William S. Rilling

Neuroendocrine hepatic metastases: does aggressive management improve survival?

Objective:The aim of this study was to determine whether aggressive management of neuroendocrine hepatic metastases improves survival. Summary Background Data:Survival in patients with carcinoid and pancreatic neuroendocrine tumors is significantly better than adenocarcinomas arising from the same organs. However, survival and quality of life are diminished in patients with neuroendocrine hepatic metastases. In recent years, aggressive treatment of hepatic neuroendocrine tumors has been shown to relieve symptoms. Minimal data are available, however, to document improved survival with this approach. Methods:The records of patients with carcinoid (n = 84) and pancreatic neuroendocrine tumors (n = 69) managed at our institution from January 1990 through July 2004 were reviewed. Eighty-four patients had malignant tumors, and hepatic metastases were present in 60 of these patients. Of these 60 patients, 23 received no aggressive treatment of their liver metastases, 19 were treated with hepatic resection and/or ablation, and 18 were managed with transarterial chemoembolization (TACE) frequently (n = 11) in addition to resection and/or ablation. These groups did not differ with respect to age, gender, tumor type, or extent of liver involvement. Results:Median and 5-year survival were 20 months and 25% for the Nonaggressive group, >96 months and 72% for the Resection/Ablation group, and 50 months and 50% for the TACE group. The survival for the Resection/Ablation and the TACE groups was significantly better (P < 0.05) when compared with the Nonaggressive group. Patients with more than 50% liver involvement had a poor outcome (P < 0.001). Conclusions:These data suggest that aggressive management of neuroendocrine hepatic metastases does improve survival, that chemoembolization increases the patient population eligible for this strategy, and that patients with more than 50% liver involvement may not benefit from an aggressive approach.

Radioembolization with 90Y Microspheres: Angiographic and Technical Considerations

The anatomy of the mesenteric system and the hepatic arterial bed has been demonstrated to have a high degree of variation. This is important when considering pre-surgical planning, catheterization, and trans-arterial hepatic therapies. Although anatomical variants have been well described, the characterization and understanding of regional hepatic perfusion in the context of radioembolization have not been studied with great depth. The purpose of this review is to provide a thorough discussion and detailed presentation of the angiographic and technical aspects of radioembolization. Normal vascular anatomy, commonly encountered variants, and factors involved in changes to regional perfusion in the presence of liver tumors are discussed. Furthermore, the principles described here apply to all liver-directed transarterial therapies.

Transcatheter Therapy for Hepatic Malignancy: Standardization of Terminology and Reporting Criteria

The field of interventional oncology includes tumor ablation as well as the use of transcatheter therapies such as embolization, chemoembolization, and radioembolization. Terminology and reporting standards for tumor ablation have been developed. The development of standardization of terminology and reporting criteria for transcatheter therapies should provide a similar framework to facilitate the clearest communication among investigators and provide the greatest flexibility in comparing established and emerging technologies. An appropriate vehicle for reporting the various aspects of catheter directed therapy is outlined, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings. Methods for standardizing the reporting of outcomes toxicities, complications, and other important aspects that require attention when reporting clinical results are addressed. It is the intention of the group that adherence to the recommendations will facilitate achievement of the groups main objective: improved precision and communication for reporting the various aspects of transcatheter management of hepatic malignancy that will translate to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes.

Research Reporting Standards for Radioembolization of Hepatic Malignancies

Primary Liver Tumors Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver; its incidence is increasing worldwide. It ranks as the sixth most common tumor and third most common cause of cancer-related mortality (1,2). Primary liver tumors include HCC and intrahepatic cholangiocarcinoma. Surgical resection is preferred over transplantation and is considered potentially curative in patients with resectable HCC and normal liver function (3). Transplantation is considered the gold standard for patients with unresectable HCC and whose disease is within the Milan criteria (4). Resection and transplantation have limited roles, given advanced disease (chronic liver disease and/or tumor extent) at presentation and limited organ availability (5–7). Chemoembolization and radiofrequency ablation represent standard therapies in treating patients and serve as a bridge to transplantation in selected patients (8,9). Radioembolization has an emerging role in “bridging” patients within criteria by delaying tumor progression. It has also been shown to downstage disease beyond the Milan, to within, transplant criteria (10–12). A recent study has demonstrated that radioembolization leads to longer time-to-progression and better toxicity profile when compared with chemoembolization (13). Patients with macrovascular tumor involvement have also exhibited evidence of clinical benefit after radioembolization (14).

Microwave ablation for hepatic malignancies: a multiinstitutional analysis.

Objective:This study hypothesized that tumor size, number of tumors, surgical approach, and tumor histology significantly affected microwave ablation (MWA) success and recurrence-free survival. Background:Although many hepatobiliary centers have adopted MWA, the factors that influence local control are not well described. Methods:Consecutive patients with hepatic malignancy treated by MWA were included from 4 high-volume institutions (2003–2011) and grouped by histology: hepatocellular carcinoma (HCC), colorectal liver metastases, neuroendocrine liver metastases, and other cancers. Independent significance of outcome variables was established with logistic regression and Cox proportional hazards models. Results:Four hundred fifty patients were treated with 473 procedures (139 HCC, 198 colorectal liver metastases, 61 neuroendocrine liver metastases, and 75 other) for a total of 875 tumors. Median follow-up was 18 months. Concurrent hepatectomy was performed in 178 patients (38%), and when performed was associated with greater morbidity. Complete ablation was confirmed for 839 of 865 tumors (97.0%) on follow-up cross-sectional imaging (10 were unevaluable). A surgical approach (open, laparoscopic, or percutaneous) had no significant impact on complication rates, recurrence, or survival. The local recurrence rate was 6.0% overall and was highest for HCC (10.1%, P = 0.045) and percutaneously treated lesions (14.1%, P = 0.014). In adjusted models, tumor size 3 cm or more predicted poorer recurrence-free survival (hazard ratio: 1.60, 95% CI: 1.02–2.50, P = 0.039). Conclusions:In this large data set, patients with 3 cm or more tumors showed a propensity for early recurrence, regardless of histology. Higher rates of local recurrence were noted in HCC patients, which may reflect underlying liver disease. There were no significant differences in morbidity or survival based on the surgical approach; however, local recurrence rates were highest for percutaneously ablated tumors.

Chemoembolization of intrahepatic cholangiocarcinoma with cisplatinum, doxorubicin, mitomycin C, ethiodol, and polyvinyl alcohol: a 2-center study.

Unresectable intrahepatic cholangiocarcinoma has a poor prognosis, with a median survival of 5 to 8 months without treatment. Response and survival after chemoembolization were evaluated.

Helical computed tomography of the normal thoracic outlet

PURPOSE This study was performed to determine the detailed anatomy of the thoracic outlet in normal subjects using helical computed tomography (CT), with particular attention to vascular compression with arm movement. METHODS Ten volunteers underwent detailed clinical evaluation and helical CT scanning of the upper thorax and neck with the arm in a neutral position and with the arm abducted 90 degrees or greater and externally rotated. Anterior scalene-clavicle distance (SC), costoclavicular distance (CC), and vessel diameters were measured with electronic calipers in each position. Comparisons were made with Students t test. RESULTS With abduction the SC decreased from 18.4 +/- 3.9 mm to 5.2 +/- 2.4 mm (p < 0.001), and the CC decreased from 12.6 +/- 2.7 mm to 6.3 +/- 3.3 mm (p = 0.005). At these same anatomic planes, the vein diameter decreased from 11.0 +/- 1.6 mm at the neutral position to 5.1 +/- 1.5 mm (p < 0.001) and from 16.1 +/- 3.0 mm to 7.4 +/- 2.6 mm with the arm abducted (p < 0.001). The artery diameter changed from 6.6 +/- 0.8 mm to 6.2 +/- 0.5 mm (p = 0.08) and from 7.2 +/- 0.8 mm to 6.0 +/- 0.5 mm (p = 0.001) with arm movement. CONCLUSIONS Both the distances between the anterior scalene muscle and the clavicle and between the clavicle and the first rib are significantly reduced with abduction of the upper extremity. Venous compression is universal at both the SC and CC spaces in normal subjects with this maneuver. Arterial narrowing occurs less frequently and appears to be minor. Minor changes in these thoracic outlet dimensions (SC/CC) may produce venous compression without movement.

Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data

Transarterial chemoembolization (TACE) using lipiodol‐based regimens, including the administration of an anticancer‐in‐oil emulsion followed by embolic agents, is widely used in the treatment of hepatocellular carcinoma (HCC). This approach has been supported by meta‐analyses of randomized, controlled trials (RCTs) performed more than a decade ago. We performed a systematic review to understand current efficacy and safety data of lipiodol TACE in treatment of HCC. A search of the literature published between January 1, 1980 and June 30, 2013 was performed using MEDLINE and EMBASE databases. All potentially relevant publications were reviewed and articles were selected based on predefined inclusion and exclusion criteria. Of a total of 1,564 articles reviewed, 101 articles, including a total of 10,108 patients treated with lipiodol TACE, were selected for the efficacy analysis. Objective response rate was 52.5% (95% confidence interval [CI]: 43.6‐61.5). Overall survival (OS) was 70.3% at 1 year, 51.8% at 2 years, 40.4% at 3 years, and 32.4% at 5 years. Median OS was 19.4 months (95% CI: 16.2‐22.6). A total of 217 articles presenting precise description on numbers of adverse events (AEs) were selected for the safety review: In these studies, a total of 21,461 AEs were reported in 15,351 patients. Liver enzyme abnormalities were the most commonly observed AE, followed by the symptoms associated with postembolization syndrome. Overall mortality rate was 0.6% and the most common cause of death was related to acute liver insufficiency. Conclusions: In a systematic literature review, survival figures of HCC patients undergoing lipiodol TACE appear to be in line with those reported in previous RCTs, and no new or unexpected safety concerns were identified. (Hepatology 2016;64:106–116)

Radioembolisation for liver metastases: Results from a prospective 151 patient multi-institutional phase II study

PURPOSE To investigate the safety, response rate, progression-free and overall survival of patients with liver metastases treated with (90)Y (glass) radioembolisation in a prospective, multicenter phase II study. METHODS 151 patients with liver metastases (colorectal n=61, neuroendocrine n=43 and other tumour types n=47) refractory to standard of care therapies were enrolled in this prospective, multicenter, phase II study under an investigational device exemption. Clinical/laboratory/imaging follow-up were obtained at 30 days followed by 3-month intervals for 1 year and every 6 months thereafter. The primary end-point was progression-free survival (PFS); secondary end-points included safety, hepatic progression-free survival (HPFS), response rate and overall survival. RESULTS Median age was 66 (range 25-88). Grade 3/4 adverse events included pain (12.8%), elevated alkaline phospatase (8.1%), hyperbilirubinemia (5.3%), lymphopaenia (4.1%), ascites (3.4%) and vomiting (3.4%). Treatment parameters including dose delivery were reproducible among centers. Disease control rates were 59%, 93% and 63% for colorectal, neuroendocrine and other primaries, respectively. Median PFS was 2.9 and 2.8 months for colorectal and other primaries, respectively. PFS was not achieved in the neuroendocrine group. Median survival from (90)Y treatment was 8.8 months for colorectal and 10.4 months for other primaries. Median survival for neuroendocrine patients has not been reached. CONCLUSION Patients with liver metastases can be safely treated with (90)Y microspheres. This study is the first to demonstrate technical and dose reproducibility of (90)Y glass microspheres between centers in a prospective setting. Based on these promising data, three international, multicenter, randomised phase III studies in colorectal and hepatocellular carcinoma have been initiated.

Chemoembolization in patients at high risk: Results and complications

PURPOSE Transarterial chemoembolization (TACE) has become a standard treatment option for unresectable hepatocellular carcinoma (HCC) and is often used to palliate hepatic metastases. Many patients who are candidates for TACE present with poor hepatic reserve, advanced tumor stage with major portal vein (PV) invasion or thrombosis, and/or biliary dilation. These factors have been associated with a poor prognosis and increased complications after chemoembolization. Accordingly, these patients are classified as being at high risk and may not be considered for therapy. The aim of this study is to evaluate the results of TACE in these patients. MATERIALS AND METHODS Over a period of 5 years, 141 patients underwent 355 TACE procedures. Thirty-six patients (26%) were in the high-risk group as a result of major PV thrombosis, increased serum bilirubin level (>2 mg/dL), and/or intrahepatic biliary dilation. HCC was the underlying tumor in 60% of patients. Thirty-seven percent of patients had Child-Pugh class B/C disease. Patients in the high-risk group received more selective embolization with fewer particles and fewer procedures (2.0 vs 2.7; P < .04). RESULTS Patients in the high-risk group were more likely to have HCC (83% vs 51%; P < .01) and were also more likely to have advanced disease according to Child-Pugh classification versus patients in the low-risk group (49% vs 20%; P < .01). The overall complication rate was 4.3%, with no significant difference in complication rate between groups (3.2% vs 8.2%; P = .12). The overall 30-day mortality rate was 2.3%, and no significant difference in 30-day mortality rate was observed between the high- and low-risk groups (5.5% vs 1.4%; P = .11). A trend toward increased survival in the low-risk group did not reach statistical significance. CONCLUSIONS These data suggest that patients with advanced disease and decreased hepatic reserve who are treated with TACE exhibit no significant increase in morbidity or mortality and no significant decrease in survival. With variations in technique, TACE can be performed safely in patients with the relative risk factors that may classify them in high-risk groups.