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Margarita Sala

Publications and source records attributed to Margarita Sala.

12 recordsLinked to original sources

Prognostic prediction in patients with hepatocellular carcinoma.

With most solid tumors, the estimation of life expectancy is related to tumor stage at diagnosis and staging is directly linked to treatment indication. By contrast, in patients with hepatocellular carcinoma (HCC) the prediction of prognosis is more complex. There is no worldwide consensus on the use of any HCC staging system. Classifications that take into account only one of the relevant prognostic parameters, such as tumor, nodes, and metastasis (TNM) or Child-Pugh staging, are useless. Several scoring systems have been developed, but unfortunately their major capacity is to identify end-stage patients and they do not link staging with therapy. The Barcelona Clinic Liver Cancer (BCLC) staging system was developed according to the results of cohort studies and randomized clinical trials. It considers tumor stage, liver functional status, physical status, and cancer-related symptoms and, by dividing patients into early, intermediate, advanced, and end-stage categories, provides a link to treatment indication.

Carcinoma, Hepatocellular↗

Non-surgical therapies of hepatocellular carcinoma.

Early detection of hepatocellular carcinoma (HCC) through surveillance programmes allows potentially curative therapies such as resection, liver transplantation and percutaneous ablation to be applied in 40% of the patients. In non-surgical candidates, percutaneous treatments are the best therapeutic approach, and may improve survival in patients with well preserved liver function and small tumours that achieve initial complete response. Applying these criteria 5-year survival rates above 50% are achieved. Radio frequency thermal ablation provides slightly better objective response rates than ethanol injection, but no survival advantages have been reported. At more advanced stages, only chemoembolization has been shown to improve survival in well-selected candidates.

Carcinoma, Hepatocellular↗

Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma.

Outcome predictors in patients with hepatocellular carcinoma (HCC) who are treated with percutaneous ablation are ill defined, and it is unknown if successful therapy is associated with improved survival. In our study, 282 cirrhotic patients with early nonsurgical HCC were treated with percutaneous ablation during a 15-year period. Single tumors were seen in 244 patients, and 2 to 3 nodules were seen in 38 patients. Initial complete response was achieved in 192 patients and was independently related to the size of the main tumor (P = .015) and tumor stage (P = .0001) (< or =2 cm, 96%; 2.1-3 cm, 78%; >3 cm, 56%; 2-3 nodules, 46%). At the end of follow-up, 80 patients presented sustained complete response. The 1-, 3-, and 5-year survival rates were 87%, 51%, and 27%, respectively. The independent predictors of survival were Child-Turcotte-Pugh class (P = .0001) and initial complete response (P = .006). Child-Turcotte-Pugh class A patients with initial complete response achieved 42% survival at 5 years; this figure increased to 63% in patients with tumors 2 cm or smaller. In conclusion, our results demonstrate that initial complete response to percutaneous ablation is associated with an improved survival in both Child-Turcotte-Pugh class A and B patients with nonsurgical HCC. Accordingly, initial complete tumor necrosis should be considered a relevant therapeutic target irrespective of tumor size and liver function.

Aged↗

High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: an indication for salvage liver transplantation.

Surgical resection and liver transplantation offer a 5-year survival greater than 70% in patients with hepatocellular carcinoma, but the high recurrence rate impairs long-term outcome after resection. Pathological data such as vascular invasion and detection of additional nodules predict recurrence and divide patients into high and low risk profile. Based on this, we proposed salvage liver transplant to resected patients in whom pathology evidenced high recurrence risk even in the absence of proven residual disease. From January 1995 to August 2003 we have evaluated 1,638 patients. Resection was indicated in 77 patients, but only 17 (22%) (all cirrhotics, 14 hepatitis C virus+) were optimal candidates for both resection and transplantation. Of them, 8 exhibited a high risk profile at pathology and were offered transplantation. Among the 8 high risk patients, 7 presented recurrence, compared with only 2 of the 9 at low risk (P = .012). Two of the high risk patients refused transplant and developed multifocal disease during follow-up. The other 6 were enlisted and all but 1 had tumor foci in the explant. Only 1 presented extrahepatic dissemination early after transplant and died 4 months later. The others are free of disease after a median follow-up of 45 months. Two recurrences were detected in low risk patients, 1 of them being transplanted 18 months after surgery. These data in a small series of patients confirm that pathological parameters identify patients at higher risk of recurrence, which allow them to be listed for liver transplantation without proven malignant disease. In conclusion, this policy is clinically effective and could further improve the outcome of resected patients.

Carcinoma, Hepatocellular↗

Selection of candidates with HCC for transplantation in the MELD era.

1. Liver transplantation is the main option for patients with early HCC who are not optimal candidates for surgical resection. 2. Shortage of donors is its main limitation, as waiting for a liver allows the tumor to progress and induce exclusion from the waiting list and death. 3. The absence of randomized controlled trials hinders the establishment of the most effective therapy to prevent tumor progression while waiting. 4. Live donation may be a cost-effective approach if optimal results are expected and the mortality risk for the donor is kept below .3%. 5. Priority policies have to be developed and refined to provide a fair and effective distribution of cadaveric organs.

Carcinoma, Hepatocellular↗

Chemoembolization for hepatocellular carcinoma.

Curative therapies for hepatocellular carcinoma (HCC), such as resection, liver transplantation, and percutaneous ablation, can be applied in selected patients with early tumors; this includes approximately 30%-40% of all cases. More advanced stages require local or systemic therapies. Data on the efficacy of these treatments are derived from small randomized controlled trials (RCT) and meta-analysis. Chemoembolization, a technique combining intra-arterial chemotherapy and selected ischemia, has produced modest survival advantages in 2 RCTs and a meta-analysis, and is currently the mainstay of treatment for these stages. The ideal candidates for this option are patients with well-preserved liver function (Child-Pugh class A) and multinodular asymptomatic tumors without vascular invasion, who constitute less than 15% of the HCC population. In these cases, the benefits derived by achieving objective responses (30%-50% of cases) are not offset by the deterioration of the liver function. Treatment-related mortality is less than 4%. No survival advantages have yet been shown with embolization or intra-arterial chemotherapy alone. Further RCTs are needed to assess the best chemotherapeutic agent and the ideal retreatment schedule. The analysis of efficacy in these trials should be adjusted for prognostic factors, such as the presence of symptoms, Child-Pugh class, and segmental vascular invasion.

Carcinoma, Hepatocellular↗

p27(Kip1) is an independent predictor of recurrence after surgical resection in patients with small hepatocellular carcinoma.

BACKGROUND/AIMS: Alterations in p27(Kip1) (p27) and cyclin E (cycE) expression are found in tumors and are related to poor prognosis. This study assesses the role of these cell cycle regulators in the development of recurrence after surgical resection in 46 cirrhotic patients (age: 61.3+/-7 years, 30 males, 44 Child-Pugh's A, 30 HCV-positive) with small hepatocellular carcinoma (HCC, size: 3.1+/-1.5cm, 40 solitary at pathological examination). METHODS: p27 and cycE expression in tumoral and non-tumoral liver were analyzed by Western blot (WB). p27 was also assessed by immunohistochemistry (IHC). RESULTS: Tumor p27 underexpression (50% decreased vs. non-tumoral liver) occurred in 12 cases. Throughout follow-up, 26 patients developed recurrence, which was significantly higher in patients with p27 underexpression than in those without (3-year recurrence: 80 vs. 44%, respectively, P=0.026). IHC showed concordant inverse findings: 13 tumors showed high p27 staining that was related to lower recurrence rate (P=0.019). Multivariate analysis identified p27 measured by WB as an improved predictor of recurrence (OR: 3.09, 95% CI: 1.26-7.08, P=0.016). By contrast, cycE, increased in 66% of the tumors, had no impact on recurrence but was associated to poor differentiation (P=0.015) and microvascular invasion (P=0.016). CONCLUSIONS: p27 underexpression is frequent in relatively early stages of HCC and constitutes an independent predictor of recurrence after surgical resection.

Aged↗

Treatment of hepatocellular carcinoma: is there an optimal strategy?

The incidence of hepatocellular carcinoma is increasing worldwide and now it accounts for as many as 1 million deaths annually, representing the third cause of cancer-related death. Surveillance programmes in the population at risk, namely cirrhotic patients, aim to detect tumours at an early stage when benefit from effective therapy may be provided. Patients with early tumours (single tumours measuring less than 5 cm or with less than 3 nodules measuring less than 3 cm in size) constitute the early stage category. These patients may be treated with surgical resection, transplantation, or percutaneous ablation, and the 5-year survival rate will exceed 50%. Patients with more advanced disease constitute the intermediate-advanced stage. Intermediate stage includes individuals without cancer-related symptoms and absence of vascular invasion and/or extrahepatic spread. They may achieve a 50% survival rate at 3 years that can be expanded by transarterial chemoembolization. Symptomatic patients with more advanced disease have a survival rate of less than 20% at 3 years. In this group of patients the efficacy of new agents should be assessed in phase II trials or randomized controlled trials versus no treatment to determine the impact of any therapy on survival. Finally, patients with end-stage disease with heavily impaired liver function (Child-Pugh class C) or severe physical impairment (performance status 3-4) die within 6 months and should receive only symptomatic treatment.

Carcinoma, Hepatocellular↗

MRI angiography is superior to helical CT for detection of HCC prior to liver transplantation: an explant correlation.

Helical computerized tomography (CT) and magnetic resonance imaging (MRI) are used for staging of hepatocellular carcinoma (HCC) prior to curative treatments but underestimate tumor extension in 30% to 50% of cases when compared with pathologic explants. This study compares a new technology, MRI angiography (MRA), with triphasic helical CT in detection of HCC. Fifty cirrhotic patients, 29 with HCC, undergoing liver transplantation were analyzed. MRA was performed with a 3-D breath-hold fast spoiled gradient-echo sequence by using an effective section thickness of 2 to 2.5 mm. The gold standard was the pathologic examination (liver cut into 5-mm slices). One hundred twenty-seven lesions were identified at the explant: 76 HCC, 13 high-grade dysplastic nodules, 31 macroregenerative nodules, 7 hemangiomas. Diameter of the main HCC nodules was 29 +/- 14 mm and 11 +/- 7 mm for the 47 additional nodules. On a per nodule basis, sensitivity of MRA was superior to CT (58/76 [76%] vs. 43/70 [61%], respectively, P =.001). Sensitivity of MRA for detection of additional nodules decreased with size (>20 mm: 6/6 [100%]; 10-20 mm: 16/19 [84%]; <10 mm: 7/22 [32%]) and was superior to CT for nodules 10 to 20 mm (84% vs. 47%, P =.016). Nonspecific hypervascular nodules >5 mm at MRA were HCC in two thirds of the cases. In conclusion, MRA has a high diagnostic accuracy for HCC > or =10 mm and is more sensitive than triphasic helical CT in nodules sized 10 to 20 mm. MRA is the optimal technique for HCC staging prior to curative therapies.

Adult↗

Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.

BACKGROUND: There is no standard treatment for unresectable hepatocellular carcinoma. Arterial embolisation is widely used, but evidence of survival benefits is lacking. METHODS: We did a randomised controlled trial in patients with unresectable hepatocellular carcinoma not suitable for curative treatment, of Child-Pugh class A or B and Okuda stage I or II, to assess the survival benefits of regularly repeated arterial embolisation (gelatin sponge) or chemoembolisation (gelatin sponge plus doxorubicin) compared with conservative treatment. 903 patients were assessed, and 112 (12%) patients were finally included in the study. The primary endpoint was survival. Analyses were by intention to treat. FINDINGS: The trial was stopped when the ninth sequential inspection showed that chemoembolisation had survival benefits compared with conservative treatment (hazard ratio of death 0.47 [95% CI 0.25-0.91], p=0.025). 25 of 37 patients assigned embolisation, 21 of 40 assigned chemoembolisation, and 25 of 35 assigned conservative treatment died. Survival probabilities at 1 year and 2 years were 75% and 50% for embolisation; 82% and 63% for chemoembolisation, and 63% and 27% for control (chemoembolisation vs control p=0.009). Chemoembolisation induced objective responses sustained for at least 6 months in 35% (14)of cases, and was associated with a significantly lower rate of portal-vein invasion than conservative treatment. Treatment allocation was the only variable independently related to survival (odds ratio 0.45 [95% CI 0.25-0.81], p=0.02). INTERPRETATION: Chemoembolisation improved survival of stringently selected patients with unresectable hepatocellular carcinoma.

Aged↗

Contrast-enhanced power Doppler sonography and helical computed tomography for assessment of vascularity of small hepatocellular carcinomas before and after percutaneous ablation.

PURPOSE: We compared the usefulness of Levovist-enhanced power Doppler imaging (PDI) and helical CT in the depiction of tumor vascularity before and after percutaneous ablation of small hepatocellular carcinomas (HCCs). METHODS: Thirty-one cirrhotic patients with solitary unresectable HCCs smaller than 5 cm (mean size, 2.7 +/- 0.8 cm; range, 1.5-5.0 cm) recruited over a 15-month period were treated with percutaneous ethanol injection (n = 9) or radiofrequency ablation (n = 22). PDI, contrast-enhanced PDI (using Levovist), and multiphase contrast-enhanced helical CT were performed before and after percutaneous ablation, and vascularity findings were compared. RESULTS: Levovist significantly increased baseline intratumoral Doppler signals on PDI compared to non-contrast PDI. The most frequent tumor vascularity pattern was heterogeneous (45%). Vascularity was identified in all tumors by both contrast-enhanced PDI and helical CT before ablation. After percutaneous ablation, intratumoral vascularity was detected in 11 tumors by contrast-enhanced PDI and in 15 tumors by CT. The sensitivity, specificity, and diagnostic accuracy of contrast-enhanced PDI in demonstrating intratumoral vascularity, with CT being the gold standard, were 66%, 93%, and 81%, respectively. There was significant agreement between the 2 modalities in the depiction of tumor vascularity after ablation (kappa = 0.6, p = 0.001). However, there were 5 false negatives and 1 false positive with contrast-enhanced PDI. Complete tumor necrosis was achieved in 21 patients (68%). CONCLUSIONS: There was a good concordance between contrast-enhanced PDI and helical CT in the depiction of HCC vascularity before and after percutaneous ablation. However, although contrast-enhanced PDI may be useful for real-time guidance of treatment, its low sensitivity makes it inadequate to accurately assess the completeness of ablation.

Aged↗