Portal Branch Ligation Research Articles

ЭФФЕКТИВНОСТЬ МЕТОДОВ ОККЛЮЗИИ ВОРОТНОГО КРОВОТОКА ПРИ ПЛАНИРОВАНИИ ОБШИРНЫХ РЕЗЕКЦИЙ У ПАЦИЕНТОВ С ЭХИНОКОККОЗОМ ПЕЧЕНИ

Background. Surgery is the main and an effective treatment option for liver echinococcosis. The choice of surgical strategy for advanced liver echinococcosis given suspected poor liver functional reserve and post-operative hepatic failure remains challenging. Objective. To present and analyze the effectiveness of portal blood flow occlusion techniques in planning two-stage extensive resections in patients with advanced liver echinococcosis. Material and methods. The article presents the outcomes of surgical treatment of 22 patients (8/36,4% men, 14/63,6% women) operated on for advanced liver echinococcosis in the surgical department No.2 of State Autonomous Healthcare Institution ‘Kuzbass Clinical Emergency Hospital named after A.I. M. A. Podgorbunsky’ (Kemerovo). The application of a two-stage extensive resection protocol was used as an entry criterion. Stage I included right portal vein branch occlusion techniques aimed at achieving vicarious hypertrophy of the contralateral lobe. A two-stage extensive resection protocol was applied in case of both expected poor hepatic functional reserve and insufficient future remnant liver volume, accounting for inability of safe implementation of a one-stage extensive resection due to predicted postoperative hepatic failure and a fatal outcome. Results. The applied two-stage resection techniques for the prevention of post-operative hepatic failure are effective in relation to the following indicators: CT volumetry (p<0,05), OK15 ICG (p<0,05), statistical model value (p<0.05). Though the laparotomic technique of the right portal vein branch ligation is of a comparable effectiveness with the laparoscopic one, the latter being less traumatic, which can significantly reduce postoperative hospital stay (p<0,05). Moreover, the laparoscopic technique was not found to cause any specific and nonspecific complications. Conclusions. The applied methods of portal blood flow occlusion are considered to be effective and safe when planning two-stage extensive resections in specialized hepatology centers and can be recommended in case of initial poor hepatic functional reserve and insufficient future remnant liver volume.

Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats.

Simple SummaryFewer than 30% of patients with liver metastases are eligible for major liver resection, because liver remaining after such a surgery would be insufficient to cover the patient’s needs; this is called a low percentage of future liver remnant (FLR). Folinic acid (FA) has been shown to play a crucial role in cellular synthesis, regeneration, and nucleotide and amino acid biosynthesis. The aim of this piece of research was to evaluate the effect of FA as a potential hypertrophic hepatic enhancer agent after selective portal vein ligation (PVL) to ensure adequate FLR. We have confirmed in our rodent model that FA accelerates liver regeneration after PVL and enhances recovery of liver function. These findings may allow more patients to be eligible for liver resection without jeopardizing postoperative liver function.Liver resection remains the gold standard for hepatic metastases. The future liver remnant (FLR) and its functional status are two key points to consider before performing major liver resections, since patients with less than 25% FLR or a Child–Pugh B or C grade are not eligible for this procedure. Folinic acid (FA) is an essential agent in cell replication processes. Herein, we analyze the effect of FA as an enhancer of liver regeneration after selective portal vein ligation (PVL). Sixty-four male WAG/RijHsd rats were randomly distributed into eight groups: a control group and seven subjected to 50% PVL, by ligation of left portal branch. The treated animals received FA (2.5 m/kg), while the rest were given saline. After 36 h, 3 days or 7 days, liver tissue and blood samples were obtained. FA slightly but significantly increased FLR percentage (FLR%) on the 7th day (91.88 ± 0.61%) compared to control or saline-treated groups (86.72 ± 2.5 vs. 87 ± 3.33%; p < 0.01). The hepatocyte nuclear area was also increased both at 36 h and 7days with FA (61.55 ± 16.09 µm2, and 49.91 ± 15.38 µm2; p < 0.001). Finally, FA also improved liver function. In conclusion, FA has boosted liver regeneration assessed by FLR%, nuclear area size and restoration of liver function after PVL.

“Reversal” ALPPS in patient with hepatocellular carcinoma and liver cirrhosis. First clinical case in Russia

Liver resection in patients with HCC is the treatment of choice. In patients with insufficient future liver remnant (FLR) and compensated liver function performing the Associated Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is possible. The classic version of ALPPS consists in ligation of the right branch of the portal vein with transection of the parenchyma and then performing right hepatectomy or right trisegmentectomy. This paper describes the first case in Russia of performing ligation of the left portal branch with transection of the parenchyma and then performing left trisegmentectomy (“reversal” ALPPS) in a patient with HCC and cirrhosis. Reversal ALPPS can be successfully performed in patients with insufficient future liver remnant in well-selected patients.

Laparoscopic portal branch ligation of the right caudate lobe concomitant with portal vein embolization for planned right hemihepatectomy in advanced hepatobiliary cancers.

The role of ligation of the portal venous branches to the caudate lobe (cPVL) as preparation for planned major hepatectomy is unclear. The aim of this study was to evaluate the efficacy of laparoscopic cPVL (Lap-cPVL) concomitant with transileocolic portal vein embolization of the right portal venous system (rTIPE), namely, Lap-cPVL/rTIPE, for planned right hemihepatectomy (rHx) in advanced hepatobiliary cancer patients. Thirty-one patients who underwent rHx after rTIPE with/without Lap-cPVL between March 2013 and March 2020 were enrolled in this study. The Lap-cPVL was performed for the portal branches of the right caudate lobe. Eight of the 31 patients underwent Lap-cPVL/rTIPE. The degree of hypertrophy was significantly increased in Lap-cPVL/rTIPE (19.3%, range 6.5-25.6%) as compared to rTIPE (7.2%, range - 1.1 to 21.2%) (p=0.027). The functional kinetic growth rate was also significantly increased in Lap-cPVL/rTIPE (5.40%, range 2.17-5.97) than that in rTIPE (1.85%, range - 0.22 to 6.45%) (p=0.046). Postoperative liver failure ≧ grade B occurred in 21.7% of patients in rTIPE, while there was no postoperative liver failure ≧ grade B in Lap-cPVL/rTIPE. Mortality rates were zero after rHx in this study. Lap-cPVL/rTIPE is safe and provides an additional effect on liver hypertrophy in advanced hepatobiliary cancers.

A Case of Multiple Primary Cancers of the Colon and Liver Treated by Right Hepatic Trisegmentectomy after Laparoscopic Portal Branch Ligation

症例は82歳の男性で，血便を主訴に当院へ紹介となる．下部消化管内視鏡検査で全周性3型のS状結腸癌を認め，内視鏡の通過は困難であった．腹部造影CTで肝S4/5/8を主座とした10cm大，肝S7に5cm大の早期濃染wash outされる腫瘍を認め，肝細胞癌と診断した．S状結腸癌の切除を先行し，二期的に右三区域切除術の方針とした．腹腔鏡下S状結腸切除術の際に，腹腔鏡下門脈右枝結紮術を施行した．予定残肝容積は521mLと約17％肥大し，予定残肝容積割合63％，予定残肝ICG-K 0.072と改善を認めた．門脈結紮術後32日目に右三区域切除術を施行した．術後合併症はなく，結腸癌に対する術後補助化学療法施行中である．結腸癌および肝細胞癌の重複癌に対して，腹腔鏡下門脈右枝結紮術を施行し，右三区域切除術を施行した．本症例のように，重複癌で複数回の開腹手術が必要な場合，腹腔鏡下門脈結紮術は簡便で安全に施行可能で経皮経肝門脈塞栓術の代替の治療選択になりうると考える．

Hepatoblastoma requiring liver transplantation. A case report

Hepatoblastoma is a rare pathology in pediatric patients, occurring in 5-10/one million children. A two year old patient was admitted to our clinic for intense abdominal pain. On examination he presented a large mass in the right hypochondrium. Abdominal ultrasound and computer tomography (CT) revealed a large, solid hepatic tumor with thrombosis of the right portal vein. Serum alpha fetoprotein (AFP) level and thrombocyte number were increased. Liver biopsy was performed and the histopathological aspect was specific for an epithelial hepatoblastoma. Chemotherapy was initiated, followed by surgery in two steps: right portal branch ligation and subsequent tumor resection. Six months after surgery a relapse was suspected, confirmed by CT and elevated AFP levels. A „rescue” liver transplantation was performed and the patient is disease-free for three years. Elevated AFP and thrombocyte levels point to the diagnosis of hepatoblastoma. Liver transplantation is the final option for extensive, inoperable or relapsing tumors.

Expression of hypoxia inducible factor-1α and its correlation with phosphoenolpyruvate carboxykinase after portal vein ligation in rats

AimsPortal vein ligation (PVL) has been used to effectively increase future liver remnant (FLR) in hepatectomy for treatment of liver cancer. However, the underlying molecular mechanisms have not been well characterized. The present study aimed to determine expression of hypoxia inducible factor-1alpha (HIF-1α) in response to PVL and assess the correlation of HIF-1α and phosphoenolpyruvate carboxykinase (PEPCK). Main methodsMale Sprague–Dawley rats underwent PVL and were sacrificed at different time points (12, 24, 48, 72, and 168h) after surgery. Hepatic HIF-1α expression in the regenerating liver was assessed by Western blot and immunohistochemistry, in parallel; PEPCK levels were quantified by ELISA. Key findingsWe found that the ligated liver lobes diminished progressively, whereas the unligated lobes underwent compensatory regeneration after 70% ligation of portal vein branches in the PVL group. Hepatic HIF-1α and PEPCK levels in the unligated liver lobes were significantly increased in the PVL group compared to the hepatic artery ligation (HAL) and the sham (SH) operation groups. Pearson's correlation analysis revealed positive correlation between HIF-1α expression and PEPCK levels in the unligated lobes after PVL. Further analysis indicated that higher levels of HIF-1α and PEPCK in response to liver regeneration were paralleled by an increase in the ratio of the mass and volume of unligated lobes to the whole liver. SignificanceHIF-1α was up-regulated and positively correlated with PEPCK during liver regeneration after PVL in rats, suggesting that HIF-1α may modulate hepatic gluconeogenesis through PEPCK, which may ensure the energy supply required for liver regeneration.

Portal branch ligation does not counteract the inhibiting effect of temsirolimus on extrahepatic colorectal metastatic growth.

The mTor-inhibitor temsirolimus (TEM) has potent anti-tumor activities on extrahepatic colorectal metastases. Treatment of patients with advanced disease may require portal branch ligation (PBL). While PBL can induce intrahepatic tumor growth, the effect of PBL on extrahepatic metastases under TEM treatment is unknown. Therefore, we analyzed the effects of TEM treatment on extrahepatic metastases during PBL-associated liver regeneration. GFP-transfected CT26.WT colorectal cancer cells were implanted into the dorsal skinfold chamber of BALB/c-mice. Mice were randomized to four groups (n = 8). One was treated daily with TEM (1.5mg/kg), PBS-treated animals served as controls. Another group underwent PBL of the left liver lobe and received daily TEM treatment. Animals with PBL and PBS treatment served as controls. Tumor vascularization and growth as well as tumor cell migration, proliferation and apoptosis were studied over 14 days. In non-PBL animals TEM treatment inhibited tumor cell proliferation as well as vascularization and growth of the extrahepatic metastases. PBL did not influence tumor cell engraftment, vascularization and metastatic growth. Of interest, TEM treatment significantly reduced tumor cell engraftment, neovascularization and metastatic groth also after PBL. PBL does not counteract the inhibiting effect of TEM on extrahepatic colorectal metastatic growth.

Rabbit model provides new insights in liver regeneration after transection with portal vein ligation

BackgroundThe rabbit model of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has not been reported before. Materials and methodsNew Zealand white rabbits were allocated to two protocols. Protocol 1 involved either liver parenchymal transection (LPT, n = 5) or portal vein ligation (PVL, n = 5). Protocol 2 involved the ligation of different portal vein branches combined with liver partition, including the LPT + 20% PVL group (n = 5; the caudate portal vein was ligated), the LPT + 50% PVL group (n = 5; the left portal vein was ligated), and the LPT + 70% PVL group (n = 10; both veins were ligated). Computed tomography liver volumetry was performed immediately after operation. Blood samples were harvested before surgery and at days 1, 3, 7, or 14 after surgery for liver function evaluation. Most rabbits were humanely euthanized on day 7. The livers were harvested, divided into lobes, and weighed; biopsies of each lobe and immunohistochemical staining were performed. ResultsIn this article, we present a new rabbit model to simulate ALPPS procedure, with a description of the regional anatomical features, surgical routes, and key techniques. The growth rate of remnant right lobe volume increased with proportionally PVL combined with LPT. Specifically, right lobe volume growth rate of the LPT + 50% PVL group overwhelmed 70% PVL alone. ConclusionsThere were putative underlying mechanisms other than portal inflow redistribution in triggering residual liver regeneration after ALPPS procedure. This rabbit model is feasible for further mechanism research of this special clinical phenomenon.

Perioperative hepatocyte growth factor (HGF) infusions improve hepatic regeneration following portal branch ligation (PBL) in rodents.

As hepatic surgery has become safer and more commonly performed, the extent of hepatic resections has increased. When there is not enough expected hepatic reserve to facilitate primary resection of hepatic tumors, a clinical adjunct to facilitating primary resection is portal vein embolization (PVE). PVE allows the hepatic remnant to increase to an appropriate size prior to resection via hepatocyte regeneration; however, PVE is not always successful in facilitating adequate regeneration. One of the strongest trophic factors for hepatocyte regeneration is hepatocyte growth factor (HGF). The purpose of this study was to improve hepatic regeneration with perioperative HGF infusions in an animal model that mimics PVE. Portal branch ligation (PBL) in rodents is equivalent to PVE in humans. We performed left-sided PBL in Sprague-Dawley rodents with the experimental group receiving perioperative HGF infusions. Baseline and postoperative liver volumetrics were obtained with CT scanning methods as performed in clinical practice. Baseline and postoperative liver functions were assessed via indocyanine green (ICG) elimination testing. HGF infused rodents had statistically significant increase in all postoperative liver volumetrics. Most clinically relevant were increased right liver volumes (RLV), 14.10 versus 7.85cm3 (p value 0.0001), and increased degree of hypertrophy (DH%), 159.23 versus 47.11% (p value 0.0079). HGF infused rodents also had a quick return to baseline liver function, 2.38days compared to 6.13days (p value 0.0001). Perioperative HGF infusions significantly increase hepatic regeneration following PBL in rodents. Perioperative HGF infusions following PVE are a possible adjunct to increase the amount of patients able to successfully undergo primary resection for hepatic tumors. Further basic science is warranted in examining the use of HGF infusions to increase hepatic regeneration and translating that basic science work to clinical practice.

Modern Methods of Liver Fragment Vicarious Hypertrophy Stimulation prior to Advanced Resections: Assessment of Efficiency and Ways to Improve the Results

Aim. To assess an efficiency of modern methods of vicarious hypertrophy stimulation of the remnant liver after advanced resection and to reduce the risk of postoperative liver failure. Material and Methods. Programmed stimulation of liver vicarious hypertrophy was applied in 119 patients including ligation and transection of portal vein branches in 76 patients (64.8%), endovascular embolization of portal vein branches in 21 patients (17.6%), endovascular embolization of the portal vein combined with chemoembolization of the hepatic artery in 15 patients (12.7%), and split in situ liver resection in 7 patients (5.9%). Volume of remnant liver was measured using computerized tomography, magnetic resonance imaging and/or ultrasound prior to and in 2–4 weeks after occlusion of portal vein branches. Results. According to CT/MRI data remnant liver volume increased from 28.4% to 48.7% (by 38.9 ± 5.5% on the average). 72 patients (60.5%) were operated: right-sided or extended right-sided hemihepatectomies were performed in 49 cases (68%), atypical liver resection – in 21 cases (29.2%). Postoperative complications were registered in 16 cases (22%). Mortality due to post-resection hepatic failure was 2.8%. Liver resection was not performed in 47 cases (39.5%) due to insufficient increase of liver fragment, newly diagnosed intrahepatic metastases or local recurrence of colorectal cancer. Conclusion. Preoperative programmed stimulation of liver fragment is a perspective method that increases percent of operable patients with liver tumors and reduces the risk of hepatic failure after extensive liver resection. Surgical and endovascular methods of preoperative programmed stimulation of liver vicarious hypertrophy are technically feasible and safe.

Tumour growth of colorectal rat liver metastases is inhibited by hepatic arterial infusion of the mTOR-inhibitor temsirolimus after portal branch ligation.

Portal branch ligation (PBL) can be performed before major hepatic resection of colorectal liver metastases (mCRC) to increase the remnant liver mass. However, PBL may also stimulate mCRC growth through hepatic arterial hyperperfusion and growth factor release. Herein, we studied whether hepatic arterial infusion (HAI) of the mTOR-inhibitor temsirolimus (Tem) is capable of inhibiting the growth of colorectal liver metastases after PBL. WAG/Rij rats were randomized to four groups (n=6 each) and underwent subcapsular implantation of 5×10(5) CC531 cells into the left liver lobe. The animals of two groups underwent simultaneous PBL of the tumour bearing liver lobe. Ten days later animals underwent a HAI either of temsirolimus (Tem and PBL Tem) or saline solution (Sham and PBL Sham). Tumour size was analyzed at days 10 and 13 using three-dimensional ultrasound. In Sham controls tumour volume increased by 43%. After PBL Sham tumour volume increased by 52%. In contrast, in animals undergoing HAI of temsirolimus the tumour growth was not only completely inhibited, but tumour volume was found decreased, irrespective of PBL. After HAI of temsirolimus immunohistochemistry revealed an increased cleaved caspase-3 activity, indicating stimulation of apoptotic cell death. In parallel temsirolimus treatment was associated with a significant reduction of PECAM-1 positive cells within the tumour tissue, implying a reduced tumour vascularisation. HAI of temsirolimus is capable of inhibiting the growth of CC531 colorectal rat liver metastases also after PBL.

Development of an Experimental Model of Portal Vein Ligation Associated With Parenchymal Transection (ALPPS) in Rats

BackgroundLiver failure might be a cause of death after major hepatectomies. The ALPPS technique appears to be a promising strategy to avoid it, however no experimental studies supporting this procedure have been previously described. The aim was to develop an experimental model of ALPPS in rats. MethodExperimental. A total of 30 Sprague Dawley rats were used. To develop the ALPPS procedure, ligation of the left portal branch of the middle lobe (LM) was performed. This demarcates the left side (SILM) from the right side (SDLM); parenchyma transection was performed following the demarcated line. The animal's weight, volume and weight of both LM were analyzed. Sacrifice at 3, 7 and 14 days after the procedure (10 per group) was performed. ResultsNo bleeding or ascites was observed during the postoperative period. The LM increased by 24.1%, 86.9% and 120.4% at 3, 7 and 14 days. The SDLM increased by 34.4%, 78.8% and 102.0% at 3, 7 and 14 days. The SILM decreased 42.6%, 64.8%, and 79.3% at day 3, 7 and 14 days respectively. ConclusionThe ALPPS procedure can be performed in rats, achieving the expected results. Comparison studies to 2-staged hepatectomy will be necessary.

Desarrollo de un modelo experimental de ligadura portal asociada a transección parenquimatosa (ALPPS) en ratas

BackgroundLiver failure migth be a cause of death after major hepatectomies. The ALPPS technique appears to be a promising strategy to avoid it, however no experimental studies supporting this procedure have been previously described. The aim was to develop an experimental model of ALPPS in rats. MethodExperimental. A total of 30 Sprague Dawley rats were used. To develop the ALPPS procedure, ligation of the left portal branch of the middle lobe (LM) was performed. This demarcates the left side (SILM) from the right side (SDLM); parenchyma transection was performed following the demarcated line. The animal's weight, volume and weight of both LM were analyzed. Sacrifice at 3, 7 and 14 days after the procedure (10 per group) was performed. ResultsNo bleeding or ascites were observed during the postoperative period. The LM increased by 24.1, 86.9 and 120.4% at 3, 7 and 14 days. The SDLM increased by 34.4, 78.8 and 102.0% at 3, 7 and 14 days. The SILM decreased 42.6, 64.8, and 79.3% at day 3, 7 and 14 days respectively. ConclusionThe ALPPS procedure can be performed in rats, achieving the expected results. Comparison studies to 2 staged hepatectomy will be necessary.

NF-E2-related factor 2 promotes compensatory liver hypertrophy after portal vein branch ligation in mice

Hepatectomy is a standard therapy that allows liver cancer patients to achieve long-term survival. Preceding hepatectomy, portal vein embolization (PVE) is frequently performed to increase the remnant liver size and reduce complications. Although the clinical importance of PVE is widely accepted, molecular mechanisms by which PVE leads to compensatory hypertrophy of nonembolized lobes remain elusive. We hypothesized that NF-E2-related factor 2 (Nrf2), a master regulator of cytoprotection, promotes compensatory liver hypertrophy after PVE. To address this hypothesis, we utilized three mouse lines and the portal vein branch ligation (PVBL) technique, which primarily induces the redistribution of the portal bloodstream in liver in a manner similar to PVE. PVBL was conducted in Kelch-like ECH-associated protein 1 (Keap1) conditional knockout (Keap1-CKO) mice in which Nrf2 is constitutively activated, along with Nrf2-deficient (Nrf2-KO) mice. We found that hypertrophy of nonligated lobes after PVBL was enhanced and limited in Keap1-CKO and Nrf2-KO mice, respectively, compared to wild-type mice. In Keap1-CKO mice, Nrf2 activity was increased, consistent with transient activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway, and reactive hepatocyte proliferation was significantly prolonged after PVBL. Importantly, Nrf2 activation by a chemical inducer was also effective for enhancement of hypertrophy after PVBL. Nrf2 supports compensatory liver hypertrophy after PVBL. This finding is particularly intriguing, because the primary effect of PVBL is limited to the alteration of bloodstream; this effect is much milder than changes resulting from hepatectomy, in which intrahepatic bloodstream and bile production cease. Our results suggest that premedication with an Nrf2 inducer may be a promising strategy to improve the outcome of PVE; this approach expands the indication of hepatectomy to patients with poorer liver function.

Effects of soluble components derived from bone marrow mesenchymal stem cells on the expression of vascular endothelial growth factor and liver regeneration in rats

Objective To investigate the effects of soluble components derived from bone marrow mesenchymal stem cells (BMSCs) on the expression of vascular endothelial growth factor (VEGF) and liver regeneration caused by 70％ portal branch ligation (PBL) in rats.Methods Isolated and cultured BMSCs were lysed by sonication.PBL was performed in male SD rats followed by splenic injection of BMSCs or PBS as control.Animals were analyzed for liver regeneration index,hepatocytes proliferation,hepatic function,histopathological changes,and hepatic genes expression.Expression of VEGF was assessed by Western blot and immunohistochemistry.Results The liver regeneration index increased in the BMSCs group especially 2 and 5 days after PBL compared with the control group (P＜0.05) and reached (51.71±1.62)％ and (76.82±0.81)％ respectively.A 2-fold increase was showed in the PCNA labeling index of hepatocytes in rats treated with BMSCs compared with the control group (P＜0.05).Histopathological findings showed that vacuolar change and sinusoidal congestion were lower in the BMSCs group.Alanine transaminase (ALT) and Aspartate transferase (AST) showed no significant difference between the two groups (P＞0.05).On post operation day 2,hepatic interleukin-6 (IL6),tumor necrosis factor α (TNFα),hepatocyte growth factor (HGF),vascular endothelial growth factor A (VEGFA),and vascular endothelial growth factor 2 (VEGFR2) mRNAs tended to increase in the BMSCs group (P＜0.05) while transforming growth factor β1 (TGFβ1) mRNA decreased (P＜0.05).Western blot showed that the expression level of VEGF in the two groups were equal 2 and 5 days after surgery (P＞0.05).On day 2 post operation,positive VEGF immunoreactivity was present in both pericentral and periportal hepatocytes in the BMSCs group,while only in periportal hepatocytes in the control group.Conclusion These results demonstrate that BMSCs accelerated liver regeneration caused by PBL,which may result from hepatoprotection,enhanced hepatocyte proliferation,and VEGF-mediated angiogenesis early after the operation,potentially creating a new avenue for the study of hepatic regeneration. Key words: Hepatocytes; Mesenchymal stem cell; Transplantation; Liver function tests; Vascular endothelial growth factors

Construction of liver tissue in vivo with preparative partial hepatic irradiation and growth stimulus: investigations of less invasive techniques and progenitor cells

BackgroundThe selective proliferation of transplanted hepatocytes with a growth stimulus, such as partial hepatectomy or hepatocyte growth factor, concomitant with hepatic irradiation (HIR), which can suppress proliferation of host hepatocytes, has been reported. We have conducted experiments that focused on less invasive and clinically applicable techniques and progenitor cells. Materials and methodsFirst, dipeptidyl-peptidase IV-F344 or jaundiced Gunn rats underwent partial HIR (only 30% of whole liver) and portal vein branch ligation (PVBL) of one lobe, followed by intrasplenic hepatocyte transplantation at 1 × 107. Second, after partial HIR and PVBL, two types of progenitor cells were transplanted (i.e., small hepatocytes (SHs) or adipose-derived mesenchymal stem cells. ResultsSixteen weeks after transplantation, the donor cells constituted > 70% of the hepatocytes of the irradiated lobe, showing connexin 32, phosphoenolpyruvate carboxykinase-1, and glycogen storage. Moreover, the serum bilirubin level had decreased significantly in the jaundiced Gunn rats and remained at this level throughout the 24 wk experimental period. The SHs grew more quickly than the hepatocytes. After 8 wk, around 40% of the host hepatocytes had been replaced by transplanted SHs. Although the donor adipose-derived mesenchymal cells were engrafted after 8 wk, their proliferation was not observed. ConclusionsHIR, combined with PVBL, can be given to a selective liver lobe and is a less-invasive but effective method for proliferation of transplanted hepatocytes. Even a smaller number of SHs can construct liver tissue with their prevailing proliferative ability.

Losartan Supports Liver Regrowth via Distinct Boost of Portal Vein Pressure in Rodents with 90 % Portal Branch Ligation

The study used a model of 90 % portal branch ligation (PBL) in rats to study the effect of losartan on portal vein pressure (PVP) and liver regeneration in rats after PBL. A total of 144 male Sprague-Dawley rats were arbitrarily designated into three treatment method groups: a sham operation group (Sham), a PBL treatment group (PBL), and a PBL plus losartan treatment group (PBL + L). Losartan (2 mg/day) was intragastrically gavaged 3 days before the PBL or sham operation to time points of study. Both the PBL and PBL + L groups showed an intense surge in PVP after PBL treatment, peaking at 12 h postsurgery, then lessening progressively afterwards. PVP was substantially greater in these two groups compared with the Sham group at 6-72 h postsurgery (p < 0.01). Compared with the PBL group, the PBL + L group showed a noticeable reduction in PVP 6-48 h postsurgery (p < 0.05); the PBL group showed considerably raised levels of plasma ALT and AST 6-72 h postsurgery (p < 0.01). Compared to the PBL group, the PBL + L group showed drastically reduced plasma ALT and AST levels 12-72 h postsurgery (p < 0.05). Losartan supports liver regeneration in 90 % of rats that underwent PBL. The mechanism may be related to losartan's ability to regulate PVP and increase serum hepatocyte growth factor levels.

Ligadura da veia porta associada à transecção para hepatectomia em dois estágios (ALPPS): uma nova abordagem nas ressecções hepáticas

Postoperative liver failure consequent to insufficiency of remnant liver is a feared complication in patients who underwent extensive liver resections. The associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a new approach for patient which tumor is previously considered unresectable. To present ALPPS as an innovative surgical technique of two-staged hepatectomy for the treatment of patients with marginally resectable or initially nonresectable primary and metastatic liver tumors. The procedure is performed in two steps. The first consists on ligation of the right portal vein branch. Subsequently, total or nearly total parenchyma dissection along the falciform ligament is performed, including the middle hepatic vein. A plastic bag is used to cover the right extended lobe, and the abdomen is drained and closed. The second one is performed after a computer tomography, six to 12 days interval. After laparotomy, the plastic bag is removed. The right artery, right bile duct and the right hepatic vein are divided. The extended right lobe is removed. Drain is placed at the resection surface, and the abdomen is closed. The associating of liver partition and portal vein ligation can enable curative resection of liver metastasis in patients with lesions previously considered unresectable.

Extrahepatic Portal Vein Ligation in Major Hepatectomies Performed under Selective Vascular Exclusion: A Case–Control Study

The aim of our study is to assess the effect of extrahepatic ipsilateral portal vein branch ligation in hepatectomies conducted under selective hepatic vascular exclusion with sharp transection of the liver parenchyma. Twenty-six patients (Group A) underwent major hepatectomy from January 2007 to December 2009, and hemostasis was achieved by ligation of the ipsilateral portal vein branch in addition to suture ligation of the cut surface vessels. A control group (Group B) was composed of 26 matched patients picked from our hospital's database, in which hemostasis was achieved by suture ligation of the cut surface vessels only. Warm ischemia time, intraoperative blood loss, blood transfusions, and liver function were compared. Reduced blood loss (450 vs 680 mL, P = 0.03), less transfusions (8 vs 20% of the patients, P = 0.04), and decreased warm ischemia time (34 vs 42 minutes, P = 0.04) were observed in Group A. Extrahepatic ligation of the ipsilateral portal vein branch is simple, safe, and effective in reducing blood loss and warm ischemia time in major hepatectomies performed under selective vascular exclusion.