Insufficient Hypertrophy Research Articles

Preliminary Results from the International Registry on Liver Venous Deprivation (EuroLVD)

Abstract Background Liver venous deprivation (LVD) is a recently developed method to reach maximal liver hypertrophy before major hepatectomy. LVD combines simultaneous portal and ipsilateral hepatic vein embolization. An international registry was created in 2021. Aims This study aimed to describe the outcomes after LVD of patients included in the registry. Methods Since its creation, 7 international expert HPB centers participated to the registry. Preoperative characteristics, data on liver regeneration after LVD, and postoperative results after hepatectomy were collected. Future liver remnant (FLR) and standardized FLR ratios were defined as FLR/total functional liver volume and FLR/total estimated liver volume. Results A total of 191 patients were included (71 women). Median age was 63 (IQR 53-69) and body-mass index 24.8 kg/m2 (IQR 22.3-28.7). Fifty-three patients were ASA III/IV. Main surgical indication was colorectal metastases (n=116). Median FLR and standardized FLR ratios before LVD were 33% (IQR 26-47) and 32% (IQR 23-39). Median time for the LVD procedure was 122 minutes (IQR 99-164). In one patient right hepatic vein embolization failed. Complications after LVD occurred in 14 patients (7%), including 7 hemorrhages/hematomas. After LVD, median FLR and standardized FLR ratios significantly increased to 46% (IQR 39-59, p<0.001) and 44% (IQR 35-50, p<0.001), corresponding to a median kinetic growth rate of 3.2%/week (IQR 1.6-5.3). Hepatectomy was performed in 142 patients (69 extended hepatectomies), while 49 dropped out (7 for insufficient hypertrophy (4%), 27 for tumor progression (14%), and 15 for other reasons (8%)). Seventy-one patients had postoperative complications (50%), and only 2 developed postoperative liver failure (1%). Median Comprehensive Complication Index was 20.9 (IQR 0-30.8) and 10 patients were reoperated (7%). Conclusion The preliminary data of this international registry showed that LVD had a high technical success rate (190/191) with few post-procedural complications and significant kinetic growth. Major hepatectomy after LVD appeared to be safe.

Abstract P2002: Mst1 Suppresses Pressure Overload-induced Cardiac Hypertrophy But Reduces Cardiac Function Through PERK Phosphorylation

Cardiac hypertrophy in response to hemodynamic overload is initially an adaptive mechanism to maintain normal cardiac function by reducing left ventricular (LV) wall stress. Conversely, insufficient hypertrophy could lead to elevated wall stress, causing increased cell death and cardiac dysfunction. The Hippo pathway plays an important role in determining organ size. Mammalian sterile 20-like kinase 1 (Mst1) is the key serine-threonine kinase in the Hippo pathway, controlling cell death, proliferation, and differentiation. Mice with cardiac-specific overexpression of Mst1 (Tg-Mst1) fail to develop compensatory hypertrophy despite LV dysfunction and dilation at baseline. To elucidate the mechanism through which Mst1 inhibits cardiac hypertrophy, pressure overload (PO) was imposed on WT and Tg-Mst1 mice by transverse aortic constriction (TAC). TAC-induced increases in LV weight/body weight were significantly suppressed in Tg-Mst1 mice (5.8 vs WT 5.1, p<0.05). LV ejection fraction (EF) after TAC was lower in Tg-Mst1 mice than in WT mice (40% vs WT 60%, p<0.01), consistent with the notion that Mst1 promotes PO-induced systolic dysfunction in part by inhibiting compensatory hypertrophy. Mst1 interacted with and induced phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK). We generated knock-in mice expressing phosphorylation-resistant PERK (PERK-KI) and performed TAC on WT and PERK-KI mice. LVEF was preserved in PERK-KI mice compared to in WT mice (67% vs WT 46%, p<0.05) after 8 weeks of TAC. PO-induced increases in lung congestion were attenuated in PERK-KI mice compared to in WT mice (10 vs WT 11.5, p<0.05). Despite the improvement in cardiac function, cardiac hypertrophy was not attenuated in PERK-KI mice. These results suggest that phosphorylation of PERK by Mst1 is detrimental for the heart during PO, in part due to suppression of compensatory hypertrophy.

Induction of Robust Future Liver Remnant Hypertrophy Before Hepatectomy With a Modified Liver Venous Deprivation Technique Using a Trans-venous Access for Hepatic Vein Embolization.

Purpose: Hepatic and/or portal vein embolization are performed before hepatectomy for patients with insufficient future liver remnant and usually achieved with a trans-hepatic approach. The aim of the present study is to describe a modified trans-venous liver venous deprivation technique (mLVD), avoiding the potential risks and limitations of a percutaneous approach to hepatic vein embolization, and to assess the safety, efficacy, and surgical outcome after mLVD. Materials and Methods: Retrospective single-center institutional review board-approved study. From March 2016 to June 2019, consecutive oncologic patients with combined portal and hepatic vein embolization were included. CT volumetric analysis was performed before and after mLVD to assess liver hypertrophy. Complications related to mLVD and surgical outcome were obtained from medical records. Results: Thirty patients (62.7 ± 14.5 years old, 20 men) with liver metastasis (60%) or primary liver cancer (40%) underwent mLVD. Twenty-one patients (70%) had hepatic vein anatomic variants. Technical success of mLVD was 100%. Four patients had complications (three minor and one major). FLR hypertrophy was 64.2% ± 51.3% (mean ± SD). Twenty-four patients (80%) underwent the planned hepatectomy and no surgery was canceled as a consequence of mLVD complications or insufficient hypertrophy. Fifty percent of patients (12/24) had no or mild complications after surgery (Clavien-Dindo 0-II), and 45.8% (11/24) had more serious complications (Clavien-Dindo III-IV). Thirty-day mortality was 4.2% (1/24). Conclusion: mLVD is an effective method to induce FLR hypertrophy. This technique is applicable in a wide range of oncologic situations and in patients with complex right liver vein anatomy.

Two stage hepatectomy (TSH) or Associating liver partition and portal vein ligation for staged hepatectomy (ALLPS) for bilobar multiple colorectal liver metastasis

Of patients with colorectal cancer, 30% to 50% present with liver metastasis at the time of diagnosis or develop metastasis later. Hepatectomy is the primary curative treatment option for patients with colorectal liver metastases (CRLMs). Patients with bilateral, multiple CRLMs and a small estimated tumor free future liver remnant (FLR) present a treatment challenge. These patients may need a two-stage hepatectomy (TSH) in which portal venous ligation (PVL) or portal venous embolization (PVE) is included in the first stage to stimulate hypertrophy of the FLR before final resection. This method generates a 27% to 39% increase in FLR volume in 4 to 8 weeks. The risks in this method are tumor progression during the waiting period and insufficient hypertrophy, making resection impossible in 25% to 38% of the patients preparing to undergo TSH. To increase liver growth rate and volume, which renders more patients resectable in a shorter time, a novel concept of liver resection, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), was described in 2011. However, in the early study 68% of the patients experienced complications and the surgical mortality rate was 12%. A recent, the only multicenter randomized controlled trial (RCT) revealed that compared with the use of TSH, the use of ALPPS for patients with CRLM resulted in a higher resection rate (92%) without a higher 90-day mortality rate (8.3%), a higher rate of severe complication rate (43%) or a lower rate of negative surgical margins in the liver. A previous meta-analysis including 9 retrospective studies showed that TSH for CRLM exhibited lower perioperative morbidity and mortality rates than ALPPS, suggesting the superiority of TSH. On the other hand, in a recent meta-analysis in 2020 including 7 retrospective studies and 1 RCT, compared with TSH, ALPPS for advanced CRLM resulted in superior surgical efficacy with comparable perioperative mortality rate and short-term oncological outcomes, while this was at the cost of increased perioperative minor complications. From a clinical perspective, traditional TSH has been frequently regarded as a preferred treatment modality in earlier studies, and ALPPS was reserved as an alternative, typically after failed PVE or PVL. At present, this paradigm may have changed, as there is growing evidence indicating that the surgical benefits given by ALPPS are at least not inferior to those given by TSH according to recent studies. ALPPS may be feasible for bilobar multiple colorectal liver metastasis. Still, long-term outcomes remain to be elucidated and therefore the role of ALPPS regarding oncological outcome remains uncertain.

Short-term outcome of portal vein embolization vs. simultaneous portal and hepatic vein embolization for major liver resection – preliminary results?

Purpose: In a retrospective analysis we compared the effect and clinical outcome of simultaneous and sequential hepatic vein embolization (HVE) compared to portal vein embolization (PVE). Method: All patients, treated with PVE only or PVE with simultaneous or sequential HVE, prior to the major hepatectomy were included in the analysis. N-butyl-cyanoacrylate was used for PVE via transhepatic /transsplenic access, whereas HVE vascular plugs were applied for HVE via the jugular vein. Future remnant liver volume (FRLV) prior and following interventions was assessed via CT volumetry. Laboratory parameters and clinical courses were obtained from the clinical charts. Results: 16 patients were treated with simultaneous PVE and HVE, whereas the other 16 patients received PVE only and another 4 received sequential PVE and HVE. Left-sided thrombosis was observed in 6 patients after the simultaneous intervention and in 1 patient in the PVE group. Significant hypertrophy was noted in all patients (1.6-fold in the PVE group and 1.5-fold in the simultaneous group). Additional HVE induced a non-significant hypertrophy following PVE. However, only 8 of 16 patients in the simultaneous group, 9 of 16 patients in the PVE only group, and only one patient in the sequential group could undergo resection. The main reason for the drop-off was disease progression (12), impaired liver function (3) and portal venous thrombus (1). Conclusion: PVE and simultaneous PVE/HVE resulted in comparable hypertrophy induction and drop-off rates, however, the simultaneous treatment caused more left-sided portal vein thrombosis, which may jeopardize the surgery. Additional HVE after PVE might be useful for initial insufficient hypertrophy.

ALPPS versus two-stage hepatectomy for colorectal liver metastases\u2014\u2013a comparative retrospective cohort study

BackgroundAssociating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and two stage hepatectomy with inter-stage portal vein embolization (TSH/PVE) are surgical maneuvers applied in patients with advanced malignancies considered unresectable by means of conventional liver surgery. The aim of this report is to compare the oncologic outcome and technical feasibility of ALPPS and TSH/PVE in the scenario of colorectal liver metastases (CRLM).MethodsAll consecutive patients who underwent either ALPPS or TSH/PVE for CRLM between 2011 and 2017 in one hepatobiliary center were analyzed and compared regarding perioperative and long-term oncologic outcome.ResultsA cohort of 58 patients who underwent ALPPS (n = 21) or TSH/PVE (n = 37) was analyzed. The median overall survival (OS) was 28 months and 34 months after ALPPS and TSH/PVE (p = 0.963), respectively. The median recurrence-free survival (RFS) was higher following ALPPS with 19 months than following TSH/PVE with 10 months, but marginally failed to achieve statistical significance (p = 0.05). There were no differences in morbidity and mortality after stages 1 and 2. Patients undergoing ALPPS due to insufficient hypertrophy after TSH/PVE (rescue-ALPPS) displayed similar oncologic outcome as patients treated by conventional ALPPS or TSH/PVE (p = 0.971).ConclusionsALPPS and TSH/PVE show excellent technical feasibility and comparable long-term oncologic outcome in CRLM. Rescue ALPPS appears to be a viable option for patients displaying insufficient hypertrophy after a TSH/PVE approach.

Surgical Removal of Inadvertent Portal Thrombosis by Rescue-ALPPS for Perihilar Cholangiocarcinoma

Introduction:Treatment of perihilar cholangiocarcinoma (PHC) usually requires extended resection after inducing hypertrophy of the future liver remnant (FLR). Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can achieve rapid hypertrophy of the FLR. Though, due to significant morbidity and mortality, portal vein embolization (PVE) is considered gold standard. Despite remaining controversies, ALPPS might suit as reserve in patients who failed to achieve adequate hypertrophy of the FLR or suffered complications following PVE. We illustrate a rescue-ALPPS after inadvertent nontarget thrombosis of the FLR following PVE in a patient with PHC. Presentation of Case:A 67-year-old patient requiring right trisectionectomy for PHC Bismuth type IV suffered inadvertent nontarget portal thrombosis of the FLR following PVE. Subsequently, insufficient FLR hypertrophy prevented the planned surgical resection. ALPPS procedure with concomitant thrombectomy of the left portal vein was used as a rescue strategy for this patient. Discussion:Since ALPPS is associated with significant limitations, especially in patients with PHC, this approach remains controversial. However, surgery still remains the only curative option for patients with PHC and thus, in case of inadequate hypertrophy of the FLR or technical failure following PVE, these patients lack further treatment options. Recent technical refinements and methods of improved patient selection have the potential to emend outcomes of ALPPS in experienced centres. Conclusion:ALPPS should be considered as reasonable rescue strategy not only in case of insufficient hypertrophy of the FLR but also in the event of technical failure or complications following PVE, even in patients with PHC.

Evaluation of portal vein occlusion with or without parenchymal splitting in the management of irresectable liver tumors

Background Portal vein embolization (PVE) has been developed with the principle of inducing hypertrophy of the future liver remnant (FLR) (10–50% after a period of 2–8 weeks). Tumor progression and insufficient hypertrophy of the FLR are the commonest causes that preclude definitive surgery in 10–30% of patients. Recently, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been proposed, with the goal of achieving a faster and magnified hypertrophy (74–87.2% in 9–13 days) for patients with extensive colorectal liver metastases or hilar cholangiocarcinoma. However, introducing ALPPS for hepatocellular carcinoma (HCC) on top of cirrhosis has been questioned and not thoroughly investigated. Patients and methods A prospective observational study was conducted on patients who were admitted to the National Liver Institute from 2016 to 2018 with nonresectable liver tumors owing to insufficient FLR. Hypertrophy of the FLR, perioperative morbidity and mortality, overall survival, and other parameters were compared between patients who underwent ALPPS and patients who underwent PVE. Results Nineteen patients, of which 17 patients had HCC, underwent first-stage ALPPS, whereas 26 patients, of which 20 patients had HCC, underwent PVE. The mean of the percentage of hypertrophy at 2 weeks for ALPPS group was 41.62±39.7. The mean of hypertrophy after PVE at 2 weeks was 37±5.77%. Fourteen (73.6%) patients could be operated upon for definitive resection in the second stage of ALPPS. Fourteen (54%) patients underwent resection after PVE. Conclusion Despite the morbidity and outcomes of ALPPS in patients with cirrhosis, it still can be introduced with strict criteria. Although ALPPS produces more extensive hypertrophy than PVE and less likely progression of the tumor to the FLR, PVE has less overall morbidity and mortality.

A predictive scoring system for insufficient liver hypertrophy after preoperative portal vein embolization

Background: The factors affecting hypertrophy of the future liver remnant (FLR) after portal vein embolization (PVE) remain unclear. The aim of this study was to clarify the clinical factors affecting the hypertrophy rate after PVE and to develop a scoring system predicting insufficient liver hypertrophy. Methods: A total of 152 patients who underwent PVE of the right portal branch between 2006 and 2016 were reviewed retrospectively. The score to predict insufficient (<25%) hypertrophy was established based on logistic regression analyses of the clinical parameters before PVE. Results: After PVE, the FLR volume significantly increased from 364 (151–801) ml, 33.3% (17.9%–53.8%) to 451 (242–866) ml, 41.9% (26.1%–65.1%). The median hypertrophy rate was 23.9% (−5.1%–95.5%). A preoperative predictive scoring system for insufficient liver hypertrophy was constructed using the following 4 factors; an initial FLR volume ≥35% (2 points), alkaline phosphatase ≥450 IU/dL (1 point), cholinesterase <220 mg/dL (1 point), and the indocyanine green disappearance rate <0.16 (1 point). The constructed scoring system showed the proportion of patients with insufficient liver hypertrophy (<25%) to be 1/22 (4.5%) in the low-score group (0 point), 33/75 (44.0%) in the medium-score group (1–2 points), and 46/55 (83.6%) in the high-score group (3–5 points). The hypertrophy rate of FLR was significantly different among the 3 groups (low-score group, 40.1% [2.1–73.2%]; medium-score group, 26.5% [−5.1–81.4%]; high-score group, 20.1% [1.1–49.8%]) (P < 0.001). Conclusion: The constructed scoring system was able to stratify patients before PVE according to the possibility of developing insufficient liver hypertrophy.

A predictive scoring system for insufficient liver hypertrophy after preoperative portal vein embolization

BackgroundThe factors which affect hypertrophy of the future liver remnant after portal vein embolization remain unclear. The aim of this study was to clarify the clinical factors affecting the hypertrophy rate after portal vein embolization and to develop a scoring system predicting insufficient liver hypertrophy. MethodsThe cases of a total of 152 patients who underwent portal vein embolization of the right portal branch between 2006 and 2016 were reviewed retrospectively. The score to predict insufficient (<25%) hypertrophy was established based on logistic regression analyses of the clinical parameters before portal vein embolization. ResultsAfter portal vein embolization, the future liver remnant volume, expressed as the median (range), significantly increased from 364 (151–801) mL, 33% (18%–54%), to 451 (242–866) mL, 42% (26%–65%). The median hypertrophy rate was 24% (−5% to 96%). A preoperative predictive scoring system for insufficient liver hypertrophy was constructed using the following 3 factors: an initial future liver remnant volume ≥35% (2 points), alkaline phosphatase ≥450 IU/dL (1 point), and cholinesterase <220 mg/dL (1 point). The constructed scoring system indicated the proportion of patients with insufficient liver hypertrophy (<25%) to be 6 out of 42 (14%) in the low-score group (0 points), 44 out of 77 (57%) in the medium-score group (1–2 points), and 30 out of 33 (91%) in the high-score group (3–4 points). The hypertrophy rate of future liver remnant was different among the 3 groups (low-score group, 38.9% [−2.4% to 81.4%]; medium-score group, 22.7% [−5.1% to 95.5%]; high-score group, 18.2% [2.4%–30.7%]) (P < .001). ConclusionThe constructed scoring system was able to stratify patients before portal vein embolization according to the possibility of developing insufficient liver hypertrophy.

ALPPS Procedure in Insufficient Hypertrophy After Portal Vein Embolization (PVE).

The main limiting factor for major liver resections is the volume and function of the future remnant liver (FLR). Portal vein embolization (PVE) is now standard in most centers for preoperative hypertrophy of FLR. However, it has a failure rate of about 20-30%. In these cases, the "Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy" (ALPPS) may represent a suitable and possibly the only alternative. We performed a retrospective analysis of nine patients who had ALPPS following an insufficient hypertrophy after PVE. Computed tomography volumetry were performed before and after PVE as well as the first step of ALPPS. Furthermore, complications, 30-day mortality and outcome were analyzed. The FLR volume rose significantly by 77.7±40.7% (FLR/TLV: 34.9±9.7%) as early as 9days after the first stage despite insufficient hypertrophy after preoperative portal vein embolization. Major complications (Grade>IIIb) occurred in 33% of the patients, and 30-day mortality was 11.1%. The OS at 1 and 2years was 78 and 44%. Four patients are presently still alive at a median of 33.4 (range 15-48)months (survival rate 44.4%). The ALPPS procedure could be a suitable alternative for patients following insufficient PVE or indeed the last chance of a potentially curative treatment in this situation. Nevertheless, the high morbidity and mortality rates and the lack of data on the long-term oncological outcome must also be taken into account.

Preoperative Portal Vein Embolization in the Combined Treatment of Malignant Liver Tumor

Aim. To improve the efficiency of preoperative portal vein mbolization as a method of prevention of postoperative liver failure after extensive resections. Material and Methods. The study included 30 patients with isolated liver tumors in whom advanced liver resection was planned. 33 embolizations were performed. In 23 observations mechanical embolization and scleroobliteration of the right branch of portal vein were made, oily chemoembolization and mechanical embolization of the right branch of the portal vein – in 10 cases. In 8 cases preoperative portal vein embolization was performed after oily chemoembolization of hepatic artery. 3 patients underwent repeated portal vein embolization due to insufficient hypertrophy of the remaining liver parenchyma. Results. Volume of remnant liver parenchyma increased by 41% after preoperative portal vein embolization on the average. In 5 cases insufficient volume of remnant liver was marked. The reasons of insufficient liver volume were partial recanalization of the embolized branches of the portal vein, the development of multiple intrahepatic portal collaterals (hemostatic spongeas as a embolic material in 3 cases), liver cirrhosis and 2 lines of previous chemotherapy in history (2 cases). In 3 patients repeated portal vein embolization using PVA particles and scleroobliteration with etoxisclerol foam was performed to achieve necessary hypertrophy. Extensive liver resection was performed in 24 patients. Postoperative mortality was noted in 2 cases. There was similar frequency of postoperative complications in patients with and without preoperative portal vein embolization. Conclusion. Preoperative portal vein embolization is a minimally invasive technique for increase of remnant liver volume prior to advanced liver resection without augmentation of postoperative complications rate. The results and technique may be improved (segment IV branch embolization, the use of foam scleroobliteration, mechanical occlusion combined with chemoembolization, combination of portal vein embolization and hepatic artery chemoembolization). Repeated embolization procedures can provide necessary liver hypertrophy in some cases

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy: A Better Approach to Treat Patients With Extensive Liver Disease.

Liver resection is the treatment of choice and a hope for cure for patients with malignant liver tumors. Resection is many times limited by the amount of future liver remnant, with liver failure being the most severe complication after major resections. To minimize this risk and expand resectability, portal vein occlusion of the tumorbearing lobe is used to redistribute portal flow and induce hypertrophy of contralateral healthy parenchyma. Right portal vein embolization (PVE) is best used before surgery when the future liver remnant is tumor free, while portal vein ligation (PVL) is usually applied as part of 2-stage procedures for patients with bilobar disease who initially require tumor removal in the liver remnant. Around 20% to 40% hypertrophy can be achieved in 8 to 12 weeks with these strategies. However, up to 40% of patients never arrive to tumor resection either because of disease progression or insufficient hypertrophy during these long interval periods. The associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) approach has emerged as an innovative 2-stage hepatectomy developed in Germany and characterized by a short interval between both surgical procedures. 1 Briefly, during the first stage, the liver parenchyma is divided in 2 hemilivers and PVL of the diseasedhemiliverisperformed.Oncesufficienthypertrophy

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): Impact of the inter-stages course on morbi-mortality and implications for management

BackgroundAssociating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was recently developed to induce rapid hypertrophy and reduce post-hepatectomy liver failure in patients with insufficient remnant liver volume (RLV). However, mortality rates >12% have been reported. This study aimed to analyze the perioperative course of ALPPS and to identify factors associated with morbi-mortality. MethodsBetween April 2011 and September 2013, 62 patients operated in 9 Franco-Belgian hepatobiliary centres underwent ALPPS for colorectal metastases (N = 50) or primary tumors, following chemotherapy (N = 50) and/or portal vein embolization (PVE; N = 9). ResultsMost patients had right (N = 31) or right extended hepatectomy (N = 25) (median RLV/body weight ratio of 0.54% [0.21–0.77%]). RLV increased by 48.6% [−15.3 to 192%] 7.8 ± 4.5 days after stage1, but the hypertrophy decelerated beyond 7 days. Stage2 was cancelled in 3 patients (4.8%) for insufficient hypertrophy, portal vein thrombosis or death and delayed to ≥9 days in 32 (54.2%). Overall, 25 patients (40.3%) had major complication(s) and 8 (12.9%) died. Fourteen patients (22.6%) had post-stage1 complication of whom 5 (35.7%) died after stage2. Factors associated with major morbi-mortality were obesity, post-stage1 biliary fistula or ascites, and infected and/or bilious peritoneal fluid at stage2. The latter was the only predictor of Clavien ≥3 by multivariate analysis (OR: 4.9; 95% CI: 1.227–19.97; p = 0.025). PVE did not impact the morbi-mortality rates but prevented major cytolysis that was associated with poor outcome. ConclusionsThe inter-stages course was crucial in determining ALPPS outcome. The factors of high morbi-mortality rates associated with ALPPS are linked to the technique complexity.

Preoperative Percutaneous Transhepatic Portal Vein Embolization With Ethanol Injection

The purpose of this article is to evaluate the feasibility and efficacy of preoperative percutaneous transhepatic portal vein embolization with ethanol injection. We retrospectively evaluated 143 patients who underwent percutaneous transhepatic portal vein embolization. Hypertrophy of the future liver remnant was assessed by comparing the volumetric data obtained from CT image data before and after percutaneous transhepatic portal vein embolization. The evaluation of effectiveness was based on changes in the absolute volume of the future liver remnant and the ratio of the future liver remnant to the total estimated liver volume. Ten of 143 patients (7.0%) underwent additional embolization because of recanalization and insufficient hypertrophy of the future liver remnant. The mean increase in the ratio of the future liver remnant was 33.6% (p < 0.0001), and the mean ratio of future liver remnant to total estimated liver volume increased from 34.9% to 45.7% (p < 0.0001). Although most of the patients complained of pain after ethanol injection, they were gradually relieved of pain in a few minutes by conservative treatment. Fever (38-39°C) was reported after 47 of 151 (31.1%) percutaneous transhepatic portal vein embolization sessions and was resolved within a few days. Transient elevation of the liver transaminases was observed after the procedures and resolved within about a week. Major complications occurred in nine of 151 (6%) percutaneous transhepatic portal vein embolization sessions, but no patients developed hepatic insufficiency or severe complications precluding successful resection. One hundred twenty patients underwent hepatic resection, and two patients developed hepatic failure after surgery. Preoperative percutaneous transhepatic portal vein embolization with ethanol is a feasible and effective procedure to obtain hypertrophy of the future liver remnant for preventing hepatic failure after hepatectomy.

Two-Stage Portal Vein Ligation Facilitates Liver Regeneration in Rats

Background/Aims: Recent reports have demonstrated that some patients are unable to undergo scheduled liver resection after preoperative portal vein embolization due to insufficient hypertrophy of the future remnant liver. The present study examined whether two-stage portal vein ligation (PVL) increases hypertrophy of the future remnant liver compared to conventional PVL in rats. Methods: Rats were divided into 3 groups: group A, ligation of left primary branch; group B, ligation of right and left primary branches; group C, ligation of the left primary branch, followed by 2-stage PVL 7 days postoperatively. To evaluate liver regeneration, the proliferating cell nuclear antigen labeling index (LI), mitotic index (MI) in the caudate lobe and weight ratio of caudate lobe to body weight were measured. Results: The weight ratio of caudate lobe to body weight was significantly higher in group C than in groups A or B 14 days postoperatively. In groups A and B, LI and MI in the caudate lobe peaked 2 days postoperatively, then decreased to preoperative levels by 7–8 days postoperatively, but remained significantly elevated until 10–14 days postoperatively in group C. Conclusion: Two-stage PVL increases hypertrophy of the future remnant liver compared to conventional PVL in rats.

Major Hepatectomy for Colorectal Metastases: Is Preoperative Portal Occlusion an Oncological Risk Factor?

This study investigates oncological risks and benefits of portal occlusion (PO) in major resection for colorectal liver metastases (CLM). Between 1995 and 2004, 107 patients were scheduled for major hepatectomy for CLM. Of these, 53 patients were selected for PO due to insufficient future liver remnant (FLR), and 54 patients had straightforward hepatectomy. Associations of clinicopathologic factors with resectability, and outcome after PO were analyzed. 21 of 53 patients (39.6%) after PO were unresectable. These patients had a significant smaller volume of the FLR than the 32 resected patients after PO (P = .029). In total, 17 patients (80.9%) did not undergo resection due to cancer progression. Among these, 11 patients (52.4%) exhibited either a progression of known metastases located in the occluded lobes, or new metastases in the nonoccluded portion of the liver. In another 4 individuals (19%), the decision against resection resulted from insufficient hypertrophy of the FLR. Following major hepatectomy, the 5-year survival was 43.66%. Although there was a significantly higher rate of extended hepatectomies versus formal hepatectomies (P < .001), more bilobar distributed metastases versus unilobar manifestations (P = .015), and a smaller resection margin (P = .01) in patients who had PO, no adverse effect on mortality, morbidity, recurrence and survival was observed. Unresectability after PO is a major problem that warrants multidisciplinary improvements, and randomization to resection with or without PO remains ethically problematic. However, following adequate patient selection, PO may provide a significant survival benefit for patients with prior unresectable CLM.

Preoperative contralateral portal vein embolization before major hepatic resection is a safe and efficient procedure: A large single institution experience

The aim of this study was to report the results of preoperative contralateral portal vein embolization (PVE) performed in a single institution. Between January 1997 and March 2006, 146 patients requiring a right or extended right hepatectomy for primary or secondary liver tumors underwent contralateral PVE when the future remnant liver volume (FRL) was less than 30% of total liver. Liver volumes and hepatic function were evaluated before and after PVE. Contralateral PVE was performed successfully in 145 patients. In one patient, the catheterization of the left portal branch failed. Complications occurred in 14 patients (10%) including a transitory fever (n = 9), a parenchymal hematoma (n = 1), a mild hemoperitoneum (n = 1), a mesenterico-portal venous thrombosis (n = 1), a pulmonary embolism (n = 1) and a systemic sepsis (n = 1). The prothrombin ratio and the platelet count were significantly lower 3 days after PVE. Insufficient hypertrophy of the FRL was observed in 8 patients, malignant disease progression in 15, and both insufficient hypertrophy and disease progression in 4. The hypertrophy rate of the FRL 4 to 8 weeks after PVE was 47.7 +/- 31.9%. Pathological type of the liver tumor, cirrhosis, diabetes mellitus, and chemotherapy did not affect the volume of the left liver hypertrophy. However, the time required to achieve an adequate liver hypertrophy was significantly shorter in patients with normal liver. One-hundred and fourteen patients (78.6%) subsequently underwent hepatic resection. The results suggest that contralateral PVE is a safe and efficient procedure inducing adequate hypertrophy of the FRL before major liver resection.

Portal vein embolisation prior to hepatic resection for colorectal liver metastases and the effects of periprocedure chemotherapy

Portal vein embolisation (PVE) is an effective method of increasing future liver remnant (FLR) but may stimulate tumour growth. The effect of periprocedure chemotherapy has not been established. 15 consecutive patients underwent PVE prior to hepatic resection for colorectal liver metastases with a FLR <30% of tumour-free liver (TFL). Liver and tumour volumes pre-PVE and 6 weeks post-PVE were calculated by CT or MRI volumetry and correlated with the periprocedure chemotherapy regimen. PVE increased the FLR from 18+/-5% of TFL to 27+/-8% post-PVE (p<0.01). Post-PVE chemotherapy did not prevent hypertrophy of the FLR but the volume increase with chemotherapy (median 89 ml, range 7-149 ml) was significantly reduced (median 135 ml, range 110-254 ml without chemotherapy) (p = 0.016). Tumour volume (TV) decreased in those receiving post-PVE chemotherapy (median TV decrease 8 ml, range -77 ml to +450 ml) and increased without chemotherapy (median TV increase 39 ml, range -58 ml to +239 ml). Of the 15 patients, eight underwent resection; four were not resected due to disease progression and three due to insufficient hypertrophy of the FLR. PVE increased the FLR by an average of 9% allowing resection in 50% of patients. Periprocedure chemotherapy did not prevent but did reduce hypertrophy. A trend towards tumour regression was observed.

Preoperative Percutaneous Portal Vein Embolization: Evaluation of Adverse Events in 188 Patients

To retrospectively assess the frequency of adverse events related to percutaneous preoperative portal vein embolization (PPVE). Institutional review board did not require its approval or patient informed consent for this study. The adverse events that occurred during PPVE or until planned hepatic surgery was performed or cancelled were retrospectively obtained from clinical, imaging, and laboratory data files in 188 patients (109 male and 79 female patients; mean age, 60 years; range, 16-78 years). Liver resection was planned for metastases (n = 137), hepatocarcinoma (n = 31), cholangiocarcinoma (n = 15), fibrolamellar hepatoma (n = 1), and benign disease (n = 4). PPVE was performed with a single-lumen 5-F catheter and a contralateral approach with n-butyl cyanoacrylate mixed with iodized oil as the main embolic agent. The rate of complications in patients with cirrhosis was compared with that in patients without cirrhosis by using the chi(2) test. Adverse events occurred in 24 (12.8%) of 188 patients, including 12 complications and 12 incidental imaging findings. Complications included thrombosis of the portal vein feeding the future remnant liver (n = 1); migration of emboli in the portal vein feeding the future remnant liver, which necessitated angioplasty (n = 2); hemoperitoneum (n = 1); rupture of a metastasis in the gallbladder (n = 1); transitory hemobilia (n = 1); and transient liver failure (n = 6). Incidental findings were migration of small emboli in nontargeted portal branches (n = 10) and subcapsular hematoma (n = 2). Among the 187 patients in whom PPVE was technically successful, there was a significant difference (P < .001) between the occurrence of liver failure after PPVE in patients with cirrhosis (five of 30) and those without (one of 157). Sixteen liver resections were cancelled due to cancer progression (n = 12), insufficient hypertrophy of the nonembolized liver (n = 3), and complete portal thrombosis (n = 1). PPVE is a safe adjuvant technique for hypertrophy of the initially insufficient liver reserve. Post-PPVE transient liver failure is more common in patients with cirrhosis than in those without cirrhosis.