Pure laparoscopic hepatectomy for hepatocellular carcinoma patients with severe liver cirrhosis

Hepatocellular carcinoma often arises in cirrhotic livers. Patients with severe liver cirrhosis who undergo hepatectomy often develop postoperative liver failure, even if the hepatectomy is limited. Here, we report six patients with severe liver cirrhosis (Child-Pugh B/C and indocyanine green retention rate at 15 min ≥ 40%) who underwent pure laparoscopic hepatectomy. Their perioperative course was favorable and comparable to that of other hepatocellular carcinoma patients with mild-moderate liver cirrhosis. In patients with severe liver cirrhosis, pure laparoscopic hepatectomy minimizes the disturbance in collateral blood and lymphatic flow caused by laparotomy and liver mobilization, as well as the mesenchymal injury caused by compression of the liver. It limits complications such as massive ascites, which can lead to severe postoperative liver failure. Good candidates for the procedure include patients with severe liver cirrhosis who have tumors on the liver surface and in whom adaptation to ablation therapy is difficult and/or who experience local recurrence after repeat treatments.     

gp96、Mcl-1在肝硬化和肝癌组织中表达及意义

目的通过研究gp96、髓样细胞白血病-1(Mcl-1)蛋白在肝硬化和肝癌组织中的表达及临床病理学意义,初步探讨其与肝硬化和肝癌发生、发展的关系。方法采用免疫组织化学ENVISION法分别检测19例肝硬化组织(癌旁肝硬化组织)、32例肝癌组织和21例对照肝组织(癌旁非硬化肝组织)中gp96、Mcl-1的表达,并分析其各自表达与肝癌临床病理学特征的关系。取来源于同一患者的肝癌组织、癌旁肝硬化组织或癌旁非肝硬化组织,分别配对检测gp96、Mcl-1,比较两者的阳性表达率。结果对照组、肝硬化组和肝癌组gp96阳性表达率逐渐递增,差异有统计学意义(P0.05);gp96的阳性表达与肿瘤有无包膜、TNM分期有关(P0.05),与患者的性别、年龄、肿瘤大小、血清甲胎蛋白(AFP)值、组织学分级及临床分期无关(P0.05)。肝癌组和肝硬化组Mcl-1阳性表达率明显高于对照组(P0.05),但肝癌组和肝硬化组之间差异无统计学意义(P0.05);Mcl-1阳性表达与肿瘤有无坏死和TNM分期有关(P0.05)。肝癌组gp96阳性表达率明显高于配对癌旁肝硬化组及配对癌旁非肝硬化组(P均0.05);而肝癌组Mcl-1阳性表达率明显高于配对癌旁非肝硬化组,与配对癌旁肝硬化组比较差异无统计学意义(P0.05)。结论 gp96、Mcl-1过表达可能与肝癌的发生、发展有关。gp96可能参与了肝硬化的发生、发展及向肝癌的恶性转化,有助于判断肝癌患者的预后。     

Hepatocellular carcinoma in advanced liver cirrhosis: CT detection in transplant patients

Computed tomography (CT) is being used as the standard pretransplantation imaging for recipients and donors in the evaluation of liver volume, liver reserve function, vascular anatomy, diagnosis of hepatocellular carcinoma and metastasis, and global information of the abdominal cavity. Whereas CT detection of hepatocellular carcinoma in noncirrhotic patients is satisfactory, detection sensitivity in severely cirrhotic patients is limited, with a reported sensitivity of 53% to 68%. Tumors smaller than 2 cm are more difficult to detect. Innumerable regenerative nodules, localized or diffuse fibrosis, arterioportal shunts, nodular surface, and distorted anatomy in end-stage liver cirrhosis make it difficult to detect small hepatocellular carcinoma. Because of the shortage of cadavers and living donors, judicious use of CT is necessary in the selection of candidates and the decision of priority for liver transplantation in patients with advanced liver cirrhosis.     

Role of computed tomography in screening for hepatocellular carcinoma in patients with cirrhosis

One hundred patients with cirrhosis underwent abdominal computed tomography (CT) using a delayed contrast technique to determine liver and spleen volume. These scans were reviewed to screen this at risk population for hepatocellular carcinoma (HCC). Fifteen of the 100 screened patients had focal abnormalities suspicious for HCC. On biopsy, only 1 patient was shown to have HCC. The other 14 patients had either fatty infiltration or focal regeneration. In the same time interval, a total of 10 patients had histologically proven HCC. All presented with symptoms and died within 4 months of diagnosis. The results show that focal hepatic lesions can be detected by CT but in this population the lesions may not be due to HCC. The incidence of HCC was approximately 1%, probably reflecting a truly low incidence in this population.     

肝癌外科治疗的进展

肝细胞癌发病率在过去二十年中在全世界范围内迅速上升。目前普遍采用的潜在的根治性治疗方式为手术切除和肝移植。约30％-40％肝癌患者采用该方式进行治疗。近年来肝癌外科的发展已不再单纯重视外科技巧方面的改进,肝脏储备功能、肿瘤可切除性的精确评估,肿瘤生物学对外科治疗的影响,肿瘤复发转移的干预等方面成为外科领域的研究热点。任何单一因素或者指标均不能充分、真实反应肝脏的储备功能。目前采用Child—Pugh评分、15分钟吲哚氰绿滞留率、门静脉压力与余肝体积的测量相联合,能提高术前评估的准确性及手术的安全性。切除术后患者5午生存率约为50％,此结果对于肝切除合并取癌栓的患者已属满意,包括门静脉癌栓和肝胆管癌栓的患者。局部切除在肝硬化患者中较为常见,而规则肝切除则多应用于没有肝硬化的肝癌患者,行局部切除还是规则肝切除目前仍有争议。肝癌肝移植的总体疗效优于手术切除治疗,目前肝移植治疗肝癌的最佳适应证仍为Milan标准,但由于现阶段移植器官的不足,肿瘤患者移植适应证的扩大应慎之又慎。手术切除后对部分肿瘤复发患者行“挽救移植”也是不错的策略。术后的复发和转移一直影响疗效的主要障碍。术前确认可预测性的复发风险因素将有助于完善预防策略。肿瘤的分子指标将有助于预测准确性的提高。可以通过使用一些药物来预防或延迟肿瘤的复发,针对肿瘤生物发生途径中的关键分子进行靶向治疗也可使肝癌治疗发展日趋完善。     

原发性血色病伴肝癌临床病理观察

目的 探讨原发性血色病的临床病理特征。方法 对1例原发性血色病伴肝癌及肝癌术后复发患者进行临床、病理组织学和特殊染色观察，并结合文献探讨其发病机制、病理形态及鉴别诊断。比较放血疗法治疗前后患者肝铁沉积变化及病理组织学改变。结果 原发性血色病为常染色体隐性遗传性铁贮积病，过量铁在肝、胰、心、肾、皮肤及脾等部位广泛沉积，造成靶器官实质细胞破坏，导致脏器功能损害。肝是最早和最严重的铁聚集部位，肝硬化和肝癌是本病的主要致死原因。反复放血排出体内的铁是此病最有效、最经济的治疗方法。结论 此病早期无特异表现，极易漏诊，确诊有赖于肝活检的病理诊断。早期诊断、早期治疗可明显延长患者的生存期。     

Intrahepatic bile duct dilatation secondary to hepatocellular carcinoma: CT features in 10 patients

Background: To determine the computed tomographic (CT) features of bile duct obstruction secondary to hepatocellular carcinoma (HCC). Methods: CT examinations of 10 patients (mean age, 58 years) with bile duct obstruction secondary to HCC were retrospectively reviewed. Results: All tumors were intrahepatic. Eight tumors were well-delineated and two were ill-defined. The largest diameters of tumor ranged from 1.5–6.0 cm (mean, 3.6 cm). All tumors were hypodense before contrast and did not contain calcification. After contrast, four tumors became hypodense, three were isodense, and three were hyperdense to the liver. No tumor demonstrated encapsulation. Diffuse intrahepatic bile duct dilatation was observed in seven patients. One patient had extrahepatic bile duct dilatation. Localized bile duct dilatation was observed in three patients, in the hemi-liver which contained the tumor. No tumor invaded the portal vein. Conclusion: Although rare, HCC should be included in the differential diagnosis of bile duct obstruction. This diagnosis should be suggested in patients with bile duct obstruction when CT shows an associated intra- or extrahepatic mass. Our results suggest that HCC responsible for bile duct obstruction is remarkable for the absence of encapsulation.     

Type 2 diabetes mellitus increases liver transplant-free mortality in patients with cirrhosis: A systematic review and meta-analysis

BACKGROUNDThe impact of type 2 diabetes mellitus (T2DM) on the prognosis and complications of liver cirrhosis is not fully clarified. AIMTo clarify the mortality and related risk factors as well as complications in cirrhotic patients with T2DM.METHODSWe searched PubMed, EMBASE, and the Cochrane Library from their inception to December 1, 2020 for cohort studies comparing liver transplant-free mortality, hepatocellular carcinoma (HCC), ascites, spontaneous bacterial peritonitis (SBP), variceal bleeding, and hepatic encephalopathy (HE) in cirrhotic patients with vs without T2DM. Odds ratios (ORs) were combined by using fixed-effects or random-effects models with RevMan software.RESULTSThe database search generated a total of 17 cohort studies that met the inclusion criteria. Among these studies, eight reported the risk of mortality, and eight reported the risk of HCC. Three studies provided SBP rates, and two documented ascites rates. Four articles focused on HE rates, and three focused on variceal bleeding rates. Meta-analysis indicated that T2DM was significantly associated with an increased risk of liver transplant-free mortality [OR: 1.28, 95% confidence intervals (CI): 1.16-1.41, P < 0.0001] and HCC incidence (OR: 1.82, 95%CI: 1.32-2.51, P = 0.003). The risk of SBP was not significantly increased (OR: 1.16 95%CI: 0.86-1.57, P = 0.34). Additionally, T2DM did not significantly increase HE (OR: 1.31 95%CI: 0.97-1.77, P = 0.08), ascites (OR: 1.11 95%CI: 0.84-1.46, P = 0.46), and variceal bleeding (OR: 1.34, 95%CI: 0.99-1.82, P = 0.06).CONCLUSIONThe findings suggest that cirrhotic patients with T2DM have a poor prognosis and high risk of HCC. T2DM may not be associated with an increased risk of SBP, variceal bleeding, ascites, or HE in cirrhotic patients with T2DM.     

超声造影与增强磁共振显像早期诊断肝硬化伴小肝癌的应用研究

目的 探讨肝硬化背景下超声造影(contrast-enhanced ultrasound CEUS)与增强磁共振显像(MR)对小肝癌(≤2.0cm)的早期诊断和鉴别诊断的差异性及临床应用的互补性.方法 临床观察45例伴有肝硬化的肝占位病变患者,术前行CEUS及增强MR检查,分别记录病灶检出个数、增强形式及诊断结果.所有病灶均经手术切除或穿刺病理证实,对两项检查结果进行回顾性对比研究.结果 45例患者增强检查后,超声造影发现病灶69个,增强MR发现病灶58个,两项检查共检出病灶75个,病理诊断肝癌病灶41个.小肝癌在超声造影与增强MR增强模式存在交叉,其中以模式Ⅰ"快进快出"及模式Ⅱ"快进慢出"最典型,将其作为诊断肝硬化伴小肝癌的标准,二者对肝癌的诊断率分别为77.3%(58/75)和62.7%(47/75)(0.50＜P＜0.75).对于不典型增强形式下的小肝癌病灶二者的诊断率差异有统计学意义(0.025＜P＜0.05).结论 CEUS及增强MR对于肝硬化伴小肝癌病灶的诊断率相似.对于不典型增强病灶,CEUS与增强MR各有优势,存在对小肝癌及良性病灶的诊断差异.     

超声造影对肝硬化合并小肝癌的早期诊断价值

目的观察肝硬化背景下不同组织类型小肝癌(≤3．0cm)的超声造影灌注时间及增强模式，探讨超声造影对小肝癌的诊断价值。方法146例肝局灶性病变行超声造影，其中经手术或穿刺病理确诊肝硬化合并小肝癌(≤3．0cm)42例48个病灶；记录分析48个病灶造影增强模式，并进行造影前后良恶性诊断5级评分比较。全部病例造影前、后半个月内行增强CT检查进行对比。结果造影后中～低分化肝癌38个病灶(79．2％)动脉期发生快速强化，实质期快速消退，呈“快进快出”型；6个高分化小肝癌呈“快进慢出”型；4个肝透明细胞癌中3个≤1．5cm灶呈“慢进慢出”型，另1个2．2cm肿瘤呈“快进快出”型。造影前仅27个病灶(56．0％)超声作出正确诊断或诊断恶性倾向；造影后14个病灶(29．0％)评分提高2～4分，17个病灶仅提高1分。最终有2个病灶仍未能获得定性诊断，有4个病灶仅诊断恶性倾向，余42个病灶被确认恶性，诊断正确率达87．5％(42／48灶)。结论灰阶超声造影对肝硬化背景下不同组织类型小肝癌增强模式的初步研究，可为小癌灶的早期诊断提供依据；作为CT等影像诊断的互补手段，超声造影可成为诊断肝硬化合并小肝癌灵敏可靠的方法。     

鲁南地区HBV基因型和HBV核心启动子双点突变与肝硬化、肝癌的关系

目的研究鲁南地区肝细胞癌(HCC)、肝硬化(LC)患者与乙型肝炎病毒(HBV)基因型及基本C区启动子(BCP)基因区A1762T/G1764A双位点变异之间的关系,探讨其相关性。方法按慢性HBV感染者111例的不同临床分型,对其中HCC、LC和慢性乙型肝炎(CHB)患者各37例,采用实时荧光定量PCR法及PCR微板核酸杂交ELLSA技术进行HBV基因定量、分型检测;采用HBV基因多态性芯片检测BCP区A1762T/G1764A双位点变异;对不同性别、年龄、病毒基因型分布、临床分型患者进行HBV基因分型、BCP区双突变,以及不同HBV基因型BCP双突变的比较。结果在CHB、LC、HCC患者中,HBeAg阴性者分别为24.3%、75.7%和83.8%;HCC患者HBeAg阴性率较CHB患者明显升高(P<0.05)。男、女性别HBV均以C基因型占优势,分别为57.3%和54.5%,性别间无统计学差异(P>0.05);年龄<30岁组HBV以B基因型(40.3%)、C基因型(51.7%)占优势,≥30岁组以C基因型(67.2%)占优势,<30岁组B基因型构成比高于≥30岁组(29.6%,P<0.05);HCC、LC患者中HBV以C基因型为主,分别占73.0%和75.6%。BCP双突变率在HCC、LC分别为64.9%和56.8%;HBVC基因型多发生BCP双突变,占63.6%(42/66)。结论鲁南地区HBV基因型以C型和B型为主,其中LC、HCC患者基因型以C型占优势,HCC患者BCP双突变率显著高于CHB患者,在慢性HBV感染者中HBVC基因型多发生BCP双突变。     

Bile duct involvement in hepatocellular carcinoma: MR demonstration

Background: To determine the magnetic resonance (MR) features of hepatocellular carcinoma (HCC) with associated bile duct involvement. Methods: MR examinations of six patients (mean age, 62 years) demonstrating bile duct involvement due to HCC were retrospectively reviewed and compared to surgical and pathologic findings. Results: Three of the tumors were solitary, and three were multifocal. In two patients, MR showed direct biliary duct invasion by tumor. On T1-weighted MR images, four tumors were hypointense compared to the liver and two were isointense. On T2-weighted MR images, four tumors were hyperintense, and two were isointense. The two tumors studied with dynamic T1-weighted MR images obtained after intravenous administration of a gadolinium chelate, displayed enhancement similar to that of the liver. There was no evidence of a tumor capsule on either unenhanced or enhanced MR images. Intrahepatic bile duct dilatation was seen in five patients. The extrahepatic bile duct was normal in all cases. Conclusion: Although rare, HCC should be included when considering the etiology of intrahepatic bile duct obstruction. Imaging features suggestive of the diagnosis by MR include intrabiliary tumor or bile duct obstruction with an associated hepatic mass.     

门冬氨酸鸟氨酸注射液治疗肝硬化肝性脑病的疗效观察

目的探讨门冬氨酸鸟氨酸注射液治疗肝硬化肝性脑病的疗效。方法将92例肝硬化肝性脑病患者随机分为门冬氨酸鸟氨酸（10—20g加5％GS250ml,静脉滴注,1次／d）,加常规治疗组（A组）和常规治疗组（B组）,（支链氨基酸和乙酰谷酰胺）,疗程皆为7d,观察治疗前后患者,临床症状和体征,检测治疗前后肝功能及血氨的变化,判断临床疗效。结果治疗后,A组中24h清醒36例,72h清醒40例,B组中24h,清醒22例,72h清醒34例,P〉0．05,A组血氨治疗前后分别为（110．30±33．4）μmol／1,（46．30±27．35）μmol／l。B组为（110．25±23．40）μmol／1,（63．21±21．91）μmol／l,A组治疗前后ALT分别为（298．61±325．15）U／L,（165．30±180．18）U／L,血清胆红素分别为：（278．01±185．21）μmol／1,（224．34±159．80）μmol／1（P〈0．01）,B组血ALT治疗前后分别为（375．60±360．80）U／L（224．34±159．80）U／L,血清胆红素分别为（334．70±170．58）μ／1（279．60±167．17）μmol／l,（P〈0．01）。结论门冬氨酸鸟氨酸能有效降低血氨及胆红素,是控制肝性脑病的有效药物。     

肝硬化及原发性肝癌患者血清半胱氨酸蛋白酶抑制剂C水平的改变及其意义

目的探讨血清半胱氨酸蛋白酶抑制剂C(Cys C)水平在肝硬化和原发性肝癌(PLC)患者中的变化及其临床意义。方法采用胶乳增强免疫透射比浊法测定90例肝硬化、153例PLC及95例肝脏良性病变患者(对照组,包括肝血管瘤、肝囊肿)血清Cys C水平,同时采用酶法检测血清肌酐(SCr)及尿素(Urea)水平。分析Cys C、SCr、Urea在肝硬化、PLC和对照组间的差异以及Cys C与SCr、Urea之间的相关性。按照Child-Pugh标准对肝硬化患者的肝功能进行分级,对肝功能不同等级间Cys C、SCr、Urea水平进行比较。结果肝硬化组血清Cys C水平为(1.04±0.24)mg/L,肝癌组为(0.98±0.28)mg/L,均高于对照组[(0.78±0.18)mg/L](P<0.001),肝硬化组亦高于肝癌组(P<0.05)。肝硬化组和肝癌组Urea和SCr水平无明显差异,但均明显高于对照组(P<0.05)。血清Cys C与SCr呈正相关(肝硬化、肝癌和对照组的r值分别为0.407、0.673、0.511,(P均<0.001)。肝硬化组和肝癌组中血清Cys C异常率均明显高于SCr及Urea(P均<0.001)。肝硬化Child-PughB+C级血清Cys C水平[(1.12±0.21)mg/L]显著高于Child-Pugh A级[(0.99±0.25)mg/L](P<0.05)。结论血清Cys C水平随着肝病的进展和患者肝功能的衰退而升高,且比SCr和Urea更能灵敏的反映慢性肝病患者的早期肾损伤。     

肝硬化患者测定血清脂蛋白及载脂蛋白的意义

目的 探讨血清脂蛋白及载脂蛋白测定在肝硬化疾病中的价值。方法 高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)采用酶法(选择遮蔽),载脂蛋白A1(apoA1)、载脂蛋白B100(apoB100)采用免疫透射比浊法。上述项目全部在O-LYMPUS1000全自动生化分析仪上检测。结果 肝硬化失代偿期血清HDL-C、LDL-C、apoA1、apoB100浓度均明显降低,与正常对照组比较有非常显著性差异(P<0.01-0.001)。肝硬化代偿期血清HDL-C及apoA1降低明显,与正常对照组比有显著性差异(P<0.05-0.01),而LDL-C、apoB100下降不明显,与正常对照组比无显著性差异(P>0.05)。结论 肝硬化患者同时检测HDL-C、LDL-C、apoA1及apoB100水平,不仅可以反映肝脏脂蛋白和载脂蛋白合成代谢水平,同时可以判断肝硬化严重程度及预后,对指导临床治疗有一定意义。     

原发性肝癌与肝硬化患者外周血IL-2及NK细胞活性的研究

目的通过检测外周血IL-2水平和NK细胞活性,探讨原发性肝癌(PHC)和肝硬化(LC)患者的细胞免疫功能变化。方法采用MTT比色法检测41例PHC和57例LC患者外周血白细胞介素2(IL-2)的水平,采用流式细胞术(FCM)检测NK细胞活性。结果PHC患者外周血IL-2水平和NK细胞活性均明显降低(P<0.001),且较LC患者也明显降低(P<0.05);LC患者外周血IL-2水平和NK细胞活性明显降低(P<0.01)。结论PHC和LC患者外周血IL-2水平和NK细胞活性明显降低,检测上述两项指标对临床了解患者细胞免疫功能状态、预测病情变化和疗效具有一定的参考价值。     

肝细胞肝癌和肝硬化组织中的卵圆细胞:电镜与免疫电镜研究

目的　从电镜和免疫电镜水平 ,探讨人类肝癌和肝硬化肝组织存在如动物肝癌形成实验中的卵圆细胞的可能性。方法　对 10例人肝细胞肝癌的手术标本及其癌旁肝硬化组织作了电镜超微结构观察 ,并用胆管上皮分化抗体CK7和肝细胞分化抗体白蛋白对以上组织作超薄切片免疫电镜标记。结果　电镜下 ,所有肝癌(10例 )和肝硬化 (10例 )组织均可找到与我们在人肝母细胞瘤、胆道闭锁肝中所见的三型小上皮细胞。这类细胞卵圆形 ,位于肝癌肿瘤边缘和增生的胆小管内 ,在肝硬化组织则位于汇管区及再生的肝结节内。免疫电镜下 ,三型卵圆细胞均表达CK7和白蛋白 ,但Ⅰ型和Ⅱ型表达CK7多些 ,Ⅲ型表达白蛋白多些。结论　人肝细胞肝癌和肝硬化肝组织中存在卵圆细胞 ,其形态和免疫表型特点与动物致癌模型肝中卵圆细胞一致。结果进一步支持肝前体细胞或干细胞样细胞的假设     

肝癌和肝病患者血清甲胎蛋白异质体的检测及临床意义

目的探讨甲胎蛋白异质体（AFP-L3）检测在肝癌鉴别诊断中的意义。方法应用微量离心柱法分离检测小扁豆凝集素结合型AFP-L3的含量,同时检测血清中AFP总含量,由此得出AFP-L3的百分含量（AFP-L3%）。结果以AFP-L3%〉10%作为阳性判断标准,27例肝癌患者血清AFP-L3阳性率为70%,肝硬化和慢性肝炎AFP-L3%分别为10%和9.6%,肝癌AFP-L3%水平明显高于肝硬化和慢性肝炎（P〈0.01）;以AFP〉25ng/ml作为阳性判断标准,肝癌、肝硬化和慢性肝炎患者血清中AFP阳性率分别为78%、60%和55%;以AFP、AFP-L3%作为诊断肝癌指标的灵敏度分别是78%、70%,特异度分别是43%、90%。结论 AFP-L3%能有效区分肝癌和慢性肝病,弥补肝癌诊断的不足,具有一定的临床实用价值。     

乙型肝炎肝硬化患者幽门螺杆菌感染与血氨水平的关系

目的:探讨乙型肝炎肝硬化患者幽门螺杆菌(Helicobacterpylori,Hp)感染与血氨的关系,为临床防治肝性脑病是否需要常规根除Hp提供理论依据。方法:收集86例乙肝肝硬化住院患者,分Hp(+)组和Hp(-)组,并选取同期住院的Hp阳性的胃溃疡或胃炎患者60例作为对照组。Hp(+)组以埃索美拉唑、克拉霉素及阿莫西林行Hp根治性治疗,分别检测各组的空腹血氨及Hp(+)组治疗前后血氨浓度变化。根据肝功能Child分级及食管静脉曲张程度进行分组,比较各组血氨水平。结果:Hp(+)组血氨浓度明显高于Hp(-)组,差异有显著性(P<0.01);Hp(+)组根除Hp后血氨浓度较治疗前明显下降,差异有显著性(P<0.005)。Hp(+)组中Child-PughB、C级血氨浓度明显高于A级,差异有显著性(P<0.01),Ⅰ°、Ⅱ°食管静脉曲张血氨水平Hp(+)组明显高于Hp(-)组,差异有显著性(P<0.05)。结论:Hp感染可使乙肝肝硬化患者血氨水平升高,根除Hp有助于预防和治疗乙肝肝硬化高氨血症。