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.

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.

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.

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.

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.

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.

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.

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.

Anti-inflammatory Effects of Alcohol Are Associated with JNK-STAT3 Downregulation in an In Vitro Inflammation Model in HepG2 Cells.

BACKGROUND: In several preclinical and in vitro models of acute inflammation, alcohol (ethanol, EtOH) has been described as an immunomodulatory agent. Similarly, in different pathologies, clinical observations have confirmed either pro- or anti-inflammatory effects of EtOH. The liver plays an important role in immunity and alcohol metabolism; therefore, we analysed dose- and time-dependent effects of EtOH on the inflammatory response of human liver cells in an in vitro model of acute inflammation. METHODS: HepG2 cells were stimulated with IL-1ß and subsequently exposed to EtOH in a low or high dose (85 mM, LoD or 170 mM, HiD) for 1 h (acute exposure) or 72 h (prolonged exposure). IL-6 and TNF-α release was determined by ELISA. Cell viability, adhesion of isolated neutrophils to HepG2 monolayers, their ICAM-1 expression, and the activation of stress-induced protein kinase/c-Jun N-terminal kinase (SAPK/JNK) or signal transducer and activator of transcription 3 (STAT3) were analysed. RESULTS: In this experimental design, EtOH did not markedly change the cell viability. Acute and prolonged exposure to EtOH significantly reduced dose-independent IL-1ß-induced IL-6 and TNF-α release, as well as adhesion capacity to pretreated HepG2 cells. Acute exposure to EtOH significantly decreased the percentage of ICAM-1-expressing cells. IL-1ß stimulation notably increased the activation of SAPK/JNK. However, low-dose EtOH exposure reduced this activation considerably, in contradiction to high-dose EtOH exposure. Acute exposure to LoD EtOH significantly diminished the IL-1ß-induced STAT3 activation, whereas an acute exposure of cells to either HiD EtOH or in a prolonged setting showed no effects on STAT3 activation. CONCLUSION: EtOH exerts anti-inflammatory potential in this in vitro model of hepatic inflammation. These effects are associated with the reduced activation of JNK/STAT3 by EtOH, particularly in the condition of acute exposure to low-dose EtOH.

Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization.

BACKGROUND: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8-86.8) vs. 40.2 Gy (12.5-83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 µmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

Diffusion-Weighted Imaging Reflects Tumor Grading and Microvascular Invasion in Hepatocellular Carcinoma.

BACKGROUND: To date, there are inconsistent data about relationships between diffusion-weighted imaging (DWI) and tumor grading/microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Our purpose was to systematize the reported results regarding the role of DWI in prediction of tumor grading/MVI in HCC. METHOD: MEDLINE library, Scopus, and Embase data bases were screened up to December 2019. Overall, 29 studies with 2,715 tumors were included into the analysis. There were 20 studies regarding DWI and tumor grading, 8 studies about DWI and MVI, and 1 study investigated DWI, tumor grading, and MVI in HCC. RESULTS: In 21 studies (1,799 tumors), mean apparent diffusion coefficient (ADC) values (ADCmean) were used for distinguishing HCCs. ADCmean of G1-3 lesions overlapped significantly. In 4 studies (461 lesions), minimum ADC (ADCmin) was used. ADCmin values in G1/2 lesions were over 0.80 × 10-3 mm2/s and in G3 tumors below 0.80 × 10-3 mm2/s. In 4 studies (241 tumors), true diffusion (D) was reported. A significant overlapping of D values between G1, G2, and G3 groups was found. ADCmean and MVI were analyzed in 9 studies (1,059 HCCs). ADCmean values of MIV+/MVI- lesions overlapped significantly. ADCmin was used in 4 studies (672 lesions). ADCmin values of MVI+ tumors were in the area under 1.00 × 10-3 mm2/s. In 3 studies (227 tumors), D was used. Also, D values of MVI+ lesions were predominantly in the area under 1.00 × 10-3 mm2/s. CONCLUSION: ADCmin reflects tumor grading, and ADCmin and D predict MVI in HCC. Therefore, these DWI parameters should be estimated for every HCC lesion for pretreatment tumor stratification. ADCmean cannot predict tumor grading/MVI in HCC.

Liver Function Changes After Technetium-99m-Macroaggregated Albumin Administration and Their Predictive Value Regarding Hepatotoxicity in Patients Undergoing Yttrium-90-Radioembolization.

BACKGROUND/AIM: Intraarterial Technetium-99m-Macroaggregated Albumin (99mTc-MAA) administration is an established method to predict particle distribution prior to radioembolization. This study aimed to analyse the impact of intraarterial administration of 99mTc-MAA on changes in liver-specific laboratory parameters and to assess whether such changes are associated with post-radioembolization hepatotoxicity. PATIENTS AND METHODS: A total of 202 patients treated with radioembolization received prior mapping angiography with 99mTc-MAA administration. All patients underwent clinical and laboratory examinations, including liver-specific parameters at certain times before and after mapping angiography/99mTc-MAA administration, as well as before radioembolization and during follow-up. RESULTS: Bilirubin increased temporarily after 99mTc-MAA administration (p<0.001), but was not clinically relevant, and returned close to the initial value before radioembolization. These changes showed no association with subsequent postradioembolic hepatotoxicity or shortened overall survival. CONCLUSION: 99mTc-MAA administration results in a significant, however, not clinically relevant transient increase in bilirubin levels, which does not provide a predictive value for subsequent radioembolization outcome or postradioembolic hepatotoxicity.

Associations between IVIM histogram parameters and histopathology in rectal cancer.

PURPOSE: Histogram analysis can better reflect tumor heterogeneity than conventional imaging analysis. The present study analyzed possible correlations between histogram analysis parameters derived from Intravoxel-incoherent imaging (IVIM) and histopathological features in rectal cancer (RC). METHODS: Seventeen patients with histopathologically proven rectal adenocarcinomas were retrospectively acquired. In all cases, pelvic MRI was performed. Diffusion weighted imaging was obtained using a multi-slice single-shot echo-planar imaging sequence with b values of 0, 50, 200, 500 and 1000 s/mm2. Simplified IVIM analysis was performed using the IntelliSpace portal, version 10 and the following images were generated: f (perfusion fraction) map, D (true diffusion coefficient) map, and ADC map utilizing all b-values. Histogram based analysis of signal intensities was performed for every IVIM map using an in-house matlab tool. Histopathology was investigated using Ki 67 specimens with calculation of Ki 67-index and cellularity. CD31 stained specimens were used for calculation of microvessel density (MVD). RESULTS: There were statistically significant correlations between Ki 67 index and mode derived from ADC as well as entropy from f, r=-0.50, p=.04 and r=-0.55, p=.02, respectively. MVD correlated well with parameters derived from f. CONCLUSION: IVIM histogram analysis parameters can reflect histopathology in RC. ADC and D values are associated with proliferation potential. Perfusion fraction f is associated with MVD.

The Impact of Unilateral 90Y-radioembolization on Functional Changes in the Contralateral Hepatic Lobe: The Prospective, Open-label RadioEmbolization, Volumetry, and Liver FuncTion Measurements (REVoluTion) Study.

Objectives: To investigate how metabolic function of the contralateral liver lobe is affected by unilateral radioembolization (RE), and to compare the changes in volume and metabolic function. Background: Unilateral RE induces contralateral liver hypertrophy, but it is unknown if metabolic liver function improves in line with volume increases. Methods: This prospective open-label, nonrandomized, therapy-optimizing study included all consecutive patients undergoing right-sided or sequential 90Y-RE for liver malignancies without underlying liver disease or biliary obstruction at a single center in Germany. Magnetic resonance imaging volumetry and hepatobiliary scintigraphy were performed immediately before RE and approximately 6 weeks after RE. Results: Twenty-three patients were evaluated (11 metastatic colorectal cancer, 4 cholangiocellular carcinoma, 3 metastatic breast cancer, 1 each of metastatic neuroendocrine tumor, hepatocellular carcinoma, renal cell carcinoma, oesophageal cancer, pancreatic ductal adenocarcinoma). In the untreated contralateral left liver lobe, mean (SD) metabolic function significantly increased from 1.34 (0.76) %/min/m2 at baseline to 1.56 (0.75) %/min/m2 6 weeks after RE (P = 0.024). The mean (SD) functional volume (liver volume minus tumor volume) of the left liver lobe significantly increased from baseline (407.3 [170.3] mL) to follow-up (499.1 [209.8] mL; P < 0.01), with an equivalent magnitude to the metabolic function increase. There were no reports of grade ≥3 adverse events. Conclusion: This study indicates that unilobar RE produces a significant increase in the metabolic function, and equivalent volume increase, of the contralateral lobe. RE may be a useful option to induce hypertrophy of the future liver remnant before surgical resection of primary or secondary liver malignancies.

Apparent Diffusion Coefficient Can Predict Response to Chemotherapy of Liver Metastases in Colorectal Cancer.

RATIONALE AND OBJECTIVES: The aim of this meta-analysis was to evaluate the suitability of apparent diffusion coefficient (ADC) as a predictor of response to systemic chemotherapy in patients with metastatic colorectal carcinoma (CRC). MATERIALS AND METHODS: MEDLINE library, SCOPUS database, and EMBASE database were screened for relationships between pretreatment ADC values of hepatic CRC metastases and response to systemic chemotherapy. Overall, five eligible studies were identified. The following data were extracted: authors, year of publication, study design, number of patients, mean value ADC and standard-deviation, measure method, b-values, and Tesla-strength. The methodological quality of every study was checked according to the Quality Assessment of Diagnostic Studies-2 instrument. The meta-analysis was undertaken by employing RevMan 5.3 software. DerSimonian and Laird random-effects models with inverse-variance weights were used to account for heterogeneity. Mean ADC values including 95% confidence intervals were calculated. RESULTS: Five studies (n = 114 patients) were included. The pretreatment mean ADC in the responder group was 1.15 × 10-3 mm2/s (1.03, 1.28) and 1.37 × 10-3 mm2/s (1.3, 1.44) in the nonresponder group. An ADC baseline threshold of 1.2 × 10-3 mm2/s, below which no nonresponder was found, can distinguish both groups. CONCLUSION: The results indicate ADC can serve as a predictor of response to chemotherapy for CRC patients.

Radiation-induced damage in the upper gastrointestinal tract: clinical presentation, diagnostic tests and treatment options.

Radiation-induced damage of the upper gastrointestinal (GI) tract results from radiation of GI tumors or structures adjacent to the GI tract. Radiation-induced damages of the upper GI tract may be acute or delayed, and ranges from lack of appetite, mucosal inflammation (i.e. esophagitis, gastritis, duodenitis) to ulcers, which may be complicated by perforation, penetration, bleeding and stenosis. Radiation-related factors as well as individual patient predisposing factors may increase susceptibility to post-radiation damage. High quality evidence for the treatment of radiation-induced GI damage is scarce and the management is often extrapolated from studies on GI lesions of different etiology. Treatment depends on severity and localization of the radiation-induced damage, and ranges from supportive and dietary measures to endoscopic interventions or surgery. Modern radiation techniques may decrease the incidence and severity of the radiation-induced upper gastrointestinal disease.

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.

Efficacy and safety of guidewireless catheterization with a steerable microcatheter in patients scheduled for yttrium-90 radioembolization: a prospective multicenter trial.

INTRODUCTION: A steerable, guidewireless microcatheter is of interest to interventional radiologists because it can improve effectiveness and reduce procedure timing and cost. AIM: To assess the feasibility and safety of yttrium 90 radioembolization with a new steerable microcatheter without the need to use a guidewire. MATERIAL AND METHODS: A steerable microcatheter (Direxion; Boston Scientific, Natick, MA, USA) was prospectively used for yttrium-90 microsphere delivery in 50 patients (57 applications). The following factors were documented: vessel anatomy; shape and position of the guiding catheter; anticipated catheter position; technical success of catheterization; degree of difficulty in maneuvering; time to reach the target position; and complications. RESULTS: The microcatheter target position was in the right hepatic artery (n = 30, 53%), the middle hepatic artery (n = 4, 7%), the left hepatic artery (n = 19, 33%), or in a segmental artery (n = 4, 7%). Vessel catheterization was successful in 53 of 57 hepatic arteries (93%). The mean time to reach the target position was 53.3 ±53.0 s. The mean degree of difficulty in maneuvering the catheter to the target position was 2.3 ±1.3 (easy) on a 6-point scale. The only complication observed was mild vasospasm in 1 patient. CONCLUSIONS: The Direxion steerable microcatheter is characterized by unique steerability, allowing yttrium 90 delivery to be performed safely without use of a guidewire.

Intra-hepatic Abscopal Effect Following Radioembolization of Hepatic Metastases.

PURPOSE: To search for abscopal effects (AE) distant to the site of radiation after sequential Yittrium-90 (Y-90) radioembolization (RE) of liver malignancies. METHODS AND MATERIALS: In this retrospective analysis, all patients treated by RE between 2007 and 2018 (n = 907) were screened for the following setting/conditions: sequential RE of left and right liver lobe in two sessions, liver-specific MRI (MRI1) acquired max. 10 days before or after first RE (RE1), liver-specific MRI (MRI2) acquired with a minimum time interval of 20 days after MRI1, but before second RE (RE2). No systemic tumor therapies between MRI1 and MRI2. No patients with liver cirrhosis. Metastases > 5 mm in untreated liver lobes were compared in MRI1 and MRI2 and rated as follows: same size or larger in MRI2 = no abscopal effect (NAE); > 30% shrinkage without Y-90 contamination in SPECT/CT = abscopal effect (AE). RESULTS: Ninety six of 907 patients met aforementioned criteria. Median time-frame between RE1 and MRI2 was 34 (20-64) days. These 96 cases had 765 metastases which were evaluable (median 5(1-40) metastases per patient). Four patients could be identified with at least one shrinking metastasis of the untreated site: one patient with breast cancer (3 metastases: 0 NAE; 3 AE), one patient with prostate cancer (6 metastases: 3 NAE; 3 metastases > 30% shrinkage but possible Y-90 contamination) and two patients with shrinkage of one metastasis each but less than 30%. CONCLUSION: Our retrospective study documents AE after RE of liver tumors in 1 out of 96 cases, 3 other cases remain unclear.

Interstitial Brachytherapy for Limited (<4 cm) and Large (≥4 cm) Hepatic Metastases from Rare and Less Common Cancers.

BACKGROUND/AIM: Interstitial brachytherapy (iBT) seems to achieve higher local tumor control rates for lesions limited in size. The objective was to evaluate the efficacy and safety of iBT in the treatment of limited and large liver metastases from rare or less common cancers (RLCC). PATIENTS AND METHODS: A total of 194 unresectable liver metastases categorized as limited (<4 cm, n=153, subgroup A) and large lesions (≥4 cm, n=41, subgroup B) were treated. Clinical and image-based follow-up was conducted every 3 months after iBT. RESULTS: Cumulative local recurrence (CLR) rate was 9.8% (19 recurrences; A: n=16; B: n=3). No significant difference in CLR was noted between subgroup A and B (A:10.5%, B:7.3%, p=0.339). Median follow-up was 6.2 months (range=2.2-92.9 months). Complication assessment revealed 5 severe adverse events (grade 3: 4.3%, grade 4 and 5: 0%) with 4 events in A and 1 event in B. CONCLUSION: IBT is a feasible, effective, and safe minimally invasive treatment for small and large liver metastases from RLCC.