Laparoscopic hepatectomy for liver neoplasms in 15 cases

Objective： The aim of our study was to retrospectively analyze 15 patients＇ clinical materials with laparoscopic resection of liver neoplasms. Methods： From December 2007, a total of 15 patients with liver neoplasms were performed with laparoscopic hepatectomy, and their clinical materials, perioperative dates, postoperative complications, postoperative recovery and short-term curative effects were analyzed and summarized respectively. Results： Laparoscopic hepatectomy （LH） were performed in 15 patients, including 1 case underwent laparoscopic hepatic left Iobectomy, 1 case of left lateral hepatectomy, 13 cases of partial liver resection. Fourteen cases of total laparoscopic liver resections for liver neoplasms, 1 case of hand-assisted laparoscopic liver resection of the tumor, there was no conversion to open approach. Of the 15 patients with liver neoplasms, 13 cases of hepatic neoplasms with the maximum diameter was 8 cm× 8 cm × 9 cm, 9 cases of the borderline micro hepatocellular carcinoma （MHCC） with the diameter not more than 2 cm, 3 cases of hepatic benign tumor. The mean operation time was （120 ± 30） min, and the intraoperative average hemorrhage was 100 mL, beginning to eat and get out of bed following 1-2 days of operation. The average postoperative hospitalization was 8 days, WBC, ALl＇, AST, albumin, bilirubin returned to normal after one week of operation. There were no postoperative complications such as hemorrhage, bile leakage or air embolism etc. Twelve patients with HCC were confirmed by postoperative pathology, 1 case of liver smooth muscle lipoma, 2 case of hepatic hemangioma. By one year of followed-up in 12 cases of HCC, the longest survival was 38 months, and no recurrence or death, 1 year survival rate was 100%. Conclusion： Among the choice of cases, the advantages of LH for liver neoplasms compared with open surgery were less trauma, faster recovery and less blood loss. it is safe and effective for choosing a reasonable surgical indication, especially for peripheral micro hepatocellular carcinoma.

FEASIBILITY STUDY OF AN ULTRASOUND CONTRAST AGENT(LEVOVIST) IN COLOR DOPPLER IMAGING OF LIVER NEOPLASMS

The purpose of this study was to determine the efficacy of using an ultrasound contrast agent(levovist)to enhance the color Doppler imaging of liver neoplasms.Thirty patients with hepatic tumors were enrolled in this study.After intravenous administration of levovist,the color Doppler signals of normal hepatic vessels were enhanced.In various hepatic tumors,the different patterns of tumor vascularity were observed,which had not been demonstrated in conventional non contrast color Doppler imaging.In 11 of 16 patients with hepatocarcinoma,additional color Doppler signals were observed in the central part of the tumors.On the contrary,3 patients with metastatic liver lesions the enhanced color Doppler signals appear only at the peripheral of tumors.A typical rim like color enhancement was seen in 2 of the 3 cases.In six patients with hepatic hemangiomas contrast enhanced color Doppler imaging demonstrated the blood vessels at the margin of the neoplasms.Contrast enhanced color Doppler imaging improves the visualization of the hepatic neoplasm vascularity.This technique holds great promise for detecting small liver tumors and differentiating hepatic neoplasms.

Strategies to rescue steatotic livers before transplantation in clinical and experimental studies

The shortage of donor livers has led to an increased use of organs from expanded criteria donors. Included are livers with steatosis, a metabolic abnormality that increases the likelihood of graft complications posttransplantation. After a brief introduction on the etiology, pathophysiology, categories and experimental models of hepatic steatosis, we herein review the methods to rescue steatotic donor livers before transplantation applied in clinical and experimental studies. The methods span the spectrum of encouraging donor weight loss, employing drug therapy, heat shock preconditioning, ischemia preconditioning and selective anesthesia on donors, and the treatment on isolated grafts during preservation. These methods work at different stages of transplantation process, although share similar molecular mechanisms including lipid metabolism stimulation through enzymes or nuclear receptor e.g. , peroxisomal proliferator-activated receptor, or anti-inflammation through suppressing cytokines e.g. , tumor necrosis factor-α, or antioxidant therapies to alleviate oxidative stress. This similarity of molecular mechanisms implies possible future attempts to reinforce each approach by repeating the same treatment approach at several stages of procurement and preservation, as well as utilizing these alternative approaches in tandem.

Warm HTK donor pretreatment reduces liver injury during static cold storage in experimental rat liver transplantation

BACKGROUND： Organ shortage has led to an increased number of transplantations from extended criteria donors. These organs are more vulnerable to ischemia-reperfusion injury. Thus, improvement of organ preservation is needed. HTK is a widely used preservation solution for static cold storage in liver transplantation. The present study was to investigate the beneficial effect of warm HTK donor pretreatment on liver preservation.

Iodine-125 interstitial brachytherapy for experimental liver cancer

Objective：To study the effect of iodine-125 interstitial brachytherapy on liver cancer. Methods： Animal model of human liver cancer was established by injecting SMMC-7721 cells cultivated in vitro subcutaneously into the flank of BALB/c nude mice. Nude mice with tumor of 5 mm in diameter were randomly divided into 2 groups （n = 10）. One iodine-125 seed of apparent activity 0.8 mCi was implanted into the center of tumor in treatment group, whereas an inactive seed was implanted in control group. The other 20 nude mice with tumor reaching 10 mm in diameter were also treated as above. The size of tumor was determined weekly after implantation, and pathological examination and blood routine were taken on the 28th day. Results： Tumor growth was obviously inhibited in treatment group of tumor of 5 mm in diameter, and there was statistically significant difference in tumor volume between treatment and control groups （P〈0.01）. Around iodine-125 seed, apparent necrosis of tumor was shown in treatment group, accompanied by karyopyknosis and reduced plasma in residual tumor cells microscopically. Tumor growth was not inhibited in either treatment or control group of tumor of 10 mm in diameter. There was no obvious adverse effect except for decreased white blood cells in treatment groups. Conclusion： There is certain effect of iodine-125 interstitial braehytherapy on liver cancer, which is associated with the size of tumor.

Application of two-phase helical CT in liver neoplasms

Objective: To assess the value of helical CT in the di- agnosis of liver diseases. Methods: 59 patients with different liver diseases were examined by two-phase or multi-phase dynamic helical CT. Results: Small hepatocellular carcinoma showed a higher density in the arterial phase, and a lower den- sity in the portal vein phase. Large hepatic carcino- ma showed a mixed pattern of higher-density in the arterial phase, and a lower density in the portal vein phase. Metastasis carcinoma showed an 'oxeye sign' in the portal vein phase. Hemangioma was not obvi- ously enhanced in the early arterial phase, marginal- ly enhanced in the arterial phase, and equally-densed in the balanced phase. Conclusion: Two-phase helical CT is of value in im- proving the detection rate of or determining the fea- tures of hepatic diseases by two-phase helical dyna- mic scan (2.0-3.0 ml/s speed, and delay time 25- 30 s and 70-85 s).

Inhibitory effects of two oligosaccharideson murine melanoma experimental liver metastasis

AIM To observe the effects of a chemically synthesized tetrose and a natural yeast mannan on experimental liver metastasis of mouse melanoma. METHODS After treated with 4mg tetrose (tetrose group) or 4mg mannan (mannan group) for 30 minutes at 37℃, 0 5ml 1×10 6 B16 MBK melanoma cells were injected into the spleen of mice. Fifty five days later, melanoma metastatic nodes on the surface of the liver and in other organs as well as mouse survival time were observed. RESULTS Of the 6 mice in control (B16 cell+PBS) group, 4 died naturally within 55 days, and 2 were killed on the 55th day. All of the 6 mice had metastases in livers, the total number of the melanoma nodes on each liver surface ranged from 2 to 30, with the largest one merging into the whole liver. One mouse had a neoplasm in the remnant site of injection, and 3 had metastases in lungs. In contrast, of the 6 mice in tetrose group, only one died on the 50th day after injection, with 3 metastases in the liver, the largest being 10mm in diameter, the other 5 mice survived until being dissected on the 55th day after injection and had no liver metastasis, but 3 of them had neoplasms in their remnant sites of injection. In mannan group, all of the 6 mice survived and no metastasis was seen except for 2 liver nodes in one mouse with the largest diameter of 1mm. Neither tetrose nor mannan group had metastasis out of the liver, and the weight of liver in the two groups was significantly lower than those in the control group. CONCLUSION Both tetrose and mannan had the effects of preventing melanoma cells from experimental metastasis to and out of the liver, and prolonging the survival time of the mouse.

Immunohistochemical study on expression of epidermal growth factor receptor at hepatocyte nuclei in experimental rat liver cirrhosis

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DYNAMIC CHANGES OF ITO CELLS IN EXPERIMENTAL LIVER CIRRHOSIS OF RAT

That Ho cells in rat liver express desmin was confirmed by immunohistochemical technique. Consequently, changes of desmin-positive cells, lysozyme-positive cells and fibronectin were further studied in experimental cirrhosis of rat. It was found that desmln- positive cells, with the transitional feature between Ito cells and myofibroblasts or fibrobiasts under electron microscope, increased in number and expression of desmin in the necrotic areas as well as in the cellular fibrous septa, but decreased in number in the fibrous septa except those areas closed to the edges of the septa. These results suggested that Ito cells, myofibroblasts and fibroblasts might belong to the same cellular system and play an important role in the pathogenesis of cirrhosis. Meanwhile, it was also noted that changes of both fibronectin and lysozymepositive cells were correlated with those of desmin-positive cells. These provide evidence in vivo that flbronectin and Kupffer cells might exert certain effects on the migration and proliferation of Ito cells in liver cirrhosis.

Bone disorders in experimentally induced liver disease in growing rats

AIM： To investigate the change of bone parameters in a new model of experimentally induced liver cirrhosis and hepatocellular carcinoma （HCC） in growing rats. METHODS： Fischer-344 rats （n = 55） were used. Carbon tetrachloride （CCh）, phenobarbital （PB）, and a single diethylnitrosamine （DEN） injection were used. Animals were killed at wk 8 and 16. Bone mineral content, femoral length, cortical index （quotient of cortical thickness and whole diameter） and ultimate bending load （Fmax） of the femora were determined. The results in animals treated with DEN＋PB＋CCh （DPC, n = 21） were com- pared to those in untreated animals （UNT, n = 14） and in control group treated only with DEN＋PB （DP, n = 20）. RESULTS： Fatty liver and cirrhosis developed in each DPC-treated rat at wk 8 and HCC was presented at wk 16. No skeletal changes were found in this group at wk 8, but each parameter was lower （P〈0.05 for each） at wk 16 in comparison to the control group. Neither fatty liver nor cirrhosis was observed in DP-treated animals at any time point. Femoral length and Fmax values were higher （P〈0.05 for both） in DP-treated animals at wk 8 compared to the UNT controls. However, no difference was found at wk 16. CONCLUSION： Experimental liver cirrhosis and HCC are accompanied with inhibited skeletal growth, reduced bone mass, and decreased mechanical resistance in growing rats. Our results are in concordance withthe data of other studies using different animal models. A novel finding is the transiently accelerated skeletal growth and bone strength after a 8-wk long phenobarbital treatment following diethylnitrosamine injection.

An experimental and clinical study of liver fibrosis

The studies were focused on the mechanisms of liver fibrosis and the methods to assess early stage of liver fibrogenesis. On the basis of their 13 years'studies and recent views on hepatic fibrosis,the authors find:(1) Accumulation of extracellular matrix(ECM) in liver fibrogenesis is the result of the increased mRNA of collagens and other connective tissue components;(2) The process of ECM increase is regulated by cytokines;(3) Consequsence of excess deposition of ECM in liver leads to liver injuries,giving rise to' sinusoidal caparilization',a typical change in fibrotic liver:(4) Assay of the serum components of ECM in patients with chronic liver diseases may be a good test for early diagnosis of liver fibrosis.

Regulating effect of Chinese herbal medicine on the peritoneal lymphatic stomata in enhancing ascites absorption of experimental hepatofibrotic mice

AIM: To observe the regulatory effect of Chinese herbal medicine on peritoneal lymphatic stomata and its significance in treating ascites in liver fibrosis model mice. METHODS: Two Chinese herbal composite prescriptions were used separately to treat the carbon tetrachloride-induced mouse model of liver fibrosis. The histo-pathologic changes of the liver sections (HE and VG stainings) were observed. The peritoneal lymphatic stomata was detected by scanning electron microscopy and computer image processing. The changes of urinary volume and sodium ion concentration were measured. RESULTS: In the model group, lots of fibrous tissue formed in liver and extended into the hepatic lobules to separate them incompletely. In the treated and prevention groups, the histo-pathologic changes of liver was rather milder, only showed much less fibrous tissue proliferation in the hepatic lobules. The peritoneal lymphatic stomata enlarged with increased density in the experimental groups (diameter: PA, 3.07 +/- 0.69 microm; PB, 2.82 +/- 0.37 microm; TA, 3.25 +/- 0.82 microm and TB, 2.82 +/- 0.56 microm; density: PA, 7.11 +/- 1.90 stomata.1000 microm(-2); PB, 8.76 +/- 1.45 stomata.1000 microm(-2); TA, 6.55 +/- 1.44 stomata.1000 microm(-2)and TB, 8.76+/-1.79 stomata.1000 microm(-2)), as compared with the model group (diameter: 2.00+/-0.52 microm density: 4.45+/-1.05 stomata.1000 microm(-2)). After treatment, the urinary volume and sodium ion excretion increased in the experimental groups (PA, 231.28+/-41.09 mmol.L(-1); PB, 171.69 +/- 27.48 mmol.L(-1) and TA, 231.44 +/- 34.12 mmol.L(-1)), which were significantly different with those in the model group (129.33 +/- 36.75 mmol.L(-1)). CONCLUSION: Chinese herbal medicine has marked effects in alleviating liver fibrosis, regulating peritoneal lymphatic stomata, improving the drainage of ascites from peritoneal cavity and causing increase of urinary volume and sodium ion excretion to reduce the water and sodium retention, and thus have favorable therapeutic effect in treating ascites.

Recurrence or metastasis of HCC:predictors,early detection and experimental antiangiogenic therapy

AIM To investigate the predictors forrecurrence or metastasis of HCC,and toevaluate the effect of antiangiogenic therapy onthe growth of transplantable human HCC in nudemice.METHODS RT-PCR was used to measure theexpression of matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)in 56 pairs of nontumorous liver andtumor samples.Sixty blood samples from humanHCC were examined by nested RT-PCR to find outAFP mRNA.Recombinant human endostatin andpolyclonal antibody against VEGF wereadministered to treat human HCC transplanted innude mice.RESULTS Thirty of 56 HCC samples showedstronger expression of MMP-9 in tumoroustissues than in nontumorous tissues.Fifteen ofthe 26 patients with relative expression level ofMMP-9 more than 0.34 developed tumorrecurrence or metastasis,whereas only 7 of 30patients with relative expression level less than0.34 developed tumor recurrence(P【0.05).There was no significant difference in therelative expression level of VEGF betweenpatients with postoperative recurrence ormetastasis and those without recurrence.AFPmRNA was detectable in 53.3% of patients withHCC.The sensitivity and specificity of AFPmRNA as a marker to detect hematogenousdissemination of HCC cells was 81.8% and84.4%,respectively.Recombinant human endostatin and polyclonal antibody against VEGFinhibited the growth of transplantable HCC innude mice by 52.2% and 45.7%,respectively.CONCLUSION MMP-9 expression in HCCcorrelates with the postoperative recurrence ormetastasis of HCC.Patients with high level ofMMP-9 expression in HCC are susceptible tometastasis.AFP mRNA could serve as anindicator of hematogenous spreading of HCCcells in circulation and a predictor of recurrenceor metastasis of HCC.Antiangiogenesis may bean adjuvant therapy for HCC.

Clinical and experimental study on regional administration of phosphorus32 glassmicrospheres in treating hepatic carcinoma

AIM To study the therapeutical effectiveness, dosage range and toxic adverse effects of domestic phosphorus 32 glass microsphere and evaluate its clinical significance. METHODS Ⅰ. Fifty two BALB/*!c tumor bearing male nude mice were allocated into treatment group( n =38) and control group( n =14). In the former group different doses of 32 P GMS were injected into the tumor mass, while in the latter 31 P GMS or no treatment was given. The experimental animals were sacrificed in batches, and then the tumors and their nearby tissues were examined by light and electron microscopy. Ⅱ. Through selective catheterization of hepatic artery, 32 P GMS was infused to 5 healthy domestic pigs in a dosage equivalent to the therapeutic dose for human being, and 31 P GMS was infused to another 5 healthy domestic pigs. Two pigs infused with contrast medium served as whole course blank controls. One pig from each group was surrendered to euthanasia at week 1, 4, 8 and 16 respectively. The ultrastructural histopath ological changes in liver tissues taken from different sites were evaluated semiquan titatively. Ⅲ. One hundred and twenty seven times of 32 P GMS intrahepatic artery interventional therapies were performed on 93 patients with hepatic carcinoma, including 79 cases of primary hepatic carcinoma and 14 cases of secondary hepatic carcinoma. 32 P GMS ( n =30), and group B, 32 P GMS and half dose of trans hepatic artery embolization (TAE) ( n =49) , and 18 patients with HCC by TAE only as control group C. Fourteen patients with secondary hepatic carcinoma were treated in the same way as group B or C. RESULTS Ⅰ. Comparing with the control group, the treatment group of tumor bearing nude mice attained the tumor inhibition rates of 59 7%-93 7% ( F =579 62, P <0 01) at 14*!d . At an absorbed dose of 7320Gy, the tumor cells were completely destroyed. When the absorbed doses ranged from 1830Gy to 3660Gy, most of the tumor cells showed the evidences of injury or necrosis, but there appeared some well differentiated tumor cells and enhanced effect of the autoimmunocytes. At an absorbed dose of 366Gy or less, some tumor cells still remained active proliferative ability. The definite anticancer effect appeared as early as 3d after intratumoral injection of 32 P GMS. Ⅱ. The cumulative amount of 32 P GMS in the target tissue after trans hepatic artery instillation attained more than 90% of the total dose administrated. Semiquantitative analysis of ultrastructral morphology in the experimental group showed no statistical difference between the nuclear abnormality (N abn ) and mitochondrial variability (M var ) at week 1 or 2, but revealed prominent difference (χ 2=6 70-9 68, P <0 01 , χ 2=65 09-115 09, P <0 001 ) as compared with those in the other groups. In the experimental group the N abn in tissues showed no significant difference between week 8 and week 16. No apparent changes were found in the stomach, spleen, kidney and lung tissues of the experimental pigs. Ⅲ. The therapeutical results of HCC patients in group A were closely approximated to those of group C, no hematological toxic side effects were noted, and the systemic reaction was mild. In some patients 2*!mos - 3*!mos after treatment some secondary foci appeared around the periphery of the primary lesion. In general better effectiveness was obtained in patients with small lesion. After analyzing by RIDIT method, the therapeutic result in group B was significantly better than that in group C, and secondary foci around the original lesion were rarely seen at 3*!mos after treatment. In group C the collateral circulation was reestablished along the periphery of primary foci and the secondary foci appeared more frequently, and required to undergo several courses of treatment. In group B, 4 cases of HCC were treated surgically as their mass decreased in size after 32 P GMS treatment.

Kupffer cell and apoptosis in experimental HCC

INTRODUCTION Our previous study has proved that Kupffer cellsmay have an inhibitory effect on the process ofhepatocarcinogenesis,however,their inhibitorymechanism needs exploring deeply.We performed acomparative study on the expression of PCNA,Bax,P53 and apoptosis of liver cancer cells usingimmunohistochemical technology and terminaldeoxynucleotidyl transferase (TdT)-mediateddUTP-digoxigenin nick end labeling(TUNEL)

Thrombospondin-1 expression correlates with angiogenesis in experimental cirrhosis

AIM:To investigate the significance of Thrombospondin-1 (TSP-1) expression and its relationship with angiogenesis during experimental fibrosis. METHODS:Cirrhosis was induced in male Wistar rats by intraperitoneal administration of diethyl nitrosamine (DEN). The serial sections from liver tissues were stained with anti-CD34 and anti-TSP-1 antibodies before being quantitated by light microscopy. RESULTS:Our results showed that of TSP-1 expression gradually increases according to the severity of fibrosis (GroupⅠvs group Ⅱ, Group Ⅲ and Group Ⅳ;Group Ⅱ vs group Ⅲ and group Ⅳ;group Ⅲ vs group Ⅳ, P < 0.05). Moreover, TSP-1 expression was found to be correlated with angiogenesis (P < 0.05). CONCLUSION:The correlative evidence of the link between TSP-1 and fibrosis or angiogenesis provided by this study suggests that besides its role as a strong promoter of transforming growth factor-β1 (TGF-β1), TSP-1 might have an additional role in liver fibrogenesis by stimulating angiogenesis and this protein could be a potential target to prevent fibrogenesis in chronic inflammatory diseases of the liver.

Changing trends of surgical treatment of hilar bile duct cancer:clinical and experimental perspectives

HISTORICAL POINT OF VIEWCarcinoma of the confluence of the hepatic ductshas been thought to be a rare disease until recently.Carcinoma of the large hepatic ducts was rarelydiagnosed correctly premorterned.Because of itsdeeply seated location,resection was once thoughtto be impossible.In 1957,Altemeier reported

Hepatitis C Virus Experimental Model Systems and Antiviral drug Research

An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics.

Free radicals in development of experimental gastric carcinoma and precan cerous lesions in ducedby N-methyl-N'-nitro-N-nitrosoguanidine in rats

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History,ethics,advantages and limitations of experimental models for hepatic ablation

Numerous techniques developed in medicine require careful evaluation to determine their indications,limitations and potential side effects prior to their clinical use.At present this generally involves the use of animal models which is undesirable from an ethical standpoint,requires complex and time-consuming authorization,and is very expensive.This process is exemplified in the development of hepatic ablation techniques,starting experiments on explanted livers and progressing to safety and efficacy studies in living animals prior to clinical studies.The two main approaches used are ex vivo isolated non-perfused liver models and in vivo animal models.Ex vivo non perfused models are less expensive,easier to obtain but not suitable to study the heat sink effect or experiments requiring several hours.In vivo animal models closely resemble clinical subjects but often are expensive and have small sample sizes due to ethical guidelines.Isolated perfused ex vivo liver models have been used to study drug toxicity,liver failure,organ transplantation and hepatic ablation and combine advantages of both previous models.