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.

Effects of Portal Preconditioning In Low-Volume Liver Remnants: Study In Rats

The increase of liver surgical indications, the expansion of the margins in hepatic resections and the lack of organ donors led to the use of more split livers from cadaver and living donors and smaller liver remnants in post-operatory patients. The use of increasingly smaller grafts associated with hepatic resections broadened the spectrum for observation of small-for size syndrome, caused by significant inflammation and early hepatic fibrosis. The small-for-size syndrome is manifested clinically by prolonged cholestasis, refractory ascites and progressive hepatic dysfunction (encephalopathy and coagulopathy). In the search for mechanisms to reduce liver damage, preconditioning is presented as a possibility of protecting the low weight remnant in experimental works. Objective: Study the hepatic tissue measuring the impact of portal preconditioning in small hepatic remnant in Wistar rats Methods: Rats weighing approximately 250g were divided in 4 groups with 7 members each. Group 1, Control group requiring only collection of the material, blood laboratory analysis and liver biopsy for pathology and immunohistochemistry; Group 2, Sham, were operated with simple laparotomy, 48 hours later they were subjected to another surgery with sample collection to do blood laboratory analysis and liver biopsy for pathology and immunohistochemistry. Group 3, hepatectomy with preconditioning. In this group was made the preconditioning procedure before the resection of 70% of the liver, 48 hours later they underwent another surgery for sample collection to do blood laboratory analysis and liver biopsy for pathology and immunohistochemistry. Group 4, hepatectomy without preconditioning. In this group the members were operated with resection of 70% of the liver, 48 hours later were reoperated with sample collection to do blood laboratory analysis and liver biopsy for pathology and immunohistochemistry. We studied and compared the impacts in morphology, laboratory, histology, immunohistochemistry.Results: There was no intraoperative mortality in the model used, there was no statistically significant difference in histological and laboratory parameters between the groups with and without preconditioning, there was an increase in the expression of PCNA with statistical significance in the hepatic remnant of the group submitted to preconditioning. Conclusion: Liver preconditioning can provide an increase in cell proliferation in small volume liver remnant.

P-L11 Comparison of clinical efficacy between LAPS and ALPPS in the Treatment of Hepatitis B Virus-related Hepatocellular Carcinoma

Background The aim of the study is to compare the safety and efficacy of modified ALPPS (laparoscopic microwave ablation and portal vein ligation for staged hepatectomy, LAPS) and classical associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods Clinical data of patients with HBV-related HCC who underwent LAPS or ALPPS surgery in our institute from April 2013 to October 2020 were retrospectively analyzed. Results 31 patients with HBV-related HCC were retrospectively collected in this study (LAPS = 8, ALPPS = 23). 7 patients with LAPS and 19 patients with ALPPS proceeded to resection (resection rate: 87.5% vs. 82.6%, P &gt; 0.05). The hypertrophy rate of future liver remnant (FLR) caused by ALPPS was higher than that of LAPS (24.3 vs. 11.7 mL/d, P = 0.024). Compared with the ALPPS, LAPS was associated with less blood loss (300ml vs. 40ml, P &lt; 0.001) during stage 1, lower comprehensive complication index (CCI) after stage 1 (8.7 vs. 0, P = 0.023) and lower total CCI (20.9 vs 0, P = 0.018) for two stages. Two years’ recurrence-free survival rate and over survival rate for ALPPS and LAPS were 17.3%, 34.3% (P = 0.105), and 28.9%, 100.0% (P = 0.011) respectively. Conclusions Compared with ALPPS, LAPS can reduce the occurrence of complications in patients with HBV-related HCC and improve patients’ prognoses.

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.