Aceite iodado de amapola para la quimio embolización selectiva de pacientes con tumores hepáticos no resecables / Iodine poppy oil for selective chemoembolization of patients with unresectable liver tumors

INTRODUCCIÓN: Los tumores hepáticos se pueden dividir en benignos y malignos. El tumor hepático benigno sólido más frecuente es el hemangioma seguido de la hiperplasia nodular focal, y el tumor quístico simple. Por otro lado, el tumor hepático maligno primario más frecuente es la hepatocarcinoma (HC). A. Cuadro clínico Los únicos tratamientos disponibles como cura potencial para el HC son el trasplante hepático y resección. Varias terapias locoregionales han sido usadas ampliamente para manejar a los pacientes con HC avanzado o como terapia puente para pacientes con enfermedad temprana e intermedia. Dentro de estas terapias, la terapia de quimioembolización convencional (TACE) usa como agente quimiembólico al aceite iodinado de amapola o lipiodol como un agente para embolizacion intra-arterial debido a su viscosidad e insolubilidad en el agua. B. Tecnología sanitária El aceite iodado de Amapola (adormidera), también conocido como "lipiodol" es un éster etílico de los ácidos grasos yodados del aceite de amapola. El aceite iodado es un producto de adición yodado de un aceite o aceites vegetales, que contiene el 30-42% de yodo orgánico combinado. Es estéril, insoluble en agua, soluble en éter, cloroformo o bencina de petróleo. Se usa como medio de contraste para estudios como histerosalpingografia, linfografia, sialografía y como uso selectivo intra-arterial hepático con diagnostico conocido de HC (para estudio y para quimio-embolizaciones). En el presente documento, cada vez que se mencione TACE convencional, se referirá a TACE utilizando lipiodol o aceite de amapola. OBJETIVO: Evaluar la eficacia y seguridad, así como documentos relacionados a la decisión de cobertura del aceite iodado de amapola para quimio embolización selectiva de pacientes con tumores hepáticos. METODOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas: MEDLINE, LILACS, COCHRANE, así como en buscadores genéricos de Internet incluyendo Google Scholar y TRIPDATABASE. Adicionalmente, se hizo una búsqueda dentro de la información generada por las principales instituciones internacionales de oncología y agencias de tecnologías sanitarias que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC). RESULTADOS: Se seleccionó una RS, un estudio observacional comparativo. Además, se seleccionaron dos GPC. No se encontraron ETS ni evaluaciones económicas regionales. CONCLUSIONES: La evidencia comparativa del uso de aceite de amapola para quimioembolización en tumores hepática es escasa. Basado en un estudio comparativo no se evidencia diferencia entre TACE convencional y del TACE con partículas cargadas con agente terapéutico. Comparado com intervenciones de cuidados paliativos, TACE convencional ofrece una alta supervivencia, enfermedad libre de progresión, entre otros. Dos GPC recomiendan el uso de TACE convencional para tratamiento de tumores no resecables. Sin embargo, consideran que TACE con partículas cargadas con agente terapéutico podría ser una opción beneficiosa en comparación del TACE convencional con aceite de amapola.

Alpha-fetoprotein assessment for hepatocellular carcinoma after transarterial chemoembolization.

PURPOSE: To evaluate whether AFP classification criteria correlate with tumor response measured using the European Association for the Study of the Liver (EASL) and predicate survival in patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). METHODS: Data from 143 consecutive patients with unresectable HCC and elevated AFP (> 20 ng/mL), who underwent TACE as initial treatment between January 2011 and December 2015 were collected, retrospectively. AFP response was classified as follows: complete response, normalization of AFP; partial response, > 50% decrease from baseline; stable disease, - 50 to + 30% change from baseline; or progressive disease, > 30% increase from baseline. Response rates according to AFP and EASL criteria were compared, and associations between the AFP response and overall survival (OS) were evaluated. RESULTS: The k value for agreement between AFP criteria and EASL criteria was 0.52 (moderate), with response rates of 42.7% and 41.3%, respectively (P = 0.811). The OS of responders was significantly longer compared with non-responders for both AFP (21 vs. 6 months, P < 0.001) and EASL (23 vs. 6 months, P < 0.001). Multivariate analysis revealed that the AFP response (hazard ratio [HR], 0.430, 95% CI, 0.233-0.794; P = 0.007), EASL response (HR, 0.343; 95% CI, 0.176-0.666; P = 0.002), and macroscopic vascular invasion (HR, 2.104; 95% CI, 1.403-3.154; P < 0.001) were significantly associated with OS. CONCLUSIONS: The defined AFP classification criteria was moderate correlated with EASL criteria and predicted the outcome in patients with HCC who underwent TACE.

Oil-based or water-based contrast for hysterosalpingography in infertile women: a cost-effectiveness analysis of a randomized controlled trial.

OBJECTIVE: To determine the cost effectiveness of the use of oil-based versus water-based contrast in infertile women undergoing hysterosalpingography (HSG). DESIGN: Economic evaluation alongside a multicenter randomized trial. SETTING: Hospitals. PATIENT(S): Infertile women with an ovulatory cycle, 18-39 years of age, low risk of tubal pathology. INTERVENTION(S): Use of oil-based versus water-based contrast during HSG. MAIN OUTCOME MEASURE(S): Costs per additional ongoing pregnancy and per live birth within 6 months of randomization, incremental cost-effective ratios (ICERs). RESULT(S): A total of 1,119 women were randomized to HSG (oil-based contrast, n = 557; water-based contrast, n = 562). After HSG, most women had no additional treatment; a minority had IUI or IVF. In the oil group, 39.7% women had an ongoing pregnancy within 6 months of randomization versus 29.1% women in the water group. There was a 10.7% increase in the live birth rate in the oil group. For ongoing pregnancy, the mean costs per couple were US$2,014 in the oil group and US$1,144 in the water group, with a corresponding ICER of US$8,198 per additional ongoing pregnancy. For live birth, the mean costs per couple were US$11,532 in the oil group and US$8,310 in the water group, with a corresponding ICER of US$30,112 per additional live birth. CONCLUSION(S): Hysterosalpingography with oil-based contrast results in higher 6-month ongoing pregnancy and live birth rate. If society is willing to pay US$8,198 for an additional ongoing pregnancy, HSG with oil-based contrast is a cost-effective strategy compared with HSG with water-based contrast for infertile, ovulatory women at low risk for tubal pathology. CLINICAL TRIAL REGISTRATION NUMBER: Dutch Trial Register, NTR 6577 (www.trialregister.nl).

Combination Therapy of Radiofrequency Ablation and Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Retrospective Study.

The treatment efficacy of unresectable hepatocellular carcinoma (HCC) is still not promising. This study aimed to compare the efficacy and safety of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) for unresectable HCC with a single treatment.Between June 2009 and June 2012, 132 patients who were diagnosed with unresectable HCC and accepted nonsurgical treatments in our center were enrolled in this retrospective study. On the basis of treatment modality, they were allocated to 3 groups: 49 patients accepted RFA (RFA group); 43 patients accepted TACE (TACE group); and 40 patients accepted RFA following TACE (combination group). Clinical data including complications, treatment success rate, hospitalization costs, intrahepatic recurrence-free survival, overall survival, and factors influencing survival were retrospectively analyzed.Patient characteristics between these groups showed no significant difference. Treatment success was achieved in all patients of 3 groups. The combination group had a significantly higher total hospitalization cost to treatment than the TACE group (63,708.14 ±â€Š9193.81 Chinese yuan vs 37,534.88 ±â€Š6802.84 Chinese yuan; P = 0.0000). All complications were controllable and no permanent adverse sequelae or procedure-related deaths were observed. The 3-year intrahepatic recurrence-free survival probability was significantly better in the combination group than in the TACE group (42.50% vs 20.93%; hazard ratio [HR], 0.5105; 95% confidence interval [CI], 0.3022-0.8625; P = 0.0094) or the RFA group (42.50% vs 22.45%; HR, 0.5233; 95% CI, 0.3149-0.8697; P = 0.0111).The 3-year overall survival probability was significantly better in the combination group than in the TACE group (45.00% vs 26.53%; HR, 0.5069; 95% CI, 0.2936-0.8752; P = 0.0100) or the RFA group (45.00% vs 27.91%; HR, 0.4913; 95% CI, 0.2928-0.8246; P = 0.0054). Main tumor size, number of tumors, and treatment modality were demonstrated to be important factors associated with 3-year intrahepatic recurrence-free survival probability and overall survival probability (P < 0.05) by univariate and multivariate analyses.Combination therapy of RFA and TACE was superior to TACE alone or RFA alone in improving survival for patients with unresectable HCC.

Clinical and economic impact of drug eluting beads in transarterial chemoembolization for hepatocellular carcinoma.

WHAT IS KNOWN AND OBJECTIVE: Drug eluting beads (DEBs) theoretically improve the efficacy and safety of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). Nonetheless, their economic profile has not been assessed. Our retrospective before/after study aimed to compare efficacy, safety and economic profile of two strategies of TACE without (Period 1) or with the possibility of using DEBs (Period 2). METHODS: All HCC patients treated by TACE in our hospital between March 2006 and May 2013 were included. Economic analyses were performed from the French Public Health Insurance point of view according to the French Diagnosis-Related Group prospective payment system and from the analytic accountability. RESULTS AND DISCUSSION: One hundred and sixty-one patients were included. Median time to treatment failure and overall survival were 13.1 and 23.8 months in Period 1 vs. 14.1 and 30.2 months in Period 2 (P = 0.45 and P = 0.40). Mean hospital durations and tariffs were 14.9 ± 7.7 days and € 11 472 ± 5901 in Period 1 vs. 12.4 ± 8.4 days and € 7654 ± 4625 in Period 2 (P = 0.03 and P < 10(-4) ). WHAT IS NEW AND CONCLUSION: The possibility of using DEBs did not improve the prognosis in HCC patients treated by TACE. Nonetheless, it had a better medico-economic profile.

Medico-economic study of the management of hepatocellular carcinoma by chemo-embolization.

PURPOSE: This study has two aims. The first is to compare conventional lipiodol chemo-embolization (Trans Arterial Chemo-Embolization - TACE) to one using pre-loaded particles (Trans Arterial Chemo-Embolisation-Drug Eluted Bead - TACE-DEB) using a cost minimization study. The second is to define the fundable nature of TACE-DEB and the conditions under which it is cost-effective. MATERIALS AND METHODS: Retrospective study of patients treated by chemo-embolization (n=31: TACE; n=32: TACE-DEB) during the year 2010. The cost minimization study was conducted from the hospital perspective. Direct medical costs were calculated and compared using the readjusted ENCC (National Studies of Costs by Common Methodology) method. The affordability of the two techniques and definition of a cost-effective hypothesis (break-even point) were also established. RESULTS: All DRGs combined, lengths of stay (TACE: 4.90 ± 3.36; TACE-DEB: 5.03 ± 3.36) does not change significantly. An average upper mean cost for TACE-DEB is described (TACE: 2869.05 €; TACE-DEB: 3960.10 €). The affordability calculations in the study show that, overall, TACE-DEB can be funded regardless of DRG. A ratio of 1.3 procedures using the conventional (TACE) method would enable TACE-DEB procedures to be funded. CONCLUSION: This medico-economic analysis demonstrates that the TACE-DEB procedure is fundable.

Preclinical anticancer effects and toxicologic assessment of hepatic artery infusion of fine-powder cisplatin with lipiodol in vivo.

We conducted an in vivo study to evaluate the anticancer effect and toxicity of fine-powder cisplatin suspended in lipiodol (fCDDP/LPD suspension) after a single administration of three different doses to rats via the intrahepatic artery after transplantation of rat ascites hepatoma cells. The toxicity of the fCDDP/LPD suspension was also assessed in the same protocol in noncancer-bearing rats and the observed toxicologic changes were compared among groups administered saline (Sal), an aqueous solution of fCDDP (fCDDP/Sal solution), and LPD alone. In parallel with the toxicity test, plasma CDDP concentrations were compared between the fCDDP/LPD suspension and fCDDP/Sal solution. The mean weight of the tumors in the fCDDP/LPD suspension groups was significantly less than in the LPD-alone group. The pathologic changes in the liver observed in the fCDDP/LPD suspension group increased with dose, were more marked compared with those in the fCDDP/Sal solution and LPD-alone groups, and were reversible. No other toxicologic effects were observed. The concentration of CDDP in the plasma in the fCDDP/LPD suspension group was slightly lower than that in the fCDDP/Sal solution group. In conclusion, the results indicate that the fCDDP/LPD suspension has sufficient anticancer efficacy and tolerability for use in the clinical treatment of hepatocellular carcinoma.

Quantitative assessment of lipiodol deposition after chemoembolization: comparison between cone-beam CT and multidetector CT.

PURPOSE: To evaluate the ability of cone-beam computed tomography (CBCT) performed directly after transarterial chemoembolization to assess ethiodized oil (Lipiodol) deposition in hepatocellular carcinoma (HCC) and compare it with unenhanced multidetector computed tomography (CT). MATERIALS AND METHODS: Conventional transarterial chemoembolization was used to treat 15 patients with HCC, and CBCT was performed to assess Lipiodol deposition directly after transarterial chemoembolization. Unenhanced multidetector CT was performed 24 hours after transarterial chemoembolization. Four patients were excluded because the margin of tumor or area of Lipiodol deposition was unclear. The image enhancement density of the entire tumor and liver parenchyma was measured by ImageJ software, and tumor-to-liver contrast (TLC) was calculated. In addition, volumetric measurement of tumor and Lipiodol was performed by semiautomatic three-dimensional volume segmentation and compared using linear regression to evaluate consistency between the two imaging modalities. RESULTS: The mean value of TLC on CBCT was not significantly different from TLC on multidetector CT (337.7 HU ± 233.5 vs 283.0 HU ± 152.1, P = .103).The average volume of the whole tumor and of only the regions with Lipiodol deposition and the calculated average percentage of Lipiodol retention on CBCT were not significantly different compared with multidetector CT (tumor volume, 9.6 cm(3) ± 11.8 vs 10.8 cm(3) ± 14.2, P = .142; Lipiodol volume, 6.3 cm(3) ± 7.7 vs 7.0 cm(3) ± 8.1, P = .214; percentage of Lipiodol retention, 68.9% ± 24.0% vs 72.2% ± 23.1%, P = .578). Additionally, there was a high correlation in the volume of tumor and Lipiodol between CBCT and multidetector CT (R(2) = 0.919 and 0.903). CONCLUSIONS: The quantitative image enhancement and volume analyses demonstrate that CBCT is similar to multidetector CT in assessing Lipiodol deposition in HCC after transarterial chemoembolization.

Islet cell liver metastases: assessment of volumetric early response with functional MR imaging after transarterial chemoembolization.

PURPOSE: To assess early response to transarterial chemoembolization by using volumetric functional magnetic resonance (MR) imaging in patients with islet cell liver metastases (ICLMs). MATERIALS AND METHODS: This retrospective institutional review board-approved HIPAA-compliant study included 215 ICLMs in 26 patients (15 men, 11 women; mean age, 59.7 years; age range, 37-79 years). Volumetric measurements were performed by an experienced radiologist on diffusion-weighted and contrast material-enhanced MR images at baseline and 1-month follow-up. Measurements included mean change (three-dimensional [3D] mean apparent diffusion coefficient [ADC], 3D mean enhancement) and percentage of tumor with change above a predetermined threshold (3D threshold ADC, 3D threshold enhancement). Response by volumetric measurements at 1-month follow-up was compared with Response Evaluation Criteria in Solid Tumors (RECIST) at 6-month follow-up. Lesions that had complete or partial response were considered responders, while those with stable or progressive disease were considered nonresponders. Statistical analysis included the t test, receiver operating characteristic (ROC) curve analysis, and logistic regression analysis. RESULTS: RECIST criteria at 6-month follow-up indicated 78 (36.3%) lesions responded, while 137 (63.7%) did not. The increase in 3D mean ADC was significantly higher in responders than in nonresponders (median, 26.2% vs 10.9%; P<.001). The 3D threshold ADC was 71.1% in responders and 47.6% in nonresponders (P<.001). Decrease in 3D mean arterial enhancement (AE) was significantly higher in responders than in nonresponders (median, 40.5% vs 18.0%; P<.001). Decrease in 3D mean venous enhancement (VE) was significantly higher in responders than in nonresponders (median, 28.0% vs 10.0%; P<.001). The 3D threshold VE and 3D threshold AE did not differ between responders and nonresponders. In unadjusted logistic regression analyses, 3D mean ADC and 3D threshold ADC had the highest odds ratio (1.02 and 1.03, respectively) and the largest area under the ROC curve (0.698 and 0.695, respectively). CONCLUSION: Volumetric functional MR imaging could be used to predict early response of hepatic ICLMs to therapy and to distinguish between responders and nonresponders.

Nitroglycerine use in transcatheter arterial (chemo)embolization in patients with hepatocellular carcinoma and dual-energy CT assessment of Lipiodol retention.

OBJECTIVES: To investigate whether the addition of nitroglycerine to transcatheter arterial (chemo)embolization (TAE/TACE) can increase the delivery and effectiveness of TAE/TACE in patients with hepatocellular carcinoma (HCC) by dual-energy CT. METHODS: HCC patients (BCLC stage A or B) were randomized to (n = 51) or not to (n = 50) receive nitroglycerine and an emulsion of Lipiodol with or without doxorubicin, followed by embolization with Gelfoam pledgets. Dual-energy CT was performed pre- and 1 to 3 months post-embolization to assess changes in tumour diameter and Lipiodol levels in tumours. RESULTS: Median tumour diameter decreased from baseline in both groups with and without nitroglycerine (7.11 % vs. 12.5 %, respectively), and was statistically significant in the group receiving nitroglycerine (P = 0.023). There was no difference between the two groups in disease response (P = 0.237). The concentration and percentage of Lipiodol retained in tumours were significantly greater in patients treated with nitroglycerine compared to those without (median concentration 15.05 mg/mL vs. 4.40 mg/mL, respectively, P < 0.001; median percentage 82.01 % vs. 36.75 %, respectively, P < 0.001). CONCLUSIONS: Nitroglycerine increased delivery of the Lipiodol emulsion via TAE/TACE to HCC tumours with significant tumour reduction. Dual-energy CT can accurately quantify the amount of Lipiodol deposited in tumours. KEY POINTS: • Nitroglycerine improves delivery of tumour-targeted therapy via enhanced permeability and retention. • In hepatocellular carcinoma, nitroglycerine added to TAE/TACE showed greater tumour reduction. • Dual-energy CT can reliably quantify the amount of Lipiodol in TAE/TACE.

Chemoembolization of liver tumor in a rabbit model: assessment of tumor cell death with diffusion-weighted MR imaging and histologic analysis.

PURPOSE: To assess the efficacy of chemoembolization of liver tumors by determining the fraction of viable tumor cells remaining after treatment with use of diffusion magnetic resonance (MR) imaging and histologic analysis. MATERIALS AND METHODS: VX2 tumor was grown in the livers of 12 rabbits. Animals were divided into a chemoembolization group and an untreated group. Conventional, perfusion, and diffusion MR imaging was performed on all rabbits. Histopathologic analysis of explanted livers was performed to document tumor cell death and measure Bcl-2 levels (inhibitor of apoptosis). RESULTS: Diffusion-weighted MR imaging delineated zones of tumor cell death as regions of lower signal intensity in both groups. Apparent diffusion coefficients were significantly greater in the area of tumor necrosis than in the area of viable tumor. Histologic analysis demonstrated a significantly lower percentage of viable cells in the treated group (<1%) than in the control group (55%). Bcl-2 expression detected within the viable areas of the tumor was greater in the treated group than in the control group. CONCLUSIONS: Chemoembolization causes extensive tumor cell destruction. Diffusion MR imaging can detect tumor cell death and can be used to assess the efficacy of chemoembolization. Bcl-2 was expressed in the treated group, suggesting an apoptotic pathway of cell death.