The usefulness of preoperative bile cultures for hepatectomy with biliary reconstruction

[Background] Infectious complications can cause lethal liver failure after hepatectomy with biliary reconstruction. This study assessed the increased risk for postoperative infectious complications in patients who underwent hepatectomy with biliary reconstruction and explored the possibility of predicting pathogenic microorganisms causing postoperative infectious complications based on preoperative monitoring of bile cultures. [Methods] This study involved 310 patients who received major hepatectomy with or without biliary reconstruction at our institution between January 2010 and December 2019. The relationship between the microorganisms detected through perioperative monitoring of bile culture and those in the postoperative infectious foci was examined. [Results] Forty-nine patients underwent major hepatectomy with biliary reconstruction, and 261 received hepatectomy without biliary reconstruction. The multivariate analysis revealed hepatectomy with biliary reconstruction to be associated with an increased risk of postoperative infectious complications (odds ratio: 22.9, 95% confidence interval: 5.2–164.3) compared to hepatectomy without biliary reconstruction. In the patients with biliary reconstruction, the concordance rates between the microorganisms detected in the postoperative infectious foci and those in preoperative bile cultures were as follows: incisional surgical site infection (44.4%), organ/space surgical site infection (52.9%), bacteremia (47.1%), and pneumonia (16.7%); the concordance rates were high, and the risk of infection increased over time. [Conclusions] Biliary reconstruction is a significant risk factor for postoperative infectious complications, and preoperative bile cultures may aid in prophylactic and therapeutic antimicrobial agent selection

En bloc excision of giant polycystic liver with hepatic cava and its auto-transplant caval reconstruction as a safe surgical procedure for liver transplantation

Safely excising a giant liver while leaving the hepatic inferior vena cava intact is difficult. Hata et al. present images and videos describing their novel technique consisting of total hepatectomy including the hepatic cava; extracorporeal retrieval; and auto‐transplant inferior vena cava reconstruction, for an extremely enlarged polycystic liver weighing 24 kg.[Image: see text

AMP N1-oxide, a unique compound of royal jelly, induces neurite outgrowth from PC12 cells via signaling by protein kinase A independent of that by mitogen-activated protein kinase

Earlier we identified adenosine monophosphate (AMP) N1-oxide as a unique compound of royal jelly (RJ) that induces neurite outgrowth (neuritegenesis) from cultured rat pheochromocytoma PC12 cells via the adenosine A2A receptor. Now, we found that AMP N1-oxide stimulated the phosphorylation of not only mitogen-activated protein kinase (MAPK) but also that of cAMP/calcium-response element-binding protein (CREB) in a dose-dependent manner. Inhibition of MAPK activation by a MEK inhibitor, PD98059, did not influence the AMP N1-oxide-induced neuritegenesis, whereas that of protein kinase A (PKA) by a selective inhibitor, KT5720, significantly reduced neurite outgrowth. AMP N1-oxide also had the activity of suppressing the growth of PC12 cells, which correlated well with the neurite outgrowth-promoting activity. KT5720 restored the growth of AMP N1-oxide-treated PC12 cells. It is well known that nerve growth factor suppresses proliferation of PC12 cells before causing stimulation of neuronal differentiation. Thus, AMP N1-oxide elicited neuronal differentiation of PC12 cells, as evidenced by generation of neurites, and inhibited cell growth through adenosine A2A receptor-mediated PKA signaling, which may be responsible for characteristic actions of RJ

SOX9 is a novel cancer stem cell marker surrogated by osteopontin in human hepatocellular carcinoma

The current lack of cancer stem cell (CSC) markers that are easily evaluated by blood samples prevents the establishment of new therapeutic strategies in hepatocellular carcinoma (HCC). Herein, we examined whether sex determining region Y-box 9 (SOX9) represents a new CSC marker, and whether osteopontin (OPN) can be used as a surrogate marker of SOX9 in HCC. In HCC cell lines transfected with a SOX9 promoter-driven enhanced green fluorescence protein gene, FACS-isolated SOX9+ cells were capable of self-renewal and differentiation into SOX9-cells, and displayed high proliferation capacity in vitro. Xenotransplantation experiments revealed that SOX9+ cells reproduced, differentiated into SOX9-cells, and generated tumors at a high frequency in vivo. Moreover, SOX9+ cells were found to be involved in epithelial-mesenchymal transition (EMT) and activation of TGFb/Smad signaling. Gain/loss of function experiments showed that SOX9 regulates Wnt/beta-catenin signaling, including cyclin D1 and OPN. Immunohistochemistry of 166 HCC surgical specimens and serum OPN measurements showed that compared to SOX9-patients, SOX9+ patients had significantly poorer recurrence-free survival, stronger venous invasion, and higher serum OPN levels. In conclusion, SOX9 is a novel HCCCSC marker regulating the Wnt/beta-catenin pathway and its downstream target, OPN. OPN is a useful surrogate marker of SOX9 in HCC

A validated proton beam therapy patch-field protocol for effective treatment of large hepatocellular carcinoma

Development of a curative local treatment for large hepatocellular carcinoma (HCC) is an important issue. Here, we investigated the dose homogeneity, safety and antitumor effectiveness of proton beam therapy (PBT) using a patch-field technique for large HCC. Data from nine patients (aged 52–79 years) with large HCC treated with patch-field PBT were investigated. The cranial–caudal diameters of the clinical target volumes (CTVs) were 15.0–18.6 cm (median 15.9). The CTV was divided cranially and caudally while both isocenters were aligned along the cranial–caudal axis and overlap of the cranial and caudal irradiation fields was set at 0–0.5 mm. Multileaf collimators were used to eliminate hot or cold spots. Total irradiation doses were 60–76.4 Gy equivalents. Irradiation doses as a percentage of the prescription dose (from the treatment planning system) around the junction were a minimum of 93–105%, a mean of 99–112%, and a maximum of 105–120%. Quality assurance (QA) was assessed in the cranial and caudal irradiation fields using imaging plates. Acute adverse effects of Grade 3 were observed in one patient (hypoalbuminemia), and a late adverse effect of Grade 3 was observed in one patient (liver abscess). Child–Pugh class elevations were observed in four patients (A to B: 3; B to C: 1). Overall survival rates at 1 and 2 years were 55 and 14%, respectively, with a median overall survival of 13.6 months. No patients showed local recurrence. Patch-field PBT supported by substantial QA therefore is one of the treatment options for large HCC

Maslinic Acid Attenuates Denervation-Induced Loss of Skeletal Muscle Mass and Strength

Maslinic acid (MA) is a pentacyclic triterpene abundant in olive peels. MA reportedly increases skeletal muscle mass and strength in older adults; however, the underlying mechanism is unknown. This study aimed to investigate the effects of MA on denervated muscle atrophy and strength and to explore the underlying molecular mechanism. Mice were fed either a control diet or a 0.27% MA diet. One week after intervention, the sciatic nerves of both legs were cut to induce muscle atrophy. Mice were examined 14 days after denervation. MA prevented the denervation-induced reduction in gastrocnemius muscle mass and skeletal muscle strength. Microarray gene expression profiling in gastrocnemius muscle demonstrated several potential mechanisms for muscle maintenance. Gene set enrichment analysis (GSEA) revealed different enriched biological processes, such as myogenesis, PI3/AKT/mTOR signaling, TNFα signaling via NF-κB, and TGF-β signaling in MA-treated mice. In addition, qPCR data showed that MA induced Igf1 expression and suppressed the expressions of Atrogin-1, Murf1 and Tgfb. Altogether, our results suggest the potential of MA as a new therapeutic and preventive dietary ingredient for muscular atrophy and strength