First human study in treatment of unresectable liver metastases from colorectal cancer with irinotecan-loaded beads (DEBIRI)

The objective of this pilot clinical study was to assess the safety, technical feasibility, pharmacokinetic (PK) profile and tumour response of DC Bead™ with irinotecan (DEBIRI™) delivered by intra-arterial embolisation for the treatment of metastatic colorectal cancer. Eleven patients with unresectable liver metastases from CRC, tumour burden <30% of liver volume, adequate haematological, liver and renal function, performance status of <2 were included in this study. Patients received up to 4 sessions of TACE with DEBIRI at 3-week intervals. Feasibility of the procedure, safety and tumour response were assessed after each cycle. PK was measured after the first cycle. Patients were followed up to 24 weeks. Only mild to moderate adverse events were observed. DEBIRI is a technically feasibile procedure; no technical complications were observed. Average Cmax for irinotecan and SN-38 was 194 ng/ml and 16.7 ng/ml, respectively, with average t½ of 4.6 h and 12.4 h following administration of DEBIRI. Best overall response during the study showed disease control in 9 patients (2 patients with partial response and 7 with stable disease, overall response rate of 18%). Our study shows that transarterial chemoembolisation with irinotecan-loaded DC beads (DEBIRI) is safe, technically feasible and effective with a good PK profile

Die transarterielle Chemoembolisation als minimal invasive lokoregionale Behandlungsmaßnahme bei nicht resektablen Malignomen der Leber

Zielsetzung: Die Evaluation der transarteriellen Chemoembolisation (TACE) bei nicht resektablen primären (CCC) und sekundären (Lebermetastasen verschiedener Primärtumoren) Lebermalignomen anhand des lokalen Tumoransprechens, des klinischen Ansprechens und der Überlebensdaten. Material und Methodik: Im Zeitraum vom 1999 bis 2009 wurden in unserem Tumorzentrum 898 Patienten mit CCC und Lebermetastasen mittels TACE behandelt. Die behandelten Tumorentitäten waren im Einzelnen das cholangiozelluläre Karzinom (CCC) (n=46; 5,1%) sowie Lebermetastasen des: kolorektalen Karzinoms (CRC) (n=463; 51,7%), Mammakarzinoms (n=208; 23,2%), Aderhautmelanoms (n=33; 3,7%), Nierenzellkarzinoms (n=22; 2,5%), neuroendokrinen Karzinoms (NET) (n=48; 5,4%), Magenkarzinoms (n=25; 2,8%), Ovarialkarzinoms (n=30; 3,3%) und nicht-kleinzelligen Bronchialkarzinoms (NSCLC) (n=21; 2,3%). Als Zytostatika wurden Mitomycin C (8 mg/m²), Gemcitabine (1000 mg/m²), Irinotecan (150 mg/m²) und Cisplatin (60 mg/m²) verwendet. Als Embolisat wurden Lipiodol und Microsphären (EmboCept®) verwendet. Mindestens drei TACE Sitzungen pro Patient wurden in vierwöchigen Abständen ambulant durchgeführt. Das radiologische Tumoransprechen wurde mittels Magnetresonanztomographie (MRT) und/oder Computertomographie (CT) bestimmt und nach den RECIST-Kriterien klassifiziert. Das klinische Ansprechen wurde im Verlauf der Behandlung in neoadjuvant, palliativ und symptomatisch eingeteilt. Die Überlebensdaten wurden nach der Kaplan-Meier-Methode berechnet. Ergebnisse: Die Mindestzahl der durchgeführten TACE war drei. Bei 46 Patienten mit CCC wurden bei 11% PR, bei 60,7% SD und bei 28,3% PD bei einer medianen Überlebenszeit von 14,5 Monaten dokumentiert. 2,2% der Patienten wurden neoadjuvant, 73,9% palliativ und 23,9% symptomatisch behandelt. Bei 463 Patienten mit Lebermetastasen des CRC wurden bei 14,7% PR, bei 48,2% SD und bei 37,1% PD dokumentiert. Die mediane Überlebenszeit lag bei 14 Monaten. 12,9% der Patienten wurden neoadjuvant, 72,4% palliativ und 14,7% symptomatisch behandelt. Bei 208 Patienten mit Lebermetastasen des Mammakarzinoms wurden bei 13% PR, bei 50,5% SD und bei 36,5% PD bei einer medianen Überlebenszeit von 18,5 Monaten dokumentiert. Die Patienten wurden zu 18,75% neoadjuvant, zu 15,38% symptomatisch und zu 65,87% palliativ behandelt. Bei Patienten mit Lebermetastasen des Aderhautmelanoms wurden bei 15,2% PR, bei 42,4% SD und bei 42,4% PD dokumentiert. Die mediane Überlebenszeit betrug 18 Monate. Die klinische Situation war zu 3% neoadjuvant, zu 24,2% symptomatisch und zu 72,8% palliativ. Bei Patienten mit Lebermetastasen des Nierenzellkarzinoms wurden bei 13,7% PR, bei 59% SD und bei 27,3% PD bei einer medianen Überlebenszeit von 6,6 Monaten dokumentiert. Die klinische Situation war zu 81,8% palliativ und zu 18,2% symptomatisch. Bei Patienten mit Lebermetastasen des NET wurden bei 18,8% PR, bei 52,1% SD und bei 29,1% PD dokumentiert. 81,2% der Patienten wurden palliativ und 18,8% symptomatisch behandelt. Patienten mit Lebermetastasen des Magenkarzinoms hatten eine mediane Überlebenszeit von 10,5 Monaten. SD wurde bei 60% und PD bei 40% dokumentiert. 76% der Patienten wurden palliativ und 24% symptomatisch behandelt. Bei den Patientinnen mit Lebermetastasen des Ovarialkarzinoms wurden bei 20% PR, bei 26,7% SD und bei 53,3% PD dokumentiert. Die mediane Überlebenszeit betrug 23,7 Monate bei folgendem klinischen Ansprechen: 13,3% symptomatisch und 86,7% palliativ. Für Patienten mit Lebermetastasen des NSCLC wurden bei 14,3% PR, bei 47,6% SD und bei 38,1% PD bei medianer Überlebenszeit von 11,7 Monaten dokumentiert. Die Patienten wurden wie folgend behandelt: 81% palliativ und 19% symptomatisch. Schlussfolgerung: TACE bei primären (CCC) und sekundären (Lebermetastasen verschiedener Primärtumoren) Lebermalignome stellt ein gut verträgliches, minimal invasives, lokoregionales Verfahren dar, das zu einem guten Tumoransprechen, Lebensverlängerung sowie Verminderung der Symptomatik führt.Purpose: To evaluate local tumor response, clinical response and survival data after transarterial chemoembolization (TACE) of nonresectable primary (CCC) and secondary (liver metastases from different primary tumors) liver tumors. Material and Methods: From 1999 to 2009, 898 patients suffering from CCC and liver metastases were treated with TACE. Treated tumor entities were CCC (n=46, 5.1%) and liver metastases from CRC (n=463, 51.7%), breast cancer (n=208, 23.2%), uveal malignant melanoma (n=33; 3.7 %), renal cell carcinoma (n=22, 2,5%), neuroendocrine tumors (n=48, 5.4%), gastric cancer (n=25, 2.8%), ovarian cancer (n=30, 3.3%) and NSCLC (n=21, 2.3%). The local chemotherapy protocol consisted of mitomycin C (8 mg/m²), gemcitabine (1000 mg/m²), irinotecan (150 mg/m²) and cisplatin (60 mg/m²). Embolization was performed with lipiodol and starch microspheres for vessel occlusion. At least 3 TACE courses on an outpatient basis in four-week-intervals were conducted. Tumor response was evaluated with MRI and/or CT. The change in tumor size was calculated and the response was evaluated and classified according to RECIST- Criteria. Clinical response to treatment was classified in neoadjuvantly, palliatively and symptomatically. The survival data were calculated using the Kaplan-Meier method. Results: A minimum of 3 TACE sessions was conducted in all patients. For the 46 patients with CCC radiological response was 11% PR, 60.7% SD and 28.3% PD with a median survival of 14.5 months. 2.2% of patients were treated neoadjuvantly, 73.9% palliativly and 23.9% symptomatically. For 463 patients with liver metastases of CRC radiological response was 14.7% PR, 48.2% SD and 37.1% PD. The median survival time was 14 months. 12.9% of the patients were treated neoadjuvantly, 72.4% palliatively and 14.7% symptomatically. In 208 patients with liver metastases of breast cancer were documented 13% PR, 50.5% SD and 36.5% PD with a median survival of 18.5 months. The patients were treated neoadjuvantly in 18.75%, palliatively in 15.38% and symptomatically in 65.87%. For patients with liver metastases from uveal malignant melanoma radiological response was PR for 15.2%, SD for 42.4% and PD for 42.4%. The median survival time was 18 months. 3% of the patients were treated neoadjuvantly, 24.2% symptomatically and 72.8% palliatively. For patients with liver metastases of renal cell carcinoma was documented 13.7% PR, 59% SD and 27.3% PD with the median survival of 6.6 months. Clinical situation was in 81.8% symptomatically and in 18.2% palliatively. For patients with liver metastases of neuroendocrine tumors was documented 18.8% PR, 52.1% SD and 29.1% PD. 81.2% of the patients were treated palliatively and 18.8% symptomatically. Patients with liver metastases of gastric cancer had a median survival of 10.5 months. SD was documented in 60% and PD in 40%. 76% of the patients were treated palliatively and 24% symptomatically. For patients with liver metastases of ovarian cancer was documented 20% PR, 26.7% SD and 53.3% PD. The median survival was 23.7 months with the following clinical response: 13.3% symptomatically and 86.7% palliativelly. For patients with liver metastases of NSCLC was documented 14.3% PR, 47.6% SD and 38.1% PD with a median survival of 11.7 months. The patients were treated: palliatively in 81% and symptomatically in 19%. Conclusion: TACE for primary (CCC) and secondary (liver metastases from different primary tumors) liver tumors represents a well tolerable, minimally invasive, locoregional and safe procedure. The goals of TACE were a good tumor response, life extension and reduction of tumor associated symptoms

Age and Oversizing Influence Iliac Dilatation after EVAR

In the past two decades, endovascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA) has become the first line treatment for infrarenal AAA repair in many countries. While short-term results are good, concerns have been raised about long-term durability. Changes in aortoiliac anatomy, especially at the landing zones, could play a role in EVAR failure over time. The current study aimed to determine certain morphological changes in the distal iliac landing zone after EVAR implantation, as well aspossible risk factors associated with iliac sealing failure. In a retrospective analysis of a tertiary single-centre registry, including patients treated with EVAR between January 2008 and July 2018, clinical follow-up data were assessed, and computer tomography (CT) imaging was evaluated regarding morphological changes in the iliac anatomy during follow-up. For clinical analysis all patients with a minimum follow-up of one year were included; for morphological analysis of iliac anatomy all patients with available CT follow-up of a minimum of one year and a minimum of two CT scans were included. Overall, 127 out of 241 treated patients (92.1% male) were included in the clinical follow-up. Complete CT imaging of 99 iliac arteries in 55 patients was available for morphological analysis. Median postoperative follow-up (FU) for these patients was 33 months (IQR 31; min–max: 12–124). Incidence of type 1b endoleak was 3% but iliac limb detachment from the vessel wall was seen in 18.2% of the target vessels. There was a significant difference in oversizing in iliac limbs with detachment (median 13.9%, IQR 23.1) vs. without detachment (median 23.1%, IQR 19.1) (p = 0.034). Iliac arteries at the landing zone showed a significant diameter increase independent of an endoleak presence (overall cohort median diameter increase at one year 23.1 mm; at two years 0 mm; at three years 4.9 mm). Iliac arteries with detachment (median 14.4%; IQR 23.9) showed a significantly higher diameter increase at the landing zone after four years compared to arteries without detachment (median 5.3%; IQR 9) (p = 0.042). Oversizing correlated positively with an iliac diameter increase at the landing zone over time (3 m: p= 0.001; one year: p p p = 0.006). Older patients showed a significantly lower diameter increase at the distal landing zone over time than younger patients in the first two years after EVAR (p < 0.001/r = −0.606 after two years). In the current study, iliac limb oversizing was associated with increased dilatation of the distal landing zone during a three-year follow-up, while iliac limb detachment was observed less often. An older age was inversely associated to the iliac diameter increase. Future studies should clarify the association between stent graft oversizing, age, and changes in the iliac anatomy in order to identify parameters that affect EVAR durability

Lipiodol as a Predictive Indicator for Therapy Response to Transarterial Chemoembolization of Hepatocellular Carcinoma

Background: To evaluate the predictive value of Lipiodol for response evaluation of hepatocellular carcinoma (HCC) treated with conventional transarterial chemoembolization (cTACE) by analysis of the enhancement pattern during angiography and in postinterventional computed tomography (CT). Materials and Methods: This retrospective study included 30 patients (mean age 63 years, range: 36 to 82 years, 22 males) with HCC. Patients received three Lipiodol-based cTACE sessions, each followed by an unenhanced CT within 24-h. Contrast-enhanced magnetic resonance imaging (MRI) was acquired before and after the treatment to determine tumor response. Lipiodol enhancement pattern, tumor vascularization, and density were evaluated by angiography and CT. Initial tumor size and response to cTACE were analyzed by MRI according to modified response evaluation criteria in solid tumors (mRECIST) in a 4-week follow-up. Results: Analysis of HCC lesions (68 lesions in 30 patients) during cTACE revealed clear visibility and hypervascularization in angiography as a potential independent parameter able to predict tumor response. A significant correlation was found for response measurements by volume (p = 0.012), diameter (p = 0.006), and according to mRECIST (p = 0.039). The amount of Lipiodol and enhancement pattern in postinterventional CT did not correlate with therapy response. Measurements of Hounsfield unit values after cTACE do not allow sufficient prediction of the tumor response. Conclusion: Hypervascularized HCC lesions with clear visibility after Lipiodol administration in the angiography respond significantly better to cTACE compared to hypo- or nonvascularized lesions

CT-guided biopsies of unspecified suspect intrahepatic lesions: pre-procedure Lipiodol-marking improves the biopsy success rate

While computed tomography (CT)-guided liver biopsies are commonly performed using unenhanced images, contrast-enhanced images are beneficial for challenging puncture pathways and lesion locations. This study aimed to evaluate the accuracy of CT-guided biopsies for intrahepatic lesions using unenhanced, intravenous (IV)-enhanced, or intra-arterial Lipiodol-marked CT for lesion marking

Evaluation of two different transarterial chemoembolization protocols using Lipiodol and degradable starch microspheres in therapy of hepatocellular carcinoma: a prospective trial

Background: This prospective randomized trial is designed to compare the performance of conventional transarterial chemoembolization (cTACE) using Lipiodol-only with additional use of degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) in BCLC-stage-B based on metric tumor response. Methods: Sixty-one patients (44 men; 17 women; range 44–85) with HCC were evaluated in this IRB-approved HIPPA compliant study. The treatment protocol included three TACE-sessions in 4-week intervals, in all cases with Mitomycin C as a chemotherapeutic agent. Multiparametric magnetic resonance imaging (MRI) was performed prior to the first and 4 weeks after the last TACE. Two treatment groups were determined using a randomization sheet: In 30 patients, TACE was performed using Lipiodol only (group 1). In 31 cases Lipiodol was combined with DSMs (group 2). Response according to tumor volume, diameter, mRECIST criteria, and the development of necrotic areas were analyzed and compared using the Mann–Whitney-U, Kruskal–Wallis-H-test, and Spearman-Rho. Survival data were analyzed using the Kaplan–Meier estimator. Results: A mean overall tumor volume reduction of 21.45% (± 62.34%) was observed with an average tumor volume reduction of 19.95% in group 1 vs. 22.95% in group 2 (p = 0.653). Mean diameter reduction was measured with 6.26% (± 34.75%), for group 1 with 11.86% vs. 4.06% in group 2 (p = 0.678). Regarding mRECIST criteria, group 1 versus group 2 showed complete response in 0 versus 3 cases, partial response in 2 versus 7 cases, stable disease in 21 versus 17 cases, and progressive disease in 3 versus 1 cases (p = 0.010). Estimated overall survival was in mean 33.4 months (95% CI 25.5–41.4) for cTACE with Lipiosol plus DSM, and 32.5 months (95% CI 26.6–38.4), for cTACE with Lipiodol-only (p = 0.844), respectively. Conclusions: The additional application of DSM during cTACE showed a significant benefit in tumor response according to mRECIST compared to cTACE with Lipiodol-only. No benefit in survival time was observed

Transarterial chemoembolization (TACE) using mitomycin and lipiodol with or without degradable starch microspheres for hepatocellular carcinoma: comparative study

Abstract Background To evaluate survival data and local tumor control after transarterial chemoembolization in two groups with different embolization protocols for the treatment of HCC patients. Methods Ninty-nine patients (mean age: 63.6 years), 78 male (78.8%) with HCC were repeatedly treated with chemoembolization in 4-week-intervals. Eighty-eight patients had BCLC-Stage-B and in 11 patients, chemoembolization was performed for bridging (BCLC-Stage-A). In total, 667 chemoembolization treatments were performed (mean 6.7 treatments/patient). The administered chemotherapeutic agent included mitomycin. For embolization, lipiodol only (n = 51;51.5%; mean age 63.8 years; 38 male), or lipiodol plus degradable starch microspheres (DSM) (n = 48; 48.5%; mean age 63.4 years; 40 male) were used. The local tumor response was assessed by MRI using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). Patient survival times were evaluated using Kaplan-Meier curves and log-rank tests. Results The local tumor control in the lipiodol-group was: PR (partial response) in 11 (21.6%), SD (stable disease) in 32 (62.7%) and PD (progressive disease) in 8 cases (15.7%). In the lipiodol-DSM-group, PR was seen in 14 (29.2%), SD in 22 (45.8%), and PD in 12 (25.0%) individuals (p = 0.211). The median survival of patients after chemoembolization with lipiodol was 25 months and in the lipiodol-DSM-group 28 months (p = 0.845). Conclusion Our data suggest a slight benefit of the use of lipiodol and DSM in comparison of using lipiodol only for chemoembolization of HCC in terms of local tumor control and survival data, this trend did not reach the level of significance

Low-dose CT pulmonary angiography on a 15-year-old CT scanner: a feasibility study

Background Computed tomography (CT) low-dose (LD) imaging is used to lower radiation exposure, especially in vascular imaging; in current literature, this is mostly on latest generation high-end CT systems. Purpose To evaluate the effects of reduced tube current on objective and subjective image quality of a 15-year-old 16-slice CT system for pulmonary angiography (CTPA). Material and Methods CTPA scans from 60 prospectively randomized patients (28 men, 32 women) were examined in this study on a 15-year-old 16-slice CT scanner system. Standard CT (SD) settings were 100 kV and 150 mAs, LD settings were 100 kV and 50 mAs. Attenuation of the pulmonary trunk, various anatomic landmarks, and image noise were quantitatively measured; contrast-to-noise ratios (CNR) and signal-to-noise ratios (SNR) were calculated. Three independent blinded radiologists subjectively rated each image series using a 5-point grading scale. Results CT dose index (CTDI) in the LD series was 66.46% lower compared to the SD settings (2.49 ± 0.55 mGy versus 7.42 ± 1.17 mGy). Attenuation of the pulmonary trunk showed similar results for both series (SD 409.55 ± 91.04 HU; LD 380.43 HU ± 93.11 HU; P = 0.768). Subjective image analysis showed no significant differences between SD and LD settings regarding the suitability for detection of central and peripheral PE (central SD/LD, 4.88; intra-class correlation coefficients [ICC], 0.894/4.83; ICC, 0.745; peripheral SD/LD, 4.70; ICC, 0.943/4.57; ICC, 0.919; all P > 0.4). Conclusion The LD protocol, on a 15-year-old CT scanner system without current high-end hardware or post-processing tools, led to a dose reduction of approximately 67% with similar subjective image quality and delineation of central and peripheral pulmonary arteries