Experimental studies of new embolizing material for portal vein embolization

BACKGROUND/AIMS: Preoperative portal vein embolization induces hypertrophy of the future remnant liver and atrophy of the liver to be resected. This procedure has been used recently to avoid hepatic failure in extensive hepatic resection, but an adequate embolizing material has not been developed. This experimental study investigated the embolization effect of a newly devised embolizing material in dogs. METHODOLOGY: The left branch of the portal vein was embolized with an emulsion of polidocanol and gelatin sponge. We studied the changes in liver weight and biochemical data up to 8 weeks after embolization. Pathological examination of the embolized portal vein and radiological study of the embolizing effect were performed. RESULTS: Complete obstruction of the portal vein was maintained until 8 weeks after embolization. Sufficient hypertrophy of the non-embolized liver and atrophy of the embolized liver were obtained during this examination. No serious complication was observed. CONCLUSIONS: The mixture of polidocanol and gelatin sponge seems to ensure perfect portal embolization without recanalization. This embolizing material is suitable for portal embolization.     

Transcatheter arterial embolization for hepatocellular carcinoma with portal vein thrombosis

Abstract In order to evaluate the possible benefits of transcatheter arterial embolization (TAE) in hepatocellular carcinoma (HCC) patients with peripheral portal vein thrombosis, 96 consecutive HCC cases with peripheral portal vein thrombosis were analysed. Of them, 35 cases received TAE and 61 cases did not. Most (77.8%) of the TAE-treated cases showed decreased α-fetoprotein (AFP) levels after treatment, but 57.1% of them suffered another rise in AFP levels and subsequently died. One patient (2.8%) developed progressive jaundice after TAE and died within 1 month, while four of the non-TAE cases died within 1 month after diagnosis. In general, TAE is safe for HCC patients with peripheral portal vein thrombosis. In addition, using Cox's regression model for multivariate survival analysis, serum total bilirubin (≤, > 2 mg/dL; P = 0.0254), AFP (≤ 3155 ng/mL, > 3155 ng/mL; P = 0.0002) and treatments (TAE, non-TAE; P = 0.0059) were found to affect their prognosis. There was significant difference in survival between TAE and non-TAE groups, the 6 month, 1 year and 2 year survival rates were 91.4 versus 62.3%, 51.4 versus 26.2% and 17.1 versus 4.9% ( P = 0.0017). The median survival times of TAE and non-TAE groups were 10.3 versus 3.7 months, respectively. Though TAE only provided palliative treatment, it did prolong survival in HCC patients with peripheral portal vein thrombosis.     

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.     

Indications for portal vein embolization in perihilar cholangiocarcinoma

Preoperative portal vein embolization (PVE) is often performed as a routine procedure before extended hepatectomy to minimize postoperative liver failure. However, the indications for PVE in perihilar cholangiocarcinoma (PCCA), which differ between institutions, remain controversial. In the present study, we examined the indications for PVE in patients with PCCA. A comprehensive meta‐analysis of PVE was performed using the PubMed, Medline, and Cochrane databases. The present study, which included 3033 patients (45 publications), compared the results of 836 cases in the PCCA group and 2197 cases in the other hepatic tumor (OHT) group. In the PCCA group, percent future remnant liver (%FRL) and ratio of %FRL to indocyanine green (ICG) were used as criteria in 71% and 25% of cases, respectively, and a %FRL < 40% was used as indication for PVE in 90% of cases. The rates of resection of the bile duct, simultaneous pancreaticoduodenectomy, and reconstruction of the portal vein and hepatic artery were high in the PCCA group (P < 0.001). Mortality after hepatectomy was 3.7% in the PCCA group and 1.9% in the OHT group (P < 0.001). The indication for PVE in PCCA patients is %FRL < 40% in many institutions. The indications for PVE in PCCA patients should be distinguished from those in other hepatic tumors because of the complex surgery required for PCCA.     

Feasibility of endoscopic ultrasound-guided portal vein embolization with Enteryx

BACKGROUND: Portal vein embolization (PVE) has been used as a preoperative strategy to induce hepatic lobar atrophy and contralateral lobe hypertrophy. We determined the feasibility of endoscopic ultrasound (EUS)-guided Enteryx (EVAL/ethylene-vinyl alcohol copolymer) embolization of the portal vein (EUS-PVE) in an animal model as a potential, minimally invasive, endoscopic technique. METHODS: EUS-guided embolization of the portal vein (EUS-PVE) using Enteryx was performed in a Yorkshire breed swine. Portal pressure measurements were obtained before and after vascular embolization. The animal was carefully monitored for seven days for evidence of abdominal pain, shock, or bleeding. An upper abdominal contrast-CT scan was performed to verify the location of the embolus. RESULTS: The PV pressure increased from 3 mmHg at baseline to a mean of 15 mmHg after EUS-PVE. The CT-scan on day 4 demonstrated Enteryx in the main portal vein with extension into the left branch. At sacrifice on day 7, a solid thrombus was visible grossly and histologically inside the main portal vein and the left branch of the portal vein. CONCLUSIONS: Selective embolization of the portal vein by EUS guidance appears to be feasible and a potential, minimally invasive, preoperative treatment option for patients undergoing extensive hepatectomy.     

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．     

Preoperative portal vein embolization for hepatocellular carcinoma: consensus and controversy

Thirty years have passed since the first report of portal vein embolization(PVE),and this procedure is widely adopted as a preoperative treatment procedure for patients with a small future liver remnant(FLR).PVE has been shown to be useful in patients with hepatocellular carcinoma(HCC)and chronic liver disease.However,special caution is needed when PVE is applied prior to subsequent major hepatic resection in cases with cirrhotic livers,and volumetric analysis of the liver segments in addition to evaluation of the liver functional reserve before PVE is mandatory in such cases.Advances in the embolic material and selection of the treatment approach,and combined use of PVE and transcatheter arterial embolization/chemoembolization have yielded improved outcomes after PVE and major hepatic resections.A novel procedure termed the associating liver partition and portal vein ligation for staged hepatectomy has been gaining attention because of the rapid hypertrophy of the FLR observed in patients undergoing this procedure,however,application of this technique in HCC patients requires special caution,as it has been shown to be associated with a high morbidity and mortality even in cases with essentially healthy livers.     

Hepatectomy for patients with transient hepatic failure after preoperative portal vein embolization

Portal vein embolization (PVE) is a preparative procedure to facilitate major hepatectomy. Most patients with various hepatobiliary diseases were tolerable to right PVE. However, a few patients revealed marked deterioration of liver function after PVE, which made surgeons hesitate whether to carry out preplanned major hepatectomy. We report 2 cases of right liver resection after an episode of PVE-induced transient liver failure. The first patient was a 42-year-old male who had hepatocellular carcinoma in the cirrhotic liver background. After right PVE, serum aspartate and alanine aminotransferases raised to 1222 IU/L and 1908 IU/L, respectively. His liver function improved very slowly, and right lobectomy could be performed after waiting of 46 days. Postoperative restoration of liver function was also delayed, but he recovered after all. The second patient was a 53-year-old male with intrahepatic cholangiocarcinoma without jaundice. Serum total bilirubin rose to 10.7 mg/dL after right PVE, and decreased slowly. Right lobectomy was carried out after waiting of 45 days and postoperative course was uneventful. Meticulous liver transection without interruption of hepatic inflow, early infusion of gabexate mesilate, and intraportal infusion of glucose-insulin-potassium solution were adopted to protected the remnant liver. We think that transient liver failure after PVE is not contraindicated for major hepatectomy if there is no definite causal risk factor, but every effort should be paid to prevent posthepatectomy liver failure.     

Preoperative portal vein embolization: an audit of 84 patients

Preoperative portal vein embolization (PVE) was performed in 84 patients before extensive liver resection for various diseases. By the criteria of liver volumetric determination, some patients were candidates for PVE, whereas others were not, even though the same surgical procedure, such as extended right lobectomy (ERL), was scheduled. PVE using gelatin sponge powder induced hypertrophy in the nonembolized lobe (0%-171%; median, 30%) and proportional atrophy in the embolized lobe in 2 weeks without eliciting any major inflammatory or necrotic reaction, as evidenced histologically and by the minimal elevations in the serum aspartate transaminase (AST) and alanine transaminase (ALT) values. Alterations in the total bilirubin level and prothrombin time were also insignificant and transient, indicating that hepatocyte functions were not impaired by PVE. Not all patients who undergo PVE proceed with the scheduled hepatic resection procedure, so it is a great advantage that gelatin sponge causes minimal damage compared with other embolizing materials such as cyanoacrylate and absolute ethanol, which have been reported to induce an inflammatory reaction or histological alteration. Our multiple regression analysis showed that three factors, diabetes mellitus, a high total bilirubin level at the time of PVE, and being male, each reduced the extent of hypertrophy in the nonembolized lobe (r2 =.30). By contrast, cholestasis appeared to accelerate the process of atrophy in the embolized lobe (r2 =.16). In conclusion, PVE by gelatin sponge powder is a safe and effective preoperative maneuver that induces hypertrophy of the section of the liver that will remain after partial hepatectomy.     

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.     

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.     

Tumour growth after portal vein embolization with pre-procedural chemotherapy for colorectal liver metastases

Background

For resection of colorectal cancer (CRC) liver metastases, pre-operative portal vein embolization (PVE) is used to increase the size of the future liver remnant (FLR) prior to advanced liver resection when indicated. PVE is speculated to cause tumour progression, but only a limited number of studies have analysed tumour growth after PVE in the context of pre-procedural chemotherapy, which was the aim of this retrospective study.

Methods

Patients treated with stabilizing chemotherapy and PVE before liver resection for CRC metastases were included. Tumour progression according to RECIST guidelines and a change in tumour volume was analysed on computed tomography (CT) scans prior to chemotherapy, before PVE and after PVE, respectively.

Results

Thirty-four patients were included, of whom 23 had bilobar disease. Of tumours in the embolized lobe, 3/34 showed progression after PVE as compared with 3/23 in the non-embolized lobe (P = 0.677). A decrease in tumour volume of 16% and 11% was noted in the embolized and non-embolized lobe, respectively (P = 0.368). Patients were off chemotherapy in a median of 16 days before PVE. There was a linear correlation between the growth of tumours and time between the end of chemotherapy and PVE (r = 0.25, P = 0.0005).

Conclusion

The rate of progression of CRC liver metastases after PVE and pre-procedural chemotherapy was lower in the present study as compared with previous reports. This applies to tumours in both the embolized and non-embolized lobes and is associated with keeping the time between the end of chemotherapy and PVE short.