Liver ischemia, catecholamines and preoperative condition influencing postoperative tachycardia in liver surgery

The aim of our study was to assess the influence of intraoperative hypoxic stress -unavoidably brought about by so called Pringle maneuver - on free and conjugated catecholamines during major hepatic resection. Judging from earlier results of fatigue-experiments in rats we also wanted to check the relationship between of poor general preoperative condition and conspicuously low triglyceride serum concentrations. The study included 26 patients with primary and secondary liver tumors. The mean age was 54 years (range 27-79). Twenty-one patients had segmental liver resections, 3 had hemihepatectomies and 2 hydatid cysts were treated by cystectomy. Blood samples were taken 2 days before and throughout surgery. Catecholamine plasma values were determined by high performance liquid chromatography. Statistical comparisons were made by t-test, ANOVA and chi square test. Free plasma catecholamines increased significantly during prolonged intraoperative ischemia (Pringle time 50-125 minutes). Patients with elevated intraoperative catecholamines had a significant correlation to postoperative episodes of tachycardia, and prolonged hospital stay. On the other hand, we could also see postoperative tachycardias in patients with short Pringle times (18-49 minutes) but with decreased preoperative serum triglycerides as an indicator of chronic stress and reduced general condition. Intraoperative hypoxic stress is associated with increased catecholamine values. Elevated catecholamines may well cause postoperative sinus-tachycardias (mean 20 hours) and are strongly related to postoperative liver failure and prolonged hospital stay.     

A preoperative model for predicting microvascular invasion and assisting in prognostic stratification in liver transplantation for HCC regarding empirical criteria

PurposeThe prediction of microvascular invasion (MVI) has increasingly been recognized to reflect prognosis involving local invasion and distant metastasis of hepatocellular carcinoma (HCC). The aim of this study was to assess a predictive model using preoperatively accessible clinical parameters and radiographic features developed and validated to predict MVI. This predictive model can distinguish clinical outcomes after liver transplantation (LT) for HCC patients.MethodsIn total, 455 HCC patients who underwent LT between January 1, 2015, and December 31, 2019, were retrospectively enrolled in two centers in China as a training cohort (ZFA center; n = 244) and a test cohort (SLA center; n = 211). Univariate and multivariate backward logistic regression analysis were used to select the significant clinical variables which were incorporated into the predictive nomogram associated with MVI. Receiver operating characteristic (ROC) curves based on clinical parameters were plotted to predict MVI in the training and test sets.ResultsUnivariate and multivariate backward logistic regression analysis identified four independent preoperative risk factors for MVI: α-fetoprotein (AFP) level (p < 0.001), tumor size ((p < 0.001), peritumoral star node (p = 0.003), and tumor margin (p = 0.016). The predictive nomogram using these predictors achieved an area under curve (AUC) of 0.85 and 0.80 in the training and test sets. Furthermore, MVI could discriminate different clinical outcomes within the Milan criteria (MC) and beyond the MC.ConclusionsThe nomogram based on preoperatively clinical variables demonstrated good performance for predicting MVI. MVI may serve as a supplement to the MC.     

Anatomic and anesthetic considerations in experimental cardiopulmonary surgery in swine

We have used immature commercial swine (13-25 kg) successfully in a variety of experimental cardiopulmonary surgical procedures in our laboratories since 1981. Multiple drug anesthetic protocols using barbiturates, narcotics, paralytic and antiarrhythmic agents have been employed in over 400 procedures per year. Complications, including fatal cardiac arrhythmias, have been greatly reduced by anesthetic protocols and surgical procedures developed through experience.     

肝肾移植术后患者隐球菌感染的临床特征分析

目的研究肝、肾移植术后患者隐球菌感染的临床特征。方法选取2010年1月到2015年7月来浙江大学医学院附属第一医院就诊的肝、肾移植术后并确诊为隐球菌感染的患者,对其临床特征进行回顾性分析。结果研究周期内有23例患者符合入组要求,其中肾移植术后21例、肝移植术后2例。对23例患者进行分析,发现单纯隐球菌肺炎6例(占26.0%)、单纯隐球菌性脑膜炎6例(占26.0%)、隐球菌性脑膜炎合并隐球菌肺炎8例(占34.7%)、隐球菌败血症2例(占8.6%),皮肤隐球菌感染1例(占4.3%)。所有隐球菌肺炎均经肺穿刺病理确诊,临床表现以发热,咳嗽咳痰,气急症状居多。胸部CT表现为结节、空洞、肿块、渗出等。所有隐球菌脑膜炎患者中9例经脑脊液培养出新生隐球菌、7例脑脊液墨汁染色见隐球菌,其中3例培养及涂片均为阳性。临床表现以头痛、发热、呕吐症状居多,1例并发癫痫,1例并发意识障碍。所有患者分别给予氟康唑、两性霉素B、氟胞嘧啶针、伏立康唑等抗真菌治疗,其中3例隐球菌脑膜炎患者予两性霉素B鞘内注射。经1~6个月治疗后,总体预后情况良好(好转22例,死亡1例)。结论肝、肾移植术后患者因免疫抑制剂的长期使用,隐球菌感染值得重视,其临床症状不典型,易误诊及漏诊,通过对其主要症状及影像学特点判断,结合肺穿刺活检、脑脊液检查、血培养等检查手段,可明显提高隐球菌感染的检出率,从而做到早诊断,早治疗,降低病死率。     

Gastric resection; preoperative and postoperative care

Perhaps in no other field of surgery does attention to minute detail play so important a role in determining success as it does in gastric operations. As surgery of the stomach develops toward even greater security and favorable results can be expected with greater confidence, the several aspects of preoperative and postoperative care hitherto regarded as secondary demand closer consideration.     

Engineered liver for transplantation

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重型肝炎患者肝移植术后真菌感染临床分析

目的分析重型肝炎肝移植受体术后真菌感染情况,进一步探讨其易感因素和防治措施。方法回顾性分析我院器官移植中心2003年3月至2006年2月间89例重型肝炎肝移植患者的临床资料并进行讨论。结果89例重型肝炎肝移植患者中21例出现术后真菌感染,感染率为23.6%,较其他病种肝移植更高,其中12例为白念珠菌(57.1%),6例为光滑念珠菌(28.6%),1例为近平滑念珠菌,1例为克柔念珠菌,1例为热带念珠菌。真菌感染多发生在术后1周内,感染部位以呼吸系统为主。结论重型肝炎肝移植患者术后真菌感染以念珠菌属的早期呼吸道感染为主。术前肝性脑病与术后发生真菌感染之间存在相关关系。而一般的白念珠菌感染不会显著地影响重型肝炎肝移植患者的预后。预防性使用抗真菌药物在重型肝炎肝移植术后真菌感染的治疗中具有重要意义。     

Bioengineering considerations in liver regenerative medicine

Background

Liver disease contributes significantly to global disease burden and is associated with rising incidence and escalating costs. It is likely that innovative approaches, arising from the emerging field of liver regenerative medicine, will counter these trends.

Main body

Liver regenerative medicine is a rapidly expanding field based on a rich history of basic investigations into the nature of liver structure, physiology, development, regeneration, and function. With a bioengineering perspective, we discuss all major subfields within liver regenerative medicine, focusing on the history, seminal publications, recent progress within these fields, and commercialization efforts. The areas reviewed include fundamental aspects of liver transplantation, liver regeneration, primary hepatocyte cell culture, bioartificial liver, hepatocyte transplantation and liver cell therapies, mouse liver repopulation, adult liver stem cell/progenitor cells, pluripotent stem cells, hepatic microdevices, and decellularized liver grafts.

Conclusion

These studies highlight the creative directions of liver regenerative medicine, the collective efforts of scientists, engineers, and doctors, and the bright outlook for a wide range of approaches and applications which will impact patients with liver disease.

     

Stem cells, cell transplantation and liver repopulation

Liver transplantation is currently the only therapeutic option for patients with end-stage chronic liver disease and for severe acute liver failure. Because of limited donor availability, attention has been focused on the possibility to restore liver mass and function through cell transplantation. Stem cells are a promising source for liver repopulation after cell transplantation, but whether or not the adult mammalian liver contains hepatic stem cells is highly controversial. Part of the problem is that proliferation of mature adult hepatocytes is sufficient to regenerate the liver after two-thirds partial hepatectomy or acute toxic liver injury and participation of stem cells is not required. However, under conditions in which hepatocyte proliferation is blocked, undifferentiated epithelial cells in the periportal areas, called "oval cells", proliferate, differentiate into hepatocytes and restore liver mass. These cells are referred to as facultative liver stem cells, but they do not repopulate the normal liver after their transplantation. In contrast, epithelial cells isolated from the early fetal liver can effectively repopulate the normal liver, but they are already traversing the hepatic lineage and may not be true stem cells. Mesenchymal stem cells and embryonic stem cells can be induced to differentiate along the hepatic lineage in culture, but at present these cells are inefficient in repopulating the liver. This review will characterize these various cell types and compare the properties of these cells and the conditions under which they do or do not repopulate the liver following their transplantation.     

Determination, proprerties and postnatal development of galactokinase in the swine liver]

1. Starting from the spectrophotometric method of Ballard optimal reaction conditions for measurements of galactokinase in piglet liver were systematically studied. These are (final conc. in the test): 100 mM triethanolamine-HCl buffer, 33 mM KCl, 16.5 mM NaF (inhibiting ATPase), 5 mM cysteine hydrochloride, 0.33 mM NADH2, 1 U pyruvate kinase and lactic dehydrogenase, 0.5 mM phosphoenolpyruvate, 1.5 mM galactose, 0.5 mM ATP and 1 mM MgCl2, final pH 7.5. 2. An optimal substrate concentration, a Mg: ATP-ratio of 2:1, pH-stability and addition of activators are important for the determination of galactokinase activity in the supernatant fraction of pig liver. 3. Using the optimized method galactokinase activity of pig liver in dependence on age, with particular reference to the perinatal period, was determined. 4. Galactokinase activity of liver of newborn piglets is 7 times that of adult pigs. In the suckling period the activity remains relatively constant at this high level and decreases remarkably immediately after weaning. 5. Galactokinase of liver of newborn piglets differs in kinetic properties (lower Km of ATP, higher maximal reaction velocity) from the enzyme of adult pigs, which is still insufficient to make sure the existence of two different forms of the enzyme.     

Immunoaffinity column cleanup procedure for analysis of ivermectin in swine liver

A simple and sensitive method for the analysis of ivermectin (22,23-dihydroavermectin B₁) in swine liver based on immunoaffinity column cleanup is described. The immunosorbent was prepared by coupling polyclonal anti-ivermectin antibodies to carbonyl diimidazole-activated Sepharose CL-4B. After extraction with methanol, ivermectin was cleaned up on an immunoaffinity column, and determined by reversed-phase liquid chromatography with UV absorbance detection at 245 nm. Recoveries of ivermectin from fortified samples of 5–100 μg kg⁻¹ levels ranged 85–102%, with coefficients of variation of 6–12%. The limit of detection was 2 μg kg⁻¹ in a 5-g sample.     

尿道下裂患者术前术后尿道细菌的研究

目的了解尿道下裂患者尿道修复前后尿道及其周围细菌的分布,为临床预防尿道下裂术后感染提供依据。方法采集30例尿道下裂患者术前尿道、会阴部,术后重建尿道、会阴部皮肤作细菌分离、培养、鉴定、统计分析、药敏试验。结果术前术后尿道与会阴部细菌分布差异无显著性（P〉0．05）,有革兰阳性菌表皮葡萄球菌、肠球菌等,革兰阴性菌变形杆菌、阴沟肠杆菌、大肠埃希菌等,以表皮葡萄球菌占多数。结论术后重建尿道内存在的细菌由会阴部皮肤表面细菌转移而入。菌株以革兰阳性菌表皮葡萄球菌占多数,菌株耐药率较高,临床选择药物要慎重。     

Controversies in patient selection for liver transplantation.

A variety of specific conditions often stimulate controversy regarding candidacy for liver transplantation. We review the published experience with liver transplantation for alcoholic liver disease, fulminant and chronic hepatitis B, and hepatocellular carcinoma and transplantation in older subjects. Liver transplantation for alcoholic liver disease and in subjects older than 60 years is becoming less controversial because recent data demonstrate that these patients have excellent survival and good quality of life after transplantation. Only 10% to 15% of persons with alcoholism return to drinking after transplantation, and most do so only transiently. Liver transplantation for patients with hepatitis B virus infection or primary liver cancer is more problematic because recurrent disease is common in both conditions. After transplantation for chronic hepatitis B, 80% to 90% of patients have reinfection of the allograft and long-term survival is 45% to 50%. Patients receiving transplants for hepatocellular carcinoma have only 20% to 30% long-term survival, but these survivors are cured of malignancy. Data are presented to support continued liver transplantation for chronic hepatitis B and hepatocellular carcinoma; however, patients must be selected based on factors that predict a favorable outcome, and experimental therapies should be employed to explore ways to improve the existing survival rates.     

Vascularized composite islet-kidney transplantation in a miniature swine model

Previous work from this laboratory has demonstrated that transplantation of allogeneic thymic tissue as part of a composite vascularized graft is far more successful in terms of both engraftment and long-term survival than transplantation of thymic tissue or cells alone. We have subsequently extended this concept to transplantation of allogeneic islets, comparing survival of islet cell suspensions to that of vascularized composite islet-kidneys (IK), prepared by injection of autologous islets underneath the renal capsule 2-3 months prior to allogeneic transplantation of the composite organ. We have utilized partially inbred miniature swine with defined MHC loci as the experimental large animals for this study, permitting reproducible transplantation across specific MHC barriers. Composite IK have been transplanted successfully across minor and full MHC mismatch barriers, using treatment regimens previously demonstrated to induce long-term tolerance of kidney allografts across these barriers. IK allografts containing ≥5000 islet equivalents (IE)/kg recipient body weight were found capable of reversing surgically induced diabetes, while injection of comparable numbers of purified islets via the portal vein or under the renal capsule did not. Studies are also being directed toward preparation of autologous “thymo-islet-kidneys” (TIK), for potential use as xenografts, in which the thymic component is intended to induce tolerance and the islets to reverse diabetic hyperglycemia. The use of both types of composite organ transplants may eventually be applicable to the treatment of type I diabetic patients suffering from end-stage diabetic nephropathy.     

Multiple vascular and gastric cannulation of swine for studies of gastrointestinal, liver, and peripheral tissue metabolism.

The implantation of multiple chronic indwelling vascular cannulas and of a gastric cannula into swine was described. Technics for housing, care, and handling of the animals pre- and post-surgically were established to reduce the incidence of infection and to allow collection of urine and feces in metabolic studies. This regimen has been used in 20 gilts to study absorption, tissue distribution, metabolism, and excretion of nutrients. On the average, the cannulas remained patent for 4 wk.