Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma

To assess intrahepatic metastasis (IM) and multicentric occurrence (MO) after initial treatment of small hepatocellular carcinomas (HCC) < or = 2 cm in diameter, we performed clinical and pathological studies in 112 patients who underwent percutaneous ethanol injection therapy (PEIT) or hepatic resection for HCC from January 1985 to December 1994. Patients with intrahepatic recurrences were classified into two groups based on the type of recurrence: the IM group (n = 29, 50.9%) and the MO group (n = 28, 49.1%). Overall recurrence rates after initial treatment were 23.7% at 1 year, 64.5% at 3 years, and 76.1% at 5 years. In patients with IM, the majority of intrahepatic recurrences were observed within 3 years of initial treatment and the primary HCC lesions were closely related to the degree of tumor cell differentiation. Alternatively, intrahepatic recurrences occurred throughout the follow-up period in patients with MO, and the evidence of underlying liver disease (anti-HCV [antibody to hepatitis C virus] positive) and elevated serum alfa-fetoprotein (AFP) concentrations were closely associated with intrahepatic recurrence. Prognoses following additional treatment in MO group patients were superior to those in IM group patients. These results suggest that differentiation between IM and MO in patients with HCC is important for understanding the development and biological behavior of the tumor. That is, the early detection of intrahepatic recurrence and the institution of appropriate additional therapy (PEIT or hepatic resection) may prolong survival in patients with MO.(Hepatology 1997 Jan;25(1):87-92)     

Randomized controlled trial to compare the dose of adjuvant chemotherapy after curative resection of hepatocellular carcinoma

BACKGROUND AND AIM: Adjuvant locoregional chemotherapy has been shown to be useful to prevent recurrence after curative resection of hepatocellular carcinoma (HCC) in some retrospective studies. Our aim was to compare the dose effect in the prevention of tumor recurrence. METHODS: A prospective randomized controlled trial was conducted in patients with curative resection of HCC; they were given either one intra-arterial dose of cisplatin/lipiodol, or received four doses, once every 3 months. The rates of recurrence, disease-free and overall survival were compared. RESULTS: During a median follow up of 818 days, 21 patients received one dose and 19 received four doses, with 10 (47.6%) and eight (42.1%) recurrences, respectively. The 1-year, 2-year and 3-year disease-free survival rates were 71%, 54% and 44% for the one-dose group and 74%, 60% and 40% for the four-dose group (P = 0.78). The respective overall survival rates were 85%, 74%, 55% and 84%, 71%, 40% (P = 0.64). The only prognostic factor was presence of vascular permeation. The side-effects were mild and tolerable. CONCLUSIONS: There is no significant difference in the survival rates between the two groups. Adjuvant chemotherapy may not be useful.     

Recurrent hepatocellular carcinoma has an increased risk of subsequent recurrence after curative treatment

BACKGROUND AND AIM: Local ablation therapy has been shown to be effective for small hepatocellular carcinoma (HCC); however, HCC recurrence is very frequent even after apparently curative treatment. In particular, recurrent HCC may be more prone to subsequent recurrence, although quantitative data are lacking. The aim of this study was to evaluate the difference in the risk for subsequent recurrence, if any, between primary and recurrent cases. METHODS: A retrospective analysis was conducted of 376 patients with HCC (uninodular and 100 ng/mL, treatment other than radiofrequency ablation, HCV antibody positivity, and tumor multinodularity also remained as significant predictors. CONCLUSION: Hepatocellular carcinoma at second or later recurrence is three times as prone to subsequent recurrence as is primary HCC, when compared with adjustment for other tumor and hepatic factors.     

Patterns of intrahepatic recurrence after curative resection of hepatocellular carcinoma

Using selective angiograms of the liver, we analyzed the patterns of intrahepatic recurrence of hepatocellular carcinomas following curative surgery. In 33 patients with intrahepatic recurrences, seven patients (21%) had a recurrence near the resected hepatic stump. The remaining 26 had either a nodular recurrence in segments away from the resected margin or a widespread multinodular recurrence in the liver remnant. There was a recurrence within the first postoperative year in five of 16 patients with a nodular recurrence and in eight of 10 patients with a widespread multinodular recurrence. In these patients, particularly those with a widespread multinodular recurrence, tumor thrombi in the portal vein present before the operation and/or disseminated during operation from such an advanced main tumor seemed to be the most important and significant factor related to the early recurrence in the remnant liver. This evidence suggests that in cases of surgery for hepatocellular carcinoma it is important to establish a technique to prevent dissemination of cancer cells due to operative manipulation and also adequate adjuvant therapy rather than attempting to obtain an ample resection margin.     

Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG

BACKGROUND AND AIMS: Experimental studies have shown that luminal bacteria may be involved in Crohn's disease. Probiotics are a possible alternative to antibiotics. The aim of this randomised placebo controlled study was to determine if Lactobacillus GG, given by mouth for one year, could prevent Crohn's recurrent lesions after surgery or to reduce their severity. METHODS: Patients operated on for Crohn's disease in whom all of the diseased gut had been removed were randomly allocated to receive 12 billion colony forming units of Lactobacillus or identical placebo for one year. Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms. Endoscopic recurrence was defined as grade 2 or higher of Rutgeerts scoring system. RESULTS: Eight of 45 patients were excluded from the trial (three for non-compliance and five for protocol violations). Clinical recurrence was ascertained in three (16.6%) patients who received Lactobacillus and in two (10.5%) who received placebo. Nine of 15 patients in clinical remission on Lactobacillus (60%) had endoscopic recurrence compared with six of 17 (35.3%) on placebo (p=0.297). There were no significant differences in the severity of the lesions between the two groups. CONCLUSIONS: Lactobacillus GG seems neither to prevent endoscopic recurrence at one year nor reduce the severity of recurrent lesions.     

Risk factors of intrahepatic recurrence after curative resection of hepatocellular carcinoma

BACKGROUND/AIMS: Although the risk factors for the development of intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (HCC) have been widely studied, little attention has been given to the prognostic factors affecting such patients. METHODOLOGY: Intrahepatic recurrence occurred in 105 (56%) of 188 patients who underwent curative hepatic resection of HCC and were discharged from the hospital. Among them, 17 (16%) also had simultaneous extrahepatic recurrence. Independent prognostic factors were evaluated by multivariate analysis using Cox's proportional hazards model. RESULTS: Multivariate analysis revealed that presence of extrahepatic recurrence, hepatitis B, and non-surgical treatments for recurrence were independent predictors of poor overall survival after initial hepatic resection or after recurrence. Risk factors of extrahepatic recurrence were young age, solitary and large HCC, high hepatitis activity, and large amount of intraoperative blood loss and blood transfusion. CONCLUSIONS: Survival of patients with intrahepatic recurrent HCC after resection should be stratified by the type of recurrence, type of hepatitis, and type of treatment for recurrence.     

Late retroperitoneal recurrence of hepatocellular carcinoma 12 years after initial diagnosis

Hepatocellular carcinoma (HCC) is an aggressive tumor with poor long-term prognosis.Here,we present an unusual patient with a solitary recurrence of HCC in the right kidney 12 years after the initial diagnosis.This illustrates the importance of considering late recurrence in patients with a history of HCC and the management of these metastases.     

A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation

Hepatitis C virus (HCV) infection recurs in liver recipients who are viremic at transplantation. We conducted a randomized, controlled trial to test the efficacy and safety of pretransplant pegylated interferon alpha-2b plus ribavirin (Peg-IFN-α2b/RBV) for prevention of post-transplant HCV recurrence. Enrollees had HCV and were listed for liver transplantation, with either potential living donors or Model for End-Stage Liver Disease upgrade for hepatocellular carcinoma. Patients with HCV genotypes (G) 1/4/6 (n = 44/2/1) were randomized 2:1 to treatment (n = 31) or untreated control (n = 16); HCV G2/3 (n=32) were assigned to treatment. Overall, 59 were treated and 20 were not. Peg-IFN-α2b, starting at 0.75 μg/kg/week, and RBV, starting at 600 mg/day, were escalated as tolerated. Patients assigned to treatment versus control had similar baseline characteristics. Combined virologic response (CVR) included pretransplant sustained virologic response and post-transplant virologic response (pTVR), defined as undetectable HCV RNA 12 weeks after end of treatment or transplant, respectively. In intent-to-treat analyses, 12 (19%) assigned to treatment and 1 (6%) assigned to control achieved CVR (P = 0.29); per-protocol values were 13 (22%) and 0 (0%) (P = 0.03). Among treated G1/4/6 patients, 23 of 30 received transplant, of whom 22% had pTVR; among treated G2/3 patients 21 of 29 received transplant, of whom 29% had pTVR. pTVR was 0%, 18%, and 50% in patients treated for <8, 8-16, and >16 weeks, respectively (P = 0.01). Serious adverse events (SAEs) occurred with similar frequency in treated versus untreated patients (68% versus 55%; P = 0.30), but the number of SAEs per patient was higher in the treated group (2.7 versus 1.3; P = 0.003). Conclusion: Pretransplant treatment with Peg-IFN-α2b/RBV prevents post-transplant recurrence of HCV in selected patients. Efficacy is higher with >16 weeks of treatment, but treatment is associated with increased risk of potentially serious complications.     

Risk factors of recurrence after curative resection of hepatocellular carcinoma in Taiwan

IntroductionThe purpose of this study was to explore the potential risk factors of hepatocellular carcinoma (HCC) recurrence after curative resection of primary HCC.MethodsThis was a hospital-based retrospective cohort study. The authors analyzed the medical records of all the subjects with HCC initially treated by hepatic resection at a medical center in Taiwan from 1995 to 2006. In all, 222 subjects were enrolled in this study. The total observational period was 3 years.resultsThere were 172 men (77.5%) and 50 women (22.5%). The mean age was 57.0 ± 13.7 years (range, 15–79 years). Among 222 subjects, the overall recurrence rates were 28.8% (64/222), 42.3% (94/222) and 47.7% (106/222) at 1, 2 and 3 years, respectively. Multivariate logistic regression analysis exhibited that tumor size ≥ 5 cm [odds ratio (OR) = 2.31, 95% confidence interval (CI) = 1.27–4.17], liver cirrhosis (OR = 2.11, 95% CI = 1.18–3.79) and preoperative aspartate aminotransferase level ≥ 34IU/L (OR = 2.02, 95% CI = 1.01–4.04) were independent risk factors of HCC recurrence.conclusionPatients who have larger tumor size, liver cirrhosis and higher preoperative aspartate aminotransferase level should be carefully followed up because they are at high risk of HCC recurrence postoperatively.     

Predictive factors of advanced recurrence after curative resection of small hepatocellular carcinoma

Background: The tumour recurrence rate after resection is still high even in patients with small hepatocellular carcinoma (HCC). The advanced patterns of recurrence occasionally occur after resection. In this study, we analysed the clinical and histological characteristics of small HCC and evaluated the predictive factors of advanced tumour recurrence. Methods: One hundred and sixty‐five patients underwent resection of small HCC measuring 3 cm or less in greatest dimension. Patterns of tumour recurrences were classified into advanced recurrence and minor recurrence based on size, number, vascular invasion and extrahepatic metastasis of recurrent tumour. We created a simple index to closely evaluate the malignant potential of small HCC, named α‐foetoprotein–size ratio index (ASRI). Results: Overall tumour recurrence was significantly associated with tumour multiplicity (P<0.001) and ASRI (P=0.001). Tumour multiplicity, ASRI and tumour differentiation were independent and significant predictive factors of advanced recurrences. The overall survival rates were lower in the advanced recurrence group than the minor recurrence or the no recurrence group. Conclusions: Patients with advanced recurrences have a poor prognosis, although they have undergone curative resection of small HCC. On the other hand, patients with minor recurrences have a relatively good prognosis. ASRI was a useful index to predict advanced recurrence after curative resection of small HCC. The therapeutic management to prevent advanced recurrences is needed.     

Risk factors for early recurrence of small hepatocellular carcinoma after curative resection

BACKGROUND:Poorer prognosis is seen in patients with hepatocellular carcinoma (HCC) after curative hepatic resection with early recurrence (≤1 year) than in those with late recurrence (>1 year).This study aimed to identify risk factors for postoperative early recurrence of small HCC (≤3 cm in diameter).METHODS:The study population consisted of 158 patients who underwent curative resection for small HCC between January 2002 and July 2004.Risk factors for early recurrence were analyzed.RESULTS:Thirty-three (2...     

Evaluation of prognostic factors on recurrence after curative resections for hepatocellular carcinoma

AIM:To select appropriate patients before surgical resection for hepatocellular carcinoma(HCC),especially those with advanced tumors.METHODS:From January 2000 to December 2012,we retrospectively analyzed the medical records of 298 patients who had undergone surgical resections for HCC with curative intent at our hospital.We evaluated preoperative prognostic factors associated with histologic grade of tumor,recurrence and survival,especially the findings of pre-operative imaging studies such as positron emission tomography-computed tomography(PETCT)and magnetic resonance imaging(MRI).And then,we established a scoring system to predict recurrence and survival after surgery dividing the patients into two groups based on a tumor size of 5 cm.RESULTS:Of the 298 patients,129(43.3%)developed recurrence during the follow-up period.The 5 year disease free survival and overall survival were 47.0%and58.7%respectively.In multivariate analysis,a serum alpha-fetoprotein(AFP)level of>100 ng/m L and a standardized uptake value(SUV)of PET-CT of>3.5 were predictive factors for histologic grade of tumor,recurrence,and survival.Tumor size of>5 cm and a relative enhancement ratio(RER)calculated from preoperative MRI were also significantly associated with prognosis in univariate analysis.We established a scoring system to predict prognosis using AFP,SUV,and RER.In those with tumors of>5 cm,it showed predicted both recurrence(P=0.005)and survival(P=0.001).CONCLUSION:The AFP,tumor size,SUV and RER are useful for prognosis preoperatively.An accurate prediction of prognosis is possible using our scoring system in large size tumors.     

Prehydration alone is sufficient to prevent contrast-induced nephropathy after day-only angiography procedures--a randomised controlled trial

BACKGROUND: Contrast agents used in angiography procedures for patients with cardiovascular disease are known to cause contrast-induced nephropathy (CIN), which may be partially due to the production of nephrotoxic oxygen-free radicals. It is uncertain whether administration of intravenous (IV) anti-oxidant, N-acetylcysteine (NAC), can prevent reduction in renal function and whether this is a cost-effective approach. METHODS: Sixty-five day-only patients with renal impairment (mean serum creatinine concentration 0.16+/-0.03 mmol/l) due to undergo coronary or peripheral angiography and/or stenting were randomly assigned to IV NAC 300 or 600 mg immediately before and after the procedure or IV fluid alone. RESULTS: Of the 60 patients with complete data, none had acute CIN (increase in serum creatinine concentration > or = 0.044 mmol/l, 48 h after administration of contrast agent). Eight patients (13%) have demonstrated an increase in their serum creatinine concentration > or = 0.044 mmol/l 30 days after administration of contrast agent: 2/19 (11%) in the control group, 2/21 (10%) in the 600 mg NAC group and 4/20 (20%) the 300 mg NAC group (p = 0.66). The mean volumes of contrast agent used and prehydration given for each of the three groups did not differ significantly (p > 0.83). There was significant improvement in creatinine clearance within each group from baseline to 30 days (p < or = 0.03), but no significant difference between the groups at 48 h and 30 days (p > or = 0.43). Considering the cost of NAC and its administration, we estimate that this would translate to a saving of dollar 26,637 per annum. CONCLUSION: For day-stay patients with mild-to-moderate chronic renal impairment undergoing angiography and/or intervention, prehydration alone is less complicated and more cost-effective than a combination of IV NAC (at doses used) and hydration.     

Prediction of recurrence of hepatocellular carcinoma after curative ablation using three tumor markers

Three tumor markers for hepatocellular carcinoma (HCC) are available in daily practice in Japan: alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3). To elucidate the predictability of these tumor markers on HCC recurrence after curative ablation, we enrolled 416 consecutive patients with na?ve HCC who had been treated by percutaneous ablation at our department from July 1997 to December 2002. Tumor marker levels were determined immediately before and 2 months after the treatment. Complete ablation was defined on CT findings as nonenhancement in the entire lesion with a safety margin. Tumor recurrence was also defined as newly developed lesions on CT that showed hyperattenuation in the arterial phase with washout in the late phase. We assessed the predictability of recurrence via tumor markers in multivariate analysis, using proportional hazard regression after adjusting for other significant factors in univariate analysis. Until the end of follow-up, tumor recurrence was identified in 277 patients. Univariate analysis revealed the following factors to be significant for recurrence: platelet count; size and number of tumors; AFP, AFP-L3, and DCP preablation; and AFP and AFP-L3 postablation. Multivariate analysis indicated that AFP >100 ng/mL and AFP-L3 >15%, both pre- and postablation, were significant predictors. The positivity of AFP and AFP-L3 preablation that turned negative postablation was not significant. In conclusion, tumor markers pre- and post-ablation were significant predictors for HCC recurrence and can complement imaging modalities in the evaluation of treatment efficacy.     

碱性成纤维细胞生长因子是预测肝细胞癌根治性切除术后转移复发的潜在指标

目的 检测肝细胞癌（hepatocellular carcinoma,HCC)患者术前血清碱性成纤维细胞生长因子（basic fibroblast growth,bFGF)水平,确定其与HCC根治性术后转移复发的关系。方法 采用Cox比例风险模型,对影响预后的临床指标进行分析,确定影响HCC切除术后转移复发的临床指标。同时应用ELISA方法,检测HCC患者术前血清bFGF水平,western blot方法对24例相应肿瘤组织bFGF表达水平进行定量分析。结果 Cox比例风险模型显示,肿瘤大小及肿瘤是否存在肝内播散,是影响HCC切除术后患者生存时间的显著因素（分别为P＝0．022和P＝0．040）,并以此划分为高和传转移复发倾向组。根治性切除术后高转移复发倾向组,HCC患者术前血清bFGF显著高于传转移复发倾向组（P＜0．01）。western blot显示,HCC患者血清bFGF水平变化与其对应肿瘤组织bFGF表达变化相一致。结论 HCC患者术前血清bFGF是预测HCC根治性切除术后转移复发的潜在指标。HCC患者血清bFGF水平升高是其对应肿瘤组织高表达的结果。