OBJECTIVES: To establish a three-dimensional (3D) visualization-based classification of the left hepatic portal vein (LHPV) and left hepatic vein (LHV) systems using 3D reconstruction technology to facilitate precise segmental/subsegmental resection of left liver lesions. METHODS: Thin-slice contrast-enhanced CT datasets from 244 patients were reconstructed using MI-3DV Works software. The spatial anatomy (origins, branching patterns, and spatial relationships) of the LHPV and LHV branches was analyzed to determine their 3D classifications and segmental liver divisions for guiding surgical planning for anatomical left liver resections. RESULTS: The 3D models of the third- and fourth-order branches of the LHPV and LHV were successfully reconstructed for all the 244 patients. Two types of the LHPV system were identified, where the LHPV either had independent origins [242 cases (99.1%)] or had right anterior portal branches arising from the LHPV trunk [2 cases (0.9%)]. 3D classifications identified two types of the Segment II of the LHPV (based on branch number), 3 types of the Segment III (by spatial distribution of the branches), compact vs dispersed types of the left lateral lobe (determined by Segment II/III branches proximity), 3 types of the Segment IV (by branch number and origin), and 3 types the fourth hilar vessels (transverse branches of the left portal vein) for their supplied segments. The LHV system had two drainage types into the inferior vena cava, and the umbilical fissure veins were classified into 3 types by drainage patterns and distance to the venous roots. These classifications combined with liver segmentations allowed individualized surgical planning for segment-specific resections. CONCLUSIONS The 3D classification of the LHPV and LHV provides valuable clinical guidance for precise anatomical resections of left liver lesions using liver segments or subsegments as anatomical units to enhance surgical accuracy and improve the outcomes of hepatobiliary surgery.
Humans ; Hepatectomy/methods* ; Imaging, Three-Dimensional ; Hepatic Veins/anatomy & histology* ; Portal Vein/anatomy & histology* ; Liver/surgery* ; Liver Neoplasms/blood supply* ; Tomography, X-Ray Computed ; Female

OBJECTIVE: Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis. METHODS: Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels. RESULTS: In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A. CONCLUSION JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
Carcinoma, Hepatocellular/blood supply* ; Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-8/metabolism* ; Liver Neoplasms/blood supply* ; Aurora Kinase A/metabolism* ; Neovascularization, Pathologic/drug therapy* ; Animals ; Signal Transduction/drug effects* ; Mice ; Drugs, Chinese Herbal/therapeutic use* ; Cell Line, Tumor ; Mice, Inbred BALB C ; Mice, Nude ; Angiogenesis

BACKGROUND/AIMS: To evaluate the enhancement patterns of liver metastases and their influencing factors using dynamic contrast-enhanced ultrasound (CEUS). METHODS: A total of 240 patients (139 male and 101 female; 58.5±11.2 years of age) diagnosed with liver metastases in our hospital were enrolled in this study to evaluate tumor characteristics using CEUS. A comparison of enhancement patterns with tumor size and primary tumor type was performed using the chi-square test. The differences between quantitative variables were evaluated with the independent-sample t-test and one-way analysis of variance. RESULTS: The enhancement patterns of liver metastases on CEUS were categorized as diffuse homogeneous hyperenhancement (133/240, 55.4%), rim-like hyperenhancement (80/240, 33.3%), heterogeneous hyperenhancement (10/240, 4.2%), and isoenhancement (17/240, 7.1%). There were significant differences in the enhancement patterns during the arterial phase based on the nodule size (p=0.001). A total of 231 of the nodules showed complete washout during the portal phase, and 237 nodules were hypoenhanced during the delayed phase. The washout time was correlated with tumor vascularity, with a longer washout time observed in hypervascular metastases compared to hypovascular metastases (p=0.033). CONCLUSIONS: Diffuse homogeneous hyperenhancement followed by rapid washout was the most common enhancement pattern of liver metastases on CEUS and was affected by the nodule size and tumor vascularity. Small metastases were prone to show diffuse homogeneous hyperenhancement. Hyper-vascular metastases showed a significantly longer washout time compared to hypovascular metastases.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Contrast Media/*therapeutic use ; Female ; Humans ; Liver/diagnostic imaging/pathology ; Liver Neoplasms/blood supply/*diagnostic imaging/secondary ; Male ; Middle Aged ; Neovascularization, Pathologic/diagnostic imaging ; Ultrasonography/*methods ; Young Adult

Objective To explore the expressions of inhibitors of DNA binding-1 (Id-1) and matrix metalloproteinase-9 (MMP-9) in colorectal carcinoma tissues and its correlation with microvessel density (MVD). Methods The expressions of Id-1 and MMP-9 as well as CD34-labelled MVD in colorectal adenocarcinoma tissues (n=50) and normal adjacent tissues (n=50) were examined by immunohistochemistry. Results The positive expressions of Id-1 and MMP-9 were seen in 72.00% (36/50) and 78.00%(39/50) of colorectal adenocarcinoma tissues,which were significantly higher than those [24.00%(12/50) and 28.00% (14/50)] in normal adjacent tissues (P=0.000). The MVD value (17.22±2.08) in colorectal adenocarcinoma tissues was significantly higher than that (5.36±2.17) in normal adjacent tissues (P=0.000). The expressions of Id-1 and MMP-9 and MVD were significantly correlated with serosa invasion,TNM stage,carcinoembryonic antigen(+),lymph node metastasis,vascular invasion,and liver metastasis (all P<0.05) but not with the patient's age,gender,tumor size,and differentiation degree (all P>0.05). The MVD value with Id-1 and MMP-9 positive expression were significantly higher than those with Id-1 and MMP-9 negative expression (all P=0.000). The expression of Id-1 in colorectal adenocarcinoma tissues showed significantly positive correlation with that of MMP-9 (r=0.429,P=0.000). Cox multivariate analysis showed that Id-1 and MMP-9 expressions were independent prognostic factors for colorectal carcinoma. Conclusions The high expressions of Id-1 and MMP-9 have high correlations with the development and progression of colorectal adenocarcinoma and have positive correlation with MVD. Both of them may be involved in the microvascular generation and the invasion and hematogenous metastasis of colorectal carcinoma.
Adenocarcinoma ; blood supply ; metabolism ; Colorectal Neoplasms ; blood supply ; metabolism ; Disease Progression ; Humans ; Immunohistochemistry ; Inhibitor of Differentiation Protein 1 ; metabolism ; Liver Neoplasms ; Lymphatic Metastasis ; Matrix Metalloproteinase 9 ; metabolism ; Microcirculation ; Microvessels ; Neovascularization, Pathologic

To investigate the correlations among total liver CT perfusion parameters, unpaired arteries (UAs) and microvessel area (MVA) in a rabbit liver VX2 tumor model, and to learn the tumoral angiogenesis condition and the mechanisms for perfusion imaging.
 Methods: Rabbits with or without the inoculated VX2 tumor in the liver underwent total liver CT perfusion imaging 2 weeks after the operation. Perfusion parameters included blood flow (BF), blood volume (BV), arterial liver perfusion (ALP), portal liver perfusion (PVP), hepatic perfusion index (HPI) for the tumor rim and the surrounding liver tissue. After the examination, the UAs and MVA of tumor tissues were obtained by immunohistochemical staining. The differences of perfusion parameters between the vital tumor rim and the surrounding liver tissue were compared. The correlations among perfusion parameters, UAs and MVA were analyzed.
 Results: There was significant difference between the CT perfusion parameters at the tumor rim and the surrounding liver tissue or liver tissue of the control group (P<0.05), but there was no significant difference between the perfusion parameters at the surrounding liver tissues of the experimental group and the control (P>0.05). There was positive correlation between UAs and MVA. UAs and MVA were positively correlated with BF, ALP and BV at the tumor rim. UAs and MVA were negatively correlated with PVP. HPI positively correlated with UAs, but it was not correlated with MVA.
 Conclusion: Total liver CT perfusion can provide quantitative information to evaluate the artery and portal vein perfusion of liver VX2 tumor, and to assess the degree of tumor angiogenesis.
Animals ; Arteries ; diagnostic imaging ; Blood Volume ; Carcinoma ; Immunohistochemistry ; Liver Circulation ; Liver Neoplasms ; blood supply ; diagnostic imaging ; Microvessels ; diagnostic imaging ; Neoplasm Transplantation ; Neoplasms, Squamous Cell ; Neovascularization, Pathologic ; diagnostic imaging ; Perfusion Imaging ; statistics & numerical data ; Portal System ; diagnostic imaging ; Rabbits ; Tomography, X-Ray Computed ; methods ; statistics & numerical data

OBJECTIVETo study the characteristics of blood flow in common hepatic tumors by 256-slice spiral CT whole-liver perfusion imaging.

METHODSSeventy-one patients with hepatic tumors were examined retrospectively by 256-slice spiral CT whole-liver perfusion. Among them, twenty-seven cases were of primary hepatic cancer, twenty-four cases of hepatic hemangioma, and twenty cases of hepatic metastases.Regions of interest (ROIs) were placed in the tumor parenchyma (Area A), peritumoral hepatic parenchyma (Area B), and normal hepatic parenchyma (Area C), respectively. The time density curves (TDC) were drawn, and perfusion parameters including hepatic arterial perfusion(HAP), portal venous perfusion(PVP), total liver perfusion(TLP) and hepatic erfusion index(HPI) were obtained. The values of ROIs were measured, and the perfusion parameters in the areas A, B, C of different hepatic tumors were statistically analyzed.

RESULTSThe values of HAP, PVP, HPI in the tumor parenchyma of primary hepatic carcinoma were (20.00 ± 11.41)ml · min(-1) · 100 ml(-1,) (32.31 ± 21.06)ml · min(-1) · 100 ml(-1,) (52.31 ± 30.55)ml · min(-1) · 100 ml(-1,) and (39.67 ± 11.19)%, showing significant difference as compared with those in peritumoral hepatic parenchyma and in normal hepatic parenchyma(P<0.05). The values of HAP, TLP, and HPI in the tumor parenchyma of hepatic hemangioma were (40.39 ± 29.23)ml · min(-1) · 100 ml(-1,) (132.72 ± 132.65) ml · min(-1) · 100 ml(-1,) and (35.51 ± 15.12)%, were significantly different as compared with those in the peritumoral hepatic parenchyma and in normal hepatic parenchyma(P<0.05). The values of HAP, PVP, HPI in the tumor parenchyma of hepatic metastases were (17.43 ± 12.27)ml · min(-1) · 100 ml(-1,) (36.19 ± 34.99) ml · min(-1) · 100 ml(-1,) and (37.86 ± 14.49)%, significantly different as compared normal hepatic parenchyma (P<0.05). The HAP, PVP, and TLP of tumor tissue and the PVP and HPI of peritumoral tissue in different hepatic tumors were statistically significantly different (P<0.05).

CONCLUSIONSThe multi-slice spiral CT whole-liver perfusion has certain value in the diagnosis of common hepatic tumors. Perfusion parameters in different areas of common hepatic tumors have their own hemodynamic characteristics.

Carcinoma, Hepatocellular ; blood supply ; diagnostic imaging ; Hemangioma ; blood supply ; diagnostic imaging ; Hepatic Artery ; diagnostic imaging ; physiology ; Humans ; Liver ; blood supply ; Liver Neoplasms ; blood supply ; diagnostic imaging ; secondary ; Perfusion Imaging ; Portal Vein ; diagnostic imaging ; physiology ; Regional Blood Flow ; Retrospective Studies ; Tomography, Spiral Computed

OBJECTIVETo explore the effect of colon cancer cell-derived interleukin-1α on the migration and proliferation of human umbilical vein endothelial cells as well as the role of IL-1α and IL-1ra in the angiogenesis process.

METHODSWestern blot was used to detect the expression of IL-1α and IL-1R1 protein in the colon cancer cell lines with different liver metastatic potential. We also examined how IL-1α and IL-1ra influence the proliferation and migration of umbilical vascular endothelial cells assessed by PreMix WST-1 assay and migration assay, respectively. Double layer culture technique was used to detect the effect of IL-1α on the proliferation and migration of vascular endothelial cells and the effect of IL-1ra on the vascular endothelial cells.

RESULTSWestern blot analysis showed that IL-1α protein was only detected in highly metastatic colon cancer HT-29 and WiDr cells, but not in the lowly metastatic CaCo-2 and CoLo320 cells.Migration assay showed that there were significant differences in the number of penetrated cells between the control (17.9±3.6) and 1 ng/ml rIL-1α group (23.2±4.2), 10 ng/ml rIL-1α group (31.7±4.5), and 100 ng/ml rIL-1α group (38.6±4.9), showing that it was positively correlated with the increasing concentration of rIL-1α (P<0.01 for all). The proliferation assay showed that the absorbance values were 1.37±0.18 in the control group, and 1.79±0.14 in the 1 ng/ml rIL-1α group, 2.14±0.17 in the 10 ng/ml rIL-1α group, and 2.21±0.23 in the 100 ng/ml rIL-1α group, showing a positive correlation with the increasing concentration of rIL-1α(P<0.01 for all). IL-1ra significantly inhibited the proliferation and migration of vascular endothelial cells (P<0.01). The levels of VEGF protein were (1.697±0.072) ng/ml, (3.507±0.064)ng/ml and (4.139±0.039)ng/ml in the control, HUVECs+ IL-1α and HUVECs+ HT-29 co-culture system groups, respectively, showing a significant difference between the control and HUVECs+ 10 pg/ml rIL-1α groups and between the control and HUVECs+ HT-29 groups (P<0.01 for both).

CONCLUSIONSOur findings indicate that colon cancer cell-derived IL-1α plays an important role in the liver metastasis of colon cancer through increased VEGF level of the colon cancer cells and enhanced vascular endothelial cells proliferation, migration and angiogenesis, while IL-1ra can suppress the effect of IL-1α and inhibit the angiogenesis in colon cancer.

Blotting, Western ; Caco-2 Cells ; Cell Line, Tumor ; Cell Movement ; physiology ; Cell Proliferation ; physiology ; Coculture Techniques ; Colonic Neoplasms ; blood supply ; metabolism ; pathology ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; Interleukin 1 Receptor Antagonist Protein ; metabolism ; physiology ; Interleukin-1alpha ; metabolism ; physiology ; Liver Neoplasms ; secondary ; Neovascularization, Pathologic ; etiology

OBJECTIVETo explore the surgical risk, perioperative outcome and the response of patients with hepatocellular carcinoma (HCC) after preoperative transcatheter arterial chemoembolization (TACE).

METHODSA retrospective case-matched study was conducted to compare the characteristics and corresponding measures of patients in the preoperative TACE group and the control group without TACE. A total of 105 patients (82 patients with selective and dynamic region-specific vascular occlusion to perform hepatectomy for patients with complex hepatocellular carcinoma) was included in this study, in which 35 patients underwent TACE therapy, and a 1:2 matched control group of 70 subjects.

RESULTSThe patients of preoperative TACE therapy group had a higher level of γ-glutamyl transpeptidase before operation (119.52±98.83) U/L vs. (67.39±61.25) U/L (P=0.040). The operation time was longer in the TACE group than that in the control group but with a non-significant difference (232.60±95.43) min vs. (218.70±75.13) min (P=0.052). The postoperative recovery of liver function and severe complications in the preoperative TACE group were similar to that in the control group (P>0.05). There were no massive hemorrhage, biliary fistula and 30-d death neither in the treatment group and matched control group.

CONCLUSIONSPreoperative TACE therapy has certain negative effect on liver function. It is preferable to use selective and dynamic region-specific vascular occlusion technique during hepatectomy and combine with reasonable perioperative treatment for this group of patients, that can ensure safety of patients and promote their rapid recovery.

Carcinoma, Hepatocellular ; blood supply ; therapy ; Case-Control Studies ; Chemoembolization, Therapeutic ; adverse effects ; methods ; Hepatectomy ; methods ; Humans ; Liver ; physiopathology ; Liver Neoplasms ; blood supply ; therapy ; Operative Time ; Preoperative Period ; Recovery of Function ; Retrospective Studies ; gamma-Glutamyltransferase ; analysis

OBJECTIVEThe purpose of this study was to compare MRI findings of solitary hypovascular hepatic nodules, benign and malignant, to identify their MRI characteristics.

METHODSWe retrospectively assessed solitary hypovascular hepatic nodules ≤ 3 cm in 135 patients, among them there were 55 malignant nodules [29 peripheral nodules of cholangiocarcinoma, PCC, and 26 hepatic metastases, HM] and 80 benign nodules [48 inflammatory myofibroblastic tumors, IMT, and 32 hepatic hemangioma, HG], proved by surgery, biopsy or follow-up imaging. Unenhanced and dynamic enhanced MRI findings of the 135 patients were analyzed retrospectively. Statistical analysis included Chi-square test or Fisher's exact test, and receiver operating characteristic (ROC) curve.

RESULTSThere was significant difference (P < 0.05) between the malignant group and benign group in terms of location, margin, T2WI signal intensity, heterogeneity or homogeneity of the nodule, and type and degree of peritumoral and intratumoral enhancement. Area under the curve at the first film reading by three radiologists was 0.678 ± 0.047, 0.920 ± 0.022 at the second time, and there was a significant difference (Z = 5.22, P < 0.05) between them.

CONCLUSIONSOur data indicated that solitary hypovascular hepatic nodules show unenhanced and dynamic enhanced MRI features. Therefore, MR imaging combined with clinical and biochemical data does provide reliable information for a proper diagnosis of such hepatic lesions and differentiation of malignant from benign nodules.

Cholangiocarcinoma ; pathology ; Diagnosis, Differential ; Hemangioma ; pathology ; Humans ; Liver ; blood supply ; pathology ; Liver Neoplasms ; blood supply ; pathology ; Magnetic Resonance Imaging ; ROC Curve ; Retrospective Studies

OBJECTIVE: To investigate the outcomes of percutaneous unilateral metallic stent placement in patients with a malignant obstruction of the biliary hila and a contralateral portal vein steno-occlusion. MATERIALS AND METHODS: Sixty patients with a malignant hilar obstruction and unilobar portal vein steno-occlusion caused by tumor invasion or preoperative portal vein embolization were enrolled in this retrospective study from October 2010 to October 2013. All patients were treated with percutaneous placement of a biliary metallic stent, including expanded polytetrafluoroethylene (ePTFE)-covered stents in 27 patients and uncovered stents in 33 patients. RESULTS: A total of 70 stents were successfully placed in 60 patients. Procedural-related minor complications, including self-limiting hemobilia (n = 2) and cholangitis (n = 4) occurred in six (10%) patients. Acute cholecystitis occurred in two patients. Successful internal drainage was achieved in 54 (90%) of the 60 patients. According to a Kaplan-Meier analysis, median survival time was 210 days (95% confidence interval [CI], 135-284 days), and median stent patency time was 133 days (95% CI, 94-171 days). No significant difference in stent patency was observed between covered and uncovered stents (p = 0.646). Stent dysfunction occurred in 16 (29.6%) of 54 patients after a mean of 159 days (range, 65-321 days). CONCLUSION: Unilateral placement of ePTFE-covered and uncovered stents in the hepatic lobe with a patent portal vein is a safe and effective method for palliative treatment of patients with a contralateral portal vein steno-occlusion caused by an advanced hilar malignancy or portal vein embolization. No significant difference in stent patency was detected between covered and uncovered metallic stents.
Adult ; Aged ; Aged, 80 and over ; Biliary Tract Neoplasms/surgery ; Cholangitis/etiology ; Cholestasis/*surgery ; Female ; Hemobilia/etiology ; Humans ; Kaplan-Meier Estimate ; Liver/blood supply/pathology/surgery ; Liver Neoplasms/surgery ; Male ; Middle Aged ; Palliative Care/methods ; Polytetrafluoroethylene ; Portal Vein/pathology/*surgery ; Retinal Vein Occlusion/*surgery ; Retrospective Studies ; Stents/*adverse effects ; Treatment Outcome