Undifferentiated embryonal sarcoma of the liver: Clinical characteristics and outcomes.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare liver malignancy originating from primary mesenchymal tissue. The clinical manifestations, laboratory tests, and imaging examinations of the disease lack specificity and the preoperative misdiagnosis rate is high. The overall prognosis is poor and survival rate is low. AIM: To investigate the diagnosis, treatment, and prognosis of UESL. METHODS: We performed a retrospective, single-center cohort study in Shengjing Hospital of China Medical University, which is a central hospital in northeast China. From 2005 to 2017, we recruited 14 patients with pathologically confirmed UESL. We analyzed the clinical manifestations, laboratory tests, imaging examinations, pathological examinations, therapy, and prognosis of these patients. RESULTS: There were nine males and five females aged 2-60 years old included in the study. The major initial symptoms were abdominal pain (71.43%) and fever (57.14%). Preoperative laboratory tests revealed that seven patients had increased leukocyte levels, four showed a decrease in hemoglobin levels, seven patients had increased glutamyl transpeptidase levels, nine had increased lactate dehydrogenase levels, and three showed an increase in carbohydrate antigen 199. There was no difference in the rate of misdiagnosis in preoperative imaging examinations of UESL between adults and children (6/6 vs 5/8, P = 0.091). The survival rate after complete resection was 6/10, while that after incomplete resection was 0/4 (P = 0.040), suggesting that complete resection is important to improve survival rate. In total, five out of the eight children achieved survival. During the follow-up, the maximum survival time was shown to be 11 years and minimum survival time was 6 mo. Six adult patients relapsed late after surgery and all of them died. CONCLUSION: Preoperative imaging examination for UESL has a high misdiagnosis rate. Multidisciplinary collaboration can improve the diagnostic accuracy of UESL. Complete surgical resection is the first choice for treatment of UESL.

Autophagy Contributes to Liver Regeneration After Portal Vein Ligation in Rats.

BACKGROUND This study investigated the effect of 70% portal vein ligation (PVL), a widely used procedure for inducing rapid liver regeneration, on the expression of autophagy-related proteins in non-ligated liver lobes in rats. MATERIAL AND METHODS Rats were subjected to either sham (n=30, major portal vein branches were exposed but kept intact) or PVL (n=30, major portal vein branches were double-ligated) operations. Liver samples were collected 12, 24, 48, 72, and 168 h after the operation. Liver volume, liver color, non-ligated liver percentage, and the expressions of light chain (LC) 3, beclin 1, and cyclin D1 in the non-ligated liver lobes were determined. RESULTS When compared to sham rats, increased (P<0.001) growth of the non-ligated liver lobes was observed in PVL rats as early as 12 h after surgery; an increased (P≤0.001) LC3 II/I ratio was observed in the non-ligated lobes of PVL rats as early as 24 h after surgery. Increased expressions of beclin 1 (P≤0.001) and cyclin D1 (P<0.001) were observed in the non-ligated lobes of PVL rats from 12 to 72 h after surgery and from 12 to 168 h after surgery, respectively, when compared to sham rats. In the non-ligated lobes, the expressions of beclin 1 and cyclin D1 were linearly and positively correlated with the LC3 II/I ratio. CONCLUSIONS Autophagy is activated in the non-ligated liver after PVL. Both beclin 1 and cyclin D1 are linearly and positively correlated with autophagy activity in the PVL-induced rapid liver regeneration model.

Preconditioning with glutamine protects against ischemia/reperfusion-induced hepatic injury in rats with obstructive jaundice.

OBJECTIVE: To ascertain whether glutamine (Gln) pretreatment protects rats with obstructive jaundice from hepatic ischemia/reperfusion (I/R) injury and to determine the underlying molecular mechanisms. METHODS: An obstructive jaundice rat model was developed by bile duct ligation. On the first day after the operation, all rats were randomized into two groups and received oral Gln or normal saline (NS) daily for 7 days. Then both groups underwent a 15-min liver ischemia via the Pringle maneuver. Blood samples as well as liver and intestinal tissues were harvested and measured after 1, 6 and 24 h of reperfusion. RESULTS: The results showed that the histological morphology of the liver and intestinal tissues significantly improved in the Gln group after I/R injury compared with the NS group. Serum proteins and enzymes associated with hepatic function also significantly improved in the Gln group. The level of glutathione increased and the levels of malondialdehyde and myeloperoxidase decreased in the Gln group. The levels of interleukin-1ß and tumor necrosis factor-α decreased in the Gln group. Moreover, bcl-2 protein expression was upregulated and intercellular adhesion molecule 1 and bax protein expression downregulated in the Gln group; the caspase 3 mRNA level significantly increased in the Gln group. CONCLUSIONS: The study demonstrates that preconditioning with Gln significantly improves hepatic structure and function after I/R injury in rats with obstructive jaundice. The protective effect of Gln was mediated by the inhibition of reactive oxygen species and inflammation as well as a reduction in hepatocyte apoptosis.

Polymyxin B protects against hepatic ischemia/reperfusion injury in a rat model of obstructive jaundice.

This study was conducted in order to investigate the effects of polymyxin B (PMB) against hepatic ischemia/reperfusion (I/R) injury in rats with obstructive jaundice. Thirty-six Wistar rats (eighteen each) with induced hepatic I/R injury by biliary tract ligation and recanalization were assigned to a control group (reperfused with normal saline) and a PMB group (reperfused with PMB). Indicators involving liver function, oxidation resistance, pro-inflammatory state, and anti-apoptosis effect were determined following the instructions. Compared with normal saline, PMB reperfusion resulted in a significant improvement of liver function (increase of glutathione and reduction of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), oxidation resistance (decreased malondialdehyde and myeloperoxidase activity), alleviation of pro-inflammatory state (less tumor necrosis factor (TNF)-α, interleukin-1 beta (IL-1ß), nuclear factor kappa B (NF-κB) mRNA, and intercellular adhesion molecule (ICAM)-1), and anti-apoptosis effect (more Bcl-2 and less Bax). PMB protects the liver from I/R injury mainly through reducing cellular oncosis and apoptosis and regulating the expression of NF-κB, TNF-α, IL-1ß, and ICAM-1.

A novel plasmid and SonoVue formulation plus ultrasound sonication for effective gene delivery in nude mice.

AIMS: This study aimed to identify the effectiveness of gene therapy mediated by ultrasound-targeted SonoVue using the herpes simplex virus-thymidine kinase (TSV-TK) driven by the kinase insert domain receptor (KDR) promoter (KDR-TK) for the treatment of ovarian carcinomas in nude mice. The optimized conditions for gene transfection were also explored. MAIN METHODS: In this study, we developed a novel technique to deliver a plasmid vector-carried gene into tumor xenografts in sixty nude mice. We first mixed plasmid DNA with SonoVue to form microbubbles and then treated the mice with ultrasound sonication to enhance plasmid gene transfection and expression in tumor xenografts. KEY FINDINGS: The data showed that injection of pBluescript-KDR-TK cDNA mixed with SonoVue into nude mice plus ultrasound sonication significantly (Group E) increased the transfection efficiency and expression of KDR-TK mRNA in tumor xenografts. The growth of tumor xenografts in nude mice was significantly suppressed in Group E compared to the other four control groups (Groups A, B, C, and D, namely, treatment with phosphate-buffered saline (PBS), KDR-TK+PBS, KDR-TK+SonoVue, KDR-TK+PBS+ultrasound sonication, respectively). TUNEL staining showed that SonoVue plus ultrasound sonication significantly induced apoptosis and reduced microvessel density (MVD). SIGNIFICANCE: This study revealed that the formulation of plasmid with SonoVue plus ultrasound could provide efficient gene delivery into tumor xenografts. Increased gene expression was observed in vivo, which effectively reduced the tumor growth and MVD of tumor xenografts and induced apoptosis in tumor cells. Future clinical trials are necessary to further analyze the relevance of this technique.

[Resection of centrally located primary liver cancer].

OBJECTIVE: To summarize the experience of hepatectomy for patients with centrally located primary liver cancer. METHODS: The clinical data of patients with centrally and non-centrally located primary liver cancer were retrospectively reviewed. The biochemical indicators, operation duration, hepatic inflow occlusion time, hospital stay, operative blood loss, amount of blood transfusion, complication, and effectiveness of three occlusion methods (semi-hepatic inflow occlusion, Pringle's manoeuvre, and modified Pringle's manoeuvre) were analyzed. RESULTS: Tumor diameter, Child-Pugh score, indocyanine green retention rate, aspartate aminotransferase, alanine aminotransferase, glutamyltransferase, total bilirubin, direct bilirubin, albumin, prealbumin, cholinesterase, hepatic inflow occlusion time, blood transfusion, postoperative complications, and operative blood loss were not significantly different between patients with centrally and non-centrally located primary liver cancer. Patients with centrally located liver cancer had significantly longer operation duration and hospital stay than patients with non-centrally located liver cancer (P < 0.05). The modified Pringle's manoeuvre of hepatic inflow occlusion had the same effectiveness of the Pringle's manoeuvre and could be performed in a simpler way. CONCLUSIONS: Hepatectomy is safe and feasible for patients with centrally located primary liver cancer. Appropriate preoperative evaluation and preparation, sufficient knowledge of liver anatomy, and proper selection of hepatic inflow occlusion method are key factors to guarantee the success of the resection.

Alanyl-glutamine dipeptide inhibits hepatic ischemia-reperfusion injury in rats.

AIM: To investigate the protective effect and mechanism of alanyl-glutamine dipeptide (Ala-Gln) against hepatic ischemia-reperfusion injury in rats. METHODS: Rats were divided into group C as normal control Group (n=16) and group G as alanyl-glutamine pretreatment (n=16). Rats were intravenously infused with 0.9% saline solution in group C and Ala-Gln -enriched (2% glutamine) 0.9% saline solution in group G via central venous catheter for three days. Then all rats underwent hepatic warm ischemia for 30 min followed by different periods of reperfusion. Changes in biochemical parameters,the content of glutathione (GSH) and the activity of superoxide dismutase (SOD) in liver tissue, Bcl-2 and Bax protein expression and morphological changes of liver tissue were compared between both groups. RESULTS: One hour after reperfusion, the levels of liver enzymes in group G were significantly lower than those in group C (P<0.05).Twenty-four hours after reperfusion, the levels of liver enzymes in both groups were markedly recovered and the levels of liver enzyme in group G were also significantly lower than those in group C (P<0.01). One and 24 h after reperfusion, GSH content in group G was significantly higher than that in group C (P<0.05). There was no statistical difference in activities of SOD between the two groups. One and 24 h after reperfusion, the positive expression rate of Bcl-2 protein was higher in group G than in group C (P<0.05) and the positive expression rate of Bax protein was lower in group G than in group C (P<0.05). Histological and ultrastructural changes of liver tissue were inhibited in group C compared to group G. CONCLUSION: Our results suggest that Ala-Gln pretreatment provides the rat liver with significant tolerance to warm ischemia-reperfusion injury,which may be mediated partially by enhancing GSH content and regulating the expression of Bcl-2 and Bax proteins in the liver tissue.