Study of small hepatocellular carcinomas

In order to evaluate the factors affecting patient survival, 32 patients with a solitary hepatocellular carcinoma (HCC) smaller than 5 cm have been studied. Most patients were diagnosed as having a HCC during the periodic follow-up examinations for their underlying liver disease. For HCCs smaller than 2 cm, ultrasonography demonstrated the highest detection rate compared with CT and angiography. In patients with tumors larger than 2 cm, a portal vein thrombus and/or satellite tumors were frequently recognized, resulting in a lower patient survival rate when compared to those with a smaller HCC. Results have indicated that early detection of such tumors without a portal vein thrombus and/or a satellite tumor, and an adequate hepatic resection, such as segmentectomy or subsegmentectomy, are most important factors HCC patient survival.     

混合型肝癌超声造影检查的研究

目的 探讨混合型肝癌的临床特点,研究超声造影检测混合型肝癌的准确率及有效性.方法 回顾性分析经超声造影检查且经手术切除病理证实为混合型肝患者50例的临床资料.结果 50例患者中54％的小型肝细胞癌可以切除,而且手术后并发症少.亚临床期没有症状的患者预后较好,可以认为是早期混合型肝癌.68％病人血清AFP＜ 200 ng/ml,且AFP值与混合型肝癌大小没有平行关系.在高发生率地区,对AFP持续微量超高者,应高度怀疑混合型肝癌,并进一步检查.混合型肝癌没有一定的回音模式,不过肿瘤越小越趋向于低回音性,直径＜2 cm的肝细胞癌,76.5％呈低回音性,3 cm以上者84.6％为高回音性病灶.结论 CT扫描对混合型肝癌(＜3 cm)诊断率比超声扫描稍差,对于混合型肝癌而言,超声造影检查敏感性最高,特异性最佳,对肿瘤的生长情况也能够完全把握.     

Hepatocellular pseudotumor in the cirrhotic liver. Report of three cases

Three cases of regenerating hyperplastic nodule in the cirrhotic liver are reported in detail. The patients were all men, ranging in age from 41 to 57 years. They were all heavy drinkers and had chronic liver disease for 6 to 10 years. All patients had slightly elevated alpha-fetoprotein levels and were positive for HBs and HBc antibodies. Radiologic findings were not uniform except for ultrasonography, which demonstrated the lesion in all cases. Preoperative diagnosis was hepatocellular carcinoma (HCC) or highly suspicious of HCC in all of them. At laparotomy, all lesions were embedded in the liver parenchyma and invisible from the hepatic surface. With the aid of intraoperative sonography, partial hepatic resections were performed. Pseudocapsule was seen in two cases. Definitive differential diagnosis of regenerating nodules from HCC in the cirrhotic liver was extremely difficult. The authors propose the name "hepatocellular pseudotumor in the cirrhotic liver" to describe such lesions.     

Early detection of hepatocellular carcinoma by real-time ultrasonography. A prospective study

For early detection of hepatocellular carcinoma (HCC), real-time ultrasonography (US) was performed prospectively in 528 patients, including 236 with cirrhosis, 81 with chronic hepatitis, 168 asymptomatic hepatitis B surface antigen carriers, and 43 with a family history of HCC. Simultaneous measurement of serum alpha-fetoprotein (AFP) level was also done. In addition, 233 patients had regular controls at 3- to 6-month intervals, with an average follow-up period of 1.4 years. On initial screening, a total of 17 patients were found to have HCC: 13 in the cirrhotic group, 3 in the HCC family group, and 1 in the asymptomatic carriers. Of these HCCs, 7 were smaller than 3 cm, 6 were between 3 to 5 cm, and 4 were larger than 5 cm. In patients with tumors smaller than 5 cm, the AFP levels were normal in 46.2%, between 20 to 400 ng/ml in another 46.2%, and only 7.6% were over 400 ng/ml. On follow-up, another seven patients, all in the cirrhotic group, were found to have HCCs varying from 1.6 to 4.7 cm; three of them had normal serum AFP level. The authors conclude that real-time US is more sensitive than AFP assay in early detection of HCC, and the high-risk subjects should receive this procedure at regular intervals.     

Surgical resection of hepatocellular carcinoma

The incidence of hepatocellular carcinoma (HCC) is increasing in the United States, primarily due to hepatitis C-related liver disease. Nearly 85%-90% of patients with HCC have underlying chronic liver disease or cirrhosis. Advanced tumor burden or prohibitive hepatic dysfunction precludes operative resection in most patients with HCC. Surgical resection is a treatment option with curative intent in patients with HCC not associated with cirrhosis or in patients with well-compensated liver disease. Tumor extent and hepatic function must be assessed preoperatively to avoid postresection hepatic failure, an often fatal condition that may require urgent liver transplantation. Appropriately selected candidates for liver resection have 5-year postoperative survival rates of 40%-70%, but recurrence rates approach 70%, especially in patients with cirrhosis. For this reason, the best resection for patients with HCC and cirrhosis is orthotopic liver transplantation, which has 5-year posttransplant survival rates of 65%-80% in well-selected candidates.     

Chronological changes of causes of death and distant metastasis in hepatocellular carcinoma

The diagnostic approaches, mode of therapies, frequencies of distant metastasis and causes of death in 139 patients with hepatocellular carcinoma (HCC) between 1976 and 1998 were studied by dividing the total study duration into three periods. The period between 1976-1980 (period I) was characterized by the absence of periodic follow-up of the patients with chronic liver diseases, and operation was the only therapeutic choice for HCC. During 1981-1986 (period II), periodic screening of patients with chronic liver diseases was started using ultrasonography, and transarterial embolization became a second choice of therapy along with operation. Period III (1986-1998) was characterized by the availability of facilities to make definitive diagnosis of HCC using small-gauge cutting needle biopsy under sonographic guidance. Data from our study show that along with the advancement of new and invasive diagnostic and therapeutic approaches, the frequency of death due to gastrointestinal bleeding decreased, whereas, the frequency of death due to respiratory failure resulting from pulmonary metastasis increased. Patients treated with transcatheter arterial embolization were more prone to develop pulmonary metastasis. These data show that patients with HCC undergoing invasive therapies should be checked for distant metastasis in addition to intrahepatic recurrence of HCC.     

Recent advances in ultrasonographic diagnosis of hepatocellular carcinoma

The diagnostic accuracy of ultrasonography (US) for hepatocellular carcinoma (HCC) was estimated by checking against the regional cancer registry, and also the clinical features, major therapy, and prognosis of HCC cases diagnosed by initial US were examined for the two periods of 1980 and 1984. The number of patients with HCC was 83 of 4442 in 1980 and 86/3393 in 1984. As for the detectability of the tumor, the sensitivity improved from 94.0% to 96.5%. Regarding the ability to confirm the detected tumor to be HCC, the sensitivity improved from 53.0% to 68.6% without decrease in the specificity of 99.9%. The size and number of nodules were more accurately diagnosed in 1984, and cases with small (less than or equal to 4 cm) single nodule increased from 2% to 9%. Active therapy was performed in more cases and the 2-year survival rate increased from 9% to 20%. The remarkable improvement was achieved in the diagnostic accuracy of US for HCC during 4 years from 1980 to 1984.     

肝超声造影监测和早期诊断微小肝癌的应用价值

背景与目的：我国肝癌发病率高,原发性肝癌常在肝硬化的基础上发生,早期诊断较为困难。本研究应用实时超声造影对肝癌高危患者进行定期跟踪监测,探讨其早期发现和诊断微小肝癌的临床应用价值。方法：2011年2月-2013年11月针对320例肝癌高危患者进行定期的肝常规超声检查和追踪定位的肝超声造影检查,根据肝内病灶在超声造影不同时相的增强表现特点鉴别诊断其良恶性。结果：320例肝癌高危患者定期随访中,经肝超声造影发现和诊断微小肝细胞癌20例,并经手术病理证实,包括直径≤1.0 cm肝癌7例、1.1~2.0 cm肝癌13例。其中6例(30.0%)呈不典型的“快进同出”型表现;病灶小,灰阶超声上呈等回声是超声造影表现不典型的主要因素。结论：常规超声和超声造影对肝癌高危患者的定期跟踪监测,可早期发现微小肝癌,使患者得到及时治疗。     

Hepatic resection for a hepatocellular carcinoma larger than 10 cm.

Twenty-one patients with hepatocellular carcinoma (HCC) larger than 10 cm diameter were treated during the 18 year period from 1971 to 1988. The mean tumor size was 13 cm (range 10-18 cm). Nineteen patients (90.5%) had subjective symptoms. Eight patients (38.1%) had alpha-fetoprotein (AFP) levels over 10,000 ng/ml, and in 18 patients (85.7%) the levels were over 20 ng/ml. Nevertheless, only three (14.3%) were detected by AFP. Scintigraphy before 1981 and ultrasonography after 1982 appears to be most helpful for detection of HCC. Nineteen lesions (90.5%) were localized in the right hepatic lobe. Large HCC showed a low incidence of histologically verified concomitant cirrhosis (33%; 7 of 21) and a relatively well preserved hepatocellular function (indocyanine green test; 13.9 +/- 6.6%). Curative resection could be done for all 21 patients. There were three (14.3%) operative deaths. The 1-, 3-, and 5-year survival rates were 72.2, 32.9, and 8.2%, respectively. One patient who underwent a left hepatic lobectomy has survived for over 5 years, with recurrence. There were 14 recurrences (66.7%) in 21 patients: 11 were hepatic and three were in the lungs. In patients with large HCC, surgical resection should be done, provided the clinical status and hepatocellular reserves are adequate.     

Hepatocellular carcinoma with extrahepatic malignancies]

A clinical investigation of 16 hepatocellular carcinoma (HCC) patients with extrahepatic malignancies (13 male, 3 female) has been conducted. The age of these patients ranged from 55 to 76 years. Three of these double cancer cases were hemocronous, and 13 were heterochronous. The duration between the occurrence of the cancers ranged from 2 years and 4 months to 22 years. As for the site of the other cancer, the stomach was the most common organ (12 cases). In nine cases out of 16, the HCC was resected, whereas the other cases were treated with a TAE and hepatic artery ligation because the cancer were far advanced stages. Early detection of an HCC by AFP or an ultrasonographic examination, and a subsequent surgical resection in cases of a postoperative cancer patient with a liver dysfunction may lead to a more favorable prognosis.     

单抗免疫酶斑点法检测GGT-Ⅱ在肝癌诊断中的价值

背景与目的：肝癌特异性γ-谷氨酰转肽酶同工酶Ⅱ(gamma-glutamyltransferase isoenzymeⅡ,GGT-Ⅱ)被认为是甲胎蛋白(AFP)以外的最佳肝癌标志物,但目前尚无简便的检测方法。本研究目的是探讨单克隆抗体免疫酶斑点法检测GGT-Ⅱ对肝细胞癌的诊断价值。方法：纯化GGT-Ⅱ同工酶,免疫BALB／c小鼠,利用杂交瘤技术制备单克隆抗体。采用免疫酶斑点法与电泳法同步检测123例肝癌和164例不同良性肝病患者血清中GGT-Ⅱ。结果：单克隆抗体免疫酶斑点法检测GGT-Ⅱ对肝细胞癌的诊断阳性率(71．5％)与电泳法(76．4％)相比无明显差异。但免疫酶斑点法假阳性率(肝硬化23．7％,慢性肝炎27．1％)高于电泳法(肝硬化10．0％,慢性肝炎8．4％)。结论：单克隆抗体免疫酶斑点法检测GGT-Ⅱ对肝细胞肝癌诊断有一定价值,但诊断特异性有待提高。     

Less invasive medical therapy for hepatocellular carcinoma

Since hepatocellular carcinoma (HCC) usually occurs in chronic liver disease, especially viral cirrhosis, it often recurs even after surgical resection. Because of the high recurrence rate of HCC, less invasive therapies have become more common recently, including percutaneous ethanol injection (PEI), percutaneous microwave coagulation therapy(PMCT), and radiofrequency ablation(RFA). A PEI needle or a coagulation electrode is usually inserted into an HCC nodule under ultrasonographic-guidance, and chemical or heat ablation is carried out with local or general anesthesia. A patient with a few numbers of small HCCs of 3 cm or less in diameter is a good candidate for these therapy modalities. Although RFA is the easiest and most effective of these therapies the best therapy for each patient is selected according to the number, size, and location of target lesions.     

肝癌组织雌激素受体表达与生物学特征的研究

目的 探讨雌激素受体（ｅｓｔｒｏｇｅｎ ｒｅｃｅｐｔｏｒ,ＥＲ）在肝细胞肝癌（ｂｅｐａｔｏｃｅｌｌｕｌａｒ ｃａｒｃｉｎｏｍａ,ＨＣＣ）中的表达及其与ＨＣＣ生物学特征的关系。方法 用免疫组织化学方法检测了４３例ＨＣＣ及对应癌旁肝组织及４例正常肝组织的雌激素受体的表达,经大体及显微镜检查了这些肝细胞肝癌的病理特征。结果 雌激素受体阳性率在肝细胞肝癌为３７．２１％,癌旁肝组织为６０．４６％,正常肝组织     

Liver resections for hepatocellular carcinoma in chronic liver disease: experience in an Italian centre.

AIM: Liver resection (LR) and transplantation are the best options for treatment of hepatocellular carcinoma (HCC). We retrospectively analysed the experience obtained with LR for HCC in chronic liver disease patients. METHODS: Up until May 2005, 248 patients with HCC were evaluated, and 113 resected. Of these, 97 with chronic liver disease, who underwent a total of 100 resections, form the basis of this study. Age of the patients was 65.6+/-9.2 years (range 32-81, male/female 76/21). In 77 cases there was unifocal and in 23 multinodular tumour; in 61 the size of the tumours was < or =5 cm and in 39>5 cm. Limited resections were performed in 15 cases, resections of 1-2 segments in 51, and major hepatectomies in 34. RESULTS: Blood transfusions were required in 28 cases. Three patients died postoperatively, from liver failure and/or sepsis. Seventeen patients had nonlethal complications (mostly liver dysfunction, often with signs of amplified inflammatory response, including ARDS, without evident sources of sepsis). The 5- and 10-year survival rates were 44% and 24%, respectively. Decreased survival was significantly related to increasing number of tumour nodules and degree of liver fibrosis/presence of cirrhosis, and with the expression of markers of carcinogenesis in a sub-group who received this assessment. At 5 years the rate of liver HCC recurrence was 46%, however, death was unrelated to recurrence in 41% of non-survivors. CONCLUSIONS: Surgery for HCC achieves acceptable early and long-term results. However, the patterns affecting perioperative outcome must be better understood, and the high recurrence rate warrants further trials to assess preventive treatments after LR.     

小肝肿瘤的诊断和术中定位

本文复习经B型超声、CT及AFP诊为小肝肿瘤36侧,内肝细胞癌23例,海绵状血管瘤11例,转移癌2例。肿瘤最大径<3cm者14例,3—5cm22例,位于右肝叶22例,左肝叶14例。 CT对肝细胞癌和肝转移癌的诊断准确率为100％,对肝海绵状血管瘤的准确率为72.7％;B型超声为81.8％。AFP在23例肝细胞癌的阳性率为66.6％。 本文介绍了在术中不能看见或不能触到的小肝肿瘤的寻找方法,7例由此发现而顺利作了切除术,计肝细胞癌4例,海绵状血管瘤2例,转移癌1例。     

Dysplastic nodules frequently develop into hepatocellular carcinoma in patients with chronic viral hepatitis and cirrhosis

BACKGROUND: Advances in imaging technology have enhanced the detection of small nodular lesions during the course of chronic liver disease. METHODS: Between 1995 and 2002, the authors examined 154 consecutive patients with small hepatic nodules without hepatocellular carcinoma (HCC) over a median duration of 2.8 years. The median size of these nodules was 14 mm (range, 7-40 mm). The initial histopathologic diagnosis included high-grade dysplastic nodule (HGDN) (n=13), low-grade dysplastic nodule (LGDN) (n=42), and regenerative nodule (RN) (n=99). RESULTS: A total of 29 (18.8%) nodules developed into HCC during the observation period. Cumulative HCC development rates at the first, third, and fifth year were 46.2%, 61.5%, and 80.8% for HGDN; 2.6%, 30.2%, and 36.6% for LGDN; and 3.3%, 9.7%, and 12.4% for RN, respectively. The rate of HCC development was significantly higher in the HGDN group than for other types (P<0.001). Multivariate analysis disclosed that histopathologic diagnosis (P<0.001) and findings on computed tomographic arterial portography (CT-AP) (P=0.004) were significantly associated with future HCC development. The hazard ratios of HGDN and LGDN were 16.8 (95% confidence interval [CI], 6.19-45.6) and 2.96 (95% CI, 1.20-7.31), respectively. A decrease in portal blood flow also showed a significantly high hazard ratio of 3.04 (95% CI, 1.42-6.50). Approximate annual development rate to HCC was 20% in patients with HGDN and 10% in LGDN. CONCLUSION: HGDN should be considered a precancerous lesion when it appears during follow-up of chronic viral hepatitis or cirrhosis. Reduced portal blood flow in the nodule on computed tomography-AP is also an important predictor for development of hepatocellular carcinoma.     

Hepatitis C and hepatocellular carcinoma

Chronic hepatitis C infection (HCV) accounts for approximately 50% of the cases of hepatocellular carcinoma (HCC) in the United States. Cirrhosis or an advanced stage of fibrosis is the major risk factor of HCC; patients with cirrhosis are recommended to undergo surveillance with alpha-fetoprotein and ultrasound. Alpha interferon (IFN-alpha) is associated with a reduced risk of HCC in patients with chronic infection but insufficient data exist to recommend treatment of patients with cirrhosis and HCV for this reason alone. Resection and liver transplantation are the only "curative" therapies available. Advanced fibrosis or cirrhosis in patients with HCC limits the number of patients for whom resection is applicable. Moreover, the remaining liver is at high risk of developing a second primary tumor. Partial hepatic resection for hepatocellular carcinoma should be restricted to patients with well-compensated cirrhosis (Child's A class). Acceptable parameters include a single lesion not exceeding 5 cm, normal levels of bilirubin, and absence of portal hypertension. Liver transplantation is the best definitive treatment for HCV-infected patients who have small, localized HCC (solitary lesion not greater than 5 cm, or no more than 3 lesions, none of which are greater than 3 cm). Limitations of liver transplantation as a therapy for HCC are the scarcity of donor organs and the prolonged waiting time during which continued tumor growth occurs. Living donors can reduce waiting time and increase the number of patients treatable by transplantation. Chemoembolization and local ablation therapies have not been shown to confer survival benefits as primary treatments for HCC. The potential benefit of these procedures in controlling tumor growth to "bridge" patients to liver transplantation must be further investigated. Similarly, systemic chemotherapy and hormonal therapy do not generally produce a survival advantage. However, recent studies that used octreotide and combination doxorubicin/cisplatin/5-FU/interferon appear to be promising.     

以外科手术为主综合治疗小肝癌134例临床报告

背景与目的：手术切除是治疗小肝癌的首选方法,但术后5年复发率高达35．4％－45．3％,是影响手术疗效的关键因素。本研究拟探讨以外科为主的综合治疗来降低小肝癌术后复发率。方法：以外科为主综合治疗小肝癌（直径≤5cm）患者134例,男119例,女15例,年龄18－70岁,中位年龄45岁;手术切除（切除组）121例,其中,不规则性肝叶切除16例,局部切除83例,肝叶或肝段切除12例,左半肝切除2例,联合胆吓切除8例;切除后切缘注射无水酒精或用渗入无水酒精的明胶海绵包埋于瘤床共22例。手术不能切除13例,行肝固有动脉结扎合并肝动脉及门静脉双插管化疗或瘤体内注射无水酒精或冷冻、射频治疗、微波固化、栓塞化疗等。结果：小肝癌手术切除率90．3％,无手术死亡。切除组术后1、3、5、10年生存率分别为89．3％、74．4％、64．6％和43．8％;术后1、3、5年复发率分别为11．9％、23．8％和32．1％。全组1、3、5、10年生存率分别为88．8％、72．2％、63．4％和41．7％;1、3、5年复发率分别为15．9％、29．1％和36．6％。结论：手术切除是治疗小肝癌的有效方法,以个体化为原则外科为主的综合治疗可降低术后复发率,提高小肝癌治疗效果。     

Chemoembolization therapy with lipiodol, cisplatin and etoposide for hepatocellular carcinoma

Chemoembolization using CDDP, VP-16 and lipiodol was carried out for 7 patients with hepatocellular carcinoma (HCC). CDDP/lipiodol, CDDP/VP-16, CDDP/lipiodol (lipiodol 2-10 ml, CDDP 1-2 mg/kg, VP-16 100 mg/body) and gelatine sponge were administered in that order through the catheter located in the proper, or right or left hepatic artery. Three patients underwent hepatic resection 38-50 days after this treatment. Complete necrosis of the tumor was recognized in the one case, although the portion of necrosis did not exceed 70% in large sized HCC as the diameter of more than 10 cm. In 4 unresectable cases the decreases in tumor size were observed by ultrasonography and computed tomography. The response was: 3 partial responses and 1 no change. One out of 4 cases could undergo hepatic resection 17 months after this treatment. Two patients are alive 20 months after this treatment, although one patient died of HCC after 25 months. Serious side effect was not observed.