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Abboud Y, Shah VP, Bebawy M, Al-Khazraji A, Hajifathalian K, Gaglio PJ. Mapping the Hidden Terrain of Hepatocellular Carcinoma: Exploring Regional Differences in Incidence and Mortality across Two Decades by Using the Largest US Datasets. J Clin Med 2024; 13:5256. [PMID: 39274469 PMCID: PMC11396507 DOI: 10.3390/jcm13175256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 08/23/2024] [Accepted: 08/29/2024] [Indexed: 09/16/2024] Open
Abstract
Background: There is an observed variation in the burden of hepatocellular carcinoma (HCC) across different US populations. Our study aims to comprehensively assess variations in HCC incidence and mortality rates across different regions of the US. Understanding these geographical differences is crucial, given prior evidence indicating variations in the incidence of viral hepatitis and metabolic dysfunction-associated steatotic liver disease and varying access to curative HCC treatment among states. Methods: HCC age-adjusted incidence rates between 2001 and 2021 were obtained from the United States Cancer Statistics (USCS) database (which covers approximately 98% of the US population). HCC age-adjusted mortality rates between 2000 and 2022 were obtained from the National Center of Health Statistics (NCHS) database (covering approximately 100% of the US population). The rates were categorized by US geographical region into West, Midwest, Northeast, and South. Incidence rates were also categorized by race/ethnicity. Time trends [annual percentage change (APC) and average APC (AAPC)] were estimated by using Joinpoint Regression via the weighted Bayesian Information Criteria (p < 0.05). Results: Between 2001 and 2021, there were 491,039 patients diagnosed with HCC in the US (74.2% males). The highest incidence rate per 100,000 population was noted in the West (7.38), followed by the South (6.85). Overall incidence rates increased between 2001 and 2015 and then significantly decreased until 2021 (APC = -2.29). Most cases were in the South (38.8%), which also had the greatest increase in incidence (AAPC = 2.74). All four geographical regions exhibited an overall similar trend with an increase in incidence over the first 10-15 years followed by stable or decreasing rates. While stratification of the trends by race/ethnicity showed slight variations among the regions and groups, the findings are largely similar to all race/ethnic groups combined. Between 2000 and 2022, there were 370,450 patients whose death was attributed to HCC in the US (71.6% males). The highest mortality rate per 100,000 population was noted in the South (5.02), followed by the West (4.99). Overall mortality rates significantly increased between 2000 and 2013 (APC = 1.90), then stabilized between 2013 and 2016, and then significantly decreased till 2022 (APC = -1.59). Most deaths occurred in the South (35.8%), which also had the greatest increase in mortality (AAPC = 1.33). All four geographical regions followed an overall similar trend, with an increase in mortality over the first 10-15 years, followed by stable or decreasing rates. Conclusions: Our analysis, capturing about 98% of the US population, demonstrates an increase in HCC incidence and mortality rates in all geographical regions from 2000 to around 2014-2016, followed by stabilizing and decreasing incidence and mortality rates. We observed regional variations, with the highest incidence and mortality rates noted in the West and South regions and the fastest increase in both incidence and mortality noted in the South. Our findings are likely attributable to the introduction of antiviral therapy. Furthermore, demographic, socioeconomic, and comorbid variability across geographical regions in the US might also play a role in the observed trends. We provide important epidemiologic data for HCC in the US, prompting further studies to investigate the underlying factors responsible for the observed regional variations in HCC incidence and mortality.
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Affiliation(s)
- Yazan Abboud
- Department of Internal Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
| | - Vraj P Shah
- Department of Internal Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
| | - Michael Bebawy
- Department of Internal Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
| | - Ahmed Al-Khazraji
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
| | - Kaveh Hajifathalian
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
| | - Paul J Gaglio
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA
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Ostapenko A, Stroever S, Eyasu L, Kim M, Aploks K, Dong XD, Seshadri R. Role of ablation therapy in conjunction with surgical resection for neuroendocrine tumors involving the liver. World J Gastrointest Surg 2024; 16:768-776. [PMID: 38577070 PMCID: PMC10989351 DOI: 10.4240/wjgs.v16.i3.768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 01/13/2024] [Accepted: 02/05/2024] [Indexed: 03/22/2024] Open
Abstract
BACKGROUND Resection of hepatic metastasis from neuroendocrine tumors (NETs) improves quality of life and prolongs 5-year survival. Ablation can be utilized with surgery to achieve complete resection. Although several studies report long-term outcomes for patients undergoing ablation, none have explored perioperative effects of ablation in patients with metastatic NETs. AIM To determine if intra-operative ablation during hepatectomy increases risk of adverse outcomes such as surgical site infections (SSIs), bleeding, and bile leak. METHODS A retrospective analysis of the hepatectomy National Surgical Quality Improvement Program database from 2015-2019 was performed to determine the odds of SSIs, bile leaks, or bleeding in patients undergoing intraoperative ablation when compared to hepatectomy alone. RESULTS Of the 966 patients included in the study, 298 (30.9%) underwent ablation during hepatectomy. There were 78 (11.7%) patients with SSIs in the hepatectomy alone group and 39 (13.1%) patients with a SSIs in the hepatectomy with ablation group. Bile leak occurred in 41 (6.2%) and 14 (4.8%) patients in the two groups, respectively; bleeding occurred in 117 (17.5%) and 33 (11.1%), respectively. After controlling for confounding variables, ablation did not increase risk of SSI (P = 0.63), bile leak (P = 0.34) or bleeding (P = 0.07) when compared to patients undergoing resection alone on multivariate analysis. CONCLUSION Intraoperative ablation with hepatic resection for NETs is safe in the perioperative period without significant increased risk of infection, bleeding, or bile leak. Surgeons should utilize this modality when appropriate to achieve optimal disease control and outcomes.
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Affiliation(s)
- Alexander Ostapenko
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Stephanie Stroever
- Department of Research and Innovation, Nuvance Health, Danbury, CT 06810, United States
| | - Lud Eyasu
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Minha Kim
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Krist Aploks
- Department of General Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Xiang Da Dong
- Division of Surgical Oncology/Hepato-Pancreato-Biliary Surgery, Danbury Hospital, Danbury, CT 06810, United States
| | - Ramanathan Seshadri
- Division of Surgical Oncology/Hepato-Pancreato-Biliary Surgery, Danbury Hospital, Danbury, CT 06810, United States
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Wicks JS, Dale BS, Ruffolo L, Pack LJ, Dunne R, Laryea MA, Hernandez-Alejandro R, Sharma AK. Comparable and Complimentary Modalities for Treatment of Small-Sized HCC: Surgical Resection, Radiofrequency Ablation, and Microwave Ablation. J Clin Med 2023; 12:5006. [PMID: 37568408 PMCID: PMC10419984 DOI: 10.3390/jcm12155006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/20/2023] [Accepted: 07/28/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Over the past decade, there has been continual improvement in both ablative and surgical technologies for the treatment of hepatocellular carcinoma (HCC). The efficacy of ablative therapy compared to surgical resection for HCC has not been thoroughly evaluated using multiple large-scale randomized controlled trials. By international consensus, if a patient is eligible, surgery is the primary curative treatment option, as it is believed to confer superior oncologic control. OBJECTIVE to determine the efficacies of percutaneous ablative therapies and surgical resection (SR) in the treatment of HCC. Data sources, study appraisal, and synthesis methods: A meta-analysis using 5 online databases dating back to 1989 with more than 31,000 patients analyzing patient and tumor characteristics, median follow-up, overall survival, and complication rate was performed. RESULTS Ablative therapies are suitable alternatives to surgical resection in terms of survival and complication rates for comparable patient populations. For the entire length of the study from 1989-2019, radiofrequency ablation (RFA) produced the highest 5-year survival rates (59.6%), followed by microwave ablation (MWA) (50.7%) and surgical resection (SR) (49.9%). In the most recent era from 2006 to 2019, surgical resection has produced the highest 5-year survival rate of 72.8%, followed by RFA at 61.7% and MWA at 50.6%. Conclusions and key findings: Depending on the disease state and comorbidities of the patient, one modality may offer superior overall survival rates over the other available techniques. Interventional ablative methods and surgical resection should be used in conjunction for the successful treatment of small-sized HCC.
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Affiliation(s)
- Jeffrey S. Wicks
- Department of Biology, University of Rochester, Rochester, NY 14642, USA;
| | - Benjamin S. Dale
- Department of Surgery, University of Rochester, Rochester, NY 14642, USA; (B.S.D.); (L.R.)
| | - Luis Ruffolo
- Department of Surgery, University of Rochester, Rochester, NY 14642, USA; (B.S.D.); (L.R.)
| | - Ludia J. Pack
- Department of Genetics, University of Rochester, Rochester, NY 14642, USA;
| | - Richard Dunne
- Division of Hematology/Oncology, Department of Medicine, University of Rochester, Rochester, NY 14642, USA;
| | - Marie A. Laryea
- Division of Gastroenterology/Hepatology, Department of Medicine, University of Rochester, Rochester, NY 14642, USA;
| | | | - Ashwani Kumar Sharma
- Division of Interventional Radiology, Department of Imaging Sciences, University of Rochester, Rochester, NY 14642, USA
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Ding J, Wen Z. Survival improvement and prognosis for hepatocellular carcinoma: analysis of the SEER database. BMC Cancer 2021; 21:1157. [PMID: 34715816 PMCID: PMC8555190 DOI: 10.1186/s12885-021-08904-3] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 10/18/2021] [Indexed: 02/07/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) incidences have been increasing in the United States. This study aimed to examine temporal trend of HCC survival and determine prognostic factors influencing HCC survival within the U.S. population. Methods The Surveillance Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with primary HCC from 1988 to 2015. Overall survival (OS) and disease-specific survival (DSS) were calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for prognostic factors and comparing survival between patients diagnosed at different periods (per 5-year interval). Results A total of 80,347 patients were included. The proportions of both young patients (< 45 years) and old patients (≥75 years) decreased over time (P < 0.001) and the male-to-female ratio increased over time (P < 0.001). Significant decreasing temporal trends were observed for HCC severity at diagnosis, including SEER stage, tumor size, tumor extent, and lymph node involvement (P < 0.001 for all). OS and DSS of patients with HCC improved over time (P < 0.001). After adjusting for patient and tumor characteristics and treatment difference, period of diagnosis retained an independent factor for improved DSS and its prognostic significance was evident for localized and regional HCC (P < 0.001), but not for distant HCC. On multivariate analyses, young age, female gender, Hispanic ethnicity, and married status were predictors favoring DSS, whereas a worse DSS was observed for patients with tumor > 5 cm, with vascular invasion, and with lymph node involvement. Patients treated with liver-directed therapy (HR = 0.54, 95% CI: 0.35–0.56), hepatic resection (HR = 0.35, 95% CI: 0.33–0.37), and transplantation (HR = 0.14, 95% CI: 0.13–0.15) had significantly longer DSS compared with those who received no surgery. In stratified analyses, the beneficial effects of surgical approach, regardless therapy type, were significant across all stages. Conclusions Our results indicate a significant improvement in survival for HCC patients from 1988 to 2015, which may be attributable to advances in early diagnosis and therapeutic approaches.
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Affiliation(s)
- Jingli Ding
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, No. 169, Donghu Road, Hubei, Wuhan, 430071, China.,Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Jiangxi, Nanchang, 330006, China
| | - Zhili Wen
- Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Jiangxi, Nanchang, 330006, China.
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Percutaneous ablation versus surgical ablation and resection of liver tumors: medicare volume and physician reimbursement trends from 2010 to 2018. Abdom Radiol (NY) 2021; 46:4056-4061. [PMID: 33772616 DOI: 10.1007/s00261-021-03054-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 03/04/2021] [Accepted: 03/09/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE The purpose of this study is to analyze trends in Medicare volume and physician reimbursement for percutaneous ablation, surgical ablation, and resection of liver tumors from 2010 to 2018. METHODS Claims from the Medicare Part B PSPSMF for the years 2010 to 2018 were extracted using the CPT codes for percutaneous and surgical ablation of liver tumors and surgical liver resection. Total procedural volume and physician payment were analyzed by procedure and physician specialty. RESULTS From 2010 to 2018, the volume of percutaneous ablation of liver tumors increased 94.3% from 1630 to 3168 procedures, and the volume of surgical ablations increased 86.2% from 593 to 1104 procedures. In contrast, there was a 16.8% decrease in liver resections from 10,807 to 8994 procedures. Physician reimbursement for percutaneous ablation decreased from $702.41 to $610.11 (- 13.1%). Conversely, reimbursement for resection increased from $849.18 to $1015.06 (19.5%). Reimbursement for surgical ablation also increased from $722.36 to $744.25 (3.0%). In 2018, physician reimbursement for resection and surgical ablation were 66% and 22% more than that for percutaneous ablation. CONCLUSION An increasing number of patients with liver tumors were treated with percutaneous ablation from 2010 to 2018. Despite higher morbidity, a dwindling set of theoretical advantages over percutaneous ablation, and higher overall costs, the volume of surgical ablation also increased over this time period. The findings of this study suggest that a reevaluation of practice and referral patterns for surgical ablation of liver tumors is warranted in many institutions.
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Kamarajah SK, Bundred JR, Littler P, Reeves H, Manas DM, White SA. Treatment strategies for early stage hepatocellular carcinoma: a systematic review and network meta-analysis of randomised clinical trials. HPB (Oxford) 2021; 23:495-505. [PMID: 33309569 DOI: 10.1016/j.hpb.2020.10.031] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 10/13/2020] [Accepted: 10/14/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Several treatment strategies for early stage hepatocellular cancers (HCC) have been evaluated in randomised controlled trials (RCTs). This network meta-analysis (NMA) aimed to explore the relative effectiveness of these different approaches on their impact on overall (OS) and recurrence-free survival (RFS). METHODS A systematic review was conducted to identify RCT's reported up to 23rd January 2020. Indirect comparisons of all regimens were simultaneously compared using random-effects NMA. RESULTS Twenty-eight RCT's, involving 3,618 patients, reporting 13 different treatment strategies for early stage HCC were identified. Median follow-up, reported in 22 studies, ranged from 12-93 months. In this NMA, RFA in combination with iodine-125 was ranked first for both RFS (HR: 0.50, 95% CI: 0.19-1.31) and OS (HR: 0.41, 95% CI: 0.19-0.94). In subgroup with solitary HCC, lack of studies reporting RFS precluded reliable analysis. However, RFA in combination with iodine-125 was associated with markedly better OS (HR: 0.21, 95% CI: 0.05-0.93). CONCLUSION This NMA identified RFA in combination with iodine-125 as a treatment delivering better RFS and OS, in patients with early stage HCC, especially for those with solitary HCC. This technique warrants further evaluation in both Asia and Western regions.
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Affiliation(s)
- Sivesh K Kamarajah
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK; Institute of Cellular Medicine, University of Newcastle, Newcastle upon Tyne, Tyne and Wear, UK; Department of Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, UK.
| | - James R Bundred
- Leeds Teaching Hospitals NHS Trust Research and Innovation Department, Leeds, UK
| | - Peter Littler
- Department of Interventional Radiology, The Freeman Hospital, Newcastle upon Tyne, UK
| | - Helen Reeves
- Newcastle University Centre for Cancer, Newcastle University Medical School, Newcastle upon Tyne, UK; Hepatopancreatobiliary Multidisciplinary Team, Newcastle upon Tyne NHS Foundation Trust, The Freeman Hospital, Newcastle upon Tyne, UK
| | - Derek M Manas
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK
| | - Steven A White
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK; Institute of Cellular Medicine, University of Newcastle, Newcastle upon Tyne, Tyne and Wear, UK
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Lin TA, Lin JS, Wagner T, Pham N. Stereotactic body radiation therapy in primary hepatocellular carcinoma: current status and future directions. J Gastrointest Oncol 2018; 9:858-870. [PMID: 30505586 DOI: 10.21037/jgo.2018.06.01] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Stereotactic body radiation therapy (SBRT) is a form of radiation therapy that has been used in the treatment of primary hepatocellular carcinoma (HCC) over the past decade. To evaluate the clinical efficacy of SBRT in primary HCC, a literature search was conducted to identify original research articles published from January 2000 through January 2018 in PubMed on SBRT in HCC. All relevant studies published from 2004 to 2018 were included. Prospective studies demonstrated 2-year local control (LC) rates ranging from 64-95% and overall survival (OS) rates ranging from 34% (2-year) to 65% (3-year). Retrospective studies demonstrated 2-year LC rates of 44-90% and 2-year OS rates of 24-67%. Reported toxicities in primary HCC patients vary but SBRT appears to be relatively well tolerated. Studies comparing SBRT to radiofrequency ablation (RFA) are few, but they suggest SBRT may be more effective than RFA in specific primary HCC populations. Additionally, SBRT appears to increase the efficacy of both transarterial chemoembolization (TACE) and sorafenib in selected primary HCC populations.
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Affiliation(s)
- Timothy A Lin
- Department of Radiation Oncology, Baylor College of Medicine, Houston, TX, USA
| | - Jessica S Lin
- Department of Radiation Oncology, Baylor College of Medicine, Houston, TX, USA
| | - Timothy Wagner
- Department of Radiation Oncology, Baylor College of Medicine, Houston, TX, USA
| | - Ngoc Pham
- Department of Radiation Oncology, Baylor College of Medicine, Houston, TX, USA
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Meta-analysis of transcatheter arterial chemoembolization plus radiofrequency ablation versus transcatheter arterial chemoembolization alone for hepatocellular carcinoma. Oncotarget 2018; 8:2960-2970. [PMID: 27936465 PMCID: PMC5356855 DOI: 10.18632/oncotarget.13813] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2016] [Accepted: 11/30/2016] [Indexed: 12/22/2022] Open
Abstract
This meta-analysis was conducted to compare transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) with TACE alone for hepatocellular carcinoma. We searched MEDLINE, EMBASE and CENTRAL for all relative randomized controlled trials (RCTs) and retrospective studies until October 31 2016. Tumor response, recurrence-free survival, overall survival and postoperative complications were the major evaluation indices. Review Manager (version 5.3) was used to analyze the data. Dichotomous data was calculated by odds ratio (OR) with 95% confidence intervals (CI). There were 1 RCT and 10 retrospective studies with 928 patients in this meta-analysis: 412 patients with TACE plus RFA and 516 patients with TACE alone. Compared with TACE alone group, TACE plus RFA group attained higher tumor response rates (OR = 6.08, 95% CI = 4.00 to 9.26, P < 0.00001), achieved longer recurrence-free survival rates (ORRFS = 3.78, 95% CI: 2.38 to 6.02, P < 0.00001) and overall survival rates (OR1-year = 3.92, 95% CI = 2.41–6.39, P < 0.00001; OR3-year = 2.56; 95% CI = 1.81–3.60; P < 0.00001; OR5-year = 2.78; 95% CI = 1.77–4.38; P < 0.0001). Serious postoperative complications were not observed, although complications were higher in TACE plus RFA group than that in TACE alone group (OR = 2.74, 95% CI = 1.07 to 7.07, P = 0.04). In conclusion, the use of TACE plus RFA for intermediate stage hepatocellular carcinoma can attain higher tumor response rates and improve survival rates than TACE alone.
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Berger NG, Herren JL, Liu C, Burrow RH, Silva JP, Tsai S, Christians KK, Gamblin TC. Ablation approach for primary liver tumors: Peri-operative outcomes. J Surg Oncol 2018; 117:1493-1499. [PMID: 29484654 DOI: 10.1002/jso.25019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 01/21/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND OBJECTIVES Ablation is a common treatment modality for malignant primary liver tumors(PLTs), outcomes following laparoscopic (LA) versus open ablation (OA) are ill-defined. This project compares peri-procedural outcomes of LA versus OA for PLTs. MATERIALS AND METHODS Patients with PLTs undergoing radiofrequency ablation were queried from ACS NSQIP Database (2005-2013) using CPT codes. Patients undergoing percutaneous ablation or hepatic resection were excluded. Multivariable logistic regression analyses determined the association of ablation approach with 30-day morbidity and mortality. RESULTS Of 5747 with PLTs, 655 (11.4%) ablations were identified: 177 (27.0%) underwent OA, 478 (73.0%) underwent LA. Patients undergoing LA had lower mortality (1.9% vs 5.1%, P = 0.026), lower minor morbidity (2.3% vs 5.7%, P = 0.031), and lower major morbidity (4.2% vs 17.0%, P < 0.001). Adjusting for demographics, disease-specific variables (preoperative ascites, total bilirubin, platelet count, albumin, and INR), 30-day mortality (OR 3.85, 95%CI: 1.38-10.80, P = 0.010), minor morbidity (OR 2.98, 95%CI: 1.16-7.67, P = 0.024), and major morbidity (OR 4.59 95%CI: 2.41-8.76, P < 0.001) were statistically lower in LA. OA demonstrated increased length of stay(LOS) (5 vs 2 days, P < 0.001), and longer operative time (152 vs 112 min, P < 0.001). CONCLUSION LA offers decreased peri-procedural morbidity, mortality, and reduced LOS. LA should be the preferred method for hepatic ablation.
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Affiliation(s)
- Nicholas G Berger
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Josi L Herren
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Chrissy Liu
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Robert H Burrow
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Jack P Silva
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Susan Tsai
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Kathleen K Christians
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - T Clark Gamblin
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
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Kim S, Kang T, Kim M, Lee M, Cho S, Paik Y, Kim MJ. Initial radiofrequency ablation failure for hepatocellular carcinoma: repeated radiofrequency ablation versus transarterial chemoembolisation. Clin Radiol 2018; 73:216.e1-216.e8. [DOI: 10.1016/j.crad.2017.07.020] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 07/13/2017] [Accepted: 07/24/2017] [Indexed: 02/07/2023]
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El-Fattah MA, Aboelmagd M, Elhamouly M. Prognostic factors of hepatocellular carcinoma survival after radiofrequency ablation: A US population-based study. United European Gastroenterol J 2017; 5:227-235. [PMID: 28344790 PMCID: PMC5349365 DOI: 10.1177/2050640616659024] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Accepted: 06/17/2016] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE To determine the survival outcome and prognostic factors of hepatocellular carcinoma (HCC) survival in patients who underwent radiofrequency ablation (RFA). METHODS The Surveillance, Epidemiology and End Results (SEER) database was queried: There were 2588 HCC patients from 2004 to 2012 who underwent RFA. The Kaplan-Meier curves and the multivariate Cox regression analysis were used to assess the prognostic factors. RESULTS With a median follow-up of 20 months, the 1-, 3- and 5-year overall survival (OS) rates were: 83%, 51% and 33%. Patients with a tumor size ≤5 cm in diameter had a better 5-year OS, as compared to patients with a tumor size >5 cm. The 5-year OS was significantly higher among patients with a normal level of alpha-fetoprotein (AFP), compared with those having elevated AFP. In an adjusted multivariate Cox regression analysis, those with ≥60 years of age (HR: 1.19; 95% CI 1.05-1.36), non-Asian race (HR: 1.53; 95% CI 1.30-1.81), tumor size >5 cm (HR: 1.43; 95% CI 1.24-1.65), elevated AFP (HR: 1.42; 95% CI 1.22-1.64), American Joint Committee on Cancer (AJCC) stages II-III (HR: 1.30; 95% CI 1.14-1.48) and the year of diagnosis from 2004-2007 (HR: 1.22; 95% CI 1.07-1.40) were significantly associated with a poor prognosis. CONCLUSIONS Age, race, tumor size, AFP level, AJCC stage and year of diagnosis were prognostic factors for OS in HCC patients who underwent RFA.
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Affiliation(s)
- Mohamed Abd El-Fattah
- Department of Internal Medicine, Faculty
of Medicine, Suez Canal University, Ismailia, Egypt
| | - Mohamed Aboelmagd
- Department of Internal Medicine,
Division of Endemic and Infectious Diseases, Faculty of Medicine, Suez Canal
University , Ismailia, Egypt
| | - Mohammed Elhamouly
- Department of Internal Medicine,
Division of Endemic and Infectious Diseases, Faculty of Medicine, Suez Canal
University , Ismailia, Egypt
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Ultrasound-guided intratumoral delivery of doxorubicin from in situ forming implants in a hepatocellular carcinoma model. Ther Deliv 2016; 7:201-12. [PMID: 27010983 DOI: 10.4155/tde-2015-0008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hepatocellular carcinomas are frequently nonresponsive to systemically delivered drugs. Local delivery provides an alternative to systemic administration, maximizing the dose delivered to the tumor, achieving sustained elevated concentrations of the drug, while minimizing systemic exposure. RESULTS Ultrasound-guided deposition of doxorubicin (Dox)-eluting in situ forming implants (ISFI) in an orthotopic tumor model significantly lowers systemic drug levels. As much as 60 µg Dox/g tumors were observed 21 days after ISFI injection. Tumors treated with Dox implants also showed a considerable reduction in progression at 21 days. CONCLUSION Dox-eluting ISFIs provide a promising platform for the treatment of hepatocellular carcinomas by which drug can be delivered directly into the lesion, bypassing distribution and elimination by the circulatory system.
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Zhou Q, Li Z, Zhou J, Joshi BP, Li G, Duan X, Kuick R, Owens SR, Wang TD. In vivo photoacoustic tomography of EGFR overexpressed in hepatocellular carcinoma mouse xenograft. PHOTOACOUSTICS 2016; 4:43-54. [PMID: 27766208 PMCID: PMC5066077 DOI: 10.1016/j.pacs.2016.04.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 04/08/2016] [Accepted: 04/18/2016] [Indexed: 05/24/2023]
Abstract
EGFR is a promising cell surface target for in vivo imaging that is highly overexpressed in hepatocellular carcinoma (HCC), a common cancer worldwide. Peptides penetrate easily into tumors for deep imaging, and clear rapidly from the circulation to minimize background. We aim to demonstrate use of an EGFR specific peptide to detect HCC xenograft tumors in mice with photoacoustic imaging. Nude mice implanted with human HCC cells that overexpress EGFR were injected intravenously with Cy5.5-labeled EGFR and scrambled control peptides respectively. Photoacoustic images collected from 0 to 24 h. Photoacoustic signal peaked in tumors at 3 h post-injection. Images from 0 to 1.8 cm beneath the skin revealed increased target-to-background (T/B) ratio from tumors. The T/B ratio was significantly greater for the EGFR versus control peptide. Clearance of signal was observed by ∼24 h. EGFR overexpression was validated with immunofluorescence and immunohistochemistry. A peptide specific for EGFR delivered systemically can detect HCC xenograft tumors in vivo with photoacoustic imaging.
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Affiliation(s)
- Quan Zhou
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, United States
| | - Zhao Li
- Department of Hepatobiliary Surgery, Peking University People’s Hospital, Beijing, China
| | - Juan Zhou
- Department of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, United States
| | - Bishnu P. Joshi
- Department of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, United States
| | - Gaoming Li
- Department of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, United States
| | - Xiyu Duan
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, United States
| | - Rork Kuick
- Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, United States
| | - Scott R. Owens
- Department of Pathology, University of Michigan, Ann Arbor, MI 48109, United States
| | - Thomas D. Wang
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, United States
- Department of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, United States
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, United States
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14
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Ignee A, Jenssen C, Cui XW, Schuessler G, Dietrich CF. Intracavitary contrast-enhanced ultrasound in abscess drainage--feasibility and clinical value. Scand J Gastroenterol 2016; 51:41-47. [PMID: 26166454 DOI: 10.3109/00365521.2015.1066423] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To evaluate the usefulness of intracavitary-applied contrast-enhanced ultrasound (ICCEUS) with BR1 in ultrasound-guided puncture and drainage of abdominal and pelvic abscesses. MATERIAL AND METHODS A total of 71 consecutive patients received ICCEUS after placement of a drainage catheter or a needle in abdominal or pelvic abscesses. Portions of 0.1 ml of BR1 and 20 ml of saline were injected through the drainage catheter or needle. Ultrasound recordings were evaluated to answer the following questions: correct placement of the catheter by showing enhancement in the cavity and the drain - ICCEUS findings suggesting incomplete enhancement in all abscess cavities - enhancement in non-abscess structures. RESULTS About 52% of patients had liver, 14% of patients had intraperitoneal, 11% had subphrenic, 14% had retroperitoneal, 6% had splenic, and 4% had pelvic abscesses. The majority of the patients received drain placement with 10-F using trocar technique. Enhancement in the drain or needle was seen in all patients. In 2% of patients, during the initial approach, a dislodgment of the catheter from the abscess cavity was diagnosed. Due to non-enhancing abscess compartments, in 36% of the patients more than one drainage treatment was necessary at the time of the first approach. In 14% of the patients communication with surrounding structures was diagnosed. Additional treatment resulted in 4% of cases. CONCLUSION ICCEUS was helpful in all patients to confirm correct placement of drain or puncture needle. In 40% of patients, as a consequence of ICCEUS, additional therapy was scheduled, either additional drainage or abscess puncture, endoscopic retrograde drainage of the biliary or pancreatic duct or thoracic intervention.
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Affiliation(s)
- Andre Ignee
- a 1 Medical clinic 2, Caritas-Krankenhaus Bad Mergentheim , Bad Mergentheim, Germany
| | - Christian Jenssen
- b 2 Department of Internal Medicine, Krankenhaus Märkisch-Oderland , Strausberg, Germany
| | - Xin-Wu Cui
- a 1 Medical clinic 2, Caritas-Krankenhaus Bad Mergentheim , Bad Mergentheim, Germany
| | - Gudrun Schuessler
- a 1 Medical clinic 2, Caritas-Krankenhaus Bad Mergentheim , Bad Mergentheim, Germany
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15
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Mohanty S, Rajaram R, Bilimoria KY, Salem R, Pawlik TM, Bentrem DJ. Assessment of non-surgical versus surgical therapy for localized hepatocellular carcinoma. J Surg Oncol 2015; 113:175-80. [PMID: 26662882 DOI: 10.1002/jso.24113] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 11/14/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Localized hepatocellular carcinoma (HCC) in patients with adequate liver function is typically treated with resection. Non-surgical modalities including trans-arterial embolization have emerged as options for intermediate/advanced HCC. Hypothesizing that non-surgical techniques have expanded to localized disease, we examined treatment patterns, factors associated with surgical therapy, and the impact of modality on survival. METHODS Non-cirrhotic, localized HCC patients were identified from the National Cancer Data Base (2003-2011). Trends were examined using average annual percent change (AAPC). Regression models were developed to determine factors associated with treatment and assess the association of modality with survival. RESULTS Of 10,187 patients (median tumor size: 3.7 cm), 6,387 (62.7%) underwent surgery and 3,800 (37.3%) non-surgical therapy. Surgery declined from 61.6% to 44.5% (AAPC, -3.7%; 95%CI, -4.9% to -2.6%, P < 0.001). Non-surgical therapies increased from 17.2% to 39.2% (AAPC 11.4%; 95%CI, 8.8-14.1%, P < 0.001). White race, higher income, and treatment in an academic center (OR = 1.37, 95%CI 1.13-1.66) were associated with surgery. Patients selected for non-surgical therapy had worse adjusted 5-year survival (HR=2.05, 95%CI 1.85-2.26). CONCLUSIONS Non-surgical therapy has become as common as surgery in the treatment of non-cirrhotic, localized HCC. Randomized studies are needed to compare the effectiveness of treatments for this disease.
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Affiliation(s)
- Sanjay Mohanty
- Division of Research and Optimal Patient Care, American College of Surgeons, Chicago, Illinois.,Department of Surgery, Surgical Outcomes and Quality Improvement Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.,Northwestern Institute for Comparative Effectiveness Research in Oncology (NICER-Onc), Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
| | - Ravi Rajaram
- Division of Research and Optimal Patient Care, American College of Surgeons, Chicago, Illinois.,Department of Surgery, Surgical Outcomes and Quality Improvement Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.,Northwestern Institute for Comparative Effectiveness Research in Oncology (NICER-Onc), Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
| | - Karl Y Bilimoria
- Division of Research and Optimal Patient Care, American College of Surgeons, Chicago, Illinois.,Department of Surgery, Surgical Outcomes and Quality Improvement Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.,Northwestern Institute for Comparative Effectiveness Research in Oncology (NICER-Onc), Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern Memorial Hospital, Chicago, Illinois
| | - Timothy M Pawlik
- Departments of Surgery and Oncology, The Johns Hopkins Hospital, Baltimore, Maryland
| | - David J Bentrem
- Department of Surgery, Surgical Outcomes and Quality Improvement Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.,Northwestern Institute for Comparative Effectiveness Research in Oncology (NICER-Onc), Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
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16
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Early Stage Hepatocellular Carcinomas Not Feasible for Ultrasound-Guided Radiofrequency Ablation: Comparison of Transarterial Chemoembolization Alone and Combined Therapy with Transarterial Chemoembolization and Radiofrequency Ablation. Cardiovasc Intervent Radiol 2015; 39:417-25. [DOI: 10.1007/s00270-015-1194-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Accepted: 07/21/2015] [Indexed: 12/16/2022]
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17
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Aydin M, Basarir K, Armangil M, Yildiz HY, Saglik Y, Bilgili H, Yumusak N. Thermal necrosis induced by electrocauterization as a local adjuvant therapy in local aggressive bone tumors, what is the safe limit for surgical margins? An experimental study. Arch Orthop Trauma Surg 2015; 135:1071-6. [PMID: 26119709 DOI: 10.1007/s00402-015-2262-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2014] [Indexed: 11/30/2022]
Abstract
OBJECTIVE In the current study, it was aimed to investigate the temperature change in the cavity wall and pathologic necrosis occurred during cauterization, which was applied at different voltages and time intervals. MATERIALS AND METHODS The right tibias of 32 male rabbits were used. Three 2-mm-diameter holes were created on the cortical surface of the tibia using a hand-held drill. Using an electrocautery device, 55 mV was applied for 3 and 5 s and 65 mV was applied for 3 and 5 s. Maximum temperatures at 3 and 6 mm distance from the application site were measured. Biopsy specimens obtained at 3 and 6 mm distance from the application site were evaluated microscopically for bone cell viability and periosteal necrosis. RESULTS Thirty-two rabbits were divided into four groups. In all groups, periosteal bone cells located at the region, extending from the application site to 3 mm distance, died. In this region, application of 55 mV for 3 s caused peripheral necrosis. There were significant differences between the four groups in terms of maximum temperatures measured at 3 mm distance from the application site (p = 0.027). On the other hand, no significant differences were noted between the four groups in terms of maximum temperatures measured at 6 mm distance from the application site (p > 0.05). CONCLUSIONS Cauterization of the cavity wall in the spray mode at 55 mV for 3 s after tumor resection caused necrosis in the cavity wall, extending from the application site to 3 mm distance. LEVEL OF EVIDENCE Experimental animal study, Level II.
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Affiliation(s)
- Murat Aydin
- Department of Orthopedics and Traumatology, Afyonkarahisar Suhut Public Hospital Medicine, Afyonkarahisar, Turkey,
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18
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Borzio M, Dionigi E, Parisi G, Raguzzi I, Sacco R. Management of hepatocellular carcinoma in the elderly. World J Hepatol 2015; 7:1521-1529. [PMID: 26085911 PMCID: PMC4462690 DOI: 10.4254/wjh.v7.i11.1521] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Revised: 03/09/2015] [Accepted: 04/10/2015] [Indexed: 02/06/2023] Open
Abstract
Mean age of hepatocellular carcinoma (HCC) patients has been progressively increasing over the last decades and ageing of these patients is becoming a real challenge in every day clinical practice. Unfortunately, international guidelines on HCC management do not address this problem exhaustively and do not provide any specific recommendation. We carried out a literature search in MEDLINE database for studies reporting on epidemiology, clinical characteristics and treatment outcome of HCC in elderly patients. Available data seem to indicate that in elderly patients the outcome of HCC is mostly influenced by liver function and tumor stage rather than by age and the latter should not influence treatment allocation. Age is not a risk for resection and older patients with resectable HCC and good liver function could gain benefit from surgery. Mild comorbidities do not seem a contraindication for surgery in aged patients. Conversely, major resection in elderly, even when performed in experienced high-volume centres, should be avoided. Both percutaneous ablation and transarterial chemoembolization are not contraindicated in aged patients and safety profile of these procedures is acceptable. Sorafenib is a viable option for advanced HCC in elderly provided that a careful evaluation of concomitant comorbidities, particularly cardiovascular ones, is taken into account. Available data seem to suggest that in either elderly and younger, treatment is a main predictor of outcome. Consequently, a nihilistic attitude of physicians towards under- or no-treatment of aged patients should not be longer justified.
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Affiliation(s)
- Mauro Borzio
- Mauro Borzio, Elena Dionigi, Ivana Raguzzi, Unità di Gastroenterologia, Azienda Ospedaliera di Melegnano, 20070 Vizzolo Predabissi, Italy
| | - Elena Dionigi
- Mauro Borzio, Elena Dionigi, Ivana Raguzzi, Unità di Gastroenterologia, Azienda Ospedaliera di Melegnano, 20070 Vizzolo Predabissi, Italy
| | - Giancarlo Parisi
- Mauro Borzio, Elena Dionigi, Ivana Raguzzi, Unità di Gastroenterologia, Azienda Ospedaliera di Melegnano, 20070 Vizzolo Predabissi, Italy
| | - Ivana Raguzzi
- Mauro Borzio, Elena Dionigi, Ivana Raguzzi, Unità di Gastroenterologia, Azienda Ospedaliera di Melegnano, 20070 Vizzolo Predabissi, Italy
| | - Rodolfo Sacco
- Mauro Borzio, Elena Dionigi, Ivana Raguzzi, Unità di Gastroenterologia, Azienda Ospedaliera di Melegnano, 20070 Vizzolo Predabissi, Italy
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19
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Borzio M, Dionigi E, Rossini A, Toldi A, Francica G, Fornari F, Salmi A, Farinati F, Vicari S, Marignani M, Terracciano F, Ginanni B, Sacco R. Trend of improving prognosis of hepatocellular carcinoma in clinical practice: an Italian in-field experience. Dig Dis Sci 2015; 60:1465-1473. [PMID: 25399329 DOI: 10.1007/s10620-014-3427-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Accepted: 11/02/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND Recent data suggest that outcome of hepatocarcinoma is improving. AIMS In order to explore whether survival is also increasing in clinical practice, we compared two multicenter independent in-field cohorts of cirrhotics with newly diagnosed HCCs. METHODS Cohort 1 (C1) consisted of 327 patients enrolled between January and December 1998, and cohort 2 (C2) included 826 patients enrolled between September 2008 and November 2012. Patients were stratified according to Child-Pugh score, MELD score, and HCC staged according to TNM, BCLC systems. RESULTS At baseline, C2 patients were significantly older, with more frequent comorbidities and better liver function. In C2, HCC was more frequently detected under regular ultrasound surveillance (P < 0.001), BCLC early stages were more frequent, and rates of smaller and uni/paucinodular tumors were significantly higher. Treatment of any type was more frequently offered to C2 patients (P < 0.001). Proportion of patients treated by TACE increased, and radiofrequency ablation was the most used ablative treatment. Survival rate was significantly higher in C2 being C1 and C2 survival at 1-3 years 72-25 and 75-44 %, respectively. Child-Pugh score A, BCLC stage A, single nodule, size ≤ 3 cm, belonging to cohort C2 and treatment per se independently predicted survival. CONCLUSIONS This in-field study showed a trend on improved HCC outcomes over time, which seems to be mainly due to a better presentation thanks to the wider application of surveillance and increased propensity to treat patients. These encouraging data should support further efforts to implement such approach to HCC in everyday clinical practice.
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Affiliation(s)
- Mauro Borzio
- U.O.C. Gastroenterologia, A.O. Melegnano, Melegnano, Italy,
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20
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Song YG, Shin SW, Cho SK, Choi D, Rhim H, Lee MW, Kim YS, Park KB, Park HS, Choo SW, Do YS, Choo IW, Hyun D. Transarterial chemoembolization as first-line therapy for hepatocellular carcinomas infeasible for ultrasound-guided radiofrequency ablation: a retrospective cohort study of 116 patients. Acta Radiol 2015; 56:70-7. [PMID: 24518688 DOI: 10.1177/0284185114520857] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND Ultrasound (US)-guided radiofrequency ablation (RFA) is frequently infeasible even for very early or early stage hepatocellular carcinoma (HCC) due to various reasons such as inconspicuous tumors or absence of a safe electrode path and the infeasibility rate is reportedly as high as 45%. In such cases, transarterial chemoembolization (TACE) is a commonly practiced alternative. PURPOSE To analyze long-term outcomes including tumor progression patterns and factors contributing to survival of patients who received TACE as the first line of therapy for very early or early stage HCC infeasible for US-guided RFA. MATERIAL AND METHODS From October 2006 through October 2009, 116 patients with very early or early stage HCCs underwent the first-line therapy TACE after their tumors were deemed infeasible for RFA. Long-term survival rates were calculated and prognostic factors were assessed by univariate and multivariate analyses. The patterns and rates of tumor progression or recurrence were also evaluated. RESULTS The 1, 3, and 5-year survival rates of the whole cohort were 94.7%, 68.4%, and 47.2% with a mean overall survival of 53.1 months (95% CI: 48.2-58.0). Preserved liver function with Child-Pugh class A was the only independent factor associated with longer survival. The most common first tumor progression pattern was intrahepatic distant recurrence. The cumulative rates of local tumor progression and intrahepatic distant recurrence at 1, 3, and 5 years were 33% and 22%, 52% and 49%, and 73% and 75%, respectively. CONCLUSION TACE is a viable first-line treatment of HCC infeasible for RFA, especially when liver function was preserved.
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Affiliation(s)
- Yun Gyu Song
- Department of Radiology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
| | - Sung Wook Shin
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sung Ki Cho
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dongil Choi
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hyunchul Rhim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Min Woo Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young-sun Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kwang Bo Park
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hong Suk Park
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sung Wook Choo
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young Soo Do
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - In-wook Choo
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dongho Hyun
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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21
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Tuttle RM, Fox JP, Ouellette JR, Hellan M. Hospital-based, acute care encounters after radiofrequency ablation of hepatic tumours. HPB (Oxford) 2014; 16:845-51. [PMID: 24467271 PMCID: PMC4159458 DOI: 10.1111/hpb.12220] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 12/17/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND The use of radiofrequency ablation (RFA) for cancer is increasing; however, post-discharge outcomes have not been well described. The aim of the present study was to determine rates of hospital-based, acute care utilization within 30 days of discharge after RFA. METHODS Using state-level data from California, patients were identified who were at least 40 years of age who underwent RFA of hepatic tumours without a concurrent liver resection from 2007-2011. Our primary outcome was hospital readmissions or emergency department visits within 30 days of discharge. A multivariable regression model was constructed to identify patient factors associated with these events. RESULTS The final sample included 1764 patients treated at 100 centres. Hospital readmissions (11.3/100 discharges), emergency department visits (6.0/100 discharges) and overall acute care utilization (17.3/100 discharges) were common. Most encounters occurred within 10 days of discharge for diagnoses related to the procedure. Patients with renal failure [adjusted odds ratio (AOR) = 1.98 (1.11-3.53)], obesity [AOR = 1.69 (1.03-2.77)], drug abuse [AOR = 2.95 (1.40-6.21)] or those experiencing a complication [AOR = 1.52 (1.07-2.15)] were more likely to have a hospital-based acute care encounter within 30 days of discharge. CONCLUSIONS Hospital-based acute care after RFA is common. Patients should be counselled regarding the potential for acute care utilization and interventions targeted to high-risk populations.
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Affiliation(s)
- Rebecca M Tuttle
- Department of Surgical Oncology, Roswell Park Cancer InstituteBuffalo, NY, USA
| | - Justin P Fox
- Department of Surgery, Wright State UniversityDayton, OH, USA
| | - James R Ouellette
- Division of Surgical Oncology, Boonshoft School of Medicine, Wright State UniversityDayton, OH, USA
| | - Minia Hellan
- Division of Surgical Oncology, Boonshoft School of Medicine, Wright State UniversityDayton, OH, USA,Correspondence, Minia Hellan, Miami Valley Hospital, Weber Center for Health Education, 128 East Apple Street, Suite 7000, Dayton, OH 45409, USA. Tel: +1 937 424 2469. Fax: +1 937 208 2105. E-mail:
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22
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Li Z, Zeng Y, Zhang D, Wu M, Wu L, Huang A, Yang H, Liu X, Liu J. Glypican-3 antibody functionalized Prussian blue nanoparticles for targeted MR imaging and photothermal therapy of hepatocellular carcinoma. J Mater Chem B 2014; 2:3686-3696. [PMID: 32263805 DOI: 10.1039/c4tb00516c] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
MRI-guided photothermal therapy is becoming a more widely accepted minimally invasive technique. In this study, glypican-3 monoclonal antibody functionalized Prussian blue nanoparticles (antiGPC3-PBNPs) were developed as a novel theranostic agent for the targeted MR imaging and photothermal therapy of hepatocellular carcinoma. The physical properties of the antiGPC3-PBNPs were characterized by SEM, TEM and Vis-NIR absorption spectra, which showed that the developed nanoprobe formed well defined nanocubes with an average diameter of 21 nm. The significantly increased targeting cellular uptake efficiency in HepG2 cells via receptor-mediated endocytosis was confirmed by confocal fluorescence microscopy and ICP-MS. Furthermore, the high photothermal cytotoxicity, excellent MR imaging contrast enhancement ability and biocompatibility of the developed nanoprobe were also confirmed. Hence, the developed antiGPC3-PBNPs could be used as a promising nanoprobe for targeted MRI diagnosis and efficient photothermal therapy for hepatocellular carcinoma.
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Affiliation(s)
- Zhenglin Li
- Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China.
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23
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Yang X, Liu H, Sun CK, Natarajan A, Hu X, Wang X, Allegretta M, Guttmann RD, Gambhir SS, Chua MS, Cheng Z, So SK. Imaging of hepatocellular carcinoma patient-derived xenografts using ⁸⁹Zr-labeled anti-glypican-3 monoclonal antibody. Biomaterials 2014; 35:6964-71. [PMID: 24836949 DOI: 10.1016/j.biomaterials.2014.04.089] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Accepted: 04/19/2014] [Indexed: 12/16/2022]
Abstract
Imaging probes for early detection of hepatocellular carcinoma (HCC) are highly desired to overcome current diagnostic limitations which lead to poor prognosis. The membrane protein glypican-3 (GPC3) is a potential molecular target for early HCC detection as it is over-expressed in >50% of HCCs, and is associated with early hepatocarcinogenesis. We synthesized the positron emission tomography (PET) probe (89)Zr-DFO-1G12 by bioconjugating and radiolabeling the anti-GPC3 monoclonal antibody (clone 1G12) with (89)Zr, and evaluated its tumor-targeting capacity. In vitro, (89)Zr-DFO-1G12 was specifically taken up into GPC3-positive HCC cells only, but not in the GPC3-negative prostate cancer cell line (PC3). In vivo, (89)Zr-DFO-1G12 specifically accumulated in subcutaneous GPC3-positive HCC xenografts only, but not in PC3 xenografts. Importantly, (89)Zr-DFO-1G12 delineated orthotopic HCC xenografts from surrounding normal liver, with tumor/liver (T/L) ratios of 6.65 ± 1.33 for HepG2, and 4.29 ± 0.52 for Hep3B xenografts. It also delineated orthotopic xenografts derived from three GPC3-positive HCC patient specimens, with T/L ratios of 4.21 ± 0.64, 2.78 ± 0.26, and 2.31 ± 0.38 at 168 h p.i. Thus, (89)Zr-DFO-1G12 is a highly translatable probe for the specific and high contrast imaging of GPC3-positive HCCs, which may aid early detection of HCC to allow timely intervention.
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Affiliation(s)
- Xiaoyang Yang
- Asian Liver Center, Department of Surgery, Stanford University, School of Medicine, Stanford, CA 94305, USA
| | - Hongguang Liu
- Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, Stanford, CA 94305, USA
| | - Chris K Sun
- Asian Liver Center, Department of Surgery, Stanford University, School of Medicine, Stanford, CA 94305, USA
| | - Arutselvan Natarajan
- Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, Stanford, CA 94305, USA
| | - Xiang Hu
- Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, Stanford, CA 94305, USA
| | - Xiaolin Wang
- Asian Liver Center, Department of Surgery, Stanford University, School of Medicine, Stanford, CA 94305, USA
| | | | | | - Sanjiv S Gambhir
- Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, Stanford, CA 94305, USA
| | - Mei-Sze Chua
- Asian Liver Center, Department of Surgery, Stanford University, School of Medicine, Stanford, CA 94305, USA.
| | - Zhen Cheng
- Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, Stanford, CA 94305, USA.
| | - Samuel K So
- Asian Liver Center, Department of Surgery, Stanford University, School of Medicine, Stanford, CA 94305, USA
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Watanabe S, Morishita A, Deguchi A, Nakai S, Sakamoto T, Fujita K, Maeda E, Nomura T, Tani J, Miyoshi H, Yoneyama H, Fujiwara S, Kobara H, Mori H, Himoto T, Masaki T. Ethanol injection therapy for small hepatocellular carcinomas located beneath a large vessel using a curved percutaneous ethanol injection therapy needle. Oncol Lett 2014; 7:1831-1834. [PMID: 24932242 PMCID: PMC4049773 DOI: 10.3892/ol.2014.2053] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Accepted: 03/14/2014] [Indexed: 11/16/2022] Open
Abstract
Percutaneous ethanol injection therapy (PEIT) has been administered as a safe therapeutic modality for patients with small hepatocellular carcinoma (HCC). Due to the nature of the straight approaching line of a PEIT or radiofrequency ablation needle, penetrating the vessels that are interposed between the dermal insertion point and the nodule is unavoidable. A device with an overcoat needle and coaxial curved PEIT needle was created that facilitated a detour around interposing large vessels in order to avoid unnecessary harmful effects that result from the PEIT procedure. Two cases of HCC located adjacent to a neighboring large vessel were treated with a curved PEIT needle. The curved PEIT needle, which is connected to an outer needle, enabled deviation around the interposing vessels and successful connection with the HCC. Careful use of the curved line of the PEIT needle enabled the safe and successful performance of the PEIT without any requirement for specific training. This hand-assisted technique may be an applicable treatment for small HCC located beneath large vessels as a direct therapeutic method using ultrasound guidance.
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Affiliation(s)
- Seishiro Watanabe
- Department of Internal Medicine, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa 760-8557, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Akihiro Deguchi
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Seiji Nakai
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Teppei Sakamoto
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Koji Fujita
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Emiko Maeda
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Takako Nomura
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Joji Tani
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Hisaaki Miyoshi
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Hirohito Yoneyama
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Shintaro Fujiwara
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Hideki Kobara
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Hirohito Mori
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Takashi Himoto
- Department of Integrated Medicine, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Miki-cho, Kida-gun, Kagawa 761-0793, Japan
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Bargellini I, Florio F, Golfieri R, Grosso M, Lauretti DL, Cioni R. Trends in utilization of transarterial treatments for hepatocellular carcinoma: results of a survey by the Italian Society of Interventional Radiology. Cardiovasc Intervent Radiol 2013; 37:438-44. [PMID: 23719667 DOI: 10.1007/s00270-013-0656-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2013] [Accepted: 04/30/2013] [Indexed: 02/06/2023]
Abstract
PURPOSE This study was designed to provide an overview of the practice of locoregional treatments for HCC by the Italian centers of Interventional Radiology (IR) with particular reference to transarterial modalities. METHODS A questionnaire of 11 questions on locoregional treatment of HCC was e-mailed to 134 Italian IR centers. RESULTS The response rate was 64.9% (87/135 centers). Of 8,959 procedures in 2011, 67% were transarterial treatments, 31% percutaneous ablations, and 2% Y90-radioembolizations. Regarding (chemo)embolization, approximately 59% of procedures were performed in the intermediate stage, 28% in the early stage, and 12.8% in the advanced stage. TACE techniques varied greatly; approximately 52% of procedures were performed with drug-eluting particles and 32% with lipiodol, drug, and reabsorbable particles. In selected cases, 53 of 78 (68%) centers combine chemoembolization and ablation, whereas 28 centers (35.9%) combine Sorafenib and chemoembolization. In 2011, 13 of 78 (16.7%) responding centers performed Y90-radioembolization, with approximately 52% of procedures performed in the advanced stage and 46% in the intermediate stage. Approximately 62% of Y90-radioembolizations were performed using resin spheres and 38% using glass spheres. CONCLUSIONS With almost 9,000 procedures performed each year, locoregional treatments of HCC, most of all transarterial (chemo)embolizations, represent a major part of daily clinical practice in many Italian IR centers. The high variability in responses regarding transarterial treatments for HCC patients highlights the need for solid scientific evidence allowing better definition of clinical indications and standardization of technical approaches.
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Affiliation(s)
- Irene Bargellini
- Diagnostic and Interventional Radiology, Pisa University Hospital, Via Paradisa 2, 56100, Pisa, Italy,
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Davila JA, Kramer JR, Duan Z, Richardson PA, Tyson GL, Sada YH, Kanwal F, El-Serag HB. Referral and receipt of treatment for hepatocellular carcinoma in United States veterans: effect of patient and nonpatient factors. Hepatology 2013; 57:1858-68. [PMID: 23359313 PMCID: PMC4046942 DOI: 10.1002/hep.26287] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Accepted: 11/27/2012] [Indexed: 01/01/2023]
Abstract
UNLABELLED The delivery of treatment for hepatocellular carcinoma (HCC) could be influenced by the place of HCC diagnosis (hospitalization versus outpatient), subspecialty referral following diagnosis, as well as physician and facility factors. We conducted a study to examine the effect of patient and nonpatient factors on the place of HCC diagnosis, referral, and treatment in Veterans Administration (VA) hospitals in the United States. Using the VA Hepatitis C Clinical Case Registry, we identified hepatitis C virus (HCV)-infected patients who developed HCC during 1998-2006. All cases were verified and staged according to Barcelona Clinic Liver Cancer (BCLC) criteria. The main outcomes were place of HCC diagnosis, being seen by a surgeon or oncologist, and treatment. We examined factors related to these outcomes using hierarchical logistic regression. These factors included HCC stage, HCC surveillance, physician specialty, and facility factors, in addition to risk factors, comorbidity, and liver disease indicators. Approximately 37.2% of the 1,296 patients with HCC were diagnosed during hospitalization, 31.0% were seen by a surgeon or oncologist, and 34.3% received treatment. Being seen by a surgeon or oncologist was associated with surveillance (adjusted odds ratio [aOR] = 1.47; 95% CI: 1.20-1.80) and varied by geography (1.74;1.09-2.77). Seeing a surgeon or oncologist was predictive of treatment (aOR = 1.43; 95% CI: 1.24-1.66). There was a significant increase in treatment among patients who received surveillance (aOR = 1.37; 95% CI: 1.02-1.71), were seen by gastroenterology (1.65;1.21-2.24), or were diagnosed at a transplant facility (1.48;1.15-1.90). CONCLUSION Approximately 40% of patients were diagnosed during hospitalization. Most patients were not seen by a surgeon or oncologist for treatment evaluation and only 34% received treatment. Only receipt of HCC surveillance was associated with increased likelihood of outpatient diagnosis, being seen by a surgeon or oncologist, and treatment.
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Affiliation(s)
- Jessica A Davila
- Houston VA Health Services Research Center of Excellence, Section of Health Services Research, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
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Molecular imaging of hepatocellular carcinoma xenografts with epidermal growth factor receptor targeted affibody probes. BIOMED RESEARCH INTERNATIONAL 2013; 2013:759057. [PMID: 23710458 PMCID: PMC3654646 DOI: 10.1155/2013/759057] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2013] [Accepted: 03/22/2013] [Indexed: 12/21/2022]
Abstract
Hepatocellular carcinoma (HCC) is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%–20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR) has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907 as a probe for positron emission tomography (PET) or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCC in vivo.
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Borzio M, Fornari F, De Sio I, Andriulli A, Terracciano F, Parisi G, Francica G, Salvagnini M, Marignani M, Salmi A, Farinati F, Carella A, Pedicino C, Dionigi E, Fanigliulo L, Cazzaniga M, Ginanni B, Sacco R. Adherence to American Association for the Study of Liver Diseases guidelines for the management of hepatocellular carcinoma: results of an Italian field practice multicenter study. Future Oncol 2013; 9:283-294. [PMID: 23414477 DOI: 10.2217/fon.12.183] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
AIM Adherence to and the applicability of practice guidelines for the management of hepatocellular carcinoma (HCC) in field practice have not been fully addressed. We designed a multicenter field practice prospective study to evaluate the adherence to the 2005 American Association for the Study of Liver Diseases guidelines in Italy. MATERIALS & METHODS The study began in September 2008 and consecutively enrolled cirrhotic patients with newly diagnosed HCC from 30 local, nonreference centers in Italy. Patients were stratified according to Child-Pugh, the model for end-stage liver disease, tumor-node metastasis, performance status and the Barcelona Clinic Liver Cancer (BCLC) classifications. The diagnostic and therapeutic strategies adopted in each individual patient were recorded. Statistical analysis was carried out on 536 patients using all of the valuable data. RESULTS A total of 286 (54.5%) patients were ≥70 years old. Comorbidities, recorded in 397 (74%) patients, were classified as moderate to severe in 170 patients (43%). Overall, 174 (59%) patients with early-stage BCLC were ≥70 years; 104 (35%) of these had moderate-to-severe comorbidities and 54% were under a regular US surveillance program. Diagnosis was performed by computed tomography in 93% of patients, contrast-enhanced ultrasound in 62% and MRI in 17%. In patients with nodules of ≤2 cm, adherence to noninvasive diagnostic criteria was 56%. Adherence to the BCLC classification was shown to be suboptimal overall, particularly regarding allocation to surgical procedures, and a total of 119 patients (40%) with BCLC stage A did not receive curative therapies. CONCLUSIONS This multicenter survey showed that, in the 'real world', adherence to the both the diagnostic and therapeutic American Association for the Study of Liver Diseases 2005 algorithms was low, particularly in patients with early-stage HCC. Difficulties in applying the algorithms in routine clinical practice and the high prevalence of older patients with relevant comorbidities may account for our findings. Strategies to help improve adherence to international guidelines for HCC in field practice are required.
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Affiliation(s)
- Mauro Borzio
- Unità di Gastroenterologia, Azienda Ospedaliera di Melegnano, Melegnano, Italy.
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Incomplete thermal ablation of hepatocellular carcinoma: effects on tumor proliferation. J Surg Res 2012; 181:250-5. [PMID: 22857919 DOI: 10.1016/j.jss.2012.07.014] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2012] [Revised: 06/20/2012] [Accepted: 07/06/2012] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Local recurrence after thermal ablation of hepatocellular carcinoma (HCC) is common, problematic, and poorly understood. The continued effects of the heat sink around major vessels have been hypothesized to increase local ablation failure and possibly enhance the growth of the incompletely ablated malignancy. The aim of this study was to evaluate the critical temperature to which incomplete ablation would occur. METHODS Established murine (Hep-6L), rodent (Hep-4IIE), and human (Hep-G2) HCC cells were cultivated and then exposed to variable 2° temperatures from 37 °C-54 °C and incubated at 37 °C for 72 h. After incubation, 3-(4, 5-dimthyl-thiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays were used to measure proliferation, metabolic activity, and apoptosis. RESULTS Reliable cell death occurred in all three cell lines by microscopy and MTT assay after treatment at temperatures above 48 °C. However, in the 72 h after treatment, we observed successive recovery or maintenance of cellular proliferation at each time endpoint at ≤47 °C. This effect was present across all cell lines at 45 °C, and was most pronounced in the Hep-6L and Hep-4IIE cell lines (P < 0.05). Hep-G2 cells demonstrated maintenance of proliferation by MTT assay over the 72 h following treatment at 45 °C. TUNEL assays were strongly positive at temperatures ≥48 °C. TUNEL positivity suggests death via apoptotic mechanisms as opposed to coagulative processes seen at higher temperatures. Cells treated at these higher temperatures had a statistically significant (P < 0.05) higher apoptotic index as measured by TUNEL positivity, despite being morphologically similar by light microscopy. CONCLUSIONS Cellular proliferation and resistance to apoptosis are significantly increased after incomplete thermal ablation, with a 2° difference in complete versus incomplete ablation.
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Fox JP, Gustafson J, Desai MM, Hellan M, Thambi-Pillai T, Ouellette J. Short-Term Outcomes of Ablation Therapy for Hepatic Tumors: Evidence from the 2006–2009 Nationwide Inpatient Sample. Ann Surg Oncol 2012; 19:3677-86. [DOI: 10.1245/s10434-012-2397-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2012] [Indexed: 01/17/2023]
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Altekruse SF, McGlynn KA, Dickie LA, Kleiner DE. Hepatocellular carcinoma confirmation, treatment, and survival in surveillance, epidemiology, and end results registries, 1992-2008. Hepatology 2012; 55:476-82. [PMID: 21953588 PMCID: PMC3868012 DOI: 10.1002/hep.24710] [Citation(s) in RCA: 207] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED Approaches to the diagnosis and management of hepatocellular carcinoma (HCC) are improving survival. In the Surveillance, Epidemiology, and End Results-13 registries, HCC stage, histological confirmation, and first-course surgery were examined. Among 21,390 HCC cases diagnosed with follow-up of vital status during 1998-2008, there were 4,727 (22%) with reported first-course invasive liver surgery, local tumor destruction, or both. The proportion with reported liver surgery or ablation was 39% among localized stage cases and only 4% among distant/unstaged cases. Though 70% of cases had histologically confirmed diagnoses, the proportion with confirmed diagnoses was higher among cases with reported invasive surgery (99%), compared to cases receiving ablation (81%) or no reported therapy (65%). Incidence rates of histologically unconfirmed HCC increased faster than those of confirmed HCC from 1992 to 2008 (8% versus 3% per year). Two encouraging findings were that incidence rates of localized-stage HCC increased faster than rates of regional- and distant-stage HCC combined (8% versus 4% per year), and that incidence rates of reported first-course surgery or tumor destruction increased faster than incidence rates of HCC without such therapy (11% versus 7%). Between 1975-1977 and 1998-2007, 5-year cause-specific HCC survival increased from just 3% to 18%. Survival was 84% among transplant recipients, 53% among cases receiving radiofrequency ablation at early stage, 47% among cases undergoing resection, and 35% among cases receiving local tumor destruction. Asian or Pacific Islander cases had significantly better 5-year survival (23%) than white (18%), Hispanic (15%), or black cases (12%). CONCLUSION HCC survival is improving, because more cases are diagnosed and treated at early stages. Additional progress may be possible with continued use of clinical surveillance to follow individuals at risk for HCC, enabling early intervention.
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Affiliation(s)
- Sean F Altekruse
- Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD 20852, USA.
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Massarweh NN, Park JO, Yeung RSW, Flum DR. Comparative assessment of the safety and effectiveness of radiofrequency ablation among elderly medicare beneficiaries with hepatocellular carcinoma. Ann Surg Oncol 2011; 19:1058-65. [PMID: 21947695 DOI: 10.1245/s10434-011-2067-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2011] [Indexed: 12/12/2022]
Abstract
BACKGROUND Radiofrequency ablation (RFA) use among patients with hepatocellular carcinoma (HCC) has increased dramatically over the last decade, but assessments outside specialized centers are lacking. This population-based study was intended to evaluate the safety and effectiveness of RFA when used to treat HCC. METHODS A cohort study of HCC patients (diagnosed 2002-2005) was performed using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Early (≤90-day) mortality and readmission as well as survival among patients undergoing RFA, resection, or no treatment were compared using multivariate and propensity score adjusted Poisson and Cox regression models. RESULTS Of 2631 patients (mean age 76.1±6.1 years, 65.9% male), 16% underwent RFA (49.6%) or resection (50.4%). Early mortality (13.6 vs. 18.7%, P=.16) and readmission (34.5 vs. 32.1%, P=.60) rates were similar among RFA and resection patients. The 1-year survival after RFA and resection was similar (72.2 vs. 79.7%, P=.18), but beyond 3 years there was a survival benefit among patients undergoing resection (39.2 vs. 58.0%, P<.001). Patients treated with RFA as a sole therapeutic intervention in the 1st year had a similar hazard of death compared with untreated patients (hazard ratio [HR] 0.84, 95% confidence interval [95% CI] 0.54-1.33). CONCLUSIONS In the general community, patients treated with RFA have a similar risk of early adverse events compared with those treated with resection with no clear survival benefit when used as a sole intervention. Although RFA has been described as a safe and effective treatment for HCC at specialized centers, this experience may not extrapolate to the general community and requires further evaluation.
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Nathan H, Segev DL, Mayo SC, Choti MA, Cameron AM, Wolfgang CL, Hirose K, Edil BH, Schulick RD, Pawlik TM. National trends in surgical procedures for hepatocellular carcinoma: 1998-2008. Cancer 2011; 118:1838-44. [DOI: 10.1002/cncr.26501] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2011] [Revised: 06/19/2011] [Accepted: 07/06/2011] [Indexed: 11/08/2022]
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Bargellini I. Hepatocellular carcinoma: MR staging and therapeutic decisions. ACTA ACUST UNITED AC 2011; 37:231-8. [PMID: 21479803 DOI: 10.1007/s00261-011-9735-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Staging of hepatocellular carcinoma (HCC) represents a controversial and complex topic, since prognosis is largely dependent on several variables other than tumor extension, such liver function and general clinical conditions. Up to now, there is no agreement regarding the most reliable clinical staging system for HCC. Ideally, the staging system should be simple and easily obtainable and should not be influenced by differences in patient populations. So far, in Western countries, the Barcelona Clinic for Liver Cancer (BCLC) staging system represents the most frequently adopted classification. It is simple and guides the clinicians through the therapeutic decision process. Magnetic resonance imaging represents the most proper imaging modality for correct staging of HCC, providing high accuracy in evaluating tumor extension as well as tumor response to treatment (after percutaneous ablation, transarterial chemoembolization, or molecular-targeted therapy). The present review describes the most frequently used staging systems and the treatment options that are recommended for the different stages of the disease.
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Affiliation(s)
- Irene Bargellini
- Department of Diagnostic and Interventional Radiology, Pisa University Hospital, Via Paradisa 2, 56124, Pisa, Italy.
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35
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Bargellini I, Sacco R, Bozzi E, Bertini M, Ginanni B, Romano A, Cicorelli A, Tumino E, Federici G, Cioni R, Metrangolo S, Bertoni M, Bresci G, Parisi G, Altomare E, Capria A, Bartolozzi C. Transarterial chemoembolization in very early and early-stage hepatocellular carcinoma patients excluded from curative treatment: a prospective cohort study. Eur J Radiol 2011; 81:1173-8. [PMID: 21466931 DOI: 10.1016/j.ejrad.2011.03.046] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2011] [Revised: 03/09/2011] [Accepted: 03/11/2011] [Indexed: 12/16/2022]
Abstract
AIM To assess clinical outcome of transarterial chemoembolization (TACE) in a series of patients with early-stage hepatocellular carcinoma (HCC), within Milan criteria, but clinically unfit for liver transplantation (OLT). METHODS From January 2006 to May 2009, 67 patients (43 males, mean age 70 ± 7.6 years) with very early or early-stage unresectable HCC, within Milan selection criteria but clinically unfit for OLT, underwent TACE. The primary endpoint of the study was overall survival. Secondary endpoints were: safety, liver toxicity, 1-month tumour response according to the amended RECIST criteria, time to local and distant intrahepatic tumour recurrence and time to radiological progression. RESULTS Two major periprocedural complications occurred (3%), consisting of liver failure. Periprocedural mortality rate was 1.5% (1 patient). A significant increase in ALT and bilirubin levels 24h after treatment was reported, with progressive decrease at discharge. At 1-month follow-up, complete and partial tumour response rates were 67.2% and 29.8%, respectively, with two cases of progressive disease. Mean follow-up was 37.3 ± 15 months. The 1-, 2-, and 3-year overall survival rates were 90.9%, 86.1%, and 80.5%, respectively. Median expected time to local tumour recurrence and intrahepatic tumour recurrence were 7.9 and 13.8 months, respectively. Radiological disease progression was observed in 12 patients (17.9%) with a mean expected time of 26.5 months. CONCLUSION In patients with early-stage HCC, clinically excluded from OLT and unfit for surgery or percutaneous ablation, TACE is a safe and effective option, with favourable long-term survival.
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Affiliation(s)
- Irene Bargellini
- Diagnostic and Interventional Radiology, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy.
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Park JO, Stephen Z, Sun C, Veiseh O, Kievit FM, Fang C, Leung M, Mok H, Zhang M. Glypican-3 targeting of liver cancer cells using multifunctional nanoparticles. Mol Imaging 2011; 10:69-77. [PMID: 21303616 PMCID: PMC3057759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/30/2023] Open
Abstract
Imaging is essential in accurately detecting, staging, and treating primary liver cancer (hepatocellular carcinoma [HCC]), one of the most prevalent and lethal malignancies. We developed a novel multifunctional nanoparticle (NP) specifically targeting glypican-3 (GPC3), a proteoglycan implicated in promotion of cell growth that is overexpressed in most HCCs. Quantitative real-time polymerase chain reaction was performed to confirm the differential GPC3 expression in two human HCC cells, Hep G2 (high) and HLF (negligible). These cells were treated with biotin-conjugated GPC3 monoclonal antibody (αGPC3) and subsequently targeted using superparamagnetic iron oxide NPs conjugated to streptavidin and Alexa Fluor 647. Flow cytometry demonstrated that only GPC3-expressing Hep G2 cells were specifically targeted using this αGPC3-NP conjugate (fourfold mean fluorescence over nontargeted NP), and magnetic resonance imaging (MRI) experiments showed similar findings (threefold R2 relaxivity). Confocal fluorescence microscopy localized the αGPC3 NPs only to the cell surface of GPC3-expressing Hep G2 cells. Further characterization of this construct demonstrated a negatively charged, monodisperse, 50 nm NP, ideally suited for tumor targeting. This GPC3-specific NP system, with dual-modality imaging capability, may enhance pretreatment MRI, enable refined intraoperative HCC visualization by near-infrared fluorescence, and be potentially used as a carrier for delivery of tumor-targeted therapies, improving patient outcomes.
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Affiliation(s)
- James O. Park
- Department of Surgery, University of Washington, Seattle, WA, USA
| | - Zachary Stephen
- Department of Materials Science and Engineering, University of Washington, Seattle, WA, USA
| | - Conroy Sun
- Department of Materials Science and Engineering, University of Washington, Seattle, WA, USA
| | - Omid Veiseh
- Department of Materials Science and Engineering, University of Washington, Seattle, WA, USA
| | - Forrest M. Kievit
- Department of Materials Science and Engineering, University of Washington, Seattle, WA, USA
| | - Chen Fang
- Department of Materials Science and Engineering, University of Washington, Seattle, WA, USA
| | - Matthew Leung
- Department of Materials Science and Engineering, University of Washington, Seattle, WA, USA
| | - Hyejung Mok
- Department of Materials Science and Engineering, University of Washington, Seattle, WA, USA
| | - Miqin Zhang
- Department of Surgery, University of Washington, Seattle, WA, USA
- Department of Materials Science and Engineering, University of Washington, Seattle, WA, USA
- Department of Radiology, University of Washington, Seattle, WA, USA
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Park JO, Stephen Z, Sun C, Veiseh O, Kievit FM, Fang C, Leung M, Mok H, Zhang M. Glypican-3 Targeting of Liver Cancer Cells Using Multifunctional Nanoparticles. Mol Imaging 2011. [DOI: 10.2310/7290.2010.00048] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Affiliation(s)
- James O. Park
- From the Departments of Surgery, Materials Science and Engineering, and Radiology, University of Washington, Seattle, WA
| | - Zachary Stephen
- From the Departments of Surgery, Materials Science and Engineering, and Radiology, University of Washington, Seattle, WA
| | - Conroy Sun
- From the Departments of Surgery, Materials Science and Engineering, and Radiology, University of Washington, Seattle, WA
| | - Omid Veiseh
- From the Departments of Surgery, Materials Science and Engineering, and Radiology, University of Washington, Seattle, WA
| | - Forrest M. Kievit
- From the Departments of Surgery, Materials Science and Engineering, and Radiology, University of Washington, Seattle, WA
| | - Chen Fang
- From the Departments of Surgery, Materials Science and Engineering, and Radiology, University of Washington, Seattle, WA
| | - Matthew Leung
- From the Departments of Surgery, Materials Science and Engineering, and Radiology, University of Washington, Seattle, WA
| | - Hyejung Mok
- From the Departments of Surgery, Materials Science and Engineering, and Radiology, University of Washington, Seattle, WA
| | - Miqin Zhang
- From the Departments of Surgery, Materials Science and Engineering, and Radiology, University of Washington, Seattle, WA
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Requarth J. Radiofrequency ablation use in hepatocellular carcinoma. J Am Coll Surg 2010; 211:293-4; author reply 293. [PMID: 20670870 DOI: 10.1016/j.jamcollsurg.2010.04.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2010] [Accepted: 04/30/2010] [Indexed: 10/19/2022]
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