Alcoholic liver cirrhosis. Treatment of hepatocellular carcinoma

TRANSPLANTATION AND RESECTION: Surgery is still the only curative treatment of hepatocellular carcinoma (HCC). For patients with cirrhosis, liver transplantation for HCC with one nodule less than 5 cm in diameter, or no more than three nodules each less than 3 cm, gives the best results with a 5-year survival rate of 70%. Resection of a single tumor for patients with good liver function may also be performed with curative intent but the rate of recurrence is high. OTHER TECHNIQUES: Cryotherapy and radiofrequency are in-situ destruction methods used for small tumors. In the future, these procedures may compete with hepatic resection. When used alone, intra-arterial treatments, such as chemoembolisation, have only a palliative intent, but they also may be combined with other procedures. The treatment of advanced HCC is still limited and there is no standard approach for its management. HCC WITHOUT CIRRHOSIS: For those with HCC without cirrhosis, the same treatments are available but resection is more often performed because of the ability of the liver to regenerate. The management of patients with HCC with or without cirrhosis may combine several treatment modalities and needs a multi-disciplinary approach.     

Hepatic resection for hepatocellular carcinoma associated with liver cirrhosis

Sixty-three patients with hepatocellular carcinoma associated with cirrhosis received various kinds of treatment at our clinic during the past 21 years. Of these, 35 patients who underwent hepatic resection were divided into a large tumor group (tumors more than 5 cm in diameter) and a small tumor group (tumors less than 5 cm in diameter), and the operative results of both groups were studied. There was a difference in the average ages between the 2 groups ( p <0.05), but there was no difference in the duration of illness or laboratory data. The resectability rate of the liver in 17 patients with small tumors was 89% and was significantly higher than that of 41% in 18 patients with large tumors ( p<0.005). The overall operative mortality rate was 14% for both groups. Patients with tumors over 3 cm already exhibited the histological findings seen in advanced cancer. Cumulative 3-year survival rates of the large and small tumor groups were 0% and 53%, respectively, and there was a significant difference in survival curves between the 2 groups ( p<0.005). The above results suggest that hepatic resection for patients with small tumors is effective as a treatment for hepatoma associated with cirrhosis.

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Resumen En el Asia se presenta un elevado nÚmero de pacientes con cirrosis y carcinoma hepatocelular asociado. Un informe del grupo de Estudio de Cancer del Hígado del Japón expedido en 1982 reveló que el 85.6% de los pacientes con carcinoma hepatocelular presentaba cirrosis o fibrosis asociada. La mayoría de los pacientes que poseen ambas enfermedades exhibe no sólo una baja tasa de resección hepática en comparación con la de los pacientes no cirróticos, sino también un pronóstico pobre después de la cirugía. Sesenta y tres pacientes con carcinoma hepatocelular asociado con cirrosis recibieron diferentes formas de tratamiento en nuestra institución en el curso de los Últimos 21 años. De éstos, 35 pacientes sometidos a resección hepática fueron divididos entre un grupo con tumores grandes (tumores de más de 5 cm de diámetro) y un grupo de tumores pequeños (tumores de menos de 5 cm de diámetro) y los resultados del tratamiento operatorio fueron evaluados en ambos grupos. Apareció una diferencia en la edad promedio entre los dos grupos (p<0.05), pero no se observó diferencia en cuanto a la duración de la enfermedad o los resultados de las determinaciones de laboratorio. La tasa de resección hepática en 17 pacientes con tumores pequeños fue de 89% y significativamente mayor que la de 41% en 18 pacientes con tumores grandes (p<0.005). La tasa global de mortalidad operatoria fue de 14% para ambos grupos. Los pacientes con tumores de más de 3 cm ya exhiben los hallazgos histológicos que se presentan en el cáncer avanzado. Las tasas de supervivencia acumulada a 3 años de los grupos con tumores grandes y pequeños fue de 0% y de 53% respectivamente, y se encontró una diferencia significativa en cuanto a las curvas de supervivencia entre los dos grupos (p< 0.005). Los anteriores resultados sugieren que la resección hepática en pacientes con tumores pequeños es efectiva como tratamiento del hepatoma asociado con cirrosis.

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Résumé Au cours des 21 dernières années les auteurs ont soumis 63 malades atteints d'un cancer hépatocellulaire sur cirrhose à différentes thérapeutiques. Parmi eux 35 ont subi une résection hépatique. Ils ont été divisé en 2 groupes: selon que le diamètre de la tumeur était supérieur ou inférieur à 5 cm. Les résultats obtenus ont été comparé en fonction de la taille de la tumeur. Il a été constaté une différence significative entre l'âge des deux groupes mais aucune différence en ce qui concerne la durée de la maladie et les données biologiques. Le taux de résection a été de 89% quand le diamètre de la tumeur était inférieur à 5 cm (17 malades) et de 41% quand il était supérieur (18 malades). La mortalité globale a été de 14%. Dès que la diamètre de la tumeur était supérieur à 3 cm les caractères histologiques étaient identiques. Le taux de survie à 3 ans a été de 0% lorsque la tumeur était importante et de 53% quand elle était peu développée. Ces résultats permettent d'affirmer que la résection hépatique est efficace lorsque les malades atteints de cirrhose sont porteurs d'une tumeur de petite taille.

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Presented at the 8th World Congress of the Collegium Internationale Chirurgiae Digestivae at Amsterdam, The Netherlands, September 1984.     

Intraoperative ultrasonography in resection of small hepatocellular carcinoma associated with cirrhosis

Preoperative detectability rates of hepatocellular carcinoma smaller than 5 cm in 113 cirrhotic patients were 91 percent by ultrasonography, 93 percent by computed tomography, and 92 percent by selective angiography. The combination of two methods produced detectability rates of 97 to 99 percent. One hundred three patients underwent various types of hepatic resection with the aid of intraoperative ultrasonography. Forty-four tumors (43 percent) were embedded in the liver, and these tumors were not detected by conventional surgical exploration. The detectability rates were 38 percent for hepatocellular carcinomas smaller than 2 cm, 57 percent for 2 to 3.5 cm tumors, and 71 percent for 3.5 to 5 cm tumors. All undetectable hepatocellular carcinomas were identified by intraoperative echography. The overall detection rate by this method was 98 percent, which was substantially higher than the preoperative rate. Intraoperative ultrasonography is a useful and indispensable method for performing atypical minor hepatectomy for the treatment of small hepatocellular carcinomas associated with liver cirrhosis.     

ALPPS治疗巨大肝癌合并肝硬化

目的 探讨联合肝脏离断和门静脉结扎的二步肝切除术（associating liver partition and portal vein ligation for staged hepatectomy,ALPPS）治疗巨大肝癌合并肝硬化的安全性及其有效性。方法 对 2018年11月温州医科大学附属第一医院肝胆外科收治的1例巨大肝癌合并肝硬化患者的临床病理资料进 行回顾分析。结果 术前评估患者右半肝切除后剩余肝脏体积（future liver volume,FLV）不足,约占标准 肝体积35.68%。患者1期手术行右侧门静脉结扎并沿肝正中裂行射频消融术,术后2周,FLV达标准肝体 积的69.35%,吲哚菁绿排泄试验（indocyanine green retention rate at 15 min,ICGR15）为 25.5%,暂缓手术, 术后1个月再次测ICGR15为8.7%,遂行右半肝切除术。两次手术过程顺利,术中无明显出血,术后患者 无手术并发症,但术后出现腹水,经治疗后顺利出院。术后随访1个月,未见复发、转移,甲胎蛋白降至 正常范围。结论 ALPPS治疗巨大肝癌合并肝硬化的是安全有效的,但对2期手术的时机需严格把握,对 合并肝硬化的患者实施ALPPS术时,在2期手术前FLV最好大于40%且ICGR15小于10%。     

血色病性肝硬化肝癌病人的外科治疗

目的 对卫生部北京医院3例血色病性肝硬化肝癌病人的外科治疗进行回顾性分析,探讨手术、射频消融、红细胞单采的治疗效果.方法 3例病人均为男性,术前诊断为血色病性肝硬化、肝癌.3例病人共进行8次外科治疗,包括手术切除、B超引导下经皮经肝肿瘤射频消融治疗.2例病人术后进行了希罗达化疗.3例病人均接受了红细胞单采治疗.结果 手术病理证实为肝细胞肝癌、肝硬化,普鲁士蓝染色阳性,诊断为血色病.3例病人术后平均存活86个月(39～154个月).结论 对血色病肝癌病人而言,最重要的是早期发现,肝移植或切除是首选治疗.对于再次复发的病人,采用包括射频消融、化疗、红细胞单采治疗等在内的综合治疗可以有效延长病人生存.     

合并肝硬化的肝癌的手术切除

目的　探讨合并肝硬化的肝癌的手术切除的手术安全性及其影响因素。方法　以 1 9 9 7年 2月为界,将 2 2 9例肝癌合并肝硬化的患者分为A组和B组。比较两组患者的一般情况、并发症、病死率。分析影响手术并发症、病死率的因素。结果　B组的平均年龄明显高于A组 (P < 0. 0 5 ),B组的手术时间、术中出血量、输血量、并发症率、病死率明显低于A组 (P< 0. 0 5 )。手术时间和出血量为影响并发症的独立因素。结论　术前准确评估肝功能和未来肝残余量以决定手术范围;术中技术的改进缩短手术时间,减少术中出血,防止胆漏;术后等量输液,使用营养支持,早期肠内营养,合并肝硬化的肝癌的手术切除的安全性大大提高。     

Alcoholic liver cirrhosis. Screening for hepatocellular carcinoma in liver cirrhosis

HIGH INCIDENCE: Because of the high incidence of hepatocellular carcinoma (HCC) in patients with cirrhosis (3 to 5% per year) and the fact that curative treatment is currently available only for small sized tumors careful screening is warranted in this high risk population. Earlier screening attempts produced disappointing results in terms of cure and survival, particularly in Europe. Progress in ultrasonography, a better understanding of the risk of developing HCC, and most importantly the advent of local percutaneous treatments have greatly affected the data which should be reexamined. SCREENING METHODS: Patients with cirrhosis, particularly alcoholic or viral cirrhosis, should undergo regular ultrasound examinations, every six months for most screening protocols although the best timing remains unknown. Assay of serum alpha-fetoprotein is of limited use due to its low sensitivity and specificity. Diagnosis of HCC is basically based on helicoidal computed tomography and/or magnetic resonance imaging findings, with or without pathological proof (ultrasound-guided biopsy) that may be difficult to obtain. A probabilistic diagnosis is therefore retained if necessary, based on the presence of risk factors and arterial hypervascularization of a liver nodule. EARLY TREATMENT: With ultrasound screening, the diagnosis of HCC can generally be established early, when curative transplantation, resection or local percutaneous destruction are still feasible. The percutaneous methods use chemical or physical agents to destroy the tumor. There are few contraindications so curative treatment can be proposed for large number of patients. Large-scale prospective studies will be completed in the upcoming years and are expected to provide evidence validating the principle of screening and early treatment.     

Prognostic factors after hepatic resection for hepatocellular carcinoma associated with Child-Turcotte class B and C cirrhosis.

OBJECTIVE: To evaluate prognostic factors after resection of hepatocellular carcinoma (HCC) in patients with Child-Turcotte class B and C cirrhosis. SUMMARY BACKGROUND DATA: Although hepatic resection remains the mainstay in the treatment of HCC and can be performed with low morbidity and mortality rates in patients without cirrhosis, its role is poorly defined for patients with severe cirrhosis. METHODS: From 1986 to 1996, partial hepatectomy was performed for HCC in 63 patients with Child-Turcotte class B (n = 46) and C (n = 17) cirrhosis. There were 46 men and 17 women, with an average age of 61.2 years (range 35 to 79 years). Associated conditions were diabetes mellitus in 45, esophageal varices in 32, severe hypersplenism in 26, cholelithiasis in 13, gastroduodenal ulcer in 6, and hiatal hernia, gastric lymphoma, splenic abscess, and pancreatic cyst each in 1. Concomitant surgical procedures were performed for most of these conditions. RESULTS: Major complications occurred in 17 patients (27%), six (9.5%) of whom died within 1 month after surgery. The overall in-hospital death rate was 14.3%. Liver failure and intraabdominal sepsis were mostly fatal complications. The overall and disease-free survival rates, respectively, were 70.2% and 64.5% at 1 year, 43.5% and 23.8% at 3 years, and 21.4% and 14.9% at 5 years. Multivariate analysis with the Cox regression model revealed that favorable factors for survival were Child class B, no transcatheter arterial embolization before surgery, young age, and low alanine aminotransferase (ALT) level before surgery. CONCLUSIONS: Hepatic resection can provide a favorable result in young patients with HCC complicating Child class B cirrhosis with low hepatitis activity, but transcatheter arterial embolization before surgery should be avoided in such patients.     

Appraisal of hepatic resection in the treatment of minute hepatocellular carcinoma associated with liver cirrhosis

During the last 6 years, 205 patients with primary hepatocellular carcinoma (HCC) were admitted to our surgical departments. Thirty-eight had HCC smaller than 3 cm in diameter. There were 34 men and 4 women with an average age of 56.5 years. All patients had underlying hepatic disease: liver cirrhosis in 35 patients and chronic active hepatitis with fibrosis in the remaining 3. Pre-operative complications included: oesophageal varices in ten, cholelithiasis in five, peptic ulcer in two, gastric cancer in one, and severe hypersplenism in one instance. A radical resection was performed in 32 cases and palliative resection in 6. Simultaneous operations were carried out for the above mentioned associated conditions: distal splenorenal shunt in six, Hassab's devascularization procedure in one, splenectomy in one, cholecystectomy in four, cholecystolithotomy in one, and partial gastrectomy in one. Four patients had postoperative complications: liver failure, rebleeding, right haemothorax, and upper gastrointestinal bleeding from acute mucosal lesion of the stomach. One patient with liver failure died in coma within 1 month. The operative and in-hospital mortality rates were 2.6 and 7.9 per cent, respectively. Survival rates during the first 4 years in 32 patients with radical hepatic resection were 89.9, 67.2, 58.8, and 58.8 per cent, respectively. We suggest that hepatic resection should be the first choice of treatment for minute HCC even in the presence of liver cirrhosis.     

Effect of glucagon on bile acid after hepatectomy in patients with hepatocellular carcinoma associated with cirrhosis

Hepatic function frequently becomes worse, after hepatectomy in patients with hepatocellular carcinoma associated with cirrhosis. We usually use insulin and glucagon to treat patients with poor hepatic function, so we examined hepatic function in these patients in relation to bile acid metabolism. 1) Total serum bile acid levels were increased in patients with cirrhosis, and serum GCDCA, TCDCA values were especially high. After surgery, they rose even higher. 2) Glucagon was shown to stimulate C-AMP and decreased total serum bile acid, and especially serum GCDCA and TCDCA values.     

Liver resection for hepatocellular carcinoma in patients with cirrhosis

BACKGROUND: Although liver resection is now a safe procedure, its role for hepatocellular carcinoma (HCC) in patients with cirrhosis remains controversial. METHODS: This study compared the results of liver resection for HCC in patients with cirrhosis over two time intervals. One hundred and sixty-one patients had resection during period 1 (1991-1996) and 265 in period 2 (1997-2002). Early and long-term results after liver resection in the two periods were compared, and clinicopathological characteristics that influenced survival were identified. RESULTS: Tumour size was smaller, indocyanine green retention rate was higher, patients were older and a greater proportion of patients were asymptomatic in period 2 than period 1. Operative blood loss, need for blood transfusion, operative mortality rate, postoperative hospital stay and total hospital costs were significantly reduced in period 2. The 5-year disease-free survival rates were 28.2 and 33.9 per cent in periods 1 and 2 respectively (P = 0.042), and 5-year overall survival rates were 45.9 and 61.2 per cent (P < 0.001). Multivariate analysis identified serum alpha-fetoprotein level, need for blood transfusion and Union Internacional Contra la Cancrum tumour node metastasis stage as independent determinants of disease-free and overall survival. CONCLUSION: The results of liver resection for HCC in patients with cirrhosis improved over time. Liver resection remains a good treatment option in selected patients with HCC arising from a cirrhotic liver.     

Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis.

To determine whether a careful evaluation of tumor extension by preoperative computed tomography scan after intra-arterial injection of ultrafluid lipiodol and by intraoperative ultrasound examination reduced the recurrence rate of hepatocellular carcinoma after resection, a series of 47 cirrhotic patients with a single tumor operated on from 1984 was studied. Alphafetoprotein level was less than 100 ng/mL in 26 patients (55%), size of the tumor was less than 5 cm in 28 patients (59%), and capsule was present in 30 patients (63%). The resection was performed with free margin measuring 1 cm or more. The overall cumulative survival rates at 3 and 5 years were 35% and 17%, respectively. Intrahepatic recurrence was observed in 28 patients (60%), located less than 2 cm from the resection margin in only four patients. The cumulative intrahepatic recurrence rate at 3 years was 81% and was significantly higher in patients with tumor greater than or equal to 5 cm and in patients with preoperative alphafetoprotein level of greater than or equal to 100 ng/mL. In this series the cumulative intrahepatic recurrence rate at 5 years was 100%. This high recurrence rate after resection, even with careful evaluation of tumor extension, indicates that liver transplantation might be envisaged for the treatment of cirrhotic patients with resectable hepatocellular carcinoma.     

合并胆汁性肝硬化胆管结石的处理

如何选择合并胆汁性肝硬化胆石症病人的手术时机,对于外科医生通常是很棘手的问题。了解其病理及临床特征,进行胆道造影检查,如内镜逆行胰胆管造影、磁共振胰胆管成像,有助于诊断及选择最佳手术治疗方案。祛除病灶、纠正胆管狭窄是治疗该病的原则,而对于复杂肝胆管结石,应考虑采用分期手术治疗,一期接受胆道引流或(和)脾切除门奇断流、门体分流等手术,半年后再行二期胆道手术。内镜技术能有效地处理残余结石或复发。     

肝硬化合并微小肝癌的诊断和治疗

肝炎、肝硬化、肝癌被认为是肝炎（主要是乙型肝炎）发展的三步曲，三者往往是相互并存的。在我国，原发性肝癌病人合并肝硬化者占53．9％～85．0％，甚至高达90％以上。临床研究结果提示，小肝癌的治疗效果明显优于大肝癌，其中微小肝癌的疗效更佳。因此，建立完善的筛查体系，运用各种检查提高微小肝癌的检出率，合理地选择治疗手段是提高肝癌治疗效果的重要步骤。     

Treatment for hepatocellular carcinoma associated with tumor embolus in the inferior vena cava

Hepatic resection and removal of the tumor embolus was performed in six patients with hepatocellular carcinoma associated with tumor embolus in the inferior vena cava, without distant metastasis. Hepatic resection was performed in five patients under total hepatic vascular exclusion (THVE) with veno-venous bypass, using a centrifugal force pump and in one patient, under simple THVE without the bypass. In one patient, partial resection of segment VIII was performed, in one, a central bi-segmentectomy, and in four, right hepatic lobectomies were performed. Surgery was safely performed in all the 5 patients under THVE using the centrifugal force pump. One patient who underwent partial hepatic resection under the simple THVE, suffered cardiac arrest during surgery, but resuscitation was successful. Three patients died of reccurence within 1 year. The other three patients survived for 10 months, 2 years and 10 months, and 3 years and 10 months, respectively, after surgery. There were recurrences in the first two, patients, in both, treated by transcatheter arterial embolization, and to date, the third patient is disease-free. Hepatic resection was safely performed in patients with hepatocellular carcinoma associated with tumor embolus in the inferior vena cava, under conditions of THVE using the centrifugal force pump. Prolonged survival can be anticipated, with favorable liver function, in those patients in whom most of the lesion is resected.