Hepatic resection for hepatocellular carcinoma in diameter of > or = 10 cm

BACKGROUND/AIMS: Definitive efficacy of hepatic resection for hepatocellular carcinoma larger than or equal to 10 cm in diameter remains to be resolved. METHODOLOGY: The surgical outcomes in 33 consecutive patients with hepatocellular carcinoma in diameter of > or = 10 cm who underwent hepatic resection were retrospectively clarified. Postresection prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. RESULTS: The overall incidence of postoperative complications was 39%, and 5 patients among them had hospital deaths (15%) including 2 (6%) operative deaths. The 3-year, 5-year, and 9-year overall survival rates after hepatic resection were 32%, 27%, and 17%, respectively. Univariate analysis revealed that liver cirrhosis and stage IV-A (pTNM staging) were significant factors of poor overall survival. By Cox's proportional hazards model, liver cirrhosis was an independently unfavorable prognostic factor of long-term survival. Hospital mortality rate in patients with cirrhosis was 31%. The 5-year overall survival rate in patients with cirrhosis (7%) was significantly shorter than that in patients without cirrhosis (43%) (P = 0.006). In addition, the 5-year overall survival rate in patients with stage IV-A (11%) was significantly shorter than that in patients with stage II and III (48%) (P = 0.024). The incidence of stage IV-A in patients with cirrhosis (77%) was significantly higher than those without cirrhosis (35%) (P = 0.032). CONCLUSIONS: Hepatic resection for hepatocellular carcinoma in diameter of > or = 10 cm was effective for patients without liver cirrhosis and with stage II or III. Appropriate selection of the candidates for partial hepatectomy based on the above prognostic factors may play an important role in the improvement of high mortality rate and poor long-term survival for such patients. Prospective randomized trials are needed to define the role of hepatic resection for cirrhotic patients with large HCC.     

Surgical treatment for hepatocellular carcinoma (HCC) 3 cm or less than 3 cm in diameter.

The efficacy of surgical treatment of small hepatocellular carcinoma (3 cm less in diameter) was studied in 30 patients with solitary tumors. The survival of the patients surviving at least three months after resection was 95% at 1 year, 69% at 2 years, 50% at 3 and 4 years. With regard to the range of resection in cases of partial resection the survival rate was 94% after 1 year, 64% after 2 years, and 47% after 3 and 4 years, while in the case of more than subsegmental resection the 4-year survival rate was 100% and a significant difference was noted. Recurrence was noted after 47% of the partial resections and 25% of the subsegmental or larger resections, and 6 of the 8 recurrent site especially in lesions of less than 2 cm were within the same segmental region. Thus, in the surgical treatment of solitary cancers smaller than 3 cm in size, resection of the segmental resection seems to be preferred whenever the functional reserves of the liver permits.     

Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma < or =4 cm

BACKGROUND & AIMS: The aim of this study was to compare the clinical outcome of percutaneous radiofrequency (RF) ablation, conventional percutaneous ethanol injection (PEI), and higher-dose PEI in treating hepatocellular carcinoma (HCC) 4 cm or less. METHODS: A total of 157 patients with 186 HCCs 4 cm or less were randomly assigned to 3 groups (52 patients in the conventional PEI group, 53 in the higher-dose PEI group, and 52 in the RF group). Clinical outcomes in terms of complete tumor necrosis, overall survival, local tumor progression, additional new tumors, and cancer-free survival were compared across 3 groups. RESULTS: The rate of complete tumor necrosis was 88% in the conventional PEI group, 92% in the higher-dose PEI group, and 96% in the RF group. Significantly fewer sessions were required to achieve complete tumor necrosis in the RF group than in the other 2 groups (P < .01). The local tumor progression rate was lowest in the RF group (vs the conventional PEI group, P = .012; vs the higher-dose PEI group, P = .037). The overall survival rate was highest in the RF group (vs the conventional PEI group, P = .014; vs the higher-dose PEI group, P = .023). The cancer-free survival rate was highest in the RF group (vs the conventional PEI group, P = .019; vs the higher-dose PEI group, P = .024). Multivariate analysis determined that tumor size, tumor differentiation, and the method of treatment (RF vs both methods of PEI) were significant factors in relation to local tumor progression, overall survival, and cancer-free survival. CONCLUSIONS: The results show that RF ablation yielded better clinical outcomes than conventional and higher-dose PEI in treating HCC 4 cm or less.     

Long-term outcomes of hepatectomy vs percutaneous ablation for treatment of hepatocellular carcinoma ≤ 4 cm

AIM: To determine which treatment modality--hepatectomy or percutaneous ablation--is more beneficial for patients with small hepatocellular carcinoma (HCC) (< or =4 cm) in terms of long-term outcomes. METHODS: A retrospective analysis of 149 patients with HCC < or =4 cm was conducted. Eighty-five patients underwent partial hepatectomy (anatomic in 47 and non-anatomic in 38) and 64 underwent percutaneous ablation (percutaneous ethanol injection in 37, radiofrequency ablation in 21, and microwave coagulation in 6). The median follow-up period was 69 mo. RESULTS: Hepatectomy was associated with larger tumor size (P<0.001), whereas percutaneous ablation was significantly associated with impaired hepatic functional reserve. Local recurrence was less frequent following hepatectomy (P<0.0001). Survival was better following hepatectomy (median survival time: 122 mo) than following percutaneous ablation (median survival time: 66 mo; P=0.0123). When tumor size was divided into < or =2 cm vs >2 cm, the favorable effects of hepatectomy on long-term survival was seen only in patients with tumors>2 cm (P=0.0001). The Cox proportional hazards regression model revealed that hepatectomy (P=0.006) and tumors < or =2 cm (P=0.017) were independently associated with better survival. CONCLUSION: Hepatectomy provides both better local control and better long-term survival for patients with HCC < or =4 cm compared with percutaneous ablation. Of the patients with HCC < or =4 cm, those with tumors >2 cm are good candidates for hepatectomy, provided that the hepatic functional reserve of the patient permits resection.     

Cost-effectiveness of radiofrequency ablation and surgical therapy for small hepatocellular carcinoma of 3cm or less in diameter.

BACKGROUND: Cost-effectiveness of radiofrequency ablation (RFA) was assessed in treatment of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: During 5 years, 153 patients with HCC of 3cm or less received RFA, and 60 underwent surgery. Judgment after RFA therapy was classified into three grades: residual tumor (grade 1), necrotic area with a less safety margin of 5mm (grade 2), and necrosis with a safety margin of 5mm in all directions (grade 3). RESULTS: Local recurrence rates after RFA and surgery were 7.9% and 0% at the third year. The rates in patients with grades 2 and 3 after RFA were 18.7% and 1.2% at the third year, respectively (P=0.0005). Among 91 patients with grades 1 and 2 necrosis after initial therapy, 52 received additional ablation. Although local recurrence rate was 24.9% in 39 patients without additional therapy, the rates after therapy repetition were 10.9% in 21 patients with eventual grade 2 necrosis, and 0% in 31 patients with grade 3 (P=0.038). Median costs of single RFA, repeated RFA, and surgery were yen849,900, yen1,086,000, and yen1,745,100, respectively. Additional ablation reduced local recurrence by 20.7% at the cost of yen236,100. CONCLUSION: Cost-effectiveness of RFA in the treatment of small HCC was superior to that of surgery.     

Prognostic factors for hepatocellular carcinoma recurrence

The recurrence of hepatocellular carcinoma, the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide, represents an important clinical problem, since it may occur after both surgical and medical treatment. The recurrence rate involves 2 phases: an early phase and a late phase. The early phase usually occurs within 2 years after resection; it is mainly related to local invasion and intrahepatic metastases and, therefore, to the intrinsic biology of the tumor. On the other hand, the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment. Since recent studies have reported that early and late recurrences may have different risk factors, it is clinically important to recognize these factors in the individual patient as soon as possible. The aim of this review was, therefore, to identify predicting factors for the recurrence of hepatocellular carcinoma, by means of invasive and non-invasive methods, according to the different therapeutic strategies available. In particular the role of emerging techniques (e.g., transient elastography) and biological features of hepatocellular carcinoma in predicting recurrence have been discussed. In particular, invasive methods were differentiated from non-invasive ones for research purposes, taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.     

Liver transplantation for solitary hepatocellular carcinoma less than 3 cm in diameter in Child A cirrhosis

Liver transplantation for hepatocellular carcinoma (HCC) is the treatment of choice for patients with unresectable tumors within the Milan criteria associated with Child B or C cirrhosis. Liver transplantation provides the best cure for both the HCC and the underlying cirrhosis. In recent years, some authors have advocated liver transplantation even for resectable early HCC associated with Child A cirrhosis, leading to a controversy of whether resection or transplantation should be the first-line therapy for patients with small HCC in Child A cirrhosis. Recent studies comparing liver resection and transplantation for early HCC demonstrated similar long-term survival of 60-70%, but liver transplantation is associated with a lower tumor recurrence rate. However, the current shortage of deceased donor liver grafts limits the applicability of liver transplantation for HCC. The use of live donor liver transplantation for patients with a small solitary HCC in Child A cirrhosis that is resectable may not be justified ethically because of the potential risk to the donors. Patients put on a transplantation waiting list run a significant risk of tumor progression and dropout, while liver resection is immediately applicable to all. Advocating primary liver transplantation for patients with early HCC associated with compensated cirrhosis will increase the waiting time for transplantation and further increases the chance of dropout. Resection first and salvage transplantation for recurrent tumors or liver failure is an alternative strategy that may reduce the use of liver grafts. However, the long-term survival result of such a strategy compared with primary liver transplantation remains unclear.     

Radiofrequency ablation for single hepatocellular carcinoma 3 cm or less as first-line treatment

AIM:To evaluate long-term outcomes of radiofrequency(RF) ablation as first-line therapy for single hepatocellular carcinoma(HCC) ≤ 3 cm and to determine survival and prognostic factors.METHODS:We included all 184 patients who underwent RF ablation as a first-line treatment for single HCC ≤ 3 cm between April 2005 and December 2013.According to the criteria of Livraghi,the 184 patients were divided into two groups:those suitable for surgical resection(84 cases) and those unsuitable for surgical resection(100 cases).The primary endpoints were the overall survival(OS) rate and safety;the secondary endpoints were primary technique effectiveness and recurrence rate.RESULTS:There were 19(10.3%) cases of ablation related minor complications.The complete tumor ablation rate after one RF session was 97.8%(180/184).The rate of local tumor progression,extrahepatic metastases and intrahepatic distant recurrence were 4.9%(9/184),9.8%(18/184) and 37.5%(69/184),respectively.In the 184 patients,the 1-,3-,and 5-year OS rates were 99.5%,81.0%,and 62.5%,respectively.The 1-,3-,and 5-year OS rates were 100%,86.9%,and 71.4%,respectively,in those suitable for surgical resection and 99.0%,76.0%,and 55.0%,respectively,in those unsuitable for surgical resection(P = 0.021).On univariate and multivariate analyses,poorer OS was associated with Child-Pugh B class and portal hypertension(P 0.05).CONCLUSION:RF ablation is a safe and effective treatment for single HCC ≤ 3 cm.The OS rate of patients suitable for surgical resection was similar to those reported in surgical series.     

Prognostic factors of spontaneously ruptured hepatocellular carcinoma

AIM: To evaluate the prognostic factors in patients with spontaneously ruptured hepatocellular carcinoma (HCC).METHODS: Seventy-nine patients experiencing spontaneous rupture of HCC between April 2004 and August 2014 were enrolled in this study. The clinical features, treatment modalities and outcomes were reviewed. The statistical methods used in this work included univariate analysis, Kaplan-Meier survival analysis with log-rank tests, and multivariate analysis using a Cox regression hazard model.RESULTS: Of the 79 patients with HCC rupture, 17 (21.5%) underwent surgery, 32 (40.5%) underwent transarterial embolization (TAE), and 30 (38%) received conservative treatment. The median survival time was 125 d, and the mortality rate at 30 d was 27.8%. Multivariate analysis revealed that lesion length (HR = 1.46, P < 0.001), lesion number (HR = 1.37, P = 0.042), treatment before tumor rupture (HR = 4.36, P = 0.019), alanine transaminase levels (HR = 1.0, P = 0.011), bicarbonate levels (HR = 1.18, P < 0.001), age (HR = 0.96, P = 0.026), anti-tumor therapy during the follow-up period (HR = 0.21, P = 0.008), and albumin levels (HR = 0.89, P = 0.010) were independent prognostic factors of survival after HCC rupture. The Barcelona-Clinic Liver Cancer (BCLC) stage was also an important prognostic factor; the median survival times for BCLC stages A, B and C were 251, 175 and 40 d, respectively (P < 0.001).CONCLUSION: Anti-tumor therapy during the follow-up period, without a history of anti-tumor therapy prior to HCC rupture, small tumor length and number, and early BCLC stage are the most crucial predictors associated with satisfactory overall survival. Other factors play only a small role in overall survival.     

经肝动脉化疗栓塞术治疗肝细胞癌的预后影响因素分析

目的探讨中晚期肝细胞癌(HCC)患者行肝动脉化疗栓塞术(TACE)的预后影响因素。方法回顾性分析南京医科大学附属淮安第一医院2007年5月-2012年5月收治的124例行TACE治疗的中晚期HCC患者的临床资料。应用Kaplan-Meier法计算累积生存率,Log-rank法进行检验;各影响因素行单因素Cox分析,再用多因素Cox逐步回归分析。结果 124例患者均获得随访,随访时间为3~40个月,患者0.5、1、2、3年累积生存率分别为97.6%、74.2%、15.5%、4.1%,中位生存时间为482 d。单因素分析显示,术前血清甲胎蛋白(AFP)水平、肿瘤大小、有无门静脉癌栓、肿瘤临床分期是HCC患者TACE预后的影响因素(P值均0.001);进一步多因素Cox逐步回归分析显示,肿瘤大小、肿瘤临床分期、术前血清AFP水平、门静脉癌栓是HCC患者TACE预后的独立危险因素(Wald值分别为7.428、7.699、15.235、5.803,P值均0.05)。结论肿瘤大小、肿瘤临床分期、术前血清AFP水平、有无门静脉癌栓是HCC患者TACE预后的独立危险因素,对临床判断预后及治疗方案的选择有指导意义。     

Prognostic factors for survival following transarterial chemoembolization in advanced hepatocellular carcinoma

The efficacy of transarterial chemoembolization in the palliative treatment of non-resectable hepatocellular carcinoma is controversial. To determine the possible existence of clinical and analytical variables with independent predictive value for survival related to the tumor and the treatment given, a multivariate analysis in a series of 111 patients who underwent transarterial chemoembolization was carried out. Overall actuarial survival was 54%, 31% and 24% at 1, 2 and 3 years respectively. Child-Pugh score (p < 0.05), tumor size (p < 0.05) and arterial occlusion after intraarterial chemotherapy (p < 0.05) reached independent predictive value. The group of patients in whom two or three of these factors were simultaneously present had a very poor prognosis with a survival of 20% and 0% at 1 and 2 years respectively, compared with 60%, 50% and 37% at 1, 2 and 3 years respectively in the group with one or none of these factors (p < 0.01). Grouping on the basis of these variables may be useful in the design of future controlled prospective studies that aim to determine the efficacy of transarterial chemoembolization.     

Prognostic factors for portal venous invasion in patients with hepatocellular carcinoma

Background Factors involved in portal venous invasion (PVI) must be clarified to enable better determination of therapeutic strategies and outcomes in patients with hepatocellular carcinoma (HCC). Methods Of 365 patients with HCC who consulted our department between January 1999 and January 2003, 53 with PVI at the initial consultation were excluded, and the other 312 without PVI were included in this study. Of these patients, we compared liver function, tumor markers, and initial treatment between 287 patients without PVI during follow-up (until December 2004) and 25 patients who developed PVI, and investigated prognostic factors. Results Multivariate analysis using a COX regression model showed that a Lens culinaris A-reactive fraction of α-fetoprotein (AFP-L3) rate of 15% or more, a des-γ-carboxy prothrombin (DCP) level of 100 mAU/ml or more, multiple tumors, and a platelet count of 130 000/mm³ or more were correlated with PVI. Conclusions HCC frequently infiltrated the portal vein in patients with a high rate of AFP-L3, a high level of DCP, or multiple tumors. Furthermore, the incidence of PVI was significantly higher in patients with a platelet count of 130 000/mm³ or more.     

Combining bronchoscopy and positron emission tomography for the diagnosis of the small pulmonary nodule < or = 3 cm

AIM: To assess the role of bronchoscopy and positron emission tomography (PET) scanning in an integrated approach for the diagnosis of noncalcified, small, chest radiologic lesions (< or = 3 cm). METHODS: Seventy-four consecutive patients (29 men; mean age, 64 years) with a pulmonary nodule < or = 3 cm undergoing both combined PET and bronchoscopy were included. When bronchoscopy and PET findings were negative, a multidisciplinary decision was taken to perform further invasive diagnostics or follow-up. RESULTS: Malignancy was diagnosed in 51 patients (69%), and a positive benign diagnosis was made in 9 patients (12%). Six patients (8%) had endobronchial lesions. Bronchoscopy was diagnostic in 53% patients (cancer, n = 35; benign, n = 4). PET findings were positive in 19 of 35 patients with a nondiagnostic bronchoscopy. In these 19 patients, malignant diagnosis was made in 14 patients (CT-fine needle aspiration [FNA], n = 3; thoracoscopic biopsy, n = 3; resection, n = 7; FNA of PET-positive supraclaviclar lymph node, n = 1), and a benign diagnosis was made in 5 patients (CT-FNA, n = 1; thoracoscopic biopsy, n = 1; resection, n = 1; follow-up, n = 2). In 16 patients with nondiagnostic bronchoscopy and negative PET findings, 5 patients had a tissue diagnosis (cancer, n = 2 [< 1 cm]; benign, n = 3) and 11 patients were followed up. Sixty-seven patients had a lesion 11 mm to 3 cm; among these, all 12 patients who were bronchoscopy negative and PET negative had benign lesions. In 24 patients without mediastinal adenopathy (solitary pulmonary nodule), bronchoscopy was diagnostic in 12 patients (cancer, n = 11; bronchiolitis obliterans organizing pneumonia, n = 1). In the remaining 12 patients, PET findings were positive in 6 patients (cancer, n = 3; resection, n = 2; CT-FNA, n = 1) and negative in 6 patients (benign, n = 2, both on resection; follow-up, n = 4). CONCLUSION: Combining bronchoscopy and PET scanning has an useful role in the diagnosis of noncalcified chest radiologic lesions < or = 3 cm in size. Bronchoscopy has a diagnostic yield of > 50% and also allows the diagnosis of endobronchial lesions. If bronchoscopy is nondiagnostic, a PET scan should be performed.     

Long-term effectiveness of radiofrequency ablation for hepatocellular carcinoma of 3.5 cm or less

BACKGROUND/AIMS: Hepatocellular carcinoma is one of the leading causes of death for cirrhosis, and patients are often not eligible for surgery. To evaluate the effectiveness of radiofrequency ablation in single (less than 3.5cm in diameter) or multiple nodules (up to 3, sized less than 3cm) in respect of acceptability, applicability, primary ablation rate, local recurrence, complications, and long-term patients outcome. METHODOLOGY: 184 hepatic nodules detected in 156 consecutive patients recruited from a local sonographic screening were treated. In 10.2% of patients under study, a laparoscopic or laparotomy guided technique was preferred to the percutaneous approach. Overall and tumor-free survivals were estimated by Kaplan-Meier method. For the multivariate analysis, the hazard ratios and their 95 percent confidence intervals were computed by Cox model regression analysis. RESULTS: No treatment-related deaths and a severe complication rate of 3.2% were recorded. Primary complete ablation was obtained in 83.7% of nodules (87.1% of patients), and in a significantly higher rate for nodules up to 2cm (91.3%; p<0.013). Acceptability was 100%, and eligibility was very high (156 out of 160 cases). Local recurrence rate at 1 and 3 years was 10% and 25% respectively. The overall 3- and 5-year survival rates after treatment were 69.3% and 34.6%. Higher survival rates were obtained in the Child A cirrhosis subgroup (p<0.03) after complete response (p<0.001) and in the absence of new lesions (p<0.023). CONCLUSIONS: Radiofrequency ablation has great acceptability and applicability, and is a safe and effective treatment to be used after sonographic screening for small hepatocellular carcinomas.     

Prognostic significance of pathological and biological factors in hepatocellular carcinoma

Prognostic factors in hepatocellular carcinoma (HCC) conventionally consist of staging with the tumour node metastasis system and grading by tumour cellular differentiation. There are also other factors useful in prognostication but most of them are clinical. With new discoveries in the pathobiology of cancers and introduction of new medical technology, pathological and biological factors of HCC in relation to prognosis have been studied quite extensively. Morphological features of the tumour, both gross and histological, have been found to be significantly related to tumour recurrence and patient survival. Recently, applications of new antibodies and techniques have enabled studies on cellular proliferation using different antibodies such as those for proliferating cell nuclear antigen and Ki-67 protein. These studies on cellular proliferation, as well as assessment of argyrophilic nucleolar organizing regions, have been shown to provide good prognostic significance. Flow cytometric studies on DNA ploidy and studies on expression of genes including the p53 gene, hormone receptors and others show less unanimous results in their prognostic significance. The influence of gender on survival is also reviewed. In conclusion, pathological and biological factors are useful and help to guide clinicians in the management of patients and in assessment of long-term prognosis.     

Prognostic factors for survival in patients with hepatocellular carcinoma after radiofrequency ablation]

BACKGROUND/AIMS: Currently there is no consensus on which staging system is the best in predicting the survival of patients with hepatocellular carcinoma (HCC). The aim of this study was to identify independent factors to predict survival and to compare 4 available prognostic staging systems in patients with early HCC after radiofrequency ablation. METHODS: We retrospectively studied 100 Korean patients with early HCC. Prognostic factors for survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, Cancer of the Liver Italian Program (CLIP), TNM and Japanese integrated staging score (JIS score) were evaluated before the treatments. RESULTS: Overall survival rates of 12, 24 and 36 months were 89%, 76%, and 64% respectively and the mean survival duration was 45 months. Multivariable analysis showed that albumin, total bilirubin and size of tumor were independent prognostic factors. Multivariate analysis showed that TNM and JIS score staging systems were significant staging systems for the prediction of prognosis. CONCLUSIONS: Both TNM and JIS score are more effective than the Okuda and CLIP staging systems in stratifying patients into different risk groups with early HCC. However, JIS score gives better prediction of prognosis in patients with HCC after radiofrequency ablation.