Application of total hemihepatic vascular exclusion in liver resection for patients with hepatocellular carcinoma and impaired liver function / 中华外科杂志

<p><b>OBJECTIVE</b>To study the clinical value of total hemihepatic vascular exclusion (THHVE) in liver resection for patients with hepatocellular carcinoma (HCC) and impaired liver function.</p><p><b>METHODS</b>The data of 70 patients who underwent liver resection for HCC with impaired liver function between January 2009 and October 2011 were analyzed retrospectively. THHVE was applied in 38 patients (THHVE group), Pringle maneuver in 25 patients (Pringle group) and no vascular occlusion in 7 patients. In the THHVE group, 36 patients were male, 2 were female, average age was (54 ± 9) years. And in Pringle group, 23 patients were male, 2 were female, average age was (53 ± 10) years. Total intraoperative blood loss, blood transfusion rate, clamping time, postoperative complication rate, postoperative hospital stay and postoperative liver function were compared between the THHVE and Pringle group.</p><p><b>RESULTS</b>Total blood loss ((317 ± 186) ml vs. (506 ± 274) ml, t = -3.025, P = 0.004) and transfusion rate (10.5% vs. 32.0%, χ(2) = 4.509, P = 0.034) were significantly lower in the THHVE group than in the Pringle group. Although the clamping time was longer ((21 ± 5) minutes vs. (17 ± 5) minutes, t = 3.209, P = 0.002), the total bilirubin levels on postoperative day 3 and 7 and ALT levels on postoperative day 1, 3, 7 were significantly lower in the THHVE group than in the Pringle group, and the pre-albumin level on postoperative day 7 was higher in the THHVE group than in the Pringle group. Total complication rate (26.3% vs. 52.0%, χ(2) = 4.291, P = 0.038) and major complication rate (7.9% vs. 28.0%, χ(2) = 4.565, P = 0.033) were lower in the THHVE group than in the Pringle group. And postoperative hospital stay duration was shorter in the THHVE group than in the Pringle group ((14.0 ± 2.6) d vs. (16.4 ± 4.0) d, t = -2.625, P = 0.012).</p><p><b>CONCLUSIONS</b>THHVE is a safe and effective technique in liver resection for patients with HCC and impaired liver function. It is associated with less blood loss, lower transfusion requirements, better postoperative liver function recovery, lower postoperative complication rate and shorter postoperative hospital stay.</p>

The effect of portal blood stasis on lung and renal injury induced by hepatic ischemia reperfusion in a rabbit model / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect and mechanism of portal blood stasis on lung and renal injury induced by hepatic ischemia reperfusion.</p><p><b>METHODS</b>A rabbit hepatic ischemia reperfusion injury model was established by hepatic portal occlusion and in situ hypothermic irrigation for 30 min. Twenty-four New Zealand white rabbits were employed and randomly divided into 3 groups equally by different dosage of portal blood stasis removal: group A5 (5 ml blood removal), group A10 (10 ml blood removal),and group B (no blood removal). Eight rabbits were served as controls with no hepatic portal occlusion and hypothermic irrigation. After reperfusion 4 h serum endotoxin content, tumor necrosis factor-alpha (TNF-alpha), urea nitrogen (BUN), and creatinine (Cr) were examined respectively, meantime lung and kidney tissues were sampled to determine the content of malondialdehyde (MDA), superoxide dismutase (SOD), the pathology, and wet to dry weight ratio, broncho-alveolar lavage fluid protein content in lung tissues.</p><p><b>RESULTS</b>Removing portal blood stasis ameliorated lung and renal injury as shown by decreasing the level of serum endotoxin, TNF-alpha, BUN, Cr, wet to dry weight ratio, broncho-alveolar lavage fluid protein content, MDA, SOD. TNF-alpha, Cr, broncho-alveolar lavage fluid protein content in lung tissues and MDA in kidney tissue in group A5 were significantly reduced compared with those in group B (P < 0.05), while in lung tissue in group A10 were also markedly reduced (P < 0.05). The activation of SOD in group A5 were significantly increased (P < 0.05).</p><p><b>CONCLUSIONS</b>Removal of portal blood stasis before the resume of splanchnic circulation may ameliorate the lung and renal injury induced by hepatic ischemia reperfusion. The possible mechanism may be that portal blood stasis removal reduces endotoxin absorption, and further decreases production of serum TNF-alpha.</p>

Recent advances and controversies in surgical management of hepatocellular carcinoma of hepatocellular carcinoma / 中国医学科学院学报

Surgical treatment of hepatocellular carcinoma (HCC) has made great progress in recent ten years, although the appropriate selection of treatment methods remains controversial. Surgical resection of HCC is still widely recognized as the first choice, which has been remarkably improved by effectively controlling intra-operative bleeding. However, the ischemia/reperfusion injury and long-term recurrence still proposes challenges to Pringle's maneuver. The indications of liver transplantation also expand in recent years, and many centers have used marginal donor liver and living donor liver. Remission of the shortage of donors, local ablation of small HCC, and surgical resection still lack the support of randomized controlled trials. In summary, the surgical treatment of HCC should strictly based on the indications of various therapies, which should be prudently verified by randomized controlled trials.

Effect of the amount of portal blood stasis removal on endotoxemia and liver function after liver transplantation / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the influence of the amount of portal blood stasis removal on endotoxemia and liver function after liver transplantation.</p><p><b>METHODS</b>Forty-seven patients who received liver transplantation from February 2006 to November 2007 were divided into 2 groups according to the amount of portal blood stasis removal during operation: group A (n = 26) 50 ml and group B (n = 21) 200 ml of portal blood stasis removal respectively. The levels of plasma endotoxin, D-lactate, tumor necrosis factor-alpha, interleukin-6, liver function and blood coagulation were examined and analyzed.</p><p><b>RESULTS</b>Under the condition of no significant difference in sex, age, primary liver diseases and Child-pugh's classification, cold ischemic time, total operation and anhepatic time, operation methods, volume of blood loss and transfusion, and all preoperative observations. Most of observations showed the restoration of the patients in group B was better than that in group A. The plasma levels of endotoxin, D-lactate, tumor necrosis factor-alpha, interleukin-6, alanine aminotransferase, aspartate aminotransferase, prothrombin time and activated partial thromboplastin time in group B were significantly lower than those in group A (P < 0.05). The level of plasma prealbumin in group B was significantly higher than that in group A (P < 0.05).</p><p><b>CONCLUSIONS</b>The removal of 200 ml portal blood stasis leads to a better results than that of 50 ml, and it can help alleviate endotoxemia and facilitate the restoration of the liver function after liver transplantation.</p>

Study of bloodless hepatectomy under occlusion of total hemi-hepatic vessel / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the preliminary clinical evaluation of hepatectomy with total hemi-hepatic vascular exclusion.</p><p><b>METHODS</b>Twenty-eight patients with primary liver cancer were divided into two groups of hepatectomy with total hemi-hepatic vascular exclusion (group A) and total hepatic inflow occlusion (group B). The time of hepatic vascular control, intraoperative blood loss, volume of removed liver, postoperative liver function recovery and complications were compared between the two groups.</p><p><b>RESULTS</b>The intraoperative blood loss in group A was (296 +/- 240) ml, which was less significantly than that in group B [(582 +/- 497) ml] (P<0.05). The serum pre-albumin levels on the day 1, 3 and 7 after operation in group A were (164 +/- 39) mg/L, (111 +/- 17) mg/L and (104 +/- 23) mg/L, which were higher significantly than that in group B [(134 +/- 34) mg/L, (90 +/- 22) mg/L and (82 +/- 35) mg/L] (P<0.05). While the time of hepatic vascular control and volume of lost liver were no difference between the groups (P>0.05). There were no significant difference in other items between the groups.</p><p><b>CONCLUSIONS</b>Intraoperative blood loss and liver damage of hepatectomy under the total hemi-hepatic vascular exclusion could be less than that under the other methods of vascular occlusion. It could be worth improving and applying further.</p>

Potent antitumoral effects of a novel gene-viral therapeutic system CNHK300-mEndostatin in hepatocellular carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The expression of therapeutic gene and its anti-tumor effects will be augmented and a synergism of oncolytic virus with the therapeutic gene is speculated. This study was undertaken to assess the anti-tumor effects of a novel gene-viral therapeutic system CNHK300-mEndostatin (CNHK300-mE) in hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>A novel gene-viral therapeutic system named CNHK300-mE was constructed using the human telomerase reverse transcriptase (hTERT) promoter to drive the expression of the adenovirus E1A gene and cloning the therapeutic gene mouse endostatin into the adenovirus genome. By the tissue culture infectious dose 50 (TCID50) method and cytoviability assay, the replicative and cytolytic capabilities of CNHK300-mE in two HCC lines (HepGII and Hep3B) and one normal cell line (MRC-5) were analyzed, and the transgene expressions of mouse endostatin in vitro and in vivo were detected by Western blotting and ELISA assay. Tumor growth suppression and anti-angiogenesis effects in vivo were investigated using nude mice xenografts model derived from SMMC-7721 HCC cells.</p><p><b>RESULTS</b>The 3296-fold replicating capacity of CNHK300-mE in HCC cell lines versus in the normal cell line at 96 hours post infection and the 25-fold effective dose for killing 50% cells (ED50) in the normal cell line versus HCC cell lines, which were both superior to ONYX-015, were observed. Tumor growth suppression of CNHK300-mE superior to either Ad-mE or ONYX-015 was demonstrated (P < 0.01) and the anti-angiogenic effects in vivo superior to Ad-mE were also observed with immunohistochemical staining of von Willebrand factor. In comparison with non-replicative adenovirus Ad-mE, the transgene expression of mE mediated by CNHK300-mE was significantly higher in vitro (P < 0.005) and in vivo (P < 0.05).</p><p><b>CONCLUSION</b>Being capable of replicating in and lysing the telomerase-positive HCC cells and mediating effective expression of the therapeutic gene in vitro and in vivo, the novel gene-viral therapeutic system CNHK300-mE is potentially effective in the treatment of HCC.</p>

In vitro gene therapy of hepatocellular carcinoma using replication-defective and tumor-specific replication-competent adenovirus carrying interleukin-12 gene / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect and the expression level of a tumor-specific replication-competent adenovirus and a replication-defective adenovirus expression mouse recombinant IL-12 (mIL-12) gene on hepatocellular carcinoma (HCC) in vitro.</p><p><b>METHODS</b>The cytotoxicity of replication-competent adenovirus with E1B-55 000 attenuated CNHK200-mIL12 and ONYX-015 (dl1520), and replication-defective adenovirus Adv-mIL12 were evaluated by MTT and replication assay in two HCC cell lines (HepG2 and Hep3B) and human normal hepatocyte line (LO2). Western blot and ELISA were used to determine the expression level of mIL-12.</p><p><b>RESULTS</b>CNHK200-mIL12 replicated in HepG2 and Hep3B with an increase of 3,160-fold and 630-fold respectively in 96 h post-infection. CNHK200-mIL12 could kill HepG2 and Hep3B cells at a very low MOI (Multiplicity of Infection) and in short time course (HepG2:MOI = 0.2, on day 4; Hep3B:MOI = 0.005, on day 2), while it had no significant effect on LO2. Furthermore, the expressing level of mIL-12 in CNHK200-mIL12 treated HCC cell lines was much higher than that in Adv-mIL12 treated one (HepG2 101-fold, Hep3B 20-fold respectively).</p><p><b>CONCLUSION</b>Replication-competent adenovirus is more effective than replication-defective adenovirus in both cytotoxicity and efficiency of gene transfer in HCC, and holds great promise in the area of HCC therapy.</p>