Paolo Vallone

Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients.

OBJECTIVE To describe the safety and efficacy of radiofrequency ablation (RFA) to treat unresectable malignant hepatic tumors in 123 patients. BACKGROUND The majority of patients with primary or metastatic malignancies confined to the liver are not candidates for resection because of tumor size, location, or multifocality or inadequate functional hepatic reserve. Local application of heat is tumoricidal; therefore, the authors investigated a novel RFA system to treat patients with unresectable hepatic cancer. PATIENTS AND METHODS Patients with hepatic malignancies were entered into a prospective, nonrandomized trial. The liver tumors were treated percutaneously or during surgery under ultrasound guidance using a novel LeVeen monopolar array needle electrode and an RF 2000 generator. All patients were followed to assess complications, treatment response, and recurrence of malignant disease. RESULTS RFA was used to treat 169 tumors (median diameter 3.4 cm, range 0.5 to 12 cm) in 123 patients. Primary liver cancer was treated in 48 patients (39.1%), and metastatic liver tumors were treated in 75 patients (60.9%). Percutaneous and intraoperative RFA was performed in 31 patients (35.2%) and 92 patients (74.8%), respectively. There were no treatment-related deaths, and the complication rate after RFA was 2.4%. All treated tumors were completely necrotic on imaging studies after completion of RFA treatments. With a median follow-up of 15 months, tumor has recurred in 3 of 169 treated lesions (1.8%), but metastatic disease has developed at other sites in 34 patients (27.6%). CONCLUSIONS RFA is a safe, well-tolerated, and effective treatment to achieve tumor destruction in patients with unresectable hepatic malignancies. Because patients are at risk for the development of new metastatic disease after RFA, multimodality treatment approaches that include RFA should be investigated.

Radiofrequency Ablation of Hepatocellular Cancer in 110 Patients With Cirrhosis

ObjectiveTo determine the treatment efficacy, safety, local tumor control, and complications related to radiofrequency ablation (RFA) in patients with cirrhosis and unresectable hepatocellular carcinoma (HCC). Summary Background DataMost patients with HCC are not candidates for resection because of tumor size, location, or hepatic dysfunction related to cirrhosis. RFA is a technique that permits in situ destruction of tumors by means of local tissue heating. MethodsOne hundred ten patients with cirrhosis and HCC (Child class A, 50; B, 31; C, 29) were treated during a prospective study using RFA. Patients were treated with RFA using an open laparotomy, laparoscopic, or percutaneous approach with ultrasound guidance to place the RF needle electrode into the hepatic tumors. All patients were followed up at regular intervals to detect treatment-related complications or recurrence of disease. ResultsAll 110 patients were followed up for at least 12 months after RFA (median follow-up 19 months). Percutaneous or intraoperative RFA was performed in 76 (69%) and 34 patients (31%), respectively. A total of 149 discrete HCC tumor nodules were treated with RFA. The median diameter of tumors treated percutaneously (2.8 cm) was smaller than that of lesions treated during laparotomy (4.6 cm). Local tumor recurrence at the RFA site developed in four patients (3.6%); recurrent HCC subsequently developed in other areas of the liver in all four. New liver tumors or extrahepatic metastases developed in 50 patients (45.5%), but 56 patients (50.9%) had no evidence of recurrence. There were no treatment-related deaths, but complications developed in 14 patients (12.7%) after RFA. ConclusionsIn patients with cirrhosis and HCC, RFA produces effective local control of disease in a significant proportion of patients and can be performed safely with minimal complications.

Early and late complications after radiofrequency ablation of malignant liver tumors in 608 patients

Background:Radiofrequency ablation (RFA) has become a common treatment of patients with unresectable primary and secondary hepatic malignancies. We performed this prospective analysis to determine early (within 30 days) and late (more than 30 days after) complication rates associated with hepatic tumor RFA. Methods:All patients treated between January 1, 1996 and June 30, 2002 with RFA for hepatic malignancies were entered into a prospective database. Patients were evaluated during RFA treatment, throughout the immediate post RFA course, and then every 3 months after RFA to assess for the development of treatment-related complications. Results:A total of 608 patients, 345 men (56.7%) and 263 women (43.3%), with a median age of 58 years (range 18–85 years) underwent RFA of 1225 malignant liver tumors. Open intraoperative RFA was performed in 382 patients (62.8%), while percutaneous RFA was performed in 226 (37.2%). The treatment-related mortality rate was 0.5%. Early complications developed in 43 patients (7.1%). Early complications were more likely to occur in patients treated with open RFA (33 [8.6%] of 382 patients) compared with percutaneous RFA (10 [4.4%] 226 patients, P < 0.01), and in patients with cirrhosis (25 [12.9%] complications in 194 patients) compared with noncirrhotic patients (31 [7.5%] complications in 414 patients, P < 0.05). Late complications arose in 15 patients (2.4%) with no difference in incidence between open and percutaneous RFA treatment. The combined overall early and late complication rate was 9.5%. Conclusions:Hepatic tumor RFA can be performed with low mortality and morbidity rates. Though relatively rare, late complications can develop and physicians performing hepatic RFA must be cognizant of these delayed treatment-related problems.

Pegylated Arginine Deiminase Treatment of Patients With Unresectable Hepatocellular Carcinoma: Results From Phase I/II Studies

PURPOSE Recently, we reported that a large number of human hepatocellular cancer (HCC) cell lines were auxotrophic for arginine. Here we report the results obtained with the amino acid-degrading enzyme arginine deiminase (ADI) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) as a means of lowering plasma arginine to treat HCC. The study was a cohort dose-escalation phase I/II study. PATIENTS AND METHODS Pharmacodynamic studies indicated an ADI-SS PEG 20,000 mw dose level of 160 U/m(2) was sufficient to lower plasma arginine from a resting level of approximately 130 micromol/L to below the level of detection (< 2 micromol/L) for more than 7 days, a dose later defined as the optimal biologic dose. All patients were to receive three cycles at the optimum biologic dose. RESULTS This therapy was well tolerated, even in patients who had no detectable plasma arginine for 3 continuous months of therapy. Of the 19 patients enrolled, two had a complete response, seven had a partial response, seven had stable disease, and three had progressive disease. The median survival for the 19 patients enrolled on this study was 410 days, with four patients still alive at present (> 680 days). CONCLUSION Elimination of all detectable plasma arginine in patients with HCC was well tolerated and seemed to be effective in the treatment of some patients with HCC. Further testing of ADI-SS PEG 20,000 mw in a larger population of individuals with HCC as well as other human tumors auxotrophic for arginine is warranted.

Significant long-term survival after radiofrequency ablation of unresectable hepatocellular carcinoma in patients with cirrhosis.

BackgroundRadiofrequency ablation (RFA) offers an alternative treatment in some unresectable hepatocellular carcinoma (HCC) patients with disease confined to the liver. We prospectively evaluated survival rates in patients with early-stage, unresectable HCC treated with RFA.MethodsAll patients with HCC treated with RFA between September 1, 1997, and July 31, 2002, were prospectively evaluated. Patients were treated with RFA by using a percutaneous or open intraoperative approach with ultrasound guidance and were evaluated at regular intervals to determine disease recurrence and survival.ResultsA total of 194 patients (153 men [79%] and 41 women [21%]) with a median age of 66 years (range, 39–86 years) underwent RFA of 289 sonographically detectable HCC tumors. All patients were followed up for at least 12 months (median follow-up, 34.8 months). Percutaneous and open intraoperative RFA was performed in 140 (72%) and 54 (28%) patients, respectively. The median diameter of tumors treated with RFA was 3.3 cm. Disease recurred in 103 (53%) of 194 patients, including 69 (49%) of 140 patients treated percutaneously and 34 (63%) of 54 treated with open RFA (not significant). Local recurrence developed in nine patients (4.6%). Most recurrence was intrahepatic. The overall complication rate was 12%. Overall survival rates at 1, 3, and 5 years for all 194 patients were 84.5%, 68.1%, and 55.4%, respectively.ConclusionsTreatment with RFA can produce significant long-term survival rates for cirrhotic patients with early-stage, unresectable HCC. RFA can be performed in these patients with relatively low complication rates. Confirmation of these results in randomized trials should be considered.

Hepatic resection and percutaneous ethanol injection as treatments of small hepatocellular carcinoma. A Cancer of the Liver Italian Program (CLIP 08)retrospective case-control study

Background Patients with small hepatocellular carcinoma (HCC) are usually treated with hepatic resection or percutaneous ethanol injection (PEI). Goals To compare the effects of hepatic resection versus PEI on survival in a matched case–control study. Study Patients with single-nodule HCC (≤5 cm) who were treated with hepatic resection (cases) or PEI (controls) were eligible. Matching criteria were date of diagnosis, Child–Pugh stage, and age at diagnosis. Kaplan–Meier survival curve of the control group was drawn weighing each stratum by the inverse of its size. Treatments were compared by a stratified Coxs model, adjusted by CLIP score. Results Of 912 patients, 197 were eligible and 82 (17 cases and 65 controls) were matched, creating 17 strata. Nine (53%) cases and 41 (63%) controls died. Cox model showed no survival difference between the two groups; hazard ratio of PEI versus hepatic resection was 1.04 (95% CI = 0.43–2.52). One- and 3-year survival rates in the hepatic resection and PEI groups were 82% versus 91% and 63% versus 65%, respectively. Conclusions Patients with small HCC treated with hepatic resection or PEI have similar survival rates. In view of the higher cost and morbidity of hepatic resection, a prospective randomized study is warranted.

Biweekly Docetaxel-Irinotecan Treatment with Filgrastim Support Is Highly Active in Antracycline-Paclitaxel-Refractory Breast Cancer Patients

Purpose: To evaluate the feasibility and activity of combination treatment with docetaxel (DTX) and irinotecan (CPT-11), given together every other week, combined with filgrastim support, in anthracycline- and paclitaxel-pretreated breast cancer (BC) patients. Patients and Methods: Advanced BC patients pretreated with anthracycline- and paclitaxel-based chemotherapy were eligible. DTX (80 mg/m2) and CPT-11 (100 mg/m2) were given biweekly with filgrastim support (300 µg/day on days 4–7). Results: Fifty patients (48 with metastatic and 2 with locally advanced cancer) were enrolled, with a total of 318 cycles being delivered. Thirty-one patients had visceral localizations. All patients had received epirubicin plus paclitaxel, with or without cisplatin, as front-line treatment for advanced disease. Overall, fatigue and diarrhea were the main chemotherapy-related toxicities in this study, being severe in 10 (20%) and 4 (8%) patients. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 18 (36%) and 6 (12%) patients, respectively. Red blood cell transfusions were required in 4 patients. A total of 32 objective responses were registered (overall response rate, ORR = 64%, 95% confidence interval = 49–77%), including 8 complete responses (16%). An additional 8 patients showed stable disease. After a median follow-up of 18 (range 4–29) months, 30 patients were still alive, and 19 were progression free; median progression-free and overall survivals were 10 and 23 months, respectively. Conclusions: Biweekly DTX/CPT-11 with G-CSF support is a well-tolerated and highly effective approach in anthracycline-/paclitaxel-pretreated patients. The very promising ORR and survival outcome observed in this subset of patients with a poor prognosis suggest that this regimen might play a major role in the management of this disease.

Levovist-enhanced Doppler sonography versus spiral computed tomography to evaluate response to percutaneous ethanol injection in hepatocellular carcinoma

The aim of the current study was to compare Levovist-enhanced power Doppler (PD) imaging with contrast-enhanced spiral computed tomography (CT) in the evaluation of intratumoral vascularity of hepatocellular carcinomas at diagnosis and after percutaneous ethanol injection (PEI). Nineteen patients with hepatocellular carcinoma (HCC) underwent PD with and without Levovist and spiral CT at diagnosis and 1 month after PEI treatment. Compared to spiral CT at baseline evaluation, the PD showed intratumoral vascularity in 36.8% of the cases; this percentage reached 78.9% after Levovist enhancement. One month after PEI, only 5 out of 19 treated HCCs appeared as hypodense areas at CT and showed no contrast enhancement. Only 3 of the 14 patients with a positive spiral CT scan were positive at the PD performed without the Levovist administration (sensitivity, 21.4%). The use of contrast-enhanced ultrasonography led to detection of residual signal in six other HCCs treated by ethanol injection (sensitivity, 64.2%). We confirm that spiral CT is the most sensitive and accurate technique in evaluating the effect of ethanol injection in HCC. It correctly identifies most cases of treatment failure as enhanced areas within the lesion. The lower rate of detection of tumoral vascularity by Doppler sonography was significantly increased by Levovist. The evidence of residual vascularity within HCC at Levovist Doppler sonography allows the targeting of additional ethanol injections.

Sonography for Locoregional Staging and Follow-up of Cutaneous Melanoma How We Do It

Objective. Sonography is being used with increasing frequency in the assessment of locoregional tumor spread in patients with melanoma. Nevertheless, to maximize its practical impact, sonography should be performed with state‐of‐the‐art equipment, by specifically trained operators, and using a careful exploration technique and well‐defined diagnostic criteria. In this “how I do it”–type article, we illustrate our practical approach to sonography of cutaneous melanoma. Methods. We first illustrate the basic and advanced technical requirements; then we describe our exploration methods and our image interpretation approach; and finally, we report on our use of sonography as a guidance tool for interventional procedures. Special emphasis is given to methodological and interpretative clues, tricks, and pitfalls. Results. Sonography can be used in the initial staging of patients with melanoma, particularly in the screening of patients scheduled for a sentinel lymph node biopsy procedure. Additionally, sonography can be used during patient follow‐up to detect locoregional recurrence earlier than palpation. Conclusions. Sonography plays a growing role in the assessment of the superficial spread of melanoma. Nevertheless, state‐of‐the‐art equipment and careful exploration by trained operators are necessary.

Transient Hepatic Echogenicity Difference on Contrast-Enhanced Ultrasonography Sonographic Sign and Pitfall

The purpose of this study was to report and analyze a new contrast‐enhanced ultrasonographic (CEUS) imaging finding, the transient hepatic echogenicity difference due to perfusion changes, using computed tomography (CT) as a reference standard.