Levels of plasma-free fatty acids and liver triglycerides in rats treated with adrenaline or theophylline: effects exerted by administration of uridine diphosphate glucose

Adrenaline or theophylline administration to rats causes increased levels of plasma-free fatty acids and liver triglycerides; however, plasma FFA and liver triglyceride values are reduced in animals treated either with adrenaline or theophylline if they receive UDPG pretreatment. The protective effect exerted by UDPG in animals receiving the combined treatment is attributable to a decrease of cAMP-dependent lipolytic activity. Furthermore, the antilipemic lowering lipid effect exhibited by UDPG is linked to the intact nucleotide molecule, because compounds structurally associated to UDPG, like uridine, UMP, UDP or glucose- 1-phosphate, are incapable of affecting the increased lipolytic activity observed in adrenaline injected rats.     

Impact of incidentally found hepatocellular carcinoma on the outcome of living donor liver transplantation

Hepatocellular carcinoma (HCC) nodules newly found in the explant liver have been observed, but the impact on patient prognosis is not known. Sixty HCC patients who underwent living donor liver transplantation were the subjects of the study. Radiologic findings prior to transplantation and pathologic findings of the explant liver were compared. Histologic characteristics of preoperatively overlooked tumors were examined. The influence of the discrepancy between these findings on tumor recurrence was evaluated. A total of 227 HCC nodules were found in the explant livers. Of these, 91 nodules (40%) were newly found by pathologic examination. They were smaller and more likely to be well differentiated than the others. The number and size of the tumors were underestimated in 50% (30/60) and 32% (19/60), respectively. There was no significant difference in the recurrence-free survival rate between patients who met the Milan criteria both in the pre- and post-transplant evaluation (n = 29) and those who met the Milan criteria preoperatively, but exceeded the criteria in the explant (n = 19). Nodules newly found in the explant liver had little impact on recurrence-free survival. A decision for liver transplantation according to the Milan criteria based on preoperative evaluation is valuable for securing an excellent outcome.     

肝细胞肝癌肝移植受者术后生存及肿瘤复发临床分析

目的比较符合米兰标准和杭州标准的肝细胞肝癌(HCC)肝移植受者术后生存及肿瘤复发情况,分析移植术后生存和肿瘤复发影响因素。 方法回顾性分析青岛大学附属医院器官移植中心2014年2月1日至2018年12月31日符合米兰标准和杭州标准的119例HCC肝移植受者临床资料。符合米兰标准受者79例(米兰标准组),超出米兰标准但符合杭州标准者受者40例(杭州标准组)。所有受者肝移植术后均规律随访,收集受者性别、年龄和手术时间等临床资料。无瘤生存时间以受者移植术后发现肿瘤复发转移为观察终点,累积生存时间以受者移植术后死亡为观察终点。采用Kaplan-Meier法绘制生存曲线,采用log-rank检验比较组间累积生存率和无瘤生存率。采用Cox比例风险模型进行影响累积生存时间和无瘤生存时间的单因素和多因素分析。P<0.05为差异有统计学意义。 结果截至2019年7月31日,119例受者术后中位随访时间为27个月(15～43个月),其中术后因肿瘤复发死亡11例复发转移27例。米兰标准组受者1、3和5年累积生存率分别为98.7%、90.2%和90.2%,杭州标准组分别为97.2%、73.9%和73.9%,差异均无统计学意义(χ²＝0.219、1.598和1.598,P均>0.05)。米兰标准组受者1、3和5年累积无瘤生存率分别为90.3%、82.1%和68.6%,杭州标准组分别为81.6%、56.0%和56.0%,两组受者术后1年和5年累积无瘤生存率差异均无统计学意义(χ²＝1.587和3.707,P均>0.05),3年累积无瘤生存率差异有统计学意义(χ²＝5.543,P<0.05)。多因素分析结果证实术前有无脉管癌栓是影响其累积生存率的独立危险因素,差异有统计学意义(HR＝0.159,P<0.05);术前有无脉管癌栓和病理分化类型是影响无瘤生存的独立危险因素,差异均有统计学意义(HR＝0.338和0.395,P均<0.05)。 结论符合杭州标准的HCC肝移植受者移植术后可获得较好的累积生存率及无瘤生存率,受者术前是否存在脉管癌栓及病理分化程度可以指导移植术后肿瘤复发的预防。     

Hepatocellular carcinoma beyond Milan criteria: Management and transplant selection criteria

Liver transplantation(LT) for hepatocellular carcinoma(HCC) has been established as a standard treatment in selected patients for the last two and a half decades. After initially dismal outcomes, the Milan criteria(MC)(single HCC ≤ 5 cm or up to 3 HCCs ≤ 3 cm) have been adopted worldwide to select HCC patients for LT, however cumulative experience has shown that MC can be too strict. This has led to the development of numerous expanded criteria worldwide. Morphometric expansions on MC as well as various criteria which incorporate biomarkers as surrogates of tumor biology have been described. HCC that presents beyond MC initially can be downstaged with locoregional therapy(LRT). Post-LRT monitoring aims to identify candidates with favorable tumor behavior. Similarly, tumor marker levels as response to LRT has been utilized as surrogate of tumor biology. Molecular signatures of HCC have also been correlated to outcomes; these have yet to be incorporated into HCC-LT selection criteria formally. The ongoing discrepancy between organ demand and supply makes patient selection the most challenging element of organ allocation. Further validation of extended HCCLT criteria models and pre-LT treatment strategies are required.     

射频消融治疗符合米兰标准的早期肝癌疗效分析

  目的   探讨射频消融治疗符合米兰标准的早期肝癌的疗效及预后危险因素。   方法   回顾性分析天津医科大学肿瘤医院72例行射频消融治疗的符合米兰标准的早期肝癌患者病例,评估其术后恢复情况,分析复发率、生存率及预后危险因素。   结果   72例患者术后并发症轻微且恢复迅速,术后1、2、3年累积复发率分别为12.50%、20.83%和33.33%;1、2、3年累积生存率分别为93.06%、87.50%、79.17%。多因素分析提示肿瘤大小与复发密切相关,肿瘤大小与术前白蛋白水平是影响总生存的独立危险因素。   结论   射频消融术治疗符合米兰标准的早期肝癌,近远期效果良好。肿瘤大小是复发的独立危险因素,肿瘤大小与术前白蛋白水平是影响总生存的重要因素。      

The role of living-donor liver transplantation in surgical treatment for hepatocellular carcinoma

Background/Purpose The role of living-donor liver transplantation (LDLT) in the surgical treatment of patients with hepatocellular carcinoma (HCC) has not been established as yet. Methods Preliminary experience gained from 24 patients who underwent LDLT for HCC between March 2002 and November 2004, and the results of the 131 patients who underwent hepatic resection (HR) for HCC between January 1990 and December 2003 were retrospectively analyzed. The exclusion criteria for LDLT for HCC included extrahepatic metastasis and major vascular invasion. Results (1) LDLT: the median age of the patients was 57 years and the Child-Pugh grades (A/B/C) of the patients were 6, 12, and 6, respectively. The tumor size was 3 cm or less in 15 patients, multinodular tumors were present in 23 patients, and 11 patients (45.8%) met the Milan Criteria. The overall 2-year survival rate was 72.3%, without a significant difference as to whether or not patients met the Milan criteria. (2) HR: on multivariate analysis, the Child-Pugh grade, the presence of cirrhosis, and the number of tumor nodules were considered as independent risk factors for unfavorable survival (P < 0.05). The 84 patients who met the Milan criteria and were Child-Pugh grade A had a 5-year survival rate of 71.3%; this was significantly better than those of the other patients (P < 0.005). Among the 57 patients with intrahepatic recurrence, 18 patients who were Child-Pugh grade A, met the Milan criteria, and were treated by re-resection or ablation therapy achieved a significantly better 5-year survival rate, of 73.1%, as compared to 19.7% in the other 39 patients (P < 0.0045). Conclusions HR could be a first-line treatment with a favorable prognosis for patients who have resectable HCC, preserved liver function, and who meet the Milan criteria. Salvage LDLT could be employed in patients with recurrent tumors that cannot be controlled by conventional treatment or in patients in whom liver function has deteriorated to Child-Pugh grade B or C.     

Preliminary Experience With Hypothermic Oxygenated Machine Perfusion in an Italian Liver Transplant Center

Background

Machine perfusion is increasingly utilized in liver transplantation to face the detrimental consequences of the use of extended-criteria donors. Hypothermic oxygenated machine perfusion (HOPE) appears to be more protective relative to static cold storage. Conversely, normothermic machine perfusion (NMP) allows a better graft evaluation. We describe a pilot prospective study on machine perfusion in selected grafts.

Influence of capillary and tissue PO2 on carbon monoxide binding to myoglobin: A theoretical evaluation

In order to evaluate how much myoglobin is linked to CO at various HbCO concentrations and at different P_O2, a three compartment model (arterial blood, venous capillary blood, and tissue myoglobin) has been considered. A steady-state condition has been assumed for O₂ consumption with no metabolization for CO. The curves obtained by computer simulation of the proposed model indicate that HbCO levels found in smokers entail values of MbCO which could be high enough to reduce intracellular oxygen transport significantly: especially where the P_O2 is physiologically low (as in subendocardium) and/or hypoxemic-ischemic conditions are present.     

Radiofrequency ablation vs surgical resection in elderly patients with hepatocellular carcinoma in Milan criteria

BACKGROUNDSurgical resection and radiofrequency ablation (RFA) represent two possible strategy in treatment of hepatocellular carcinoma (HCC) in Milan criteria.AIMTo evaluate short- and long-term outcome in elderly patients (> 70 years) with HCC in Milan criteria, which underwent liver resection (LR) or RFA.METHODSThe study included 594 patients with HCC in Milan criteria (429 in LR group and 165 in RFA group) managed in 10 European centers. Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching (PSM) and Cox regression.RESULTSAfter PSM, we compared 136 patients in the LR group with 136 patients in the RFA group. Overall survival at 1, 3, and 5 years was 91%, 80%, and 76% in the LR group and 97%, 67%, and 41% in the RFA group respectively (P = 0.001). Disease-free survival at 1, 3, and 5 years was 84%, 60% and 44% for the LR group, and 63%, 36%, and 25% for the RFA group (P = 0.001).Postoperative Clavien-Dindo III-IV complications were lower in the RFA group (1% vs 11%, P = 0.001) in association with a shorter length of stay (2 d vs 7 d, P = 0.001).In multivariate analysis, Model for End-stage Liver Disease (MELD) score (> 10) [odds ratio (OR) = 1.89], increased value of international normalized ratio (> 1.3) (OR = 1.60), treatment with radiofrequency (OR = 1.46) ,and multiple nodules (OR = 1.19) were independent predictors of a poor overall survival while a high MELD score (> 10) (OR = 1.51) and radiofrequency (OR = 1.37) were independent factors associated with a higher recurrence rate.CONCLUSIONDespite a longer length of stay and a higher rate of severe postoperative complications, surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients (> 70 years) with HCC in Milan criteria.