Right hepatectomy with preservation of the entire caudate lobe in patients with metastatic liver tumors: a case of a new hepatectomy technique and treatment strategy for patients with marginal liver function

Background Performing major hepatectomy for patients with marginal hepatic function is challenging. In some cases, the procedure is contraindicated owing to the threat of postoperative liver failure. In this case report, we present the first case of marginal liver function (indocyanine green clearance retention rate at 15 min [ICGR15]: 28%) successfully treated with right hepatectomy, resulting in total caudate lobe preservation. Case presentation A 71-year-old man was diagnosed with sigmoid colon cancer with three liver metastases (S5, S7, and S8). All of metastatic lesions shrunk after chemotherapy, but his ICGR15 and indocyanine green clearance rate (ICGK) were 21% and 0.12, respectively. Moreover, the remnant liver volume was only 39%. Therefore, portal venous embolism (PVE) of the right portal vein was suggested. Portography showed divergence of the considerably preserved right caudate lobe branch (PV1R) from the root of the right portal vein. The liver function was reevaluated 18 days after PVE was suggested. During this time, the ICGR15 (21–28%) and ICGK rate (0.12–0.10) deteriorated. The right caudate lobe was significantly enlarged; thus, a total caudate lobe-preserving hepatectomy (TCPRx) was performed. Patients eligible for TCPRx included those with (1) hepatocellular carcinoma or metastatic liver cancer, (2) no tumor in the caudate lobe, (3) marginal liver function (ICG Krem greater than 0.05 if TCPRx was adapted; otherwise, less than 0.05) and Child–Pugh classification category A, and (4) preserved PV1R and right caudate bile duct branch. The procedure was performed through (A) precise estimation of the remnant liver volume preoperatively, (B) repeated intraoperative cholangiography to confirm the biliary branch of the right caudate lobe (B1R) conservation, and (C) stapler division of posterior and anterior Glisson’s pedicles laterally to avoid injuries to the PV1R and B1R. Conclusions Right hepatectomy with total caudate lobe preservation, following PVE, was a safe and viable surgical technique for patients with marginal liver function.

The Mechanisms and Physiological Consequences of Diurnal Hepatic Cell Size Fluctuations: A Brief Review.

Liver size in mammals fluctuates throughout the day and correlates with changes in hepatocyte size. However, the role of these daily changes in liver and hepatocyte size and the underlying molecular mechanisms remain largely unknown. In this review, we highlight the view that hepatocyte size, and thus, overall organ size, is subject to regulation by the circadian clock and feeding/fasting cycles. To that end, we provide an overview of the current literature dealing with this phenomenon and elaborate the role of feeding and nutrients in this process. We will discuss the role of hepatic protein content and synthesis, which are both subject to diurnal regulation, in daily hepatocyte and liver size fluctuations. Although there is evidence that changes in hepatocyte and liver size are associated with daily variations in macromolecule content, there is also evidence that these changes in size may be actively regulated by modifications of the cells' osmotic environment. Future research will need to examine the intriguing possibility that hepatocyte and liver size fluctuations may be required for normal liver function and to reveal the underlying molecular mechanisms behind this process.

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.

Protective Effects of Honey-Processed Astragalus on Liver Injury and Gut Microbiota in Mice Induced by Chronic Alcohol Intake

Honey-processed Astragalus (HPA) is a mixture of Astragalus and honey, which is a processed product of Chinese medicine. It has the active ingredients of Astragalus and the unique effects of honey. However, the mechanism of HPA for improving alcoholic liver disease (ALD) is not clear. The purpose of this study is to explore the ameliorating effect and mechanism of HPA (4 and 8 g/kg bw) on alcoholic liver injury. Two doses of HPA were orally administered to alcohol-treated mice for four weeks. The results showed that HPA could effectively reduce triglycerides (TG) by 59% and free fat acid (FFA) and total cholesterol (TC) in serum and hepatic were reduced by least 25.9%. HPA could cause a decrease in serum low-density lipoprotein cholesterol (LDL-C) from 0.145 mM to 0.117 mM, and the serum high-density lipoprotein cholesterol (HDL-C) was increased. After alcohol-treated mice were supplemented with HPA, antioxidant markers (superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and Glutathione peroxidase (GSH-Px)), liver function index (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)), proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)), and liver tissue were all significantly improved. This is related to the fact that HPA can promote the expression of oxidative stress-related genes and inhibit the expression of inflammation-related genes. In addition, HPA could also regulate the disturbance of the intestinal microflora. In general, HPA could significantly improve the accumulation of serum and liver lipids caused by alcohol and the imbalance of intestinal flora in mice. It could also improve liver function, oxidative stress, and inflammation.

New IMB16-4 Nanoparticles Improved Oral Bioavailability and Enhanced Anti-Hepatic Fibrosis on Rats

Liver fibrosis is challenging to treat because of the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamido) benzamide referred to as IMB16-4. However, its poor aqueous solubility and poor oral bioavailability obstruct the drug discovery programs. To increase the dissolution, improve the oral bioavailability and enhance the antifibrotic activity of IMB16-4, PVPK30 was selected to establish the IMB16-4 nanoparticles. Drug release behavior, oral bioavailability, and anti-hepatic fibrosis effects of IMB16-4 nanoparticles were evaluated. The results showed that IMB16-4 nanoparticles greatly increased the dissolution rate of IMB16-4. The oral bioavailability of IMB16-4 nanoparticles was improved 26-fold compared with that of pure IMB16-4. In bile duct ligation rats, IMB16-4 nanoparticles significantly repressed hepatic fibrogenesis and improved the liver function. These findings indicate that IMB16-4 nanoparticles will provide information to expand a novel anti-hepatic fibrosis agent.