Lynn A. Brody

Combined Portal Vein Embolization and Neoadjuvant Chemotherapy As a Treatment Strategy for Resectable Hepatic Colorectal Metastases

Objectives:The objectives of this study are 1) to determine whether the future liver remnant will grow after portal vein embolization (PVE) in patients with colon cancer on concurrent chemotherapy and 2) to determine whether recovery after extended hepatectomy is improved after PVE. Purpose:Neoadjuvant chemotherapy followed by hepatic resection is an increasingly used therapeutic strategy for curative treatment for colorectal metastases. However, such chemotherapy may result in steatosis, liver damage, and compromised liver regeneration and recovery. This study aims to determine whether PVE can be used during neoadjuvant therapy to enhance growth of future residual liver and to improve postoperative recovery. Methods:From September 1999 to September 2004, 100 patients with colorectal metastases to the liver were subjected to PVE as preparation for extended hepatic resection, 43 of whom were embolized during neoadjuvant chemotherapy. Liver growth was examined by computed tomography volumetric analysis. Clinical outcomes of the 71 patients subsequently resected were compared with 100 consecutive patients subjected to extended resection without PVE (controls). Results:After a median wait of 30 ± 2 days after PVE, patients on neoadjuvant chemotherapy experienced a median contralateral (nonembolized) liver growth of 22% ± 3% compared with 26% ± 3% for those without chemotherapy (P = NS). The number of patients with <5% growth was also similar: 4 of 43 versus 6 of 57 (P = NS). Comparison of patients resected after PVE to a simultaneous cohort of 100 consecutive patients subjected to extended resection without prior PVE demonstrated a lower fresh frozen plasma requirement (P = 0.01), a lower peak bilirubin (P = 0.002), and a shorter length of stay (P = 0.03). Mortality was similar (0% vs. 2%). Conclusions:Liver growth occurs after PVE even when cytotoxic chemotherapy is administered. No major complications occurred with PVE. Patients requiring major hepatic resection should be considered for PVE during neoadjuvant chemotherapy to improve subsequent recovery after resection.

Particle Embolization of Hepatic Neuroendocrine Metastases for Control of Pain and Hormonal Symptoms

PURPOSE To evaluate treatment outcome with respect to the indication for treatment in patients with neuroendocrine tumors metastatic to the liver undergoing hepatic artery embolization with polyvinyl alcohol (PVA) particles. MATERIALS AND METHODS Charts and radiographs were reviewed of 35 patients undergoing 63 separate sessions of embolotherapy between January 1993 and July 1997. Patient demographics, tumor type, indication for embolization, and complications were recorded. Symptomatic and morphologic responses to therapy were noted, as well as duration of response. RESULTS Fourteen men and 21 women underwent embolization of 21 carcinoid and 14 islet cell tumors metastatic to the liver. These patients underwent 63 separate episodes of embolotherapy. Of 48 episodes that could be evaluated, response to treatment was noted following 46 episodes (96%). The duration of response was longest in patients treated for hormonal symptoms with (17.5 months) or without (16 months) pain, and was shortest (6.2 months) when the indication was pain alone. Complications occurred after 11 of the 63 embolizations (17%), including four (6%) deaths. Cumulative 5-year survival following embolotherapy was 54%. CONCLUSION Hepatic artery embolization with PVA particles is beneficial for patients with neuroendocrine tumors metastatic to the liver and may be used for control of pain as well as hormonal symptoms. This therapy should be used cautiously when more than 75% of the hepatic parenchyma is replaced by tumor.

Transcatheter Arterial Embolization with Only Particles for the Treatment of Unresectable Hepatocellular Carcinoma

PURPOSE To determine the survival of patients with hepatocellular carcinoma (HCC) treated with a standardized method of transcatheter arterial embolization (TAE) with small embolic particles intended to impart terminal vessel blockade, and to evaluate prognostic factors that impact overall survival. MATERIALS AND METHODS A total of 322 patients with HCC who underwent 766 embolizations from January 1997 to December 2004 were retrospectively reviewed. Selective embolization of vessels feeding individual tumors was performed with small (50 microm) polyvinyl alcohol or spherical embolic particles (40-120 microm) intended to cause terminal vessel blockade. Repeat embolization was performed in cases of evidence of persistent viable tumor or development of new lesions. Patient, tumor, and treatment characteristics were prospectively recorded and tested for prognostic significance by univariate and multivariate analysis. RESULTS The median survival time was 21 months, with 1-, 2-, and 3-year overall survival rates of 66%, 46%, and 33%, respectively. In patients without extrahepatic disease or portal vein involvement by tumor, the overall 1-, 2-, and 3-year survival rates increased to 84%, 66%, and 51%, respectively. Okuda stage, extrahepatic disease, diffuse disease (> or =5 tumors), and tumor size were independent predictors of survival on multivariate analysis. There were 90 complications (11.9%) in 75 patients, including eight deaths (2.5%), within 30 days of embolization. CONCLUSIONS Hepatic arterial embolization with small particles to cause terminal vessel blockade is an effective treatment method for patients with unresectable HCC. These data support our hypothesis that particles alone may be the critical component of catheter-directed embolotherapy.

Particle Embolization for Hepatocellular Carcinoma

PURPOSE To evaluate the outcome of all patients undergoing particle embolization for hepatocellular carcinoma at a single institution from January 1, 1993, through December 31, 1995. MATERIALS AND METHODS The charts and radiographs of all patients undergoing particle embolization during the study period were reviewed. The following information was collected: patient demographics, Child class and Okuda stage, number of embolization treatment sessions, length of hospital stay, complications related to the embolization procedure, including postembolization syndrome, current patient status, and date of death. RESULTS Forty-six patients underwent 86 embolization sessions during the study period. Postembolization syndrome developed after 70 of the 86 sessions (81%); in four cases (4.6%) this required treatment that extended the patients hospital stay. Three other complications occurred (3.5%), including a splenic infarct and two episodes of transient hepatic failure, all treated supportively. There was one death within 30 days, but it was not directly attributable to embolotherapy. Follow-up was available for all of the patients who underwent treatment. Thirty-four patients were classified as Child class A, and 12 were classified as Child class B. Thirty patients were classified as Okuda stage I, 14 were classified as Okuda stage II, and two were classified as Okuda stage III. Overall actuarial survival was 50% at 1 year and 33% at 2 years. There was a statistically significant difference in survival between Okuda stage I and stage II patients, but not between Child class A and class B patients. CONCLUSION Particle embolization for hepatocellular carcinoma is well tolerated and demonstrates actuarial survival of 50% at 1 year and 33% at 2 years.

Randomized Trial of Hepatic Artery Embolization for Hepatocellular Carcinoma Using Doxorubicin-Eluting Microspheres Compared With Embolization With Microspheres Alone

PURPOSE Transarterial chemoembolization is accepted therapy for hepatocellular carcinoma (HCC). No randomized trial has demonstrated superiority of chemoembolization compared with embolization, and the role of chemotherapy remains unclear. This randomized trial compares the outcome of embolization using microspheres alone with chemoembolization using doxorubicin-eluting microspheres. MATERIALS AND METHODS At a single tertiary referral center, patients with HCC were randomly assigned to embolization with microspheres alone (Bead Block [BB]) or loaded with doxorubicin 150 mg (LC Bead [LCB]). Random assignment was stratified by number of embolizations to complete treatment, and assignments were generated by permuted blocks in the institutional database. The primary end point was response according to RECIST 1.0 (Response Evaluation Criteria in Solid Tumors) using multiphase computed tomography 2 to 3 weeks post-treatment and then at quarterly intervals, with the reviewer blinded to treatment allocation. Secondary objectives included safety and tolerability, time to progression, progression-free survival, and overall survival. This trial is currently closed to accrual. RESULTS Between December 2007 and April 2012, 101 patients were randomly assigned: 51 to BB and 50 to LCB. Demographics were comparable: median age, 67 years; 77% male; and 22% Barcelona Clinic Liver Cancer stage A and 78% stage B or C. Adverse events occurred with similar frequency in both groups: BB, 19 of 51 patients (38%); LCB, 20 of 50 patients (40%; P = .48), with no difference in RECIST response: BB, 5.9% versus LCB, 6.0% (difference, -0.1%; 95% CI, -9% to 9%). Median PFS was 6.2 versus 2.8 months (hazard ratio, 1.36; 95% CI, 0.91 to 2.05; P = .11), and overall survival, 19.6 versus 20.8 months (hazard ratio, 1.11; 95% CI, 0.71 to 1.76; P = .64) for BB and LCB, respectively. CONCLUSION There was no apparent difference between the treatment arms. These results challenge the use of doxorubicin-eluting beads for chemoembolization of HCC.

Current Management of Pyogenic Liver Abscess: Surgery is Now Second-Line Treatment

BACKGROUND The objective of this study was to examine the current treatment for liver abscess and to assess the factors associated with failure of percutaneous drainage. STUDY DESIGN Records of 58 patients with pyogenic hepatic abscess, from 1998 to 2009, were examined. Clinicopathologic variables were analyzed as predictors of failure of percutaneous drainage using multivariable logistic regression. The results of surgical intervention after failure of percutaneous treatment were also examined. RESULTS Fifty-one patients (88%) had a history of malignancy including pancreas (36%), cholangiocarcinoma (17%), colon (12%), and gallbladder (10%). Recent hepatic artery embolization or radiofrequency ablation preceded development of abscess in 13 patients (22%). Fifteen patients (26%) had evidence of biliary tract communication, and 14 of 15 (93%) of these patients had concomitant biliary tract obstruction. Percutaneous drainage was successful in 38 patients (66%) with a median drain dwell time of 26 days (range 3 to 319 days). Five patients (9%) required operative intervention and 2 of these patients (3% overall) died postoperatively from septic complications. Fifteen patients (26%) died with percutaneous drains in place; 9 (60%) of these patients died of cancer progression without evidence of sepsis. Independent predictors of failure of percutaneous drainage included abscesses containing yeast (p = 0.003) and communication of the abscess cavity with the biliary tree (p = 0.02). CONCLUSIONS Pyogenic hepatic abscess was treated successfully in the majority of patients with advanced malignancy, although mortality remained high. The presence of yeast and communication with an untreated obstructed biliary tree were associated with failure of percutaneous drainage. The need for surgical salvage was associated with a high mortality.

Percutaneous Radiofrequency Ablation of Colorectal Cancer Liver Metastases: Factors Affecting Outcomes—A 10-year Experience at a Single Center

PURPOSE To identify predictors of oncologic outcomes after percutaneous radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLMs) and to describe and evaluate a modified clinical risk score (CRS) adapted for ablation as a patient stratification and prognostic tool. MATERIALS AND METHODS This study consisted of a HIPAA-compliant institutional review board-approved retrospective review of data in 162 patients with 233 CLMs treated with percutaneous RFA between December 2002 and December 2012. Contrast material-enhanced CT was used to assess technique effectiveness 4-8 weeks after RFA. Patients were followed up with contrast-enhanced CT every 2-4 months. Overall survival (OS) and local tumor progression-free survival (LTPFS) were calculated from the time of RFA by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariate and multivariate analysis to identify predictors of outcomes. RESULTS Technique effectiveness was 94% (218 of 233). Median LTPFS was 26 months. At univariate analysis, predictors of shorter LTPFS were tumor size greater than 3 cm (P < .001), ablation margin size of 5 mm or less (P < .001), high modified CRS (P = .009), male sex (P = .03), and no history of prior hepatectomy (P = .04) or hepatic arterial infusion chemotherapy (P = .01). At multivariate analysis, only tumor size greater than 3 cm (P = .01) and margin size of 5 mm or less (P < .001) were independent predictors of shorter LTPFS. Median and 5-year OS were 36 months and 31%. At univariate analysis, predictors of shorter OS were tumor size larger than 3 cm (P = .005), carcinoembryonic antigen level greater than 30 ng/mL (P = .003), high modified CRS (P = .02), and extrahepatic disease (EHD) (P < .001). At multivariate analysis, tumor size greater than 3 cm (P = .006) and more than one site of EHD (P < .001) were independent predictors of shorter OS. CONCLUSION Tumor size of less than 3 cm and ablation margins greater than 5 mm are essential for satisfactory local tumor control. Tumor size of more than 3 cm and the presence of more than one site of EHD are associated with shorter OS.

Radiofrequency Ablation in the Management of Liver Metastases from Breast Cancer

OBJECTIVE Systemic chemotherapy remains the standard treatment for patients with breast cancer hepatic metastases. Resection of metastases has survival advantages in a small percentage of selected patients. Radiofrequency ablation has been used in small numbers of selected patients. This small series was undertaken to review our experience with radiofrequency ablation in the management of patients with breast cancer hepatic metastases. CONCLUSION Radiofrequency ablation of breast cancer hepatic metastases is safe and may be used to control hepatic deposits in patients with stable or no extrahepatic disease.

A Herpes Oncolytic Virus Can Be Delivered Via the Vasculature to Produce Biologic Changes in Human Colorectal Cancer

Genetically engineered herpes simplex viruses (HSVs) can selectively infect and replicate in cancer cells, and are candidates for use as oncolytic therapy. This long-term report of a phase I trial examines vascular administration of HSV as therapy for cancer. Twelve subjects with metastatic colorectal cancer within the liver failing first-line chemotherapy were treated in four cohorts with a single dose (3 x 10(6) to 1 x 10(8) particles) of NV1020, a multimutated, replication-competent HSV. After hepatic arterial administration, subjects were observed for 4 weeks before starting intra-arterial chemotherapy. All patients exhibited progression of disease before HSV injection. During observation, levels of the tumor marker carcinoembryonic antigen (CEA) decreased (median % drop = 24%; range 13-74%; P < 0.02). One of three individuals at the 10(8) level showed a 39% radiologic decrease in tumor size by cross-section and 75% by volume. HSV infection was documented from liver tumor biopsies. After beginning regional chemotherapy, all patients demonstrated a further decrease in CEA (median 96%; range 50-98%; P < 0.008) and a radiologic partial response. Median survival for this group was 25 months. During follow-up, no signs of virus reactivation were found. Multimutated HSV can be delivered safely into the human bloodstream to produce selective infection of tumor tissues and biologic effects.

Treatment of metastatic sarcoma to the liver with bland embolization

The authors evaluated the impact of bland particle embolization on survival in patients with metastatic sarcoma to the liver.