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BACKGROUND: Cirrhosis patients often exhibit clinical symptoms such as right liver atrophy, portal hypertension, spleen enlargement and increased blood supply, which exhibit considerable variation between the left and right liver sections. These differences are hypothesized to stem from disparities in blood flow within the left and right portal vein (PV) branches. However, rigorous quantitative evidence remains scarce. PURPOSE: We mainly aim at quantitatively revealing the relationship between the blood flow rates of two PV branches and liver volumes, and providing quantitative evidence and theoretical support for the diagnosis and treatment of cirrhosis from the perspective of hemodynamics. METHODS: Five cirrhotic patients and two healthy volunteers from Beijing Friendship Hospital are investigated. Their PV blood flow models are established based on computed tomography (CT) images and finite volume simulations. The volume of the left and right liver lobes are measured in 3-matic. The distributions of blood source in the PV branches are tracked by streamline analysis. The blood flow rates are quantitatively counted by integrating the blood source velocities. Linear analysis is performed to build the relationship between liver volumes and PV blood flow distributions. RESULTS: Streamline analysis reveals significant differences in blood distribution between the left and right PV branches. The majority of blood from the superior mesenteric vein (SMV) flowed into the right portal vein (RPV), while most blood from the splenic vein (SV) entered the left portal vein (LPV). The main PV pressure drop linearly increases with the SV blood velocity for all PV structures of patients and healthy volunteers. The flow rate ratio QRPV/QLPV demonstrates an increase in tandem with the volume ratio VR/VL, exhibiting a linear correlation with the Pearson correlation coefficient being 0.93. CONCLUSION: The differences in the blood distributions are consistent with the clinicians' knowledge and validate our simulations. We demonstrated a linear increase in PV pressure with elevated SV blood velocity. Additionally, the volumes of the left and right hepatic lobes exhibited a positive correlation with blood flow rates in the corresponding PV branches.
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PURPOSE: Sinusoidal obstruction syndrome (SOS) is a fatal complication of hematopoietic stem cell transplantation (HSCT). Previously, we established a scoring system (Hokkaido ultrasound-based scoring system-10; HokUS-10) comprising 10 ultrasound parameters for SOS diagnosis. In HokUS-10, the portal vein time-averaged flow velocity (PV TAV) and hepatic artery resistive index (HA RI) are measured using subcostal scanning. However, measurement errors and delineation difficulties occur. Therefore, we aimed to prospectively evaluate PV TAV and HA RI measurements obtained via intercostal scanning as an alternative method to subcostal scanning and determine their cutoff values. METHODS: HokUS-10 was administered before and after HSCT. PV TAV and HA RI were measured on subcostal and right intercostal scans. RESULTS: We performed 366 scans on 74 patients. The median value (range) of PV TAV in the main and right portal veins was 15.0 cm/s (2.2-49.6 cm/s) and 10.5 cm/s (1.6-22.0 cm/s), respectively. A low correlation was observed between the two values (r = 0.39, p < 0.01). The highest diagnostic value of the right portal vein was less than 8.0 cm/s. The median value (range) of HA RI in the proper and right hepatic arteries was 0.72 (0.52-1.00) and 0.70 (0.51-1.00), respectively. A strong correlation was observed between the two values (r = 0.65, p < 0.01). The highest diagnostic value of the right HA RI was 0.72 or higher. CONCLUSION: Quantitative measurement of PV TAV and HA RI using intercostal scanning can be appropriately performed as an alternative method to using subcostal scanning.
Subject(s)
Hematopoietic Stem Cell Transplantation , Hepatic Veno-Occlusive Disease , Humans , Hepatic Veno-Occlusive Disease/diagnostic imaging , Hepatic Veno-Occlusive Disease/etiology , Hepatic Artery/diagnostic imaging , Portal Vein/diagnostic imaging , Hemodynamics , Hematopoietic Stem Cell Transplantation/adverse effectsABSTRACT
BACKGROUND: Circulating tumor cells (CTCs) were a promising liquid biopsy for pancreatic cancer (PC) but circulate in low counts in peripheral blood. We evaluated the diagnostic and prognostic values of portal vein (PoV) CTCs in PC patients. METHODS: PoV was aspirated under EUS guidance from 40 patients with suspected pancreaticobiliary cancers. Epithelial-mesenchymal-transition-related subtypes of CTCs were identified via immunofluorescence using EpCAM and Twist antibodies. The diagnostic and prognostic performance of PoV CTCs was investigated by receiver-operating characteristic (AUC) curve and Kaplan-Meier survival analysis. RESULTS: In total, 40 patients including 31 with PC, 4 with non-pancreatic periampullary cancer and 5 with benign pancreatic diseases (BPD) were enrolled. CTCs were detected more in PoV compared with peripheral blood. PoV CTC numbers in BPD patients were lower than in PC patients. The number of PoV CTCs, especially mesenchymal-CTCs (M-CTCs), was positively correlated with the tumor burden, instead of epithelial-CTCs (E-CTCs). The combination of PoV CTC numbers and CA19-9 demonstrated better diagnostic efficiency (AUC value 0.987) than either alone in differentiating PC with BPD. Moreover, the diagnostic efficacy of PoV CTCs and M-CTCs were obviously better than that of E-CTCs and CA19-9 in distinguishing early and late stage PC. Lastly, high PoV CTC and M-CTC numbers were both associated with shorter overall survival. CONCLUSION: Acquisition of the PoV samples in PC patients via EUS-guided procedures has been proved safe and feasible. PoV CTCs, especially M-CTCs, have great potentials in diagnosing and predicting the prognosis of PC, especially in combination with CA19-9.
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BACKGROUND: The detection and quantification of circulating tumour cells (CTCs) in pancreatic cancer (PC) has the potential to provide prognostic information. The aim of this review was to provide an overview of the literature surrounding CTCs in PC. METHODS: A systematic literature review on CTCs in PC between 2005-2020 was performed. Data based on peripheral vein samples were used to determine the positivity rate of CTCs, their prognostic significance and their relative numbers compared to portal vein (PV) samples. RESULTS: The overall CTC detection rate in forty-four articles was 65% (95%CI: 55-75%). Detection rate for CellSearch was 26% (95%CI: 14-38%), which was lower than for both filtration and microfluidic techniques. In nine studies with >50 patients, overall survival was worse with CTC positivity (HR 1.82; 95%CI: 1.61-2.05). Five of seven studies which described PV CTC collection provided patient-level data. PV CTC yield was 7.7-fold (95%CI 1.35-43.9) that of peripheral blood. CONCLUSIONS: CTCs were detected in the peripheral circulation of most patients with PC and may be related to prognosis and disease stage. PV blood contains more CTCs than peripheral blood sampling. This review points to the maturation of techniques of CTC enrichment, and its evidence base for eventual clinical deployment.
Subject(s)
Neoplastic Cells, Circulating/pathology , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/pathology , HumansABSTRACT
Objective:To investigate the predictive value of portal vein (PoV) blood circulating tumor cells (CTCs) count in patients with pancreatic cancer on the postoperative prognosis.Methods:The data of 58 patients receiving radical resection of pancreatic cancer and PoV CTCs detection at People's Hospital of Zhengzhou University from Aug 2018 to Jun 2020 were collected. According to the cut-off value of PoV CTCs>10/5 ml made by receiver operating characteristic curve (ROC), patients were divided into high CTCs group and low CTCs group and the differences in clinicopathological parameters and prognosis of the two groups were compared.Results:Postoperative progression-free survival rate of the low CTCs group was higher than that of the high CTCs group ( χ 2=12.97, P<0.001).Univariate COX regression analysis showed that tumor diameter >4 cm, lymph node invasion, TNM staging, CTCs>10/5 ml, postoperative CA199>37 U/m were risk factors for postoperative prognosis. Multivariate COX regression analysis demonstrated that TNM stage ( OR=2.782, P=0.024), CTCs count >10/5 ml ( OR=2.583, P=0.047), postoperative CA199>37 U/m ( OR=3.775, P=0.004) were the independent risk factors of prognosis. Conclusion:A higher PoV CTCs count was a risk factor for poor prognosis of patients with pancreatic cancer after radical resection.
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BACKGROUND: Insufficient portal vein blood flow, such as portal vein stenosis (PVS), plays a significant influence on liver regeneration. Early prediction of poor liver regeneration induced by severe PVS is critical. Ultrasound serves as a first-line imaging technique in diagnosing PVS based on the changes of portal vein hemodynamics. However, there is still no consensus on the criteria for evaluating the degree of PVS. Moreover, which degree of PVS can induce poor liver regeneration still is unclear. Therefore, it is essential to determine the stenosis degree that leads to significantly poor liver regeneration and to evaluate the value of ultrasonographic hemodynamics for predicting poor liver regeneration induced by severe PVS. METHODS: Rats were randomly subjected to sham operation rats group (SOR), PH group (group A), and PVS groups with mild, moderate, or severe stenosis flowing PH (groups B-D). PH group was set up a model of 70% hepatectomy, and PVS groups were produced by different degrees of partial portal vein ligation following PH. In the SOR group and PH group, the portal vein diameter (PVD) and portal vein velocity (PVV) were measured by Ultrasound at preoperative and postoperative 1, 3, 7, and 14 d. In PVS groups, PVD and PVV at the stenotic (PVDs, PVVs) and pre-stenotic (PVDpre, PVVpre) sites were also detected on 1, 3, 7, and 14 d after surgery, calculating the diameter stenosis ratio (DSR) and accelerating blood flow velocity ratio (AVR). Rats were sacrificed at 1, 3, 7, and 14 d post-surgery, and the expression of proliferating cell nuclear antigen (PCNA) and the liver regeneration rate (LRR) at 14 d were evaluated. The PVVs, DSR, and AVR in the different groups were analyzed combined with the status of liver regeneration, and receiver operating characteristic (ROC) analysis was also applied to assess the value of PVVs, DSR, and AVR in diagnosing severe PVS and the resulting poor liver regeneration. RESULTS: Seventy-two rat models of different degrees of PVS were successfully set up following 70% PH. The stenosis ratios (SRs) of each PVS group were 45.16%±3.44%, 59.21%±3.83%, and 69.56%±2.16%, respectively. Poor liver regeneration appeared to be significant when PVS was greater than 65% (group D), of which the LRR at 14 d was significantly lower compared to PH group (group A) and PVS groups with SR ≤50% (group B) and SR >50-65% (group C), respectively (all P<0.05). Meanwhile, PCNA expression of group D was significantly lower compared to group C at 1 d and groups A-C at 3 d (all P<0.05). Differences were also detected at 3 d between groups A and B and groups A and C (both P<0.05). Among PVS groups, PVVs accelerated dramatically, with significant differences demonstrated between group D and groups B and C at 1 d, as well as group B and groups C and D at 3 d (all P<0.05). At 1, 3, and 7 d, DSR of groups C and D were significantly higher than that of group A (all P<0.05). At 1 and 3 d, AVR of group D was significantly higher than that of groups B and C (all P<0.05). ROC analysis showed the AUC of PVVs at 1 d in diagnosing severe PVS was 0.84, while at 3 d, it was unable to differentiate from mild-moderate or severe PVS by PVVs (P>0.05 vs. AUC =0.50). At 1 and 3 d, the AUC of DSR and AVR in diagnosing severe PVS were all greater than 0.80, comparatively much better in AVR (AUC >0.95). The best cut-off points of AVR at 1 and 3 d were 6.91 and 5.36, with the sensitivity and specificity respectively 100%, 91.67% at 1 d, and 100%, 83.33% at 3 d. CONCLUSIONS: Poor liver regeneration could be significantly induced when PVS was greater than 65%. Ultrasound can well prove the changes of portal vein hemodynamics in different degrees of PVS in rats. The parameters PVVs could be regarded as a valid index for diagnosing PVS but were not applicable for evaluating the stenosis degree. Comparatively, the parameters DSR and AVR, especially AVR, proved to be useful for differentiating severe PVS (>65%) in the early postoperative period, predicting the resulting poor liver regeneration.
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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with poor prognosis. This is due to late diagnosis and lack of reliable prognostic biomarkers. In this study, we focused on exosomal microRNA (miRNA) in portal vein blood (PVB) as a potential biomarker to identify patients at high-risk for recurrence and poor postoperative outcome. METHODS: Exosomal miR-4525, miR-451a and miR-21 expressions were assessed using PVB and peripheral blood (PB) collected from 55 PDAC patients during curative pancreatectomy. Correlation between the miRNA expressions and clinical outcomes, and target genes expressions was investigated. RESULTS: Exosomal miR-4525, miR-451a and miR-21 levels were upregulated in PVB, which were higher than those in the PB. High expression of miR-4525, miR-451a and miR-21 in PVB was associated with recurrence with a higher sensitivity, specificity, and accuracy than that in PB. Cox regression analysis showed miR-4525, miR-451a and miR-21 levels in PVB were independent prognostic factors for overall survival and disease-free survival. There was a negative correlation between the expressions of miR-4525 and MEN1 mRNA, miR-451a and CAB39 mRNA, and t miR-21 and PDCD4 mRNA. CONCLUSIONS: miR-4525, miR-451a and miR-21 in PVB are potential biomarkers identifying patients at high-risk for recurrence and poor survival in resected PDAC patients.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Pancreatic Ductal/blood , Exosomes , MicroRNAs/blood , Pancreatic Neoplasms/blood , Portal Vein , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/therapy , Female , Gene Expression Regulation, Neoplastic , Humans , Male , MicroRNAs/genetics , Middle Aged , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/mortality , Pancreatectomy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/therapy , Up-RegulationABSTRACT
AIMS/HYPOTHESIS: The mechanisms for improved glycemic control after bariatric surgery in subjects with type 2 diabetes (T2D) are not fully known. We hypothesized that dynamic hepatic blood responses to a mixed-meal are changed after bariatric surgery in parallel with an improvement in glucose tolerance. METHODS: A total of ten morbidly obese subjects with T2D were recruited to receive a mixed-meal and a glucose-dependent insulinotropic polypeptide (GIP) infusion before and early after (within a median of less than three months) bariatric surgery, and hepatic blood flow and volume (HBV) were measured repeatedly with combined positron emission tomography/MRI. Ten lean non-diabetic individuals served as controls. RESULTS: Bariatric surgery leads to a significant decrease in weight, accompanied with an improved ß-cell function and glucagon-like peptide 1 (GLP-1) secretion, and a reduction in liver volume. Blood flow in portal vein (PV) was increased by 1.65-fold (P = 0.026) in response to a mixed-meal in subjects after surgery, while HBV decreased in all groups (P < 0.001). When the effect of GIP infusion was tested separately, no change in hepatic arterial and PV flow was observed, but HBV decreased as seen during the mixed-meal test. CONCLUSIONS/INTERPRETATION: Early after bariatric surgery, PV flow response to a mixed-meal is augmented, improving digestion and nutrient absorption. GIP influences the post-prandial reduction in HBV thereby diverting blood to the extrahepatic sites.
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Objective To analyze the concentration changes of insulin and c peptide of in portal vein and peripheral blood, and explore the feasibility of using insulin and c peptide concentration changes in assessment of liver function. Methods The portal vein and peripheral blood samples were extracted from 82 clinical liver cancer patients, and the insulin and c peptide concentration were detected. The differences in the insulin and c peptide concentration in portal vein and peripheral blood were statistically analyzed. Results The insulin concentration in the portal vein and peripheral blood values were 32.43 μ U/ml and 8.05 μ U/ml, respectively, there was a significant difference (P0.05) . Conclusion Liver metabolizes insulin as the target organ of insulin, while c-peptide dose not be metabolized in vivo, so it is possible to assess liver function by comparative analysis of the metabolic rate of insulin and c-peptide changes.
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Objective To investigate the relations between the portal parameters of homodynamic and stages of liver fibrosis of chronic hepatic B patients.Methods Fibrosis parameters of blood serum of one hundred and two patients with chronic viral hepatic B were measured with Doppler ultrasonic technique.The inner diameters,blood flow velocity,blood flow volume of their portal veins were investigated.And,the pathological changes of liver tissues were examined.Results The blood flow velocity of portal vein correlates very well with the stages of liver fibrosis,and reduces with the development of the degree of liver fibrosis.The blood flow velocity of severe fibrosis patients is obviously smaller than that of mild patients,and is 28.4% slower compared stage 4 with stage 1(P
