Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging.

BACKGROUND: Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized. PURPOSE: To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features. ANIMAL MODEL: Established PBDL models. POPULATION: Fifty-four mice were randomly divided into four timepoints PBDL groups and one sham group. FIELD STRENGTH/SEQUENCE: 3.0 T; MRI sequences included T1-weighted fast spin-echo (FSE), T2-weighted single shot FSE, variable flip angle T1 mapping, multi-echo SE T2 mapping, multi-echo gradient-echo T2* mapping, and multi-b-value diffusion-weighted imaging. ASSESSMENT: MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native-T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D* ) within the entire ligated (PBDL), non-ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system. STATISTICAL TESTS: One-way ANOVA, Spearman's rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS: Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non-ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2* than other livers. Spearman's correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = -0.718) than inflammation (r = 0.564 and r = -0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956. DATA CONCLUSION: Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Tumescence Anesthesia Solution-Assisted Laser Ablation Treatment of Lower Limb Varicose Veins: The Effect of Temperature of the Tumescence Anesthesia Solution on Intraoperative and Postoperative Pain, Clinical Observations, and Comprehensive Nursing Care.

PURPOSE: To investigate the effect of cold and room temperature tumescence anesthesia solution (TAS) on the treatment of lower limb varicose veins via endovenous laser ablation. DESIGN: On the basis of the TAS temperature, patients were divided into two groups: group A (n = 26) received room temperature (24°C) TAS, and group B (n = 25) received cold (4°C) TAS. METHODS: A numerical rating scale was used to evaluate pain. Perioperative and intraoperative nursing care and clinical observations were performed following a generalized standard. FINDINGS: Percentages of patients who felt pain in groups A and B were 69.2% and 36.0%. Average numerical rating scale scores of patients in the two groups (A and B) on the day of surgery and on postoperative days 1, 2, and 3 were 4.3 versus 2.1, 3.5 versus 1.0, 3.0 versus 0.8, and 1.6 versus 0.3, respectively. CONCLUSIONS: Cold TAS reduces intraoperative and postoperative pain more effectively than room temperature.

Irradiation stents vs. conventional metal stents for unresectable malignant biliary obstruction: A multicenter trial.

BACKGROUND & AIMS: Placement of an irradiation stent has been demonstrated to offer longer patency and survival than an uncovered self-expandable metallic stent (SEMS) in patients with unresectable malignant biliary obstruction (MBO). We aim to further assess the efficacy of an irradiation stent compared to an uncovered SEMS in those patients. METHODS: We performed a randomized, open-label trial of participants with unresectable MBO at 20 centers in China. A total of 328 participants were allocated in parallel to the irradiation stent group (ISG) or the uncovered SEMS group (USG). Endpoints included stent patency (primary), technical success, relief of jaundice, overall survival, and complications. RESULTS: The first quartile stent patency time (when 25% of the patients experienced stent restenosis) was 212 days for the ISG and 104 days for the USG. Irradiation stents were significantly associated with a decrease in the rate of stent restenosis (9% vs. 15% at 90 days; 16% vs. 27% at 180 days; 21% vs. 33% at 360 days; p = 0.010). Patients in the ISG obtained longer survival time (median 202 days vs. 140 days; p = 0.020). No significant results were observed in technical success rate (93% vs. 95%; p = 0.499), relief of jaundice (85% vs. 80%; p = 0.308), and the incidence of grade 3 and 4 complications (8.5% vs. 7.9%; p = 0.841). CONCLUSIONS: Insertion of irradiation stents instead of uncovered SEMS could improve patency and overall survival in patients with unresectable MBO. LAY SUMMARY: For patients with unresectable malignant biliary obstruction (MBO), placement of a self-expandable metallic stent (SEMS) is a recommended palliative modality to relieve pruritus, cholangitis, pain, and jaundice. However, restenosis is a main pitfall after stent placement. Data from this first multicenter randomized controlled trial showed that insertion of an irradiation stent provided longer patency and better survival than a conventional metal stent. ClinicalTrials.gov ID: NCT02001779.

Rare hepatic malignant tumors: dynamic CT, MRI, and clinicopathologic features: with analysis of 54 cases and review of the literature.

AIM: To evaluate the dynamic CT, MRI, and clinicopathologic characteristics of rare hepatic malignant tumors (HRMTs), improving the understanding and diagnosis of the tumors. METHODS: A retrospective analysis of 54 cases of HRMTs diagnosed by pathology in our hospital during January 1, 2005 to September 1, 2011. RESULTS: The types of tumors included hepatic sarcoma (n = 8), malignant lymphoma (n = 4), malignant fibrous histiocytoma (MFH, n = 7), malignant melanoma (MM, n = 4), squamous cell carcinoma (SCC, n = 5), primary clear cell carcinoma of the liver (PCCCL, n = 7), stromal tumors (ST n = 4), hepatoblastoma (HB, n = 8), carcinoid (n = 6), primary primitive neuroectodermal tumor (pPNET, n = 1). Age of the patients ranged from 1 to 79 years (mean = 46.7 years). There were more men in this group (34/54). Symptoms of HRMTs show no specificity. Except PCCCL and HB, the serum AFP of most HRMTs was negative. 43 patients had a single hepatic mass, and 11 patients had multiple hepatic masses. Diameters ranged from 2 to 15 cm (mean = 7.7 cm). Precontrast CT revealed that most masses had uneven density (n = 46) and ill-demarcated margin (n = 37). Enhanced CT showed most lesions unevenly enhanced (n = 49), of which PCCCL had a prompt enhancement in the arterial phase and rapid wash-out on the portal venous phase and delayed phase; malignant lymphoma and ST had slight enhancement, MFH and undifferentiated embryonal sarcoma had gradual delayed enhancement. Most masses had low-signal on T1WI and high-signal on T2WI, while MM had high-signal on T1WI and low-signal on T2WI. CONCLUSIONS: Although there is frequent overlap in the CT, MRI, and clinicopathologic appearances between the rare malignant tumors, some HRMTs have characteristic imaging features that can suggest a specific diagnosis.

Advances in application of novel magnetic resonance imaging technologies in liver disease diagnosis.

Liver disease is a major health concern globally, with high morbidity and mor-tality rates. Precise diagnosis and assessment are vital for guiding treatment approaches, predicting outcomes, and improving patient prognosis. Magnetic resonance imaging (MRI) is a non-invasive diagnostic technique that has been widely used for detecting liver disease. Recent advancements in MRI technology, such as diffusion weighted imaging, intravoxel incoherent motion, magnetic resonance elastography, chemical exchange saturation transfer, magnetic resonance spectroscopy, hyperpolarized MR, contrast-enhanced MRI, and ra-diomics, have significantly improved the accuracy and effectiveness of liver disease diagnosis. This review aims to discuss the progress in new MRI technologies for liver diagnosis. By summarizing current research findings, we aim to provide a comprehensive reference for researchers and clinicians to optimize the use of MRI in liver disease diagnosis and improve patient prognosis.

PD-1/PD-L1 inhibitor treatment and its impact on clinical imaging in non-small cell lung cancer: a systematic review and meta-analysis of immune-related adverse events.

Background: In the contemporary era of cancer treatment, lung cancer (LC) holds the unenviable position of being the primary contributor to cancer-induced mortality worldwide. Although immunotherapy has expanded the therapeutic landscape for metastatic non-small cell lung cancer (NSCLC), the advent of immune checkpoint inhibitors has been accompanied by a concomitant increase in immune-related adverse events (irAEs). Timely detection of irAEs is pivotal for efficacious management and enhanced patient outcomes. Diagnostic imaging, encompassing x-ray and CT scans, can facilitate the identification and supervision of irAEs, thereby ensuring the prompt recognition of associated patterns and alterations for expeditious treatment. Methods: The present inquiry undertook a systematic exploration of multiple databases, incorporating a diverse array of studies such as randomized controlled trials and observational analyses. Patient demographics, imaging outcomes, and risk of bias were extracted from the data. Meta-analysis was executed utilizing R Statistical Software, with the results of the risk of bias assessment summarized accordingly. Findings: The analysis unveiled a higher prevalence of irAEs in patients receiving first-line treatment for NSCLC compared to those receiving subsequent treatments, with a statistically significant distinction observed for both high- and low-grade irAEs (p < 0.001). Pneumonitis, thyroiditis, and colitis emerged as the most frequently reported irAEs, whereas hepatitis and pancolitis were less commonly documented. This investigation signifies a crucial advancement in elucidating the function of imaging in the treatment of NSCLC with PD-1/PD-L1 inhibitors and emphasizes the imperative for ongoing research in this domain.

Corrigendum: Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis.

[This corrects the article DOI: 10.3389/fgene.2023.1124330.].

Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis.

Liver fibrosis is a repair response to injury caused by various chronic stimuli that continually act on the liver. Among them, the activation of hepatic stellate cells (HSCs) and their transformation into a myofibroblast phenotype is a key event leading to liver fibrosis, however the mechanism has not yet been elucidated. The molecular basis of HSC activation involves changes in the regulation of gene expression without changes in the genome sequence, namely, via epigenetic regulation. DNA methylation is a key focus of epigenetic research, as it affects the expression of fibrosis-related, metabolism-related, and tumor suppressor genes. Increasing studies have shown that DNA methylation is closely related to several physiological and pathological processes including HSC activation and liver fibrosis. This review aimed to discuss the mechanism of DNA methylation in the pathogenesis of liver fibrosis, explore DNA methylation inhibitors as potential therapies for liver fibrosis, and provide new insights on the prevention and clinical treatment of liver fibrosis.

Hepatic perivascular epithelioid cell tumor (PEComa): dynamic CT, MRI, ultrasonography, and pathologic features--analysis of 7 cases and review of the literature.

OBJECTIVE: To evaluate the dynamic CT, MRI, ultrasonography, and pathologic features of hepatic perivascular epithelioid cell tumor (PEComa), improving the understanding and diagnosis of the tumor. METHODS: A retrospective analysis of CT, MRI, ultrasonography, and pathologic features of 7 hepatic PEComas diagnosed by pathology during 1st January 2005 to 1st September 2011 in our hospital. RESULTS: The performance of dynamic CT, MRI, and ultrasonography revealed that lesions were regular masses with well-defined borders, the maximum diameters were 2.5-8.5 cm (mean = 4 cm), density was homogeneous, contrast-enhanced CT and MRI showed the lesions were significantly and heterogeneously enhanced on arterial phase, less enhanced on portal venous phase, and slightly hypodense on delayed phase. One patient had multiple hepatic lesions and had delayed enhancement. There were no backgrounds of hepatitis and cirrhosis, enlarged lymph nodes, or distant metastases. Pathology showed the gross appearance of the tumor was smooth. Tumor cells were round or polygonal, with clear boundaries and clear membranes, and had abundant translucent cytoplasm. Nuclei were round, with medium size. Tumor cells were epithelial-like cells and arranged in dense sheets. Immunohistochemistry showed that most of them were positive in HMB45 and MelanA, S-100, SMA, while negative in CgA, Syn, CK, CD117, CD10, and CD34. CONCLUSIONS: Dynamic CT, MRI, ultrasonography, and pathology of PEComa had some characteristics of benign tumor's performance. Enhanced scan showed PEComa quickly enhanced on arterial phase and enhanced less on portal venous phase. Knowing these characteristics could help to improve the understanding and diagnosis of hepatic PEComa.

Sodium Butyrate Pre-Treatment Enhance Differentiation of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) into Hepatocytes and Improve Liver Injury.

OBJECTIVE: The treatment of liver failure by stem cell transplantation has attracted growing interest. Herein, we aim to explore the role of sodium butyrate (NaB) in the hepatic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) under liver-specific factors induction in vitro and vivo. MATERIALS & METHODS: We isolated BM-MSCs from the mononuclear cell fraction of rabbit bone marrow samples and identified the cells by Immunophenotypic analysis. We investigated the effects of different concentrations and induction conditions. The histone deacetylase inhibitor NaB induced hepatic differentiation of BM-MSCs under liverspecific factors induction in vitro. Morphological features, liver-specific gene and protein expression, and functional analyses in vitro and vivo were performed to evaluate the hepatic differentiation of BM-MSCs. RESULTS: Our results showed that pre-treated NaB inhibited the expression of the liverspecific protein in a dose-dependent manner. The induction efficiency of NaB with 24h pre-treatment was higher than that of NaB continuous intervention. 0.5 mM 24h NaB pre-treated cells can improve liver tissue damage in vivo. The liver ALB, AAT, and the serum TP were significantly increased, while the serum ALT was significantly reduced. CONCLUSION: Continuous NaB treatment can inhibit BM-MSCs proliferation in a dosedependent manner at a certain concentration range. 0.5 mM 24h pre-treatment of NaB enhanced differentiation of BM-MSCs into hepatocytes and improved liver injury in vitro and vivo.

Newly found variations of the right posterior portal vein identified radiologically in 1,003 Chinese patients: a cross-sectional study.

Background: The anatomy of the right posterior portal vein (RPPV) plays an important role in planning hepatic resection, living transplantation and interventional radiological procedures, yet the incidence of variations of RPPV without a common trunk in Chinese persons is still unclear. Therefore, we conducted this study and discussed its clinical implications. Methods: A retrospective analysis of multidetector computed tomography (MDCT) scans was performed in 1,933 patients with various abdominal pathologies between September 28, 2018 through May 23, 2019. After excluding 930 patients, a total of 1,003 patients were included in this study. Variations of the RPPV without a common trunk were classified according to classification standards. Results: A total of 1,003 patients were included. RPPV without a common trunk was found in 216 (21.54%, 216/1,003) patients. Among them, we identified three variations of the origin from the right portal vein (RPV): first separate origin of P6, P7, or simultaneous separate origin of P6 and P7, and the incidences of these three variations were 1.50% (15/1,003), 6.58% (66/1,003) and 13.46% (135/1,003), respectively. Among 1,003 patients included in this study, 787 patients (78.46%, 787/1,003) showed that RPPV normally divided into P6 and P7 branches. Conclusions: Variations of the RPPV without a common trunk were not rare in Chinese population. Knowledge of this anatomic variation of the RPPV is extremely important for hepatic and transplant surgeons and interventional radiologists.

[The experimental study of magnetic resonance diffusion-weighted imaging to the treatment of acute hepatic injury with allogeneic MBMCs transplantation into liver].

OBJECTIVE: To investigate the therapeutic effect of mononuclear bone marrow cells (MBMCs) transplantation to rabbit liver with acute hepatic injury (AHI) and the feasibility that evaluated the functional recovery of acute hepatic injury model with MR-DWI. METHODS: 10 healthy rabbits were chosen to be normal control group which was only carried out MR-DWI scan of normal liver. 42 model rabbits of acute liver injury were randomly selected and divided into 2 groups:transplanted group (n = 21) and control group(n = 21). Each rabbit of the transplanted group was infused 5 ml MBMCs suspension (about containing 2 × 107 MBMCs) into its liver at multiple sites. All manipulations to each rabbit in the control group were as same as those in the transplanted group except that 5 ml of D-Hanks solution was injected instead of MBMCs suspension.7 model rabbits respectively chosen from the transplanted group and the control group were carried out MR-DWI scan and calculated the mean ADC value of the injury liver and then were killed on day 7, day 14 and day 28 of AHI establishment after transplantation. Other comparative assays were performed including: functional assay of liver, pathological examination of liver sections. RESULTS: Before MBMCs transplantation, the difference of liver function was not significant between the transplanted group and the control group. But after MBMCs transplantation, the liver functions of the transplanted group were significantly better than those of the control group at all time points tested (P < 0.05). On day 7 of AHI establishment after MBMCs transplantation, the mean ADC values of the transplanted group and the control group were significant lower than those of the normal control group (P < 0.05). The mean ADC values of the transplanted group and the control group increased to the mean ADC values of the normal control group over time. At the same time point, the mean ADC values of the transplanted group were significantly higher than those of the control group. In the transplanted group, the difference of average ADC values between any two time points were significantly (P < 0.05). In the control group, the mean ADC values on day 7 were lower than those on day 14 and day 28 (P < 0.05), the mean ADC values on day 14 were lower than those on day 28 (P = 0.417). The correlation between the average ADC value and the ALT or AST was negative (P < 0.05), the correlation between the average ADC value and the ALB was positive (P < 0.05). Along with the increase of the average ADC value, the liver function of the AHI model rabbit gradually got better. CONCLUSION: Transplantation of MBMCs promoted the recovery of liver function of AHI model rabbit. The recovery of the injury liver could be detected with observing dynamic change of its mean ADC value.

Neoadjuvant intra-arterial versus intravenous chemotherapy in colorectal cancer.

ABSTRACT: To investigate the clinical benefits of transcatheter arterial infusion chemotherapy compared with intravenous chemotherapy in patients with colorectal cancer (CRC).From May 2013 to March 2018, 83 patients (50 men and 33 women) with surgically proven CRC were retrospectively included. Before surgery, 62 patients received conventional systemic chemotherapy, and 21 transcatheter arterial chemotherapy. Basic characteristics, disease control rate (DC), adverse reactions, postoperative complications, and toxicity profiles were collected and compared between the 2 groups.The sigmoid colon (43.37%) was the most common primary tumor location, and the least was the transverse colon (6.02%). Most lesions invaded the subserosa or other structures T3-4 (78.31%), and other lesions invaded the muscular layer T1-2 (21. 69%). The overall DC was 80.65% in the intravenous chemotherapy group and 90.48% in the arterial chemotherapy group (P < .05). Adverse events included myelosuppression and gastrointestinal reactions such as nausea, vomiting, diarrhea, abnormal liver function, and neurotoxicity, which were significantly less common in the intra-arterial group than in the intravenous group (P < .05). Postoperative complications included abdominal infection (11.29% vs 14.29%), intestinal obstruction (6.45% vs 4.76%), anastomotic bleeding (1.61% vs 0.00%), and anastomotic fistula (6.45% vs 4.76%) in the intravenous and intra-arterial groups, respectively (P > .05).Preoperative transcatheter arterial infusion chemotherapy is a safe and effective neoadjuvant chemotherapy measure for CRC with fewer adverse reactions and a higher overall DC.

Multiparameter magnetic resonance imaging of liver fibrosis in a bile duct ligation mouse model.

BACKGROUND: Bile duct ligation (BDL) in animals is a classical method for mimicking cholestatic fibrosis. Although different surgical techniques have been described in rats and rabbits, mouse models can be more cost-effective and reproducible for investigating cholestatic fibrosis. Magnetic resonance imaging (MRI) has made great advances for noninvasive assessment of liver fibrosis. More comprehensive liver fibrotic features of BDL on MRI are important. However, the utility of multiparameter MRI to detect liver fibrosis in a BDL mouse model has not been assessed. AIM: To evaluate the correlation between the pathological changes and multiparameter MRI characteristics of liver fibrosis in a BDL mouse model. METHODS: Twenty-eight healthy adult male balb/c mice were randomly divided into four groups: sham, week 2 BDL, week 4 BDL, and week 6 BDL. Multiparameter MRI sequences, included magnetic resonance cholangiopancreatography, T1-weighted, T2-weighted, T2 mapping, and pre- and post-enhanced T1 mapping, were performed after sham and BDL surgery. Peripheral blood and liver tissue were collected after MRI. For statistical analysis, Student's t-test and Pearson's correlation coefficient were used. RESULTS: Four mice died after BDL surgery; seven, six, five and six mice were included separately from the four groups. Signal intensities of liver parenchyma showed no difference on TI- and T2-weighted images. Bile duct volume, ΔT1 value, T2 value, and the rate of liver fibrosis increased steadily in week 2 BDL, week 4 BDL and week 6 BDL groups compared with those in the sham group (P < 0.01). Alanine aminotransferase and aspartate transaminase levels initially surged after surgery, followed by a gradual decline over time. Strong correlations were found between bile duct volume (r = 0.84), T2 value (r = 0.78), ΔT1 value (r = 0.62), and hepatic fibrosis rate (all P < 0.01) in the BDL groups. CONCLUSION: The BDL mouse model induces changes that can be observed on MRI. The MRI parameters correlate with the hepatic fibrosis rate and allow for detection of cholestatic fibrosis.

Magnetic resonance spectroscopy on hepatocellular carcinoma after transcatheter arterial chemoembolization.

BACKGROUND AND OBJECTIVE: Proton magnetic resonance spectroscopy (MRS) of the liver in vivo is in experimental phase. MRS observation on liver cancer after transcatheter arterial chemoembolization (TACE) has seldom been reported. This study was to investigate the value of MRS in assessing the metabolic changes of hepatocellular carcinoma (HCC) after TACE. METHODS: Twenty-five consecutive patients with pathologically-confirmed HCC received 1H MRS of all hepatic lesions using 1.5T whole body MR scanner before TACE and at 3-10 days after TACE. Choline-to-lipid (Cho/Lip), glucogen/glucose-to-lipid (Glu/Lip), and glytamine/glutamate-to-lipid (Glx/Lip) ratios were measured and analyzed statistically. RESULTS: The Cho/Lip, Glu/Lip, and Glx/Lip ratios were 0.21 +/- 0.08, 0.11 +/- 0.05, 0.28 +/- 0.10 before TACE, respectively, and were 0.10 +/- 0.08, 0.07 +/- 0.07, 0.18 +/- 0.12 after TACE, respectively, with significant differences (P < 0.05). CONCLUSIONS: Using MRS can evaluate the early metabolic responses of HCC to TACE.

Validity of venous phase delay assessment in balloon occlusion test of internal carotid artery.

The aim of the present study was to investigate the utility of venous phase delay assessment to evaluate the balloon occlusion test (BOT) of the internal carotid artery (ICA). A total of 38 patients who received BOT of the ICA were included in this retrospective study. Clinical examination and venous phase assessment were performed in all patients to evaluate their suitability for the evaluation of the BOT of the ICA. The venous phase delay assessment compared the venous phase of supratentorial and infratentorial structures between hemispheres. Venous phase delay was defined as the time lag for opacification of the first cortical vein between the occluded hemisphere and the hemisphere examined. The results of the clinical examination and the venous phase delay assessment were compared. In most patients negative on clinical examination, the venous phase delay was no more than 2 sec, while for most patients positive on clinical examination, the delay was >2 sec. All patients with a venous phase delay of >4 sec had a positive clinical result. The present results indicated that venous phase delay assessment is a reliable method for evaluating BOT of the ICA, and in those with a delay of <2 sec, parent vessel occlusion of the ICA, which may be used as a pre-operative procedure prior to tumor resection for patients suffering from neck or skull-base tumors, was considered safe.

Characteristics of liver on magnetic resonance diffusion-weighted imaging: dynamic and image pathological investigation in rabbit liver VX-2 tumor model.

AIM: To investigate dynamical and image pathological characteristics of the liver on magnetic resonance (MR) diffusion-weighted imaging (DWI) in the rabbit VX-2 tumor model. METHODS: Forty New Zealand rabbits were included in the study and VX-2 tumor piece was implanted intrahepatically. Fifteen animals received two intrahepatic implantations while 25 had one intrahepatical implantation. DWI, T1- and T2-weighted of magnetic resonance imaging (MRI) were carried out on the 7th and the 14th d after implantation and DWI was conducted, respectively on the 21st d. Ten VX-2 tumor samples were studied pathologically. RESULTS: The rate of lump detected by DWI, T1WI and T2WI was 78.7%, 10.7% and 53.5% (c2=32.61, P<0.001) on the 7th d after implantation and 95.8%, 54.3% and 82.9% (c2=21.50, P<0.001) on the 14th d. The signal of most VX-2 tumors on DWI was uniform and it was equal on the map of apparent diffusion coefficient (ADC). The signal of VX tumors did not decrease on the 7th d after implantation, most of them slowly growing during the week following implantation without significant cell dying within the tumor. VX-2 tumors grew increasingly within 14 d after implantation but the signal of most VX-2 tumors on DWI or on the map of ADC was uniform or uneven and ADC of VX tumors decreased obscurely or slightly because tumor necrosis was still not obvious. On the 21st d after implantation, the signal of most VX-2 tumors on DWI or on the map of ADC was uneven because tumor necrosis was evident and ADC of VX-2 tumor necrotic areas decreased. The areas of viable cells in VX-2 tumors manifested a high signal on DWI and a low signal on the map of ADC. The areas of dead cells or necrosis in VX-2 tumors manifested low signals on DWI and low, equal or high signals on the map of ADC but they manifested high signals on DWI and on the map of ADC at the same time when the areas of necrotic tumor became liquefied or cystic. The border of tumors on DWI appeared gradually distinct and internal signals of tumor became progressively uneven. CONCLUSION: The manifestations of viable, necrotic and liquefied or cystic areas in VX-2 tumors on DWI are typical and DWI is of significant and potential values in clinical application in both the early detection and diagnosis of liver tumors.

Gene expression and MR diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model.

AIM: To investigate the dynamic characteristics and the correlation between PCNA, Bax, nm23, E-cadherin expression and apparent diffusion coefficient (ADC) on MR diffusion-weighted imaging (DWI) after chemoembolization in rabbit liver VX-2 tumor model. METHODS: Forty New Zealand rabbit liver VX-2 tumor models were included in the study. DWI was carried out periodically after chemoembolization. All VX-2 tumor samples in each group were examined by histopathology and Strept Avidin-Biotin Complex (SABC) immunohistochemical staining. RESULTS: The PCNA expression index in VX-2 tumors was higher than in the normal parenchyma around the tumor (P < 0.001). Nm23, Bax or E-caderin expression index in VX-2 tumors were lower than in the normal parenchyma around the tumor (all P < 0.001). PCNA and nm23 expression in the VX-2 tumor periphery first increased and then decreased (P < 0.001 and P = 0.03, respectively), while the expression of Bax and E-cadherin before and after chemoembolization was insignificant. When b-value was 100 s/mm(2), there was a linear correlation between PCNA expression and ADC in the area of VX-2 tumor periphery (P < 0.001), and PCNA expression in VX-2 tumor periphery influenced the ADC. CONCLUSION: The potential of VX-2 tumor infiltrating and metastasizing decreases, while its ability to proliferate increases for a short time after chemoembolization. To some degree, the ADC value indirectly reflects the proliferation of VX-2 tumor cells.

[Comparison between pathological findings and MR diffusion-weighted imaging in primary hepatocellular carcinoma after transcatheter arterial chemoembolization].

OBJECTIVE: To explore the pathological basis of diffusion-weighted imaging (DWI) findings in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). METHODS: DWI was performed in 15 patients with HCC treated by TACE within 24 - 48 hours before II-phase operation. The DWI findings of the liver lesions were analyzed and correlated with pathological findings including macroscopic observation, HE staining and immunohistochemical staining for bFGF. RESULTS: (1) The viable tumor area showed mostly hypersignal intensity (12/15), whereas coagulative necrotic lesions showed hyposignal (8/15) or isosignal intensity (6/15). The ADC values of zones of viable tumor and necrosis in tumor were (1.42 +/- 0.16) x 10(-3) mm(2)/s and (1.58 +/- 0.18) x 10(-3) mm(2)/s, respectively. There was a significant difference of ADC values between the two zones (t = 2.618, P < 0.05). (2) There was a significant difference in ADC values of viable tumor between well and poorly differentiated tumors (t = -2.646, P < 0.05). The distinction of ADC values of the whole tumor was significant among tumors with different degree of necrosis (chi(2) = 7.236, P < 0.05). (3) A negative correlation was observed between bFGF protein expression index and ADC values of viable parts of the tumors in the study group (r = -0.552, P = 0.033). CONCLUSION: DWI shows certain characteristic features of the HCC after TACE, and can be used to distinguish viable and necrotic tumor tissues in HCC after TACE.

Continuous zebularine treatment enhances hepatic differentiation of mesenchymal stem cells under liver-specific factors induction in vitro.

AIMS: To investigate the effect of zebularine, a stable inhibitor of DNA methylation, on hepatic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) under liver-specific factors induction in vitro. MAIN METHODS: BM-MSCs were isolated from the mononuclear cell fraction of rabbit bone marrow samples. The identification of these cells was carried out by immunophenotype analysis. The three hepatic differentiation protocols of BM-MSCs were as follows: liver-specific factors (hepatocyte growth factor and epidermal growth factor) without zebularine, liver-specific factors combined with a 24 h zebularine pre-treatment, and liver-specific factors combined with continuous zebularine treatment. BM-MSCs cultured in basic medium without the differentiation stimuli were set as the control. Morphological features, liver-specific gene and protein expression, and functional analyses were assessed to evaluate hepatic differentiation of BM-MSCs. Global DNA methylation status was tested for investigating the underlying mechanism. KEY FINDINGS: Flow cytometry immunophenotyping proved the isolated cells with plastic adherence and a spindle shape were CD29, CD90 positive and CD34, CD45 negative. Albumin (ALB) and alpha-fetoprotein (AFP) messenger RNA and protein expression, glycogen storage and urea production were significantly higher in the continuous zebularine-treated group than the other groups while the differences between the zebularine-untreated group and 24 h zebularine pre-treated group were not significant. Meanwhile, significant decrease of global DNA methylation was observed in the continuous zebularine-treated group. SIGNIFICANCE: We conclude that continuous zebularine treatment can improve hepatic differentiation of BM-MSCs under liver-specific factors induction in vitro, and the decrease of global DNA methylation maybe involved in this process.