Cytopathologic features of hepatic epithelioid hemangioendothelioma

We present the cytological features of hepatic epithelioid hemangioendothelioma (EH), which is considered to be a vascular proliferation of intermediate malignant potential. The case report concerns a 52-yr-old previously healthy man discovered to have multiple hepatic masses upon evaluation for abnormal liver function tests. Fine-needle aspiration demonstrated a neoplasm composed of interanastomosing epithelioid cells that contained intracytoplasmic lumens. Histologic sections, immunohistochemistry, and ultrastructural evaluation were confirmatory. Although hepatic EH is a rare tumor, its characteristic cytological, histological, and ultrastructural features permit a straightforward diagnosis. It is important to distinguish this entity from adenocarcinoma and angiosarcoma because long-term disease-free survival is possible, especially in the setting of orthotopic liver transplantation. Diagn. Cytopathol. 17:50–53, 1997. © 1997 Wiley-Liss, Inc.     

Epithelioid hemangioendothelioma with marked liver deformity and secondary Budd–Chiari syndrome: Pathological and radiological correlation

A case of malignant epithelioid hemangioendothelioma of the liver in a 48-year-old woman with severe portal hypertension and marked deformity of the liver is presented. This woman had a history of mild liver dysfunction since the age of 30 years, and abdominal distention, esophageal varices, splenomegaly and ascites since October 1996. Imaging examinations revealed liver deformity with severe atrophy of the left lobe and the anterior segment of the right lobe. Celiac arteriography showed narrowing and upward deviation of the proper hepatic artery, and occlusion of the left and right anterior hepatic arteries. Since March 1997, hepatic venography showed stenosis in the right hepatic vein truncus. Budd-Chiari syndrome was clinically diagnosed. She died in June 1997. The autopsy disclosed massive tumor embolism in the left and right anterior portal branches, few in the hepatic artery, and occlusion of the left and right anterior hepatic arteries. The extensive tumor embolism resulted in portal hypertension, and atrophy of the left lobe. The anterior segment of the right lobe was probably caused by the occlusion of both the hepatic arteries and the portal veins. The posterior segment of the right lobe, without massive tumor embolism in its portal branch, appeared hypertrophic.     

494例次移植肝穿刺活检病理组织学分析

目的 通过对354例(494例次)移植肝穿刺活检组织进行病理分析,观察移植肝的组织学变化,探讨其出现肝功能不全的原因。方法 移植肝穿刺活检组织经10％中性福尔马林固定,快速石蜡连续切片,常规HE染色。部分病例做VG、Masson、PAS、网状纤维组织化学和免疫组织化学染色,抗体为HBsAg、HBcAg、HcVAg、CMV、CD8、CD4、CK19。对排斥反应病例,依照国际统一的BANFF标准进行急性排斥反应分级,应用排斥活动指数(RAI)进行排斥反应程度评分。结果 急性细胞性排斥反应最常见,180例(50．85％),慢性排斥反应11例(3．11％),再灌注缺血损伤20例(5．65％),胆汁淤滞及急慢性小胆管炎64例(18．08％),药物性肝损害18例(5．08％),移植肝无功1例(0．28％),CMV感染24例(6．78％),乙肝病毒再感染及乙肝复发27例(7．63％),丙型肝炎复发2例(0．56％),原发性硬化性胆管炎复发1例(0．28％),难以诊断6例(1．69％)。结论 移植肝穿刺活检对移植术后并发症的诊断及选择治疗方案具有重要价值。     

Malignant epithelioid haemangioendothelioma of the liver: a clinicopathological and histochemical study of 12 cases

We describe the clinicopathological findings in 12 cases of hepatic epithelioid haemangioendothelioma in order to identify diagnostic and prognostic features of this unusual vascular neoplasm. Three main tumour patterns were observed histologically: (1) a peripheral pattern with neoplastic cells scattered between fairly normal liver cell plates; (2) a cellular pattern showing a confusing admixture of pleomorphic tumour cells and atrophied hepatocytes set in a small amount of fibrous stroma; and (3) a scarred pattern with sparse tumour cells in a dense fibrous matrix. There were two types of vascular invasion: tuft-like intravascular proliferations of epithelioid cells and fibro-thrombotic venous occlusions. Awareness of these different aspects is important, as they are variably sampled by biopsy needles. The clinical course in this series was less favourable than that previously reported. Eight patients have died, in six instances of liver failure within 4-41 months of diagnosis. Extensive involvement of both lobes of the liver heralds imminent hepatic failure. The slow growth of metastases may justify liver transplantation in order to prolong life.     

Prognostic assessment in patients with hepatic encephalopathy

Hepatic encephalopathy (HE) is a common complication of liver failure that is associated with poor prognosis. However, the prognosis is not uniform and depends on the underlying liver disease. Acute liver failure is an uncommon cause of HE that carries bad prognosis but is potentially reversible. There are several prognostic systems that have been specifically developed for selecting patients for liver transplantation. In patients with cirrhosis the prognosis of the episode of HE is usually dictated by the underlying precipitating factor. Acute-on-chronic liver failure is the most severe form of decompensation of cirrhosis, the prognosis depends on the number of associated organ failures. Patients with cirrhosis that have experienced an episode of HE should be considered candidates for liver transplant. The selection depends on the underlying liver function assessed by the Model for End-stage Liver Disease (MELD) index. There is a subgroup that exhibits low MELD and recurrent HE, usually due to the coexistence of large portosystemic shunts. The recurrence of HE is more common in patients that develop progressive deterioration of liver function and hyponatremia. The bouts of HE may cause sequels that have been shown to persist after liver transplant.     

Diffuse hepatocyte ballooning in liver biopsies from orthotopic liver transplant patients

Mild to moderate liver injury to the orthotopically transplanted liver may result from acute rejection, mild ischaemia, or viral hepatitis. Because these conditions are often clinically indistinguishable, liver biopsy is frequently helpful. We previously characterized and reported the morphological spectrum of mild-to-moderate ischaemic injury from 170 liver biopsies (51 liver transplant patients). During this review, we found eight patients with a diffuse hepatocyte ballooning pattern. This pattern had some similarity to 'preservation injury' described by others, and in fact seven of the eight patients had these changes within the first 2 weeks post-transplant. However, two of the seven patients also displayed these changes up to 6 months post-transplant and the eighth patient developed these histological patterns only after the early post-transplant period. Follow-up data on patients with diffuse hepatocyte ballooning showed that some reverted to normal histology, some transformed to well-delineated perivenular ballooning, and some progressed to perivenular necrosis and/or infarction. Only when superimposed perivenular necrosis became apparent did the injury become irreversible, necessitating allograft removal or resulting in death. The pathogenesis of diffuse hepatocyte ballooning is unclear. However, the association of some of the cases with 'preservation injury' pattern in the early post-transplant period and the progression of others to necrosis and infarction, suggest an ischaemic basis for this lesion.     

肝脏上皮样血管内皮瘤穿刺标本的病理诊断与鉴别诊断

目的 提高对经皮肝穿刺活检标本中上皮样血管内皮瘤(EH)的认识.方法 收集北京肿瘤医院1999-2010年3016例肝穿刺活检标本中5例诊断EH的病例,回顾性分析5个病例的光镜下病理形态学特点、免疫组织化学(polymer二步法)检测结果,以及患者的临床表现、实验室检查和影像学结果.结果 5例均为女性,年龄23～47岁,平均39岁.4例B超显示肝多发实性肿物并考虑转移癌;实验室检查各项指标未见明显异常.光镜下肿瘤细胞上皮样、排列成短条索状或小巢状,包埋于特征性黏液玻璃样基质中,可见明显的胞质内空泡;瘤细胞形态温和,未见核分裂;免疫组织化学表达血管标志物CID31、CD34、第八因子相关抗原,偶见表达平滑肌肌动蛋白.结论肝穿刺活检标本中,如果病变具有典型的EH形态特点和免疫组织化学表达,同时又有临床及影像学支持,即可明确诊断;应用多种抗体组合有助于肝穿刺活检标本EH的诊断与鉴别诊断.

Abstract：

Objective To evaluate the pathologic diagnosis of hepatic epithelioid hemangioendothelioma (EH) in needle biopsy specimens. Methods Five cases of hepatic EH diagnosed in needle biopsies encountered during the period from 1999 to 2010 in Beijing Cancer Hospital were retrospectively reviewed. The specimens were formalin-fixed, paraffin-embedded and stained with hematoxylin and eosin. Immunohistochemical study was also carried out. Results All the 5 patients were females. The age ranged from 23 to 47 years ( mean = 39 years). The tumors in 4 patients were multiple and diagnosed as "metastasis" on ultrasound examination. The blood test results in all of the 5 patients were normal. Histologically, the tumor cells had an epithelioid appearance and were arranged in cords, solid nests or isolation, amongst a myxoid or hyaline matrix. The tumor cells contained scattered intracytoplasmic vacuoles which sometimes harbored red blood cells. There was no evidence of significant cellular pleomorphism, high mitotic activity and necrosis. Immunohistochemically, all of the 5 cases were positive for at least two endothelial markers (CD31, CD34 and factor Ⅷ-related antigen). Smooth muscle actin was expressed in 1 case. Conclusions The diagnosis of hepatic EH can be established in needle biopsy specimens. The histologic pattern, when coupled with immunohistochemical findings, is useful in arriving at the correct diagnosis.     

Regulation of hepatic blood flow in patients with liver cirrhosis and after liver transplantation

We studied liver blood flow at rest and its regulatory changes after exercise and food intake in ten patients with advanced liver cirrhosis and in 14 patients more than 10 months after orthotopic liver transplantation. The results were compared with those obtained in ten healthy volunteers. Sorbitol steady state infusion was employed to measure functional liver blood flow (FLBF). Thirty minutes of half-maximal muscular work, performed on a supine position ergometer and consumption of a standard meal were used as stimuli to study regulatory changes in hepatic perfusion. Results: FLBF at rest was reduced in end stage cirrhosis (mean 1257±105 ml/min in cirrhosis vs. 1707±76 ml/min in controls; P<0.01). After liver transplantation FLBF at rest was normalized (mean 1922±169 ml/min) in patients with stable graft function. Muscular exercise led to a reduction in FLBF, which in the transplanted patients was the same range as in normal controls (−26.7±3.7%; −24.7±0.7, respectively), but was reduced in cirrhosis (−19.1±2.1%; P<0.05). After ingestion of a standard meal FLBF increased substantially in normal controls (+40.2±2.3%), while in patients with cirrhosis this increase was rather small (+10.1±1.9%; P<0.001). After transplantation the food-induced increase in FLBF(+20.5±3.6%) was larger than in cirrhosis (P<0.05) but remained smaller than in the controls (P<0.01). We conclude that in cirrhosis FLBF is reduced and adaptive changes after exercise or food intake are impaired. After transplantation FLBF is normalized, but blood flow regulation, especially after food intake remains abnormal.     

左外叶活体肝移植肝静脉的临床应用解剖

目的 :观察肝左叶静脉解剖结构 ,模拟左外叶活体肝移植肝静脉切取方法。方法 :解剖正常人肝脏标本 30具 ,观察肝脏铸型标本 30具 ,测量肝左静脉长度、管径及属支分布情况。结果 :肝左静脉主要由左外叶上段静脉支和下段静脉支汇合并延续而成 ,主要接收或不接收较有意义的属支有左后上缘静脉支和左叶间裂静脉支。结论 :肝左外叶静脉血管解剖变异较多 ,活体取肝前应仔细研究其结构特点 ,设计合理的切取模式 ;移植前肝静脉需行必要的整形 ,以便与受体静脉进行吻合。少数情况下肝左外叶活体移植为禁忌证。     

选择性肝动脉栓塞治疗肝外伤术后胆道出血

目的 介绍选择性肝动脉栓塞治疗肝外伤术后胆道出血的体会。方法 采用Seldinger法于右股动脉穿刺将5F的RH导管选择性或超选择性地插和病灶区的肝动脉分支内，经DSA造影证实插管无误后，将明绞海绵微粒注入，进行肝动脉栓塞止血。结果 本组病例经1次栓塞达到了止血目的，无死亡及严重并发症。结论 该方法不需麻醉，对患者影响小，随着DSA和DTA的应用，插管更准确，栓塞止血效果更确切，并发症少，有效地挽救了那些不能耐受再次手术的患者的生命，被认为是目前治疗肝外伤术后胆道出血的十分有效的方法。     

原位肝移植供肝血管及胆道修整

目的探讨原位肝移植供肝血管及胆道系统的修整处理方法。方法回顾性分析31例原位肝移植其供肝动脉变异及胆道内异常情况的处理资料。结果肝动脉变异5例,其中2例肝左动脉来自胃左动脉,2例肝右动脉来自肠系膜上动脉,1例肝总动脉来自肠系膜上动脉。来自肠系膜上动脉的2例肝右动脉,1例吻合到脾动脉的断端;另1例将腹腔干吻合到肠系膜上动脉的近端。供肝的肝内胆管行冲洗时发现有寄生虫2例。结论避免变异的供肝动脉损伤,选择适当的肝动脉吻合方式可以保证移植肝脏的动脉血供。正确的供肝胆道处理,可以减少胆道的并发症。     

左外叶下段活体肝移植肝裂的应用解剖

目的;为左外叶下段活体肝脏移植直术提供肝裂的应用解剖学资料。方法：在３０例成人尸肝上观察肝左叶间裂和左外叶段间介和铸型后部分界之间的关系。结果：肝左叶间裂以状韧带为外部分界标志,与内部真正的分界不完全一致,该裂中部向左右偏移可分别达１～２ｃｍ。左外叶段间裂膈面分界９０％偏 上、／４～２／５部,脏面８０％偏前（下）１／３～１／２部,其中５０％偏差２／５～１／２部,左外叶下段膈面较脏面大。结论：左外叶     

肝癌患者肝移植术中酸碱平衡及电解质的变化

目的 探讨肝癌病人肝移植术中血液酸碱平衡及电解质浓度变化的规律，为肝癌病人行肝移植术时针对血液酸碱及电解质紊乱治疗提供参考依据。方法系统回顾分析16例因肝癌行肝移植术病人术中血液钾、钠、钙离子浓度和pH、HCO3^-、BE值的变化规律。结果血K^ 从无肝期开始下降；开放后即刻呈现一过性升高表现，部分病人表现为暴发性高血钾。血游离钙在无肝期和新肝期降低明显。无肝期和新肝期pH、HCO3^-、BE值的变化表现为代谢性酸中毒。结论手术开始后，从无肝期就应注意纠正低血钾和低血钙，开放瞬间注意暴发性高血钾。保持血液动力学的稳定,同时进行过度通气和给予适当的碱性物质有助于减轻酸性物质的产生和酸中毒。     

供肝肝动脉解剖变异及其临床意义

目的 总结原位肝移植供肝切取所见肝动脉解剖变异类型及重建方式。回顾性分析1999年2月至2001年1月间21例肝移植供肝肝动脉解剖结构及整形重建过程。直视下以7／0Prolene缝线完成供肝动脉血管整形重建。术后一周内每天以Doppler超声扫描监测肝动脉血流,其后定期监测。结果 21例供肝中,14例为正常解剖结构,7例存在肝动脉解剖变异需整形后与受体肝动脉吻合。1例术后5d时肝动脉栓形成。14例随访1－19月（平均6．9月）,Doppler超声扫描提示肝动脉血流正常,胆道造影未见肝外胆管狭窄,血清学检查提示肝功能状态良好。结论 供肝动脉变异时宜采取适宜的方式整形重建肝动脉以形成单一备吻合血管。     

慢性肝病肝剪切波速与血清肝纤维化标志物在肝纤维化诊断中的对比研究

目的 探讨慢性肝病肝剪切波速及血清肝纤维化标志物在肝纤维化分级诊断中的临床应用价值.方法 选择235例慢性肝病患者(肝纤维化组),其中男性179例,女性56例;年龄17～64岁,平均年龄36.3岁.40例健康对照者,其中男性25例,女性15例;年龄25～62岁,平均年龄43.2岁.先进行肝剪切波速和抽血实验室检查,然后在超声引导下穿刺活组织检查,以病理结果为标准,分析剪切波速及血清肝纤维化标志物在评价肝纤维化分级之间的关系.并将检查结果与健康对照者进行比较.结果 235例慢性肝病患者有215例进行肝穿刺活组织检查,除F0级肝病患者与健康对照组F0级之间剪切波速比较差异无统计学意义(P＞0.05)外,其余肝病各分组剪切波速随肝纤维化程度的增高而波速增快;且血清肝纤维化标志物含量亦随肝纤维化病理分期的增高而增高.结论 肝剪切波速及血清肝纤维化标志物对肝纤维化患者的病理分期有良好相关性,对肝纤维化的诊断及疗效观察有重要的临床应用价值.     

Expression of MTA2 and Ki-67 in hepatocellular carcinoma and their correlation with prognosis

The aim of this study was to investigate the relationship among MTA2, Ki-67 and HCC patient prognosis. Tissue microarray and immunohistochemistry were used to detect the expression of MTA2 and Ki-67 in HCC samples and corresponding adjacent samples. We found MTA2 and Ki-67 were both increased in HCC tissues than those in adjacent tissues and nuclear MTA2 was associated with Ki-67 (P = 0.019). Moreover, nuclear MTA2 was a risk factor of distant metastasis in patients with HCC andKi-67 showed a negative correlation with histological grade (P < 0.05, P < 0.01, respectively). Multivariate Cox model analysis revealed that Ki-67 expression was an independent prognosis factor in HCC patients (P = 0.020). These results indicated there might be a tight correlation among MTA2, Ki-67 and HCC prognosis. MTA2 combined with Ki-67 might be used to predict HCC patient prognosis.     

Activation of hepatic stellate cells in liver tissue of patients with fulminant liver failure after treatment with bioartificial liver

We studied the explanted livers from 12 patients with fulminant hepatic failure who were treated with a bioartificial liver and subsequently underwent orthotopic liver transplantation and from 18 patients who underwent orthotopic liver transplantation without previous treatment. Ten normal livers were used as controls. In addition to morphologic evaluation, an immunohistochemical analysis was performed with the monoclonal antibodies for alpha-smooth muscle actin and proliferation marker Ki-67. The expression of these markers was graded semiquantitatively from 0 to 3+ in a blinded fashion. The zonal distribution of activated hepatic stellate cells was also evaluated. In all cases, the hepatic stellate cells were activated and expressed alpha-smooth muscle actin. In all patients with submassive or massive liver cell necrosis, the distribution of activated hepatic stellate cells was predominantly in zone 1 of the acinus (periportal area). In contrast, in cases with early nodular regeneration and no significant fibrosis, the activated hepatic stellate cells were distributed throughout the liver parenchyma, involving zones 2 and 3 of the acinus. Expression of the proliferation marker Ki-67 was graded 3+ in all patients treated with the bioartificial liver who had orthotopic liver transplantation and 2+ in patients who underwent orthotopic liver transplantation only.     

Proliferative processes in the epidermis of patients with atopic dermatitis treated with thymodepressin

Proliferative activity of the epidermis in skin biopsy specimens from patients with atopic dermatitis before and during therapy with thymodepressin (immunosuppressant) was studied by immunohistochemical method (by expression of Ki-67 antigen). The number of Ki-67-positive keratinocyte nuclei in atopic dermatitis considerably surpassed the corresponding parameter in intact skin (32.46±3.06% vs. 8.73±1.28%, p<0.05). Two 10-day courses of thymodepressin (0.1% solution, 1 ml intramuscularly) for 30 days reduced the number of Ki-67-positive keratinocyte nuclei to 20.78±3.36%. Clinical improvement was also achieved (sleep became normal, itching decreased, erythema and desquamation also decreased or disappeared). These findings suggest that disorders in keratinocyte proliferation are an important component in the pathogenesis of atopic dermatitis and confirm high efficiency of thymodepressin in the treatment of this condition.     

Veno-occlusive disease of the liver in patients receiving immunosuppressive therapy

Summary The paper presents the morphological findings and clinical data of 4 patients with veno-occlusive disease of the liver developing after immunosuppressive therapy with azathioprine and prednisolone. The pathogenesis and a possible causal relationship of hepatic veno-occlusive disease with long term azathioprine therapy are discussed.Presented in part at the XIIIth International Congress of the International Academy of Pathology, Paris, September 15–19th 1980