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

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.

Portal Vein Embolization Using N-Butyl Cyanoacrylate-Glue: What Impact Does a Central Vascular Plug Have?

Purpose To examine if the addition of a central vascular plug (CVP) to portal vein embolization (PVE) with N-butyl cyanoacrylate-glue (NBCA) increases future liver remnant (FLR) growth. Material and Methods This is a single-center retrospective study of 115 consecutive patients with colorectal liver metastases undergoing PVE in 2013–2019. All patients were embolized with NBCA as the main embolic agent. In 2017–2019 NBCA was combined with a CVP in the central part of the right portal vein. Growth of the FLR and standardized FLR (sFLR) including degree of hypertrophy (DH) and kinetic growth rate (KGR) were analyzed, as well as procedure data such as use of cone-beam CT (CBCT), dose area product (DAP), fluoroscopy time and contrast dose. Results A total of 40 patients (35%) underwent PVE with a combination of CVP and NBCA. The DH was higher in these patients after 4 weeks, mean 13.6% (SD 7.8) vs. 10.5% (SD 6.4; p = 0.022), verified in multivariate analysis (coefficient 4.1, p = 0.015). A CVP did not significantly increase the resection rate (90% vs 82%, p = 0.4). Cone beam CT was used in 65 patients (57%). Use of CBCT did not affect FLR growth, and fluoroscopy time and contrast doses were not different in patients having a CBCT or not. Slightly lower DAP (median 3375 vs. 4499 cGy*cm2; p = 0.09) was seen in procedures where CBCT was used. Conclusion A CVP in addition to NBCA embolization was associated with increased growth of the FLR compared to NBCA alone.

Extensive liver resection in a child with an extremely low future liver remnant volume

The incidence of posthepatectomy liver failure in adult patients and a large number of complications of two-stage liver resections require a search for criteria that allow highly accurate assessment of the risk of liver failure. For this purpose, the study of the future liver remnant volume and function have been widely introduced among adult patients, and the future liver remnant function measurement reflects the greater sensitivity. The absence of references to posthepatectomy liver failure, as well as the experience of determining the functional reserve of the future liver remnant in children, let us to suggest the possibility of a wider using one-stage liver resections when the future liver remnant volume is below the generally accepted threshold (25% of the healthy liver parenchyma volume) in the case of the functional reserve sufficient value. This clinical case describes the successful extended right hemihepatectomy and segmentectomy 1 in a 3-year patient with a future liver remnant volume of 16.5% without clinical signs of postresection hepatic failure, which confirms the thesis of the need to assess the functional liver reserve in pediatric oncology to reduce the frequency of two-stage resections and liver transplants. The patient’s parents gave consent to the use of their child’s data, including photographs, for research purposes and in publications.

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.

The Correlation between the CT Liver Volume and the Actual Weight of the Resected Cirrhotic Liver in Transplantation Patients

Objective: Volumetric assessment with computed tomography (CT), known as CT volumetry, is the preferred method for estimating future liver remnant. However, the data regarding the usage of CT volumetry to estimate future liver remnant of the diseased liver is still lacking. This study was designed to evaluate the correlation between the liver volume, calculated by CT, and the actual weight of the resected liver in patients who underwent orthotopic liver transplantation.Material and Methods: A total of 32 patients having underwent liver transplantation; from March 2009 to June 2015, were included. A radiologist retrospectively reviewed the pre-operative CT and performed the volume measurement. Statistical analysis was performed to determine the relationship between the estimated liver volume and the actual liver weight.Results: The estimated liver volume was significantly different among the cirrhosis of different etiology (p-value=0.001 for the total liver volume and p-value=0.003 for the functional liver volume). Compared with the total liver volume, the functional liver volume had a stronger correlation with the actual weight of the resected liver (r=0.955 vs. r=0.786). The following formula can be used to accurately estimate the expected weight of the resected liver (expected liver weight: ELW), based on the estimated functional liver volume (FLV) derived by CT volumetry: ELW=489.531+(0.618*FLV). The R-squared for this regression model was 0.914.Conclusion: CT volumetry is reliable and accurate in predicting the actual amount of the resected liver parenchyma in cirrhotic patients.

Case Report: Hepatic Artery Infusion Chemotherapy After Stage I ALPPS in a Patient With Huge HCC

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can induce rapid hypertrophy of the liver remnant. However, with a background of liver cirrhosis or other chronic liver diseases, patients with a huge hepatocellular carcinoma (HCC) may sometimes face insufficiency of hepatocellular regeneration after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Herein, we report a 56-year-old male with a vast HCC (13.3 × 8.5 × 13 cm) whose ratio of the future liver remnant (FLR)/standard liver volume (SLV) was 28.7% when the disease was first diagnosed. Inadequate hypertrophy of FLR was shown in postoperative volumetric assessment a month after stage I ALPPS. After multidisciplinary team discussion (MDT), the patient was decided to follow three courses of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4). The last HAIC was performed together with transhepatic arterial embolization (TAE). Finally, ratio of the FLR/SLV increased from 28.7% to 40% during three-month intervals, meeting the requirements of the surgery. Stage II ALPPS, right trisectionectomy, was then successfully performed. There was no recurrence at half years of follow-up. In our case, HAIC seems to be more potent than transcatheter arterial chemoembolization (TACE) in maintaining the hyperplasia of the liver remnant, reducing tumor load, and preventing tumor progression in patients with a large HCC during ALPPS procedure. HAIC, following the first step of ALPPS, a pioneering treatment modality aiming for inadequate hypertrophy of FLR induced by ALPPS, could be an alternative procedure for patients with a vast HCC in clinical practice.

Rescue partial ALPPS for left hemihepatectomy with reconstruction of the middle hepatic vein

Major hepatectomy in patients with insufficient future liver remnant (FLR) volume and impaired liver functional reserve has considerable risks for posthepatectomy liver failure (PHLF). The patient was a male in his 70 with an intrahepatic cholangiocarcinoma (ICC) in left hemiliver, involving the middle hepatic vein (MHV). Although FLR volume after left hemihepatectomy was estimated to be 64.4% of the total liver volume, an indocyanine green retention rate at 15 min (ICG-R15) value was 24.2%, thus the patient underwent left portal vein embolization (PVE). The FLR volume increased to 71.3%, however, the non-congestive FLR volume was re-estimated as 45.8% after resection of the MHV, the ICG-R15 value was 29.0%, and ICG-Krem was calculated as 0.037. We performed partial rescue ALPPS (Associating Liver Partition and Portal vein occlusion for Staged hepatectomy) for left hemihepatectomy with the MHV reconstruction. On the first stage, partial liver partition was done along Rex-Cantlie’s line, preserving the MHV and sacrificing the remaining branches to segment 8. The FLR volume increased to 77.4% on day 14. The ICG-R15 value was 29.6%, but ICG-Krem after MHV reconstruction was estimated to be 0.059. The second stage operation on day 21 was left hemihepatectomy with the MHV reconstruction using the left superficial femoral vein graft. The usage of rescue partial ALPPS may contribute to preventing PHLF by introducing occlusion of the portal and/or venous branches in the left hemiliver before curative hepatectomy.

Repeatability and reproducibility of deep-learning-based liver volume and Couinaud segment volume measurement tool

Purpose Volumetric and health assessment of the liver is crucial to avoid poor post-operative outcomes following liver resection surgery. No current methods allow for concurrent and accurate measurement of both Couinaud segmental volumes for future liver remnant estimation and liver health using non-invasive imaging. In this study, we demonstrate the accuracy and precision of segmental volume measurements using new medical software, Hepatica™. Methods MRI scans from 48 volunteers from three previous studies were used in this analysis. Measurements obtained from Hepatica™ were compared with OsiriX. Time required per case with each software was also compared. The performance of technicians and experienced radiologists as well as the repeatability and reproducibility were compared using Bland–Altman plots and limits of agreement. Results High levels of agreement and lower inter-operator variability for liver volume measurements were shown between Hepatica™ and existing methods for liver volumetry (mean Dice score 0.947 ± 0.010). A high consistency between technicians and experienced radiologists using the device for volumetry was shown (± 3.5% of total liver volume) as well as low inter-observer and intra-observer variability. Tight limits of agreement were shown between repeated Couinaud segment volume (+ 3.4% of whole liver), segmental liver fibroinflammation and segmental liver fat measurements in the same participant on the same scanner and between different scanners. An underestimation of whole-liver volume was observed between three non-reference scanners. Conclusion Hepatica™ produces accurate and precise whole-liver and Couinaud segment volume and liver tissue characteristic measurements. Measurements are consistent between trained technicians and experienced radiologists. Graphic abstract