Is surgery for large hepatocellular carcinoma justified?

BACKGROUND/AIMS: Most hepatocellular carcinomas are still discovered at an advanced stage and are left untreated as large hepatocellular carcinomas are contraindications to liver transplantation and percutaneous ethanol injection and are usually considered as poor indications for liver resection. The aim of this study was to reassess the results of surgery in these patients. METHODS: Between 1984 and 1996, 256 patients underwent resection of biopsy-proven, non-fibrolamellar hepatocellular carcinoma. Of these, 121 had a tumour diameter of less than 5 cm (small hepatocellular carcinomas) and 94 a tumour diameter of more than 8 cm (large hepatocellular carcinomas). The short- and long-term outcome of patients with small and large hepatocellular carcinomas were compared. RESULTS: The in-hospital mortality rate following resection of small and large hepatocellular carcinomas was comparable (11.5 vs. 10.6%), even after stratifying for the presence and severity of an underlying liver disease. In patients with a chronic liver disease, large hepatocellular carcinomas were associated with a greater risk of death and recurrence during the first 2 operative years. In the long term, however (3-5 years), survival and disease-free survival following resection of small and large hepatocellular carcinomas were comparable (34 vs. 31% and 25 vs. 21% at 5 years). Similarly, treatment of and survival after the onset of recurrence were not influenced by the size of the initial tumour. CONCLUSIONS: Patients with large hepatocellular carcinomas should not be abandoned and should be considered for liver resection as this treatment may be associated with an in-hospital mortality rate and a long-term survival comparable to that observed after resection of small hepatocellular carcinomas.     

Is thrombolytic therapy effective in elderly patients?

Thrombolytic therapy (TT) is applied in patients (<75 years of age) with acute myocardial infarction (AMI) with ST-segment elevation. It is recommended for elderly patients who have percutaneous transluminal coronary angioplasty (PTCA) or bypass surgery. For PTCA and bypass surgery a cardiosurgery medical team, which can be found in large medical hospitals, has to be prepared. Patients with AMI with ST-segment elevation who are older than 75 and who do not have TT have a dubious prognosis for longevity and quality of life. The aim of this study was to propose recommendations and behavior for reperfusion with TT of the coronary arteries of elderly patients. The investigation was conducted for a period of 5 years (2000 to 2004). Investigators registered 2462 patients, 502 of whom had AMI, and 103 (54 men, 49 women) of whom were older than 75 years. Reteplase (Rapilysin, Hoffman La Roche, Switzerland) was applied to 10 patients. The general and mental state of patients as well as comorbidity were assessed. The H2- blocker Famotidine (Quamatel-Gedeon-Richter, Hungary) was used to prevent bleeding from the gastrointestinal tract. The applied TT had a positive effect on these >75-year-old patients. The oldest woman was 89 years old and the oldest man was 93. There were no complications during the treatment of these elderly patients. Aging related to serious health problems can be improved with the application of TT to elderly patients with AMI, and ST-segment elevation is an excellent reperfusion therapy. It is possible to achieve a dose reduction of the thrombolytic agent, arterial pressure no higher than 160/100 mmHg, individual risk assessment for intracranial hemorrhage, and prevention of bleeding from the gastrointestinal tract.     

Is percutaneous ethanol injection therapy still effective for hepatocellular carcinoma in the era of radiofrequency ablation?

Percutaneous ethanol injection (PEI) therapy has been replaced by more-effective thermal ablation techniques that have lower local recurrence rates. However, PEI therapy remains useful in certain settings. Since PEI can be performed in any portion of the liver, PEI therapy can be valuable when tumors are located in close proximity to intestinal loops or other positions that are risky for thermal local ablative techniques. PEI therapy is also valuable in other situations where radiofrequency ablation (RFA) is difficult, including technically difficult masses that are not detected with ultrasound (US), are located in the hepatic dome, in the subcapsular area, and exophytically, or are surrounded by large vessels. PEI therapy contributes to combination therapy with transcatheter arterial chemoembolization or RFA in advanced-stage hepatocellular carcinoma (HCC), and also to the treatment of large HCC or extrahepatic metastasis from HCC. These roles of PEI therapy should be stressed for the treatment of HCCs in appropriate clinical situations. This comprehensive review of articles related to PEI therapy illustrates the recent role and indications of this therapy, which is currently valuable for HCC in the era of RFA.     

Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?

AIM: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) resistant to transarterial chemoembolization (TACE).METHODS: This study was conducted on 42 patients who received HAIC for advanced HCC between 2001 and 2010 at our hospital. 5-fluorouracil (5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir. Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU. The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010 (written in Japanese); one group of patients who did not fulfill the criteria for TACE resistance (group A, n = 23), and another group who fulfilled the criteria for TACE resistance (group B, n = 19). We compared the outcomes in terms of the response and survival rates between the two groups.RESULTS: Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B (response rate: 48% vs 16%, P = 0.028, tumor suppression rate: 87% vs 53%, P = 0.014). Furthermore, both the progression-free survival rate and survival time were significantly superior in group A than in group B (3-, 6-, 12-, and 24-mo = 83%, 70%, 29% and 20% vs 63%, 42%, 16% and 0%, respectively, P = 0.040, and 9.8 mo vs 6.2 mo, P = 0.040). A multivariate analysis (Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival (P = 0.007).CONCLUSION: HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE. Other tools for treatment, i.e., molecular-targeting agents may be considered for these cases.     

Surveillance for early diagnosis of hepatocellular carcinoma: is it effective in intermediate/advanced cirrhosis?

OBJECTIVES: Surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC), based on ultrasonography and alpha-fetoprotein (AFP) measurement, is widely used. Its effectiveness depends on liver function, which affects the feasibility of treatments and cirrhosis-related mortality. We assessed whether patients with intermediate/advanced cirrhosis benefit from surveillance. METHODS: We selected 468 Child-Pugh class B and 140 class C patients from the ITA.LI.CA database, including 1,834 HCC patients diagnosed from January 1987 to December 2004. HCC was detected in 252 patients during surveillance (semiannual 172, annual 80 patients; group 1) and in 356 patients outside surveillance (group 2). Survival of surveyed patients was corrected for the estimated lead time. RESULTS: Child-Pugh class B: cancer stage (P < 0.001) and treatment distribution (P < 0.001) were better in group 1 than in group 2. The median (95% CI) survivals were 17.1 (13.5-20.6) versus 12.0 (9.4-14.6) months and the survival rates at 1, 3, and 5 yr were 60.4%versus 49.2%, 26.1%versus 16.1%, and 10.7%versus 4.3%, respectively (P= 0.022). AFP, gross pathology, and treatment of HCC were independent prognostic factors. Child-Pugh class C: cancer stage (P= 0.001) and treatment distribution (P= 0.021) were better in group 1 than in group 2. Nonetheless, median survival did not differ: 7.1 (2.1-12.1) versus 6.0 (4.1-7.9) months (P= 0.740). CONCLUSIONS: These results suggest surveillance be offered to class B patients and maintained for class A patients who migrate to the subsequent class. Surveillance becomes pointless in class C patients probably because the poor liver function adversely affects the overall mortality and HCC treatments.     

Is transarterial chemoembolization beneficial for patients with diffuse infiltrative hepatocellular carcinoma?

Purpose

Diffuse infiltrative hepatocellular carcinoma (D-HCC) is an incurable disease with short survival time. Transarterial chemoembolization (TACE) was often used to alleviate patient’s symptoms and reduce tumor burden. However, it remains unknown if the TACE benefits the survival of D-HCC patients.

Methods

A hospital-based retrospective study was conducted at a large referral hospital in Taiwan for a 9-year period (2000–2008).

Results

Of the 150 D-HCC patients, 106 patients were related to hepatitis B virus (HBV), 17 to hepatitis C virus (HCV), 3 to both HBV and HCV, and 24 not to HBV or HCV. Multivariate Cox regression analysis showed treatment strategy, serum alpha-fetoprotein level, model for end-stage liver disease (MELD) score, serum gamma glutamyl transferase, and serum lactic acid dehydrogenase were associated with survival time. Compared to supportive treatment, the adjusted hazard ratios of transarterial chemoembolization (TACE) and chemotherapy including oral or systemic chemotherapy were 0.383 (p < 0.001) and 0.711 (p = 0.289), respectively.

Conclusion

TACE is a preferred therapy for D-HCC patients.     

Is hepatic resection absolutely contraindicated for hepatocellular carcinoma in Child-Pugh class C cirrhotic patients?

BACKGROUND/AIMS: Liver resection for hepatocellular carcinoma (HCC) in Child-Pugh class C cirrhotic patients is considered to be high risk and even contraindicated. This study examined our results of hepatectomy for HCC in such cirrhotic patients. METHODOLOGY: A retrospective review of the clinicopathological features, as well as early and late resection results of Child-Pugh class A (n = 181) and class C patients (n = 13) were compared. The extent of hepatectomy was based on the pre-operative liver function test and indocyanine-green (ICG) clearance rate. RESULTS: The tumor size in class C patients was smaller than that in class A patients. There were no significant differences with regard to operative blood loss, amount of blood transfusion, operative morbidity or mortality. The surgical margins of class C patients were narrower (p = 0.003). The tumors of class C patients had higher incidences of well-formed capsules and absence of satellite nodules. The 5-year disease-free and actuarial survival rates of class A and C patients were 35.4% and 40.7% (p = 0.28), and 48% and 50% (p = 0.13), respectively. CONCLUSIONS: Not all HCCs in Child-Pugh class C cirrhotic patients are contraindicated for liver resection. In the absence of uncontrollable ascites, marked jaundice and encephalopathy, surgical resection is still justified in some selected cases, in spite of a narrow surgical margin.     

Is the treatment outcome of hepatocellular carcinoma inferior in elderly patients?

In view of the increasing life expectancy in different parts of the world, a larger proportion of elderly patients with hepatocellular carcinoma(HCC) requiring oncological treatment is expected. The clinicopathological characteristics of HCC in elderly patients and in younger patients are different. Elderly patients, in general, also have more comorbidities. Evaluation of the efficacy of different HCC treatment options in elderly patients is necessary to optimize treatment outcomes for them. Treatment modalities for HCC include hepatectomy, liver transplantation, radiofrequency ablation, transarterial chemoembolization, and molecular-targeted therapy with sorafenib. In this review, current evidence on the risks and outcomes of the different HCC treatments for elderly patients are discussed. According to data in the literature, elderly patients and younger patients benefited similarly from HCC treatments. More clinical data are needed for the determination of selecting criteria on elderly HCC patients to maximize their chance of getting the most appropriate and effective treatments. As such,further studies evaluating the outcomes of different HCC treatment modalities in elderly patients are warranted.     

Does interferon therapy prevent hepatocellular carcinoma in patients with chronic viral hepatitis?

Chronic hepatitis C and B are well-recognized and potentially preventable risk factors for hepatocellular carcinoma (HCC) development. Clinical and epidemiological studies suggest that therapy with interferon-α may reduce the overall risk of HCC development in patients with chronic hepatitis C, who achieve sustained virological response, but even in those who fail to eradicate the infection. In chronic hepatitis B, interferon therapy reduces the risk of HCC development in HBeAg-positive and cirrhotic patients who achieve persistent suppression of viral replication, while in HBeAg-negative patients the beneficial effect of interferon-α is not definitively confirmed. The preventive role of interferon-α after potentially curative treatment for HCC in both chronic hepatitis B and C is uncertain due to methodological flaws of the existing studies and prospective randomized controlled trials with pegylated interferon-α are needed to clarify this issue.     

Survival impact of delayed treatment in patients with hepatocellular carcinoma undergoing locoregional therapy: is there a lead-time bias?

OBJECTIVE: Many reports indicate the importance of active treatment for hepatocellular carcinoma (HCC), but there are few studies available that address the impact of delayed therapy on survival or take the lead-time bias into account. The objective of this study was to investigate whether patients with delayed locoregional therapy for HCC truly have a shortened survival from the time of diagnosis. MATERIAL AND METHODS: Survival rates were compared between 48 HCC patients with treatment delay and 96 age- and gender-matched controls without delay. All patients underwent transarterial chemoembolization or percutaneous ethanol or acetic acid injection for HCC. Treatment delay was defined as a >2 months' time interval between diagnosis and treatment. RESULTS: Baseline comparison showed that patients with treatment delay had higher scores in the model for endstage liver disease compared with those of patients without delay (12.3+/-1.8 versus 11.1+/-2.5, p=0.01). In the Cox multivariate model, advanced cancer stage (relative risk (RR): 2.66, p=0.001), Child-Turcotte-Pugh class B (RR: 3.81, p<0.001), tumor size >5 cm (RR: 2.02, p=0.011) and treatment delay (RR: 2.91, p=0.001) were independent poor prognostic predictors. Among patients with treatment delay, disease progression was registered in 30 (63%) patients. Patients with prolonged treatment delay (>3 months) were more likely to have tumor progression (p=0.013). In the Cox model, a treatment delay of >3 months independently predicted a poor rate of survival (RR: 3.67, p=0.002). CONCLUSIONS: Delayed HCC treatment is linked with shortened overall survival unrelated to the lead-time bias in patients undergoing locoregional therapy. Prolonged treatment delay of more than 3 months in these patients may worsen the long-term outcome.