Prediction of Protumorigenic Effects after Image-Guided Radiofrequency Ablation of Hepatocellular Carcinoma Using Biomarkers.

PURPOSE: To perform radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) and to assess serological and histopathological markers of tumorigenesis in distant untreated tumors to determine whether these were associated with unfavorable outcomes such as early relapse and increased biological aggressiveness. MATERIALS AND METHODS: The study cohort comprised 13 patients from a prospective single-arm study. All patients underwent 2 ablation sessions of multifocal HCC nodules 14 days apart. Core biopsy samples of untreated tumors were acquired at baseline and at the time of the second ablation session. Samples were stained immunohistochemically with Ki-67 (proliferation) and CD34 (microvasculature). Blood plasma was obtained at baseline and 2 days after the initial ablation session and analyzed for hepatocyte growth factor (HGF), vascular endothelial growth factor C, and angiopoietin-2 using an enzyme-linked immunosorbent assay. The clinical follow-up period ranged from 7 to 25 months. Patients were stratified as responders (complete remission or limited and delayed recurrence at >6 months; n = 6) or nonresponders (any recurrence within 6 months or >3 new tumors or any new tumor of >3 cm thereafter; n = 7). RESULTS: In 3 of 7 nonresponders, the Ki-67 index markedly increased in untreated tumors, whereas Ki-67 was stable in all responders. Microvascular density strongly increased in a single nonresponder only. HGF and angiopoietin-2 increased by >30% in 3 of 7 and 4 of 7 nonresponders, respectively, whereas they were stable or decreased in responders. Overall, ≥2 biomarkers were elevated in 6 of 7 (85.7%) nonresponders, whereas 4 of 6 responders demonstrated no increased biomarker and 2 patients demonstrated increase in 1 biomarker only (P = .002). CONCLUSIONS: RF ablation of HCC can produce protumorigenic factors that induce effects in distant untreated tumors. These may potentially function as biomarkers of clinical outcome.

Pretreatment Apparent Diffusion Coefficient Cannot Predict Histopathological Features and Response to Neoadjuvant Radiochemotherapy in Rectal Cancer: A Meta-Analysis.

AIM: Our purpose was to perform a systemic literature review and meta-analysis regarding use of apparent diffusion coefficient (ADC) for prediction of histopathological features in rectal cancer (RC) and to prove if ADC can predict treatment response to neoadjuvant radiochemotherapy (NARC) in RC. METHODS: MEDLINE library, EMBASE, Cochrane, and SCOPUS database were screened for associations between ADC and histopathology and/or treatment response in RC up to June 2020. Authors, year of publication, study design, number of patients, mean value, and standard deviation of ADC were acquired. The methodological quality of the collected studies was checked according to the Quality Assessment of Diagnostic Studies instrument. The meta-analysis was undertaken by using the RevMan 5.3 software. DerSimonian and Laird random-effects models with inverse-variance weights were used to account the heterogeneity between the studies. Mean ADC values including 95% confidence intervals were calculated. RESULTS: Overall, 37 items (2,015 patients) were included. ADC values of tumors with different T and N stages and grades overlapped strongly. ADC cannot distinguish RC with a high- and low-carcinoembryonic antigen level. Regarding KRAS status, ADC cannot discriminate mutated and wild-type RC. ADC did not correlate significantly with expression of vascular endothelial growth factor and hypoxia-inducible factor 1a. ADC correlates with Ki 67, with the calculated correlation coefficient: -0.52. The ADC values in responders and nonresponders overlapped significantly. CONCLUSION: ADC correlates moderately with expression of Ki 67 in RC. ADC cannot discriminate tumor stages, grades, and KRAS status in RC. ADC cannot predict therapy response to NARC in RC.

Apparent Diffusion Coefficient Can Predict Therapy Response of Hepatocellular Carcinoma to Transcatheter Arterial Chemoembolization.

AIM: The goal of this meta-analysis was to assess the apparent diffusion coefficient (ADC) as a pre- and posttreatment (ADC value changes [ΔADC]) predictive imaging biomarker of response to transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). METHODS: Scopus database, Embase database, and MEDLINE library were scanned for connections between pre- and posttreatment ADC values of HCC and response to TACE. Six studies qualified for inclusion. The following parameters were collected: authors, publication year, study design, number of patients, drugs for TACE, mean ADC value, standard deviation, measure method, b values, and Tesla strength. The Quality Assessment of Diagnostic Studies 2 instrument was employed to check the methodological quality of each study. The meta-analysis was performed by utilizing RevMan 5.3 software. DerSimonian and Laird random-effects models with inverse-variance were used to regard heterogeneity. The mean ADC values and 95% confidence intervals were computed. RESULTS: Six studies (n = 271 patients with 293 HCC nodules) were included. The pretreatment mean ADC in the responder group was 1.20 × 10-3 mm2/s (0.98, 1.42) and 1.14 × 10-3 mm2/s (0.89, 1.39) in the nonresponder group. The analysis of post-TACE ΔADC revealed a threshold of ≥20% to identify treatment responders. No suitable pretreatment ADC threshold to predict therapy response or discriminate between responders and nonresponders before therapy could be discovered. CONCLUSION: ΔADC can facilitate early objective response evaluation through post-therapeutic ADC alterations ≥20%. Pretreatment ADC cannot predict response to TACE.

Apparent diffusion coefficient cannot discriminate metastatic and non-metastatic lymph nodes in rectal cancer: a meta-analysis.

BACKGROUND: Our aim was to provide data regarding use of diffusion-weighted imaging (DWI) for distinguishing metastatic and non-metastatic lymph nodes (LN) in rectal cancer. METHODS: MEDLINE library, EMBASE, and SCOPUS database were screened for associations between DWI and metastatic and non-metastatic LN in rectal cancer up to February 2021. Overall, 9 studies were included into the analysis. Number, mean value, and standard deviation of DWI parameters including apparent diffusion coefficient (ADC) values of metastatic and non-metastatic LN were extracted from the literature. The methodological quality of the studies was investigated according to the QUADAS-2 assessment. The meta-analysis was undertaken by using RevMan 5.3 software. DerSimonian, and Laird random-effects models with inverse-variance weights were used to account the heterogeneity between the studies. Mean DWI values including 95% confidence intervals were calculated for metastatic and non-metastatic LN. RESULTS: ADC values were reported for 1376 LN, 623 (45.3%) metastatic LN, and 754 (54.7%) non-metastatic LN. The calculated mean ADC value (× 10-3 mm2/s) of metastatic LN was 1.05, 95%CI (0.94, 1.15). The calculated mean ADC value of the non-metastatic LN was 1.17, 95%CI (1.01, 1.33). The calculated sensitivity and specificity were 0.81, 95%CI (0.74, 0.89) and 0.67, 95%CI (0.54, 0.79). CONCLUSION: No reliable ADC threshold can be recommended for distinguishing of metastatic and non-metastatic LN in rectal cancer.

Ethanol Intoxication Alleviates the Inflammatory Response of Remote Organs to Experimental Traumatic Brain Injury.

Traumatic brain injury (TBI) may cause damage to distant organs. Acute ethanol intoxication (EI) induces complex local and systemic anti-inflammatory effects and influences the early outcomes of traumatized patients. Here, we evaluated its effects on the BI-induced expression of local inflammatory mediators in the trauma-remote organs the lungs and liver. Male mice were exposed to ethanol as a single oral dose (5g·kg-1, 32%) before inducing a moderate blunt TBI. Sham groups underwent the same procedures without TBI. Ether 3 or 6h after the TBI, the lung and liver were collected. The gene expression of HMGB1, IL-6, MMP9, IL-1ß, and TNF as well as the homogenate protein levels of receptor for advanced glycation end products (RAGE), IL-6, IL-1ß, and IL-10 were analyzed. Liver samples were immunohistologically stained for HMGB1. EI decreased the gene expressions of the proinflammatory markers HMGB1, IL-6, and MMP9 in the liver upon TBI. In line with the reduced gene expression, the TBI-induced protein expression of IL-6 in liver tissue homogenates was significantly reduced by EI at 3h after TBI. While the histological HMGB1 expression was enhanced by TBI, the RAGE protein expression in the liver tissue homogenates was diminished after TBI. EI reduced the histological HMGB1 expression and enhanced the hepatic RAGE protein expression at 6h post TBI. With regard to the lungs, EI significantly reduced the gene expressions of HMGB1, IL-6, IL-1ß, and TNF upon TBI, without significantly affecting the protein expression levels of inflammatory markers (RAGE, IL-6, IL-1ß, and IL-10). At the early stage of TBI-induced inflammation, the gene expression of inflammatory mediators in both the lungs and liver is susceptible to ethanol-induced remote effects. Taken together, EI may alleviate the TBI-induced pro-inflammatory response in the trauma-distant organs, the lungs and liver, via the HMGB1-RAGE axis.

Biliary duct stenosis after image-guided high-dose-rate interstitial brachytherapy of central and hilar liver tumors : A systematic analysis of 102 cases.

OBJECTIVE: Image-guided high-dose-rate interstitial brachytherapy (iBT) with iridium-192 is an effective treatment option for patients with liver malignancies. Little is known about long-term radiation effects on the bile duct system when central hepatic structures are exposed to iBT. This retrospective analysis investigates the occurrence of posthepatic cholestasis (PHC) and associated complications in patients undergoing iBT. MATERIALS AND METHODS: We identified patients who underwent iBT of hepatic malignancies and had point doses of ≥1 Gy to central bile duct structures. Patients with known bile duct-related diseases or prior bile duct manipulation were excluded. RESULTS: 102 patients were retrospectively included. Twenty-two patients (22%) developed morphologic PHC after a median of 17 (3-54) months; 18 of them were treated using percutaneous transhepatic cholangiopancreatography drainage or endoscopic retrograde cholangiopancreatography. The median point dose was 24.8 (4.4-80) Gy in patients with PHC versus 14.2 (1.8-61.7) Gy in those without PHC (p = 0.028). A dose of 20.8 Gy (biological effective dose, BED3/10 = 165/64.1 Gy) was identified to be the optimal cutoff dose (p = 0.028; 59% sensitivity, 24% specificity). Abscess/cholangitis was more common in patients with PHC compared to those without (4 of 22 vs. 2 of 80; p = 0.029). Median survival did not differ between patients with and without PHC (43 vs. 36 months; p = 0.571). CONCLUSION: iBT of liver malignancies located near the hilum can cause PHC when the central bile ducts are exposed to high point doses. Given the long latency and absence of impact of iBT-induced PHC on median survival, the rate of cholestasis and complications seen in our patients appears to be acceptable.

Transarterial embolisation for the treatment of acute gynecological cancer bleeding.

PURPOSE: Acute bleeding in patients with gynecological cancer may result in serious life-threatening complications. In these situations, immediate diagnostic and appropriate treatment is a challenge for attending physicians. Accordingly, transarterial embolisation (TAE) has been described as an increasing and effective treatment alternative to surgery and radiotherapy. METHODS: In the present retrospective study, 25 patients were included who underwent a TAE in the period from January 2006 to June 2013 due to acute gynecological cancer bleeding. The objective of this study was to assess the efficiency and outcome of TAE. RESULTS: The primary technical success rate was 92.0% (n = 23). 21 patients were analyzed in the 30-day follow-up. The clinical success rate was achieved in 90.5% (n = 19). A clinical failure due to rebleeding was observed in 9.5% (n = 2). No associations were revealed between rebleeding and technical/clinical factors. Within 30 days after the last TAE, the complication and mortality rates were 0.0% and 5.0% (n = 1), respectively. CONCLUSION: TAE was found as an effective and safe treatment in the clinical setting of acute gynecological cancer bleeding. An important component of efficient management is an early and interdisciplinary care. Optimal treatment can be achieved by close cooperation between gynecologists, radiotherapists and interventional radiologists.

Small renal carcinoma: the "when" and "how" of operation, active surveillance, and ablation.

Small, locally restricted renal cell carcinoma less than 4 cm in size should ideally be removed operatively by nephron-sparing tumour enucleation (partial kidney resection). In an increasingly elderly population, there is a growing trend toward parallel incidence of renal cell carcinoma and chronic renal insufficiency, with the latter's associated general comorbidities. Thus, for some patients, the risks of the anaesthesia and operation increase, while the advantage in terms of survival decreases. Transcutaneous radio-frequency ablation under local anaesthesia, transcutaneous afterloading high-dose-rate brachytherapy under local anaesthesia, and percutaneous stereotactic ablative radiotherapy may offer a less invasive alternative therapy. Active surveillance is to be regarded as no more than a controlled bridging up to definitive treatment (operation or ablation), while watchful waiting, on account of the lack of prognostic relevance and the symptomatology of renal cell carcinoma, with its comorbidity-related, clearly reduced life expectancy, does not involve any further diagnostic or therapeutic measures.

Improvement of image quality and dose management in CT fluoroscopy by iterative 3D image reconstruction.

OBJECTIVES: The objective of this study was to assess the influence of an iterative CT reconstruction algorithm (IA), newly available for CT-fluoroscopy (CTF), on image noise, readers' confidence and effective dose compared to filtered back projection (FBP). METHODS: Data from 165 patients (FBP/IA = 82/74) with CTF in the thorax, abdomen and pelvis were included. Noise was analysed in a large-diameter vessel. The impact of reconstruction and variables (e.g. X-ray tube current I) influencing noise and effective dose were analysed by ANOVA and a pairwise t-test with Bonferroni-Holm correction. Noise and readers' confidence were evaluated by three readers. RESULTS: Noise was significantly influenced by reconstruction, I, body region and circumference (all p ≤ 0.0002). IA reduced the noise significantly compared to FBP (p = 0.02). The effect varied for body regions and circumferences (p ≤ 0.001). The effective dose was influenced by the reconstruction, body region, interventional procedure and I (all p ≤ 0.02). The inter-rater reliability for noise and readers' confidence was good (W ≥ 0.75, p < 0.0001). Noise and readers' confidence were significantly better in AIDR-3D compared to FBP (p ≤ 0.03). Generally, IA yielded a significant reduction of the median effective dose. CONCLUSION: The CTF reconstruction by IA showed a significant reduction in noise and effective dose while readers' confidence increased. KEY POINTS: • CTF is performed for image guidance in interventional radiology. • Patient exposure was estimated from DLP documented by the CT. • Iterative CT reconstruction is appropriate to reduce image noise in CTF. • Using iterative CT reconstruction, the effective dose was significantly reduced in abdominal interventions.

Hepatopulmonary shunting after surgical, interventional and systemic therapy in patients with liver malignancies scheduled for radioembolization.

BACKGROUND: Hepatopulmonary shunts (HPS) lead to radiation exposure of the lungs in patients undergoing radioembolization (RE) of malignant liver tumors. PURPOSE: To retrospectively analyze how HPS is affected by prior systemic or local therapy of the liver. MATERIAL AND METHODS: The percentage HPS was calculated from SPECT/CT scans obtained after technetium-99 m macroaggregated albumin administration into hepatic arteries in 316 patients evaluated for RE. RESULTS: Patients with partial liver resection (n = 80) did not differ in HPS from the remaining patient population (n = 236) (HPS (median [range]) = 10.2 [2.1-48.3]resection% vs. 8.9 [2.3-32.9]no resection%; P = 0.527). In patients undergoing sequential RE, HPS was significantly higher in the liver lobe treated second (n = 10; HPS = 6.4 [2.1-10.2]firstlobe/session% vs. 12.0 [2.0-24.6]second lobe/session%; P = 0.019). (Chemo-)embolization (n = 19; HPS = 11.0 [2.8-48.3]%) or transcutaneous ablation (n = 63; HPS = 8.8 [3.0-32.9]%) had no effect on HPS compared to patients without prior interventions (no (chemo-)embolization: n = 297; HPS = 9.3 [2.1-47.3]%; P = 0.489; no ablation: n = 253; HPS = 9.5 [2.1-48.3]%; P = 0.382). Pretreatment with sorafenib (HPS = 9.5 [2.3-35.9]yes% vs. 10.2 [2.8-42.0]no%; P = 0.777) orbevacizumab (HPS = 10.7 [2.1-30.6]yes% vs. 9.0 [3.9-23.3]no%; P = 0.870) had no effect on HPS. CONCLUSION: Sequential RE results in an increase in the HPS in the contralateral liver lobe at the time of the second RE session. Other investigated therapy do not affect HPS.

Locally ablative treatment of breast cancer liver metastases: identification of factors influencing survival (the Mammary Cancer Microtherapy and Interventional Approaches (MAMMA MIA) study).

BACKGROUND: Liver metastases from breast cancer (LMBC) are typically considered to indicate systemic disease spread and patients are most often offered systemic palliative treatment only. However, retrospective studies suggest that some patients may have improved survival with local treatment of their liver metastases compared to systemic therapy alone. In the absence of randomized trials, it is important to identify patient characteristics indicating that benefit from local treatment can be expected. METHODS: 59 patients undergoing radiofrequency ablation (RFA), interstitial brachytherapy (BT), or radioembolization (RE) of LMBC as a salvage treatment were studied. Potential factors influencing survival were analyzed in a multivariate Cox model. For factors identified to have an independent survival impact, Kaplan-Meier analysis and comparison of overall survival (OS) using the log-rank test was performed. RESULTS: Median OS following local interventional treatment was 21.9 months. Considering only factors evaluable at treatment initiation, maximum diameter of liver metastases (≥3.9 cm; HR: 3.1), liver volume (≥ 1376 mL; HR: 2.3), and history of prior chemotherapy (≥ 3 lines of treatment; HR: 2.5-2.6) showed an independent survival impact. When follow-up data were included in the analysis, significant factors were maximum diameter of liver metastases (≥ 3.9 cm; HR: 3.1), control of LMBC during follow-up (HR: 0.29), and objective response as best overall response (HR: 0.21). Neither the presence of any extrahepatic metastases nor presence of bone metastases only had a significant survival impact. Median OS was 38.7 vs. 16.1 months in patients with metastases < vs. ≥ 3.9 cm, 36.6 vs. 10.2 months for patients having objective response vs. stable/progressive disease, and 38.5 vs. 14.2 months for patients having controlled vs. non-controlled disease at follow-up. CONCLUSION: Local control of LMBC confers a survival benefit and local interventional treatment for LMBC should be studied in a randomized trial. Patients with small metastases and limited history of systemic LMBC treatment are most likely to benefit from local approaches. Limited extrahepatic disease should not lead to exclusion from a randomized study and should not be a contraindication for local LMBC treatment as long as no randomized data are available.

Anatomic variants of arteries often coil-occluded prior to hepatic radioembolization.

BACKGROUND: Prior to radioembolization (RE) treatment of malignant liver lesions, many interventionalists occlude the right gastric artery (RGA), the cystic artery (CA), and the gastroduodenal artery (GDA) to prevent radioactive microspheres from entering non-target vessels. PURPOSE: To systematically analyze anatomic variants of arteries that are important to know for the interventional radiologist performing RE of the liver. MATERIAL AND METHODS: The computed tomography (CT) angiographies and conventional angiographies of 166 patients evaluated for RE were retrospectively analyzed for the presence of anatomic variants of the RGA, GDA, and CA. RESULTS: The RGA was found to arise from the left hepatic artery in 42% of cases, from the proper hepatic artery in 40%, from the GDA in 10%, from the right hepatic artery in 4%, and from the common hepatic artery in 3% of cases. The GDA originated in the common hepatic artery in 97% of cases, in the left hepatic artery in 2%, and in the celiac trunk in 1% of cases. The CA arose from the right hepatic artery in 96% of cases and from the GDA in 2% of cases; in 2% of our study population, the gallbladder was supplied by small branches from the liver parenchyma. CONCLUSION: Variant anatomy of the RGA is common, while it is quite rare for the GDA and CA. Knowledge of the variations of liver supplying arteries helps the interventionalist to embolize necessary vessels prior to RE.

Uterine artery embolization in single symptomatic leiomyoma: do anatomical imaging criteria predict clinical presentation and long-term outcome?

BACKGROUND: Uterine artery embolization (UAE) has proven to be an effective treatment alternative for women suffering from symptomatic uterine leiomyomas. However, long-term clinical evaluation reveals treatment failure in approximately 25% of patients. To cope with the great variability in the extent of leiomyoma disease former studies are based on the simplifying assumption that the largest leiomyoma mainly causes the symptoms. PURPOSE: To evaluate whether anatomical characteristics in women with a single symptomatic leiomyoma influence clinical presentation and outcome after UAE. MATERIAL AND METHODS: Ninety-one patients with a single leiomyoma underwent UAE. Age, uterine and fibroid volume, fibroid location, and clinical symptoms (bleeding- and/or bulk-related symptoms) were documented. The need for reinterventions (i.e. repeat UAE, hysterectomy, myomectomy) and unchanged or worsened symptoms after UAE were classified as treatment failure (TF). Contrast-enhanced magnetic resonance imaging (MRI) 48-72 h after UAE was available in 38 women. The rate of fibroid infarction was determined and patients were assigned to one of three groups: complete (100%), almost complete (90-99%), or partial infarction (<90%). Cox regression analysis (CRA) was used to determine the influence of morphological and clinical parameters on outcome. RESULTS: Follow-up was available in 79/91 (87%) women (median age, 42 years; range, 33-56 years) at a median of 5 years (range, 3.1-9.2 years) after UAE. Anatomical leiomyoma criteria neither connected to specific clinical presentation nor influenced clinical outcome. Younger women showed a higher risk for TF with every year older lowering the risk by the factor of 0.86 (P = 0.024). Subgroup analysis showed predictive value of fibroid infarction with a cumulative survival free from TF of 91% for complete vs. 0% for partial infarction (P < 0.001). CONCLUSION: Even in women with single leiomyomas, anatomical criteria do not specify clinical presentation or predict clinical outcome. Younger patient age and incomplete fibroid infarction relate to higher rates of TF.

Clinical long-term outcome after uterine artery embolization: sustained symptom control and improvement of quality of life.

PURPOSE: To evaluate long-term clinical efficacy of uterine artery embolization (UAE) for uterine fibroids with respect to symptom control and improvement in quality of life. MATERIALS AND METHODS: Between October 2000 and October 2007, 380 consecutive women underwent UAE. To determine long-term efficacy, the rate of reinterventions (ie, repeat UAE, hysterectomy, myomectomy) and the clinical response regarding symptoms related to bleeding and bulk were documented. Persistence, worsening, or recurrence of symptoms and reinterventions were classified as treatment failure (TF). The cumulative rate of freedom from TF was determined by Kaplan-Meier analysis. Cox regression was used to identify possible clinical or morphologic predictors of outcome. Secondary outcome measures were changes in disease-specific quality of life and onset of menopause. RESULTS: Follow-up was available for a median of 5.7 years (range, 3.1-10.1 y) after treatment in 304 of 380 (80%) patients. There were 54 TFs with subsequent reintervention in 46 women. Kaplan-Meier analysis revealed a cumulative TF rate of 23.3% after 10 years. Cox regression demonstrated a significantly higher likelihood of TF in patients<40 years old compared with patients>45 years old (hazard ratio, 2.28; P = .049). Women without TF showed sustained normalization of disease-specific quality of life (P <.001). Cessation of menstruation at a median age of 51 years was reported by 57 (22.8%) of 250 women. CONCLUSIONS: UAE leads to long-term control of fibroid-related symptoms and normalization of quality of life in approximately 75% of patients. Younger women seem to have a higher risk of TF than older women closer to menopause.

Local tumor control of intermediate and advanced stage hepatocellular carcinoma after local ablative treatment with image-guided interstitial high-dose-rate brachytherapy: A subgroup analysis of 286 HCC nodules.

PURPOSE: Image-guided interstitial high-dose-rate brachytherapy (iBT) has been demonstrated to offer high local tumor control rates (LTC) of >90% after local ablation of intermediate and advanced hepatocellular carcinoma (HCC; BCLC B and C). The purpose of this study was to show the efficacy of iBT stratified by subgroups and to identify clinical characteristics associated with superior local tumor control (LTC) based on a highly heterogenous patient population METHODS AND MATERIALS: A cumulative number of 286 HCC nodules in 107 patients were retrospectively analyzed. Clinical and imaging follow-ups were conducted every 3 months after treatment. Analyzed clinical factors were: etiology, presence of liver cirrhosis, radiographic features, lesion size, pretreatment, administered dose, presence of portal hypertension, portal vein thrombosis, and level of alpha-fetoprotein (AFP). RESULTS: LTC rate was 88.8% for a median follow-up of 14.3 months (range 3-81 months; 95% CI: 85-92%). Median minimal enclosing tumor dose (D100) was 16.1 Gy (range 7.1-30.3 Gy; reference dose 15 Gy). Subgroup analysis showed significant fewer local recurrences for alcoholic liver disease (ALD)-related HCCs compared to those related to other causes of liver cirrhosis (nonalcoholic fatty liver disease, virus-related liver cirrhosis and other causes) (p = 0.015). LTC was significantly lower after prior surgical resection (p = 0.046). No significant variance was observed for the applied D100 in each group or for all other clinical factors tested. CONCLUSIONS: IBT achieves high LTC rates across treated subgroups. However, further studies should particularly address the possible impact of underlying etiology on local recurrence with emphasis on a possible higher radiosensitivity of ALD-related HCCs.

Feasibility of fast dynamic MRI for noninvasive monitoring during ectopic liver cell transplantation to the spleen in a porcine model.

OBJECTIVE: Liver cell transplantation is a promising approach for the treatment of metabolic liver disorders. However, a method for noninvasive monitoring during liver cell transplantation is not available clinically. The aim of this study was to investigate the feasibility of fast dynamic MRI monitoring during liver cell infusion to the spleen, which is considered an ectopic implantation site for liver cell transplantation. MATERIALS AND METHODS: Porcine liver cells were labeled with micron-sized iron oxide particles and infused to the spleens of pigs (n = 5) via the lineal artery. MRI was performed using a 3-T MR scanner. Initially, T1- and T2-weighted pulse sequences were tested. Thereafter, fast dynamic MRI was performed during cell infusion. MR findings were verified by immunohistological examinations. RESULTS: Images from static MRI (TR/TE, 2500/105.2) showed significantly lower signal intensity and signal-to-noise ratio after cell infusion compared with pretransplant images. T2-weighted fast dynamic MRI enabled visualization of signal decrease of the spleen during cell infusion. When cells were infused systemically, no signal changes in the spleen were observed. CONCLUSION: This study shows that fast dynamic MRI can enable noninvasive monitoring during liver cell transplantation to the spleen. This approach could be useful for preclinical studies and for quality control of clinical liver cell transplantation.

Radioablation of Upper Abdominal Malignancies by CT-Guided, Interstitial HDR Brachytherapy: A Multivariate Analysis of Catheter Placement Assisted by Ultrasound Imaging.

PURPOSE: To evaluate the use of ultrasound (US) during catheter placement in interstitial brachytherapy (iBT) of abdominal malignancies as an alternative to computed tomography (CT) fluoroscopy. MATERIALS AND METHODS: Catheter placement for CT-guided iBT was, if US visibility was sufficient, assisted by sonography in 52 consecutive patients with 82 lesions (liver N = 62; kidney N = 16; peritoneum N = 4) of various malignancies. We collected data on lesion visibility, location, depth, size, and dosimetry. Comparison of CT fluoroscopy versus US-assisted catheter placement was performed by Fisher's exact test for frequencies and U-test for lesion visibility and dosimetric data. Factors predicting the utility of sonography were determined in a lesion-based multivariate regression analysis. A p-value < 0.05 was regarded as statistically significant. RESULTS: 150 catheters (1 to 6 per lesion; mean diameter 3.6 ±â€Š2.4 cm) were implanted. CT fluoroscopy was used for 44 catheters, and US was used for 106 catheters. Lesion visibility assessed by 5-point Likert scale was significantly better in US (median 2 vs. 3; p = 0.011) and effective dose was significantly reduced if US guidance was applicable (median 1.75 vs. 8.19 mSv; p = 0.014). In a multivariate regression analysis, we identified increased lesion size and caudal location within the target organ to independently predict the utility of ultrasound in catheter placement for iBT. CONCLUSION: Sonography is a helpful technique to assist CT-guided interstitial brachytherapy of upper abdominal malignancies. Especially for larger lesions localized in the lower liver segments or lower half of the kidney, superior visibility can be expected. As the effective dose of the patient is also reduced, radiation exposure of the medical staff may be indirectly lowered. KEY POINTS: · Ultrasound-assisted catheter placement in CT-guided brachytherapy of upper abdominal malignancies significantly improves lesion visibility.. · Predictors of successful ultrasound application are larger lesions within the lower portion of the liver and kidney.. · By reducing the need for CT fluoroscopy during intervention, radiation exposure to the medical staff may be indirectly lowered.. CITATION FORMAT: · Damm R, Damm R, Heinze C et al. Radioablation of Upper Abdominal Malignancies by CT-Guided, Interstitial HDR Brachytherapy: A Multivariate Analysis of Catheter Placement Assisted by Ultrasound Imaging. Fortschr Röntgenstr 2022; 194: 62 - 69.

Reduced phagocytosis, ROS production and enhanced apoptosis of leukocytes upon alcohol drinking in healthy volunteers.

BACKGROUND: Alcohol drinking is associated with a serious risk of developing health problems as well as with a large number of traumatic injuries. Although chronic alcohol misuse is known to contribute to severe inflammatory complications, the effects of an acute alcohol misuse are still unclear. Here, the impact of acute alcohol drinking on leukocyte counts and their cellular functions were studied. METHODS: Twenty-two healthy volunteers (12 female, 10 male) received a predefined amount of a whiskey-cola mixed drink (40% v/v), at intervals of 20 min, over 4 h to achieve a blood alcohol concentration of 1‰. Blood samples were taken before drinking T0, 2 h (T2), 4 h (T4), 6 h (T6), 24 h (T24) and 48 h (T48) after starting drinking alcohol. Leukocytes, monocytes and granulocyte counts and their functions regarding the production of reactive oxidative species (ROS), phagocytosis and apoptosis were analyzed by flow cytometry. RESULTS: Total leukocyte counts significantly increased at T2 and T4, while granulocyte and monocyte counts decreased at T4 and T6 vs. T0. Monocytes increased significantly at T24 and T48 vs. T0. While the total number of ROS-producing leukocytes and notably granulocytes significantly increased, in parallel, the intracellular ROS intensity decreased at T2 and T6. The numbers of ROS-positive monocytes have shown a delayed modulation of ROS, with a significant reduction in the total number of ROS-producing cells at T48 and a significantly reduced intracellular ROS-intensity at T24. Phagocyting capacity of leukocytes significantly decreased at T4 and T6. In general leukocytes, and notably granulocytes demonstrated significantly increased early (T2), while monocyte exerted significantly increased late apoptosis (T24 and T48). CONCLUSIONS: Alcohol drinking immediately impacts leukocyte functions, while the impact on monocytes occurs at even later time points. Thus, even in young healthy subjects, alcohol drinking induces immunological changes that are associated with diminished functions of innate immune cells that persist for days.

LiMAx Prior to Radioembolization for Hepatocellular Carcinoma as an Additional Tool for Patient Selection in Patients with Liver Cirrhosis.

BACKGROUND AND AIMS: Radioembolization (RE) has recently demonstrated a non-inferior survival outcome compared to systemic therapy for advanced hepatocellular carcinoma (HCC). Therefore, current guidelines recommend RE for patients with advanced HCC and preserved liver function who are unsuitable for transarterial chemoembolization (TACE) or systemic therapy. However, despite the excellent safety profile of RE, post-therapeutic hepatic decompensation remains a serious complication that is difficult to predicted by standard laboratory liver function parameters or imaging modalities. LiMAx® is a non-invasive test for liver function assessment, measuring the maximum metabolic capacity for 13C-Methacetin by the liver-specific enzyme CYP 450 1A2. Our study investigates the potential of LiMAx® for predicting post-interventional decompensation of liver function. PATIENTS AND METHODS: In total, 50 patients with HCC with or without liver cirrhosis and not amenable to TACE or systemic treatments were included in the study. For patients prospectively enrolled in our study, LiMAx® was carried out one day before RE (baseline) and 28 and 90 days after RE. Established liver function parameters were assessed at baseline, day 28, and day 90 after RE. The relationship between baseline LiMAx® and pre-and post-interventional liver function parameters, as well as the ability of LiMAx® to predict hepatic decompensation, were analyzed. RESULTS: We observed a strong association between baseline LiMAx® and bilirubin, albumin, ALBI grade, and MELD score. Patients presenting with Child-Pugh score B 28 days after RE or with a deterioration in Child-Pugh score by at least one point had a significantly lower baseline LiMAx® compared to those with Child-Pugh score A or with stable Child-Pugh score. The ability of LiMAx® to predict hepatic decompensation after RE was determined using ROC curve analysis and was compared to MELD score and ALBI grade. LiMAx® achieved a substantial AUC of 0.8117, comparable to MELD score and ALBI grade. CONCLUSION: Patients with lower LiMAx® values at baseline have a significantly increased risk for hepatic decompensation after RE, despite being categorized as Child-Pugh A. Therefore, LiMAx® can be used as an additional tool to identify patients at high risk of post-interventional hepatic failure.

Systemic transplantation of progenitor cells accelerates wound epithelialization and neovascularization in the hairless mouse ear wound model.

BACKGROUND: Impaired wound healing due to local injury, infection, or systemic diseases, such as diabetes, is a major clinical problem. Recent studies have shown that endothelial progenitor cells (EPC) isolated from peripheral blood, bone marrow, as well as the spleen accumulate in granulation tissue at the site of neovascularization, causing secretion of growth factors and cytokines and thus accelerating wound healing. MATERIALS AND METHODS: In the present study, we transplanted systemic EPC and then measured epithelialization and neovascularization in the hairless mouse ear wound model. RESULTS: Systemic EPC transplantation significantly accelerated epithelialization and neovascularization compared with control wounds receiving phosphate-buffered saline without calcium and magnesium (PBS). The EPC group had significantly higher vascular density than did the PBS-treated group as determined by immunohistochemistry for CD31 and CD90. Fluorescence microscopy revealed accumulation "homing" of the transplanted EPC at the sites of neovascularization in the granulation tissue throughout healing. Furthermore, transplantation of EPC also increased the expression of the angiogenic cytokine stromal cell-derived factor 1α (SDF1α). CONCLUSIONS: This appears to be the first demonstration of EPC recruitment to the site of wound neovascularization throughout the healing process. These findings demonstrate that transplanting systemic EPC into "normal" healing wounds promotes epithelialization and neovascularization and thus could be an useful method for accelerating wound healing.