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.

Solitary colorectal liver metastasis: overview of treatment strategies and role of prognostic factors

The following is an overview of the treatment strategies and the prognostic factors to consider in the therapeutic choice of patients characterized by solitary colorectal liver metastasis. Liver resection is the only potential curative option; nevertheless, only 25% of the patients are considered to be eligible for surgery. To expand the potentially resectable pool of patients, surgeons developed multidisciplinary techniques like portal vein embolization, two-stage hepatectomy or associating liver partition and portal vein ligation for staged hepatectomy. Moreover, mini-invasive surgery is gaining support, since it offers lower post-operative complication rates and shorter hospital stay with no differences in long-term outcomes. In case of unresectable disease, various techniques of local ablation have been developed. Radiofrequency ablation is the most commonly used form of thermal ablation: it is widely used for unresectable patients and is trying to find its role in patients with small resectable metastasis. The identification of prognostic factors is crucial in the choice of the treatment strategy. Previous works that focused on patients with solitary colorectal liver metastasis obtained trustable negative predictive factors such as presence of lymph-node metastasis in the primary tumour, synchronous metastasis, R status, right-sided primary colon tumor, and additional presence of extrahepatic tumour lesion. Even the time factor could turn into a predictor of tumour biology as well as further clinical course, and could be helpful to discern patients with worse prognosis.

The Role of Farnesoid X Receptor in Accelerated Liver Regeneration in Rats Subjected to ALPPS

Background: the role of bile acid (BA)-induced farnesoid X receptor (Fxr) signaling in liver regeneration following associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was investigated in a rat model. Methods: Male Wistar rats underwent portal vein ligation (PVL) (n = 30) or ALPPS (n = 30). Animals were sacrificed pre-operatively and at 24, 48, 72, or 168 h after intervention. Regeneration rate, Ki67 index, hemodynamic changes in the hepatic circulation, and BA levels were assessed. Transcriptome analysis of molecular regulators involved in the Fxr signaling pathway, BA transport, and BA production was performed. Results: ALLPS induced more extensive liver regeneration (p < 0.001) and elevation of systemic and portal BA levels (p < 0.05) than PVL. The mRNA levels of proteins participating in hepatic Fxr signaling were comparable between the intervention groups. More profound activation of the intestinal Fxr pathway was observed 24 h after ALPPS compared to PVL. Conclusion: Our study elaborates on a possible linkage between BA-induced Fxr signaling and accelerated liver regeneration induced by ALPPS in rats. ALPPS could trigger liver regeneration via intestinal Fxr signaling cascades instead of hepatic Fxr signaling, thereby deviating from the mechanism of BA-mediated regeneration following one-stage hepatectomy.

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.

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.