbits with VX2 liver tumors underwent multi-slice CT perfusion(MSCTP)on day 14 after tumor inoculation.CTP parameters included hepatic blood flow(HBF),hepatic blood volume(HBV),mean transit time(MTT),permeability of capillary vessel surface(PS),hepatic artery index(HAI),hepatic artery perfusion(HAP),and hepatic portal perfusion(HPP).The border of the tumor was stained with CD34 and VEGF immunohistochemical stains,and MVD was measured by anti-CD34.Then,CTP parameters were determined whether they were correlated with MVD and VEGF using Pearson’s correlation coefficient.RESULTS:The positive expression of MVD was different in the center and border of the tumor(P【0.01).There was a positive correlation between MVD and VEGF in the border(P【0.05).As more VEGF was expressed,the number of microvessels increased.Correlation analyses were also made between the perfusion parameters and MVD and VEGF in the border of the tumor.HBF,PS,HAI,and HAP values were positively correlated with MVD and VEGF(P【0.05),HPP was negatively correlated with MVD and VEGF(P【0.01),and HBV and MTT values were not correlated with MVD and VEGF(P】0.05).CONCLUSIONS:Significant correlations were found between perfusion parameters and MVD and VEGF.Therefore,MSCTP can be used to evaluate tumor angiogenesis in vivo.

Spectral CT imaging as a new quantitative tool? Assessment of perfusion defects of pulmonary parenchyma in patients with lung cancer

Objective： This study investigated the capability of dual-energy spectral computed tomography （CT） to quantitatively evaluate lung perfusion defects that are induced by central lung cancer. Methods： Thirty-two patients with central lung cancer underwent CT angiography using spectral imaging. A univariate general linear model was conducted to analyze the variance of iodine concentration/CT value with three factors of lung fields. A paired t-test was used to compare iodine concentrations and CT values between the distal end of lung cancer and the corresponding area in the contralateral normal lung. Results： Iodine concentrations increased progressively in the far, intermediate and near ground sides in the normal lung fields at 0.60±0.28, 0.93±0.27 and 1.25±0.38 mg/mL, respectively （P〈0.001）. The same trend was observed for the CT values [-（840.64±49.08）, -（812.66±50.85） and -（760.83±89.17） HU, P〈0.001]. The iodine concentration （0.70±0.42 mg/mL） of the lung field in the distal end of lung cancer was significantly lower than the corresponding area in the contralateral normal lung （1.19±0.62 mg/mL） （t=-7.23, P〈0.001）. However, the CT value of lung field in the distal end of lung cancer was significantly higher than the corresponding area in the contralateral normal lung [-（765.29±93.34） HU vs. -（800.07±76.18） HU, t=3.564, P=0.001]. Conclusions： Spectral CT imaging based on the spectral differentiation of iodine is feasible and can quantitatively evaluate pulmonary perfusion and identify perfusion defects that are induced by central lung cancer. Spectral CT seems to be a promising technique for the simultaneous evaluation of both morphological and functional lung information.

Intraperitoneal perfusion of cytokine-induced killer cells with local hyperthermia for advanced hepatocellular carcinoma

AIM:To study the effect and tolerance of intraperitoneal perfusion of cytokine-induced killer(CIK) cells in combination with local radio frequency(RF) hyperthermia in patients with advanced primary hepatocellular carcinoma(HCC).METHODS:Patients with advanced primary HCC were included in this study.CIK cells were perfused intraperitoneal twice a week,using 3.2 × 10 9 to 3.6 × 10 9 cells each session.Local RF hyperthermia was performed 2 h after intraperitoneal perfusion.Following an interval of one month,the next course of treatment was administered.Patients received treatment until disease progression.Tumor size,immune indices(CD3 +,CD4 +,CD3 + CD8 +,CD3 + CD56 +),alpha-fetoprotein(AFP) level,abdominal circumference and adverse events were recorded.Time to progression and overall survival(OS) were calculated.RESULTS:From June 2010 to July 2011,31 patients diagnosed with advanced primary HCC received intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia in our study.Patients received an average of 4.2 ± 0.6 treatment courses(range,1-8 courses).Patients were followed up for 8.3 ± 0.7 mo(range,2-12 mo).Following combination treatment,CD4 +,CD3 + CD8 + and CD3 + CD56 + cells increased from 35.78% ± 3.51%,24.61% ± 4.19% and 5.94% ± 0.87% to 45.83% ± 2.48%(P = 0.016),39.67% ± 3.38%(P = 0.008) and 10.72% ± 0.67%(P = 0.001),respectively.AFP decreased from 167.67 ± 22.44 to 99.89 ± 22.05 ng/mL(P = 0.001) and abdominal circumference decreased from 97.50 ± 3.45 cm to 87.17 ± 4.40 cm(P = 0.002).The disease control rate was 67.7%.The most common adverse events were low fever and slight abdominal erubescence,which resolved without treatment.The median time to progression was 6.1 mo.The 3-,6-and 9-mo and 1-year survival rates were 93.5%,77.4%,41.9% and 17.4%,respectively.The median OS was 8.5 mo.CONCLUSION:Intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia is safe,can efficiently improve immunological status,and may prolong survival in HCC patients.

Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease

BACKGROUND:Hepatocellular carcinoma(HCC)is a common malignant tumor in China,and early diagnosis is critical for patient outcome.In patients with HCC,it is mostly based on liver cirrhosis,developing from benign regenerative nodules and dysplastic nodules to HCC lesions,and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection.Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion,blood volume and permeability.These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion(CTP)imaging and can be used to assess the growth of HCC.This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhotic liver disease by this fast imaging method. METHODS:CTP was performed in 30 volunteers without liver disease(control subjects)and 49 patients with liver disease (experimental subjects:27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre-and post-contrast triple-phase CT and CTP study.A mathematical deconvolution model was applied to provide hepatic blood flow(HBF),hepatic blood volume(HBV), mean transit time(MTT),permeability of capillary vessel surface(PS),hepatic arterial index(HAI),hepatic arterial perfusion(HAP)and hepatic portal perfusion(HPP)data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC.RESULTS:In normal liver,the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC.The value of HBF at the tumor rim was significantly higher than that in the controls.HBF,HBV,HAI,HAP and HPP,but not MTT and PS,were significantly higher in the cirrhotic liver parenchyma involved with HCC than those of the controls. Perfusion parameters were not significantly different between the controls and the cirrhotic liver parenchyma not involved with HCC. CONCLUSIONS:CTP can clearly distinguish tumor from cirrhotic liver parenchyma and controls and can provide quantitative information about tumor-related angiogenesis, which can be used to assess tumor vascularization in cirrhotic liver disease.