Factors affecting liver regeneration after right portal vein embolization

BACKGROUND/AIMS: The factors influencing the effect of portal vein embolization performed prior to hepatectomies are not clearly understood. METHODOLOGY: In 18 patients who underwent portal vein embolization, serum transforming growth factor-alpha levels and the nonembolized liver volume were studied after portal vein embolization. The increase in the nonembolized liver volume was compared with the change in serum transforming growth factor-alpha levels and several other clinical variables. RESULTS: The volume of the nonembolized liver significantly increased from 430+/-114 cm3 to 521+/-113 cm3. The serum transforming growth factor-alpha levels significantly increased on the 7th day after portal vein embolization and peaked on the 18th day. The percentage increase in the nonembolized liver volume 14 days after portal vein embolization was significantly correlated with the nonembolized liver volume and the increase in the portal flow velocity, and it was independently and significantly correlated with the increase in the transforming growth factor-alpha level 14 days after portal vein embolization (r2=0.674, P=0.0014 and r=0.761, P<0.0005). CONCLUSIONS: The increase in the transforming growth factor-alpha level 14 days after portal vein embolization was the only independent factor related to the hypertrophy of the nonembolized liver. Measurement of its serum level may be a useful indicator in the scheduling of subsequent extensive hepatectomies.     

Impaired liver function attenuates liver regeneration and hypertrophy after portal vein embolization

AIM To clarify the clinical factors associated with liver regeneration after major hepatectomy and the hypertrophic rate after portal vein embolization(PVE).METHODS A total of 63 patients who underwent major hepatectomy and 13 patients who underwent PVE in a tertiary care hospital between January 2012 and August 2015 were included in the analysis.We calculated the remnant liver volume following hepatectomy using contrast-enhanced computed tomography(CT) performed before and approximately 3-6 mo after hepatectomy.Furthermore,we calculated the liver volume using CT performed 2-4 wk after PVE.Preoperative patient characteristics and laboratory data were analyzed to identify factors affecting postoperative liver regeneration or hypertrophy rate following PVE.RESULTS The remnant liver volume/total liver volume ratio negatively correlated with the liver regeneration rate after hepatectomy(ρ =-0.850,P 0.001).The regeneration rate was significantly lower in patients with an indocyanine green retention rate at 15 min(ICG-R15) of ≥ 20% in the right hepatectomy group but not in the left hepatectomy group.The hypertrophic rate after PVE positively correlated with the regeneration rate after hepatectomy(ρ = 0.648,P = 0.017).In addition,the hypertrophic rate after PVE was significantly lower in patients with an ICG-R15 ≥ 20% and a serum total bilirubin ≥ 1.5 mg/d L.CONCLUSION The regeneration rate after major hepatectomy correlated with hypertrophic rate after PVE.Both of them were attenuated in the presence of impaired liver function.     

Experimental and clinical studies on liver regeneration following transcatheter portal embolization

BACKGROUND/AIMS: We studied compensatory hypertrophy following transcatheter portal embolization experimentally in dogs and clinically under the condition of cholestasis. METHODOLOGY: Experimental study: Sixteen dogs were used for this study. Transcatheter portal embolization was performed in the left lobes (70% of the total liver) using Gelfoam powder in dogs with 2-week obstructive jaundice. Liver weight, liver blood flow and the intracellular adenosine triphosphate content of isolated hepatocytes were measured after transcatheter portal embolization. Clinical Study: transcatheter portal embolization of the right portal branch was performed in 13 patients with cancer of the biliary tract and 3 patients with hepatocellular carcinoma before (extended) right lobectomy, using Gelfoam powder and thrombin. Six patients who had a total bilirubin level > 5 mg/dLunderwent a percutaneous transhepatic biliary drainage before transcatheter portal embolization. Liver function tests, a volumetric study with computed tomography and immunohistochemical staining for profilerating cell nuclear antigen and apoptosis in the resected livers were performed. RESULTS: Experimental study: The weight ratio of the non-embolized lobes to the total liver, 2 weeks after transcatheter portal embolization in the dogs with jaundice, was significantly lower than that of the normal dogs with transcatheter portal embolization (40.5 +/- 4.5% vs. 47.6 +/- 3.2%), but significantly larger than that of the dogs without transcatheter portal embolization. The cellular adenosine triphosphate content and tissue blood flow in the embolized lobes were significantly lower than those in the nonembolized lobes in the normal and cholestatic livers. Clinical study: The postoperative course in all patients was uneventful, with no serious complication or liver dysfunction. Extended right lobectomy with caudate lobectomy was equivalent to 65% before transcatheter portal embolization and to 56% after, transcatheter portal embolization owing to compensatory hypertrophy of the left lobe. However, there was no significant difference in liver volume in the patients with or without obstructive jaundice. Apoptosis was observed in the embolized lobe. CONCLUSIONS: Preoperative transcatheter portal embolization with percutaneous transhepatic biliary drainage for the purpose of liver regeneration would be useful for treating extended hepatectomy with obstructive jaundice.     

Comparison of percutaneous transhepatic portal vein embolization and unilateral portal vein ligation

AIM: To compare the effect of percutaneous transhepatic portal vein embolization (PTPE) and unilateral portal vein ligation (PVL) on hepatic hemodynamics and right hepatic lobe (RHL) atrophy.METHODS: Between March 2005 and March 2009, 13 cases were selected for PTPE (n = 9) and PVL (n = 4) in the RHL. The PTPE group included hilar bile duct carcinoma (n = 2), intrahepatic cholangiocarcinoma (n = 2), hepatocellular carcinoma (n = 2) and liver metastasis (n = 3). The PVL group included hepatocellular carcinoma (n = 2) and liver metastasis (n = 2). In addition, observation of postoperative hepatic hemodynamics obtained from computed tomography and Doppler ultrasonography was compared between the two groups.RESULTS: Mean ages in the two groups were 58.9 ± 2.9 years (PVL group) vs 69.7 ± 3.2 years (PTPE group), which was a significant difference (P = 0.0002). Among the indicators of liver function, including serum albumin, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, platelets and indocyanine green retention rate at 15 min, no significant differences were observed between the two groups. Preoperative RHL volumes in the PTPE and PVL groups were estimated to be 804.9 ± 181.1 mL and 813.3 ± 129.7 mL, respectively, with volume rates of 68.9% ± 2.8% and 69.2% ± 4.2%, respectively. There were no significant differences in RHL volumes (P = 0.83) and RHL volume rates (P = 0.94), respectively. At 1 mo after PTPE or PVL, postoperative RHL volumes in the PTPE and PVL groups were estimated to be 638.4 ± 153.6 mL and 749.8 ± 121.9 mL, respectively, with no significant difference (P = 0.14). Postoperative RHL volume rates in the PTPE and PVL groups were estimated to be 54.6% ± 4.2% and 63.7% ± 3.9%, respectively, which was a significant difference (P = 0.0056). At 1 mo after the operation, the liver volume atrophy rate was 14.3% ± 2.3% in the PTPE group and 5.4% ± 1.6% in the PVL group, which was a significant difference (P = 0.0061).CONCLUSION: PTPE is a more effective procedure than PVL because PTPE is able to occlude completely the portal branch throughout the right peripheral vein.     

Liver regeneration following portal blood arterialization and splenectomy in acute hepatic failure

BACKGROUND/AIMS: The purpose of the experiment was to estimate an influence of portal blood arterialization in animals with tetrachloromethane-induced acute hepatic failure. METHODOLOGY: Thirty-five pigs were divided into four groups: three groups of 10 and a control group of 5 animals. On day 1 of the experiment an intraperitoneal dose of 477 mg CCl4//kg body wt. in a suspension of corn oil was given to the trial groups to induce an acute hepatic failure. On day 3 after the intoxication all animals were operated on. Aortovenous splenic anastomosis without splenectomy, aorto-venous splenic anastomosis with splenectomy, and splenectomy procedure alone, were performed in groups I, II, and III, respectively. In the control group only laparotomy was performed. Histopathologic estimation of hematoxylin- and eosin-stained specimens and immunohistochemical analysis of regenerating hepatocytes by applying monoclonal serum for CK19, CD56, CD117 were carried out. RESULTS: Liver biopsies demonstrated no quantitative differences concerning the surface of damaged lobules between groups I, II, and III. The phenomenon of parenchyma regeneration was observed in both groups (with and without splenectomy procedure performed). Small stem cells could be observed mainly in the central part of lobules. The immunohistochemical analysis showed that part of the regenerating cells had CD56 and CD117 antigens' receptors, demonstrating no expression of antigen CK19. In the third group of animals (splenectomy without blood arterialization) neither the phenomenon of parenchyma regeneration nor the presence of cells of hepatoblast phenotype were observed. CONCLUSIONS: The arterialization of portal blood in pigs with acute hepatic failure triggered off the regeneration of damaged parenchyma through the colonization of impaired areas of lobules by small stem cells. The lack of the receptor for antigen CK19 could mean that the cells do not originate in bile duct epithelium.     

门静脉栓塞术应用进展

肝癌是我国最常见的恶性肿瘤之一,在肝脏移植尚不能普及的今天,手术切除是目前治疗肝癌的最有效方法．但是术后剩余肝脏组织 (future liver remnant,FLR)过少则是造成术后肝功能衰竭等并发症的重要因素,限制了肝癌手术的进行,从而使一些患者失去了手术的机会．肝切除术前门静脉栓塞术(portal vein embolization,PVE)可以使栓塞侧肝叶萎缩和对侧肝叶增生,使术后FLR增大,功能提高,从而使不能直接手术切除的肝癌患者获得手术切除的机会,扩大了手术指征．PVE的实施通常采用超声引导下经皮经肝门静脉栓塞术,常用的栓塞材料有:纤维蛋白胶(fibrin glue)、氰基丙烯酸 碘油、明胶海绵 凝血酶,弹簧圈, 微粒(如PVA颗粒)和无水乙醇等．目前PVE主要用于原发性肝癌、转移性肝癌、肝门胆管癌和胆囊癌等需要行肝大部切除或扩大肝切除的患者以及多发肝转移瘤需行二期肝切除患者．但在患有严重门静脉高压症的患者不适合行PVE治疗．同时PVE的应用仍存在许多问题:PVE患者的选择尚无统一标准;PVE理想栓塞材料的研究;PVE与现行肝癌治疗手段如动脉栓塞术、辅助化疗等的联合应用等都需要深入的研究．严格把握适应证,PVE在肝癌的治疗中将会发挥越来越重要的作用．     

Liver abscess, portal vein thrombosis and cavernoma formation following umbilical vein catherisation in two neonates.

Liver abscess is a rare condition in neonates and its diagnosis requires a high degree of suspicion. CT scan and ultrasound are the most sensitive diagnostic modalities for detecting hepatic abscess. Portal vein thrombosis and cavernoma formation are rare complications following neonatal liver abscess and sepsis. We describe the case of two neonates with hepatic abscess following umblical vein catheterisation, with rare complications of portal vein thrombosis and portal vein cavernoma formation. Therefore, unreserved caution should be exercised in performing umbilical cannulation in neonates due to the inherent risks involved with this procedure.     

Effects of portal vein embolization before major hepatectomy

BACKGROUND/AIMS: Major hepatectomy can now be successfully performed after portal vein embolization, but the effects of portal vein embolization have not been clearly delineated. Our objective is to examine whether portal vein embolization really contributes to the success of major hepatectomy. METHODOLOGY: Thirty-eight patients underwent portal vein embolization and hepatectomy of two subsegments or more. They all belonged to a high-risk group according to a prognostic score. We selected 9 of 38 patients with liver metastases (PE-meta group) and 32 patients who had undergone hepatectomy without portal vein embolization (non-PE-meta group) during the study period to compare the serum levels of total bilirubin after hepatectomy. Fifteen of 38 patients had the levels of polymorphonuclear leukocyte elastase and thrombin-antithrombin complex examined after hepatectomy (PE group) and so did 20 patients without portal vein embolization (non-PE group). RESULTS: The maximum levels of total bilirubin in non-PE-meta group correlated with the percentage of hepatic parenchyma to be resected. In the patients receiving portal vein embolization, the pre-PE and post-PE levels were both below the regression. Similar shifts were seen in the graphs of polymorphonuclear leukocyte elastase and thrombin-antithrombin complex. CONCLUSIONS: The effects of preoperative portal vein embolization on safety in major hepatectomy were proved by its suppression of rise in total bilirubin, polymorphonuclear leukocyte elastase and thrombin-antithrombin complex after hepatectomy.     

Human erythrocyte polyamine levels after portal vein embolization

BACKGROUND/AIMS: Polyamine levels in erythrocytes are related to liver regeneration and could be used as an index of liver regeneration after partial hepatectomy. We investigated liver regeneration after portal vein embolization according to the changes of erythrocyte polyamine levels. METHODOLOGY: Levels of polyamines (putrescine, spermidine, and spermine) in erythrocytes were assayed by high-pressure liquid chromatography for 13 patients with hepatocellular carcinoma after portal vein embolization and 16 patients (8 from group reported earlier) after right bisegmentectomy of the liver for hepatocellular carcinoma. In the first group, embolization preceded surgery by 3 weeks. RESULTS: The mean total polyamine level in erythrocytes and the levels of spermidine and spermine were significantly higher at day 7 after embolization, decreasing later. Spermidine and spermine increased by day 7 after partial hepatectomy, decreasing later. Their mean increase was smaller and more gradual when embolization was done before resection than without embolization. CONCLUSIONS: Embolization causes regeneration of the non-embolized portion of the liver, and embolization before liver resection allows regenerative activities of the liver remaining after resection to be lower than without the embolization.     

Changes in clinicopathological findings after portal vein embolization

BACKGROUND/AIMS: Portal vein embolization is becoming more common as a method of preventing hepatic failure after an extended hepatectomy but its mechanism is not well understood. This clinicopathological study focused on its mechanism. METHODOLOGY: Thirty patients who underwent extended hepatectomy after portal vein embolization were evaluated. Liver volume was measured before and after portal vein embolization, and histological studies were performed to examine morphological changes, morphometric parameters and apoptosis of hepatocytes. RESULTS: The mean volume of the non-embolized lobe grew significantly from 392 to 462 mL after portal vein embolization (P < 0.0001). The hypertrophy ratio of the non-embolized lobe (100 x volume change during portal vein embolization/volume before portal vein embolization, %) was correlated closely with the volume of the non-embolized lobe before portal vein embolization (r = -0.65, P < 0.0001). Histological study showed the embolized lobe hepatocytes to be atrophic, partly necrotic and apoptotic. In the non-embolized lobe, the mean hepatocyte volume was 8686 micron 3 (control: 6544 micron 3) and the mean hepatocyte count was 109 x 10(6)/mL (control: 122 x 10(6)/mL). CONCLUSIONS: The enlargement of the non-embolized lobe was caused by hypertrophy rather than hyperplasia suggesting hyperfunction. The resection of the atrophic embolized lobe, leaving the hypertrophic non-embolized lobe was thought to be less surgically stressful than hepatectomy without portal vein embolization.     

Role of portal vein embolization in hepatobiliary malignancy

BACKGROUND/AIMS: Inadequate remnant liver volume is the major cause of postoperative liver failure. Preoperative portal vein embolization (PVE) is the well accepted procedure to increase future liver remnant (FLR) volume and decrease the incidence of this complication. This study described the author's experience of preoperative PVE at King Chulalongkorn Memorial Hospital since 2002. METHODOLOGY: The clinical data of 29 patients who underwent PVE were reviewed. The FLR volumes before and after the procedure were calculated by CT volumetry. PVE was performed when estimated FLR volume was < 25% in normal liver or < 40% in damaged liver and also when major liver resection combined with major intraabdominal surgery was planned. The complications after PVE and hepatectomy were recorded. RESULTS: There were no deaths or complications after PVE. The mean growth of FLR was 11%. Power of liver regeneration was suboptimal in old age patients. Sixteen patients underwent liver resection (resectability rate 55.17%). There were 2 cases of postoperative hyperbilirubinemia (12.5%). The hospital mortality rate was 1/16 (6.25%). CONCLUSIONS: PVE is a useful and safe optional procedure to increase FLR. It not only reduces the postoperative liver failure but also increases the chance of curative resection.