Von Willebrand Factor Antigen Improves Risk Stratification for Patients with a Diagnosis of Resectable Hepatocellular Carcinoma.

BACKGROUND: Posthepatectomy liver failure (PHLF), complications of portal hypertension, and disease recurrence determine the outcome for hepatocellular carcinoma (HCC) patients undergoing liver resection. This study aimed to evaluate the von Willebrand factor antigen (vWF-Ag) as a non-invasive test for clinically significant portal hypertension (CSPH) and a predictive biomarker for time to recurrence (TTR) and overall survival (OS). METHODS: The study recruited 72 HCC patients with detailed preoperative workup from a prospective trial (NCT02118545) and followed for complications, TTR, and OS. Additionally, 163 compensated patients with resectable HCC were recruited to evaluate vWF-Ag cutoffs for ruling out or ruling in CSPH. Finally, vWF-Ag cutoffs were prospectively evaluated in an external validation cohort of 34 HCC patients undergoing liver resection. RESULTS: In receiver operating characteristic (ROC) analyses, vWF-Ag (area under the curve [AUC], 0.828) was similarly predictive of PHLF as indocyanine green clearance (disappearance rate: AUC, 0.880; retention rate: AUC, 0.894), whereas computation of future liver remnant was inferior (AUC, 0.756). Cox-regression showed an association of vWF-Ag with TTR (per 10%: hazard ratio [HR], 1.056; 95% confidence interval [CI] 1.017-1.097) and OS (per 10%: HR, 1.067; 95% CI 1.022-1.113). In the analyses, VWF-Ag yielded an AUC of 0.824 for diagnosing CSPH, with a vWF-Ag of 182% or lower ruling out and higher than 291% ruling in CSPH. Therefore, a highest-risk group (> 291%, 9.7% of patients) with a 57.1% incidence of PHLF was identified, whereas no patient with a vWF-Ag of 182% or lower (52.7%) experienced PHLF. The predictive value of vWF-Ag for PHLF and OS was externally validated. CONCLUSION: For patients with resectable HCC, VWF-Ag allows for simplified preoperative risk stratification. Patients with vWF-Ag levels higher than 291% might be considered for alternative treatments, whereas vWF-Ag levels of 182% or lower identify patients best suited for surgery.

Ultra-low-dose vs. standard-of-care-dose CT of the chest in patients with post-COVID-19 conditions-a prospective intra-patient multi-reader study.

OBJECTIVES: To conduct an intrapatient comparison of ultra-low-dose computed tomography (ULDCT) and standard-of-care-dose CT (SDCT) of the chest in terms of the diagnostic accuracy of ULDCT and intrareader agreement in patients with post-COVID conditions. METHODS: We prospectively included 153 consecutive patients with post-COVID-19 conditions. All participants received an SDCT and an additional ULDCT scan of the chest. SDCTs were performed with standard imaging parameters and ULDCTs at a fixed tube voltage of 100 kVp (with tin filtration), 50 ref. mAs (dose modulation active), and iterative reconstruction algorithm level 5 of 5. All CT scans were separately evaluated by four radiologists for the presence of lung changes and their consistency with post-COVID lung abnormalities. Radiation dose parameters and the sensitivity, specificity, and accuracy of ULDCT were calculated. RESULTS: Of the 153 included patients (mean age 47.4 ± 15.3 years; 48.4% women), 45 (29.4%) showed post-COVID lung abnormalities. In those 45 patients, the most frequently detected CT patterns were ground-glass opacities (100.0%), reticulations (43.5%), and parenchymal bands (37.0%). The accuracy, sensitivity, and specificity of ULDCT compared to SDCT for the detection of post-COVID lung abnormalities were 92.6, 87.2, and 94.9%, respectively. The median total dose length product (DLP) of ULDCTs was less than one-tenth of the radiation dose of our SDCTs (12.6 mGy*cm [9.9; 15.5] vs. 132.1 mGy*cm [103.9; 160.2]; p < 0.001). CONCLUSION: ULDCT of the chest offers high accuracy in the detection of post-COVID lung abnormalities compared to an SDCT scan at less than one-tenth the radiation dose, corresponding to only twice the dose of a standard chest radiograph in two views. CLINICAL RELEVANCE STATEMENT: Ultra-low-dose CT of the chest may provide a favorable, radiation-saving alternative to standard-dose CT in the long-term follow-up of the large patient cohort of post-COVID-19 patients.

Imaging features facilitate diagnosis of porto-sinusoidal vascular disorder.

OBJECTIVES: Porto-sinusoidal vascular disorder (PSVD) is a recently defined vascular liver disease. Since diagnosis remains challenging, we aimed to evaluate radiological features that are distinct between PSVD and cirrhosis. METHODS: Clinical, laboratory, and radiological parameters (CT/MRI) of patients with histologically-confirmed PSVD vs. cirrhosis vs. non-cirrhotic parenchymal liver disease were retrospectively evaluated. RESULTS: Sixty-three PSVD, 155 cirrhosis, and 41 non-cirrhotic patients were included. As compared to cirrhosis, PSVD patients were younger and had lower HVPG, liver stiffness, and MELD. Routine clinical and imaging findings indicative of portal hypertension were similarly common. Intrahepatic portal tract abnormalities (49% vs. 15%; p < 0.001), FNH-like lesions (30% vs. 1%; p < 0.001), and abnormal liver morphology defined as peripheral parenchymal atrophy and compensatory hypertrophy of central segments (32% vs. 7%; p < 0.001) were significantly more common in PSVD patients. Hypertrophy of segment I (70% vs. 84%; p = 0.019), atrophy of segment IV (24% vs. 47%; p = 0.001), and nodular liver surface (22% vs. 89%; p < 0.001) were more common in patients with cirrhosis. In patients with gadoxetic acid-enhanced MRI, we identified the distinct imaging feature of "periportal hyperintensity" in the hepatobiliary phase (HBP) in 42% of patients with PSVD (14/33) vs. 1% in cirrhosis (1/95) vs. 0% in non-cirrhotic controls (0/41); p < 0.001). CONCLUSIONS: Diagnosis of PSVD must be considered in younger patients presenting with clinical features of portal hypertension, portal tract abnormalities, and FNH-like lesions on CT/MRI. 'Periportal hyperintensity' in the HBP of gadoxetic acid-enhanced MRI was identified as a specific radiological feature of PSVD. KEY POINTS: • Cross-sectional imaging can provide essential information to identify patients with porto-sinusoidal vascular disorder (PSVD). • Intrahepatic portal tract abnormalities, FNH-like lesions, and abnormal liver morphology are common in PSVD patients. • Periportal hyperintensity on the hepatobiliary phase of gadoxetic acid-enhanced MRI seems to be specific for patients with PSVD.

Ultrahigh-Resolution Photon-Counting Detector CT of the Lungs: Association of Reconstruction Kernel and Slice Thickness With Image Quality.

BACKGROUND. Prior work has shown improved image quality for photon-counting detector (PCD) CT of the lungs compared with energy-integrating detector CT. A paucity of the literature has compared PCD CT of the lungs using different reconstruction parameters. OBJECTIVE. The purpose of this study is to the compare the image quality of ultra-high-resolution (UHR) PCD CT image sets of the lungs that were reconstructed using different kernels and slice thicknesses. METHODS. This retrospective study included 29 patients (17 women and 12 men; median age, 56 years) who underwent noncontrast chest CT from February 15, 2022, to March 15, 2022, by use of a commercially available PCD CT scanner. All acquisitions used UHR mode (1024 × 1024 matrix). Nine image sets were reconstructed for all combinations of three sharp kernels (BI56, BI60, and BI64) and three slice thicknesses (0.2, 0.4, and 1.0 mm). Three radiologists independently reviewed reconstructions for measures of visualization of pulmonary anatomic structures and pathologies; reader assessments were pooled. Reconstructions were compared with the clinical reference reconstruction (obtained using the BI64 kernel and a 1.0-mm slice thickness [BI641.0-mm]). RESULTS. The median difference in the number of bronchial divisions identified versus the clinical reference reconstruction was higher for reconstructions with BI640.4-mm (0.5), BI600.4-mm (0.3), BI640.2-mm (0.5), and BI600.2-mm (0.2) (all p < .05). The median bronchial wall sharpness versus the clinical reference reconstruction was higher for reconstructions with BI640.4-mm (0.3) and BI640.2-mm (0.3) and was lower for BI561.0-mm (-0.7) and BI560.4-mm (-0.3) (all p < .05). Median pulmonary fissure sharpness versus the clinical reference reconstruction was higher for reconstructions with BI640.4-mm (0.3), BI600.4-mm (0.3), BI560.4-mm (0.5), BI640.2-mm (0.5), BI600.2-mm (0.5), and BI560.2-mm (0.3) (all p < .05). Median pulmonary vessel sharpness versus the clinical reference reconstruction was lower for reconstructions with BI561.0-mm (-0.3), BI600.4-mm (-0.3), BI560.4-mm (-0.7), BI640.2-mm (-0.7), BI600.2-mm (-0.7), and BI560.2-mm (-0.7). Median lung nodule conspicuity versus the clinical reference reconstruction was lower for reconstructions with BI561.0-mm (-0.3) and BI560.4-mm (-0.3) (both p < .05). Median conspicuity of all other pathologies versus the clinical reference reconstruction was lower for reconstructions with BI561.0 mm (-0.3), BI560.4-mm (-0.3), BI640.2-mm (-0.3), BI600.2-mm (-0.3), and BI560.2-mm (-0.3). Other comparisons among reconstructions were not significant (all p > .05). CONCLUSION. Only the reconstruction using BI640.4-mm yielded improved bronchial division identification and bronchial wall and pulmonary fissure sharpness without a loss in pulmonary vessel sharpness or conspicuity of nodules or other pathologies. CLINICAL IMPACT. The findings of this study may guide protocol optimization for UHR PCD CT of the lungs.

Added value of quantitative, multiparametric 18F-FDG PET/MRI in the locoregional staging of rectal cancer.

PURPOSE: The purpose of this study was to determine whether multiparametric positron emission tomography/magnetic resonance imaging (mpPET/MRI) can improve locoregional staging of rectal cancer (RC) and to assess its prognostic value after resection. METHODS: In this retrospective study, 46 patients with primary RC, who underwent multiparametric 18F-fluorodeoxyglucose (FDG) PET/MRI, followed by surgical resection without chemoradiotherapy, were included. Two readers reviewed T- and N- stage, mesorectal involvement, sphincter infiltration, tumor length, and distance from anal verge. In addition, diffusion-weighted imaging (DWI) and PET parameters were extracted from the multiparametric protocol and were compared to radiological staging as well as to the histopathological reference standard. Clinical and imaging follow-up was systematically assessed for tumor recurrence and death. RESULTS: Locally advanced rectal cancers (LARC) exhibited significantly higher metabolic tumor volume (MTV, AUC 0.74 [95% CI 0.59-0.89], p = 0.004) and total lesion glycolysis (TLG, AUC 0.70 [95% CI 0.53-0.87], p = 0.022) compared to early tumors. T-stage was associated with MTV (AUC 0.70 [95% CI 0.54-0.85], p = 0.021), while N-stage was better assessed using anatomical MRI sequences (AUC 0.72 [95% CI 0.539-0.894], p = 0.032). In the multivariate regression analysis, depending on the model, both anatomical MRI sequences and MTV/TLG were capable of detecting LARC. Combining anatomical MRI stage and MTV/TLG led to a superior diagnostic performance for detecting LARC (AUC 0.81, [95% CI 0.68-0.94], p < 0.001). In the survival analysis, MTV was independently associated with overall survival (HR 1.05 [95% CI 1.01-1.10], p = 0.044). CONCLUSION: Multiparametric PET-MRI can improve identification of locally advanced tumors and, hence, help in treatment stratification. It provides additional information on RC tumor biology and may have prognostic value.

Long-Term Follow-Up after Surgery for Chronic Pancreatitis: A Bicentric Retrospective Experience.

INTRODUCTION: The impact of surgery on nutritional status, pancreatic function, and symptoms of patients affected by chronic pancreatitis (CP) has not been unequivocally determined. This study aimed to evaluate clinical follow-up after surgery for CP in an Italian-Austrian population. MATERIALS AND METHODS: Patients operated for CP at two high-volume centers between 2000 and 2018 were analyzed. The following parameters were compared between the pre- and postoperative period: nutritional status, endocrine and exocrine pancreatic functions, and chronic pain. RESULTS: Overall, 186 patients underwent surgery for CP. Among these, 68 (40%) answered a specific follow-up questionnaire. The body mass index showed a significant increase between pre- and postoperative assessments (21.1 vs. 22.5 p = 0.003). Furthermore, a 60% decrease in the prevalence of chronic pain (81 vs. 21%, p < 0.001) was observed. On the contrary, both exocrine and endocrine pancreatic functions pointed toward a worsening after surgery, with consistent higher rates of patients presenting with diabetes mellitus, as well as patients requiring insulin therapy and oral intake of pancreatic enzymes. The analysis of body composition performed on 40 (24%) patients with a complete imaging pack revealed no significant change in the nutritional status after surgery. DISCUSSION/CONCLUSION: Despite the good results observed in terms of pain relief, the surgical approach led to a consistent worsening of the global pancreatic function. No significant influence of surgery on the nutritional status of patients was detected.

Effect of liver resection-induced increases in hepatic venous pressure gradient on development of postoperative acute kidney injury.

BACKGROUND: The impact of changes in portal pressure before and after liver resection (defined as ΔHVPG) on postoperative kidney function remains unknown. Therefore, we investigated the effect of ΔHVPG on (i) the incidence of postoperative AKI and (ii) the renin-angiotensin system (RAAS) and sympathetic nervous system (SNS) activity. METHODS: We included 30 patients undergoing partial liver resection. Our primary outcome was postoperative AKI according to KDIGO criteria. For our secondary outcome we assessed the plasma renin, aldosterone, noradrenaline, adrenaline, dopamine and vasopressin concentrations prior and 2 h after induction of anaesthesia, on the first and fifth postoperative day. HVPG was measured prior and immediately after liver resection. RESULTS: ΔHVPG could be measured in 21 patients with 12 patients HVPG showing increases in HVPG (∆HVPG≥1 mmHg) while 9 patients remained stable. AKI developed in 7/12 of patients with increasing HVPG, but only in 2/9 of patients with stable ΔHVPG (p = 0.302). Noradrenalin levels were significantly higher in patients with increasing ΔHVPG than in patients with stable ΔHVPG. (p = 0.009). Biomarkers reflecting RAAS and SNS activity remained similar in patients with increasing vs. stable ΔHVPG. CONCLUSIONS: Patients with increased HVPG had higher postoperative creatinine concentrations, however, the incidence of AKI was similar between patients with increased versus stable HVPG.

Immune checkpoints and liver resection after neoadjuvant chemotherapy including bevacizumab in patients with microsatellite-stable colorectal liver metastases.

BACKGROUND: The clinical value of immune checkpoint expression as prognostic biomarker in bevacizumab-pretreated patients with resected microsatellite-stable (MMS) colorectal liver metastases is unclear and was retrospectively investigated in this study. METHODS: Expression analyses of IDO-1, PD-L1, and CTLA-4 were performed by immunohistochemistry in resected bevacizumab-pretreated colorectal liver metastases. Association of immune checkpoint expression in tumor cells and immune cells with response and clinical outcome was investigated. Expression profiles were compared with those of patients with anti-EGFR-targeted therapy and lung metastases, respectively. RESULTS: One hundred thirty-six patients with MMS disease were investigated (79 (58.1%) male/57 (41.9%) female, median age 62.9 years (range 31.0-80.4)). High expression of IDO-1 in immune cells was associated with longer OS (not reached versus 44.8 months, HR 0.23 (95% CI 0.09, 0.55), P = 0.001). Low expression of CTLA-4 in tumor cells was associated with better histological response (26 major, 19 partial, 18 none versus 14 major, 23 partial, 30 none, P = 0.032). Expression profiles differed compared to patients with anti-EGFR-targeted therapy and patients with lung metastases. CONCLUSION: Immune checkpoint expression was associated with response and survival. IDO-1 may serve as a novel prognostic and/or predictive biomarker in patients with MMS colorectal liver metastases.

18F FDG PET/MRI with hepatocyte-specific contrast agent for M staging of rectal cancer: a primary economic evaluation.

PURPOSE: Rectal cancer is one of the most frequent causes of cancer-related morbidity and mortality in the world. Correct identification of the TNM state in primary staging of rectal cancer has critical implications on patient management. Initial evaluations revealed a high sensitivity and specificity for whole-body PET/MRI in the detection of metastases allowing for metastasis-directed therapy regimens. Nevertheless, its cost-effectiveness compared with that of standard-of-care imaging (SCI) using pelvic MRI + chest and abdominopelvic CT is yet to be investigated. Therefore, the aim of this study was to analyze the cost-effectiveness of whole-body 18F FDG PET/MRI as an alternative imaging method to standard diagnostic workup for initial staging of rectal cancer. METHODS: For estimation of quality-adjusted life years (QALYs) and lifetime costs of diagnostic modalities, a decision model including whole-body 18F FDG PET/MRI with a hepatocyte-specific contrast agent and pelvic MRI + chest and abdominopelvic CT was created based on Markov simulations. For obtaining model input parameters, review of recent literature was performed. Willingness to pay (WTP) was set to $100,000/QALY. Deterministic sensitivity analysis of diagnostic parameters and costs was applied, and probabilistic sensitivity was determined using Monte Carlo modeling. RESULTS: In the base-case scenario, the strategy whole-body 18F FDG PET/MRI resulted in total costs of $52,186 whereas total costs of SCI were at $51,672. Whole-body 18F FDG PET/MRI resulted in an expected effectiveness of 3.542 QALYs versus 3.535 QALYs for SCI. This resulted in an incremental cost-effectiveness ratio of $70,291 per QALY for PET/MRI. Thus, from an economic point of view, whole-body 18F FDG PET/MRI was identified as an adequate diagnostic alternative to SCI with high robustness of results to variation of input parameters. CONCLUSION: Based on the results of the analysis, use of whole-body 18F FDG PET/MRI was identified as a feasible diagnostic strategy for initial staging of rectal cancer from a cost-effectiveness perspective.

Surgery for chronic pancreatitis: the comparison of two high-volume centers reveals lack of a uniform operative management.

PURPOSE: Many aspects of surgical therapy for chronic pancreatitis (CP), including the correct indication and timing, as well as the most appropriate operative techniques, are still a matter of debate in the surgical community and vary widely across different centers. The aim of the present study was to uncover and analyze these differences by comparing the experiences of two specialized surgical units in Italy and Austria. METHODS: All patients operated for CP between 2000 and 2018 at the two centers involved were included in this retrospective analysis. Data regarding the clinical history and the pre- and perioperative surgical course were analyzed and compared between the two institutions. RESULTS: Our analysis showed a progressive decrease in the annual rate of pancreatic surgical procedures performed for CP in Verona (no. = 91) over the last two decades (from 3% to less than 1%); by contrast, this percentage increased from 3 to 9% in Vienna (no. = 77) during the same time frame. Considerable differences were also detected with regard to the timing of surgery from the first diagnosis of CP - 4 years (IQR 5.5) in the Austrian series vs two (IQR 4.0) in the Italian series -, and of indications for surgery, with a 12% higher prevalence of groove pancreatitis among patients in the Verona cohort. CONCLUSION: The comparison of the surgical attitude towards CP between two surgical centers proved that a consistent approach to this pathology still is lacking. The identification of common guidelines and labels of surgical eligibility is advisable in order to avoid interinstitutional treatment disparities.

Does the Functional Liver Imaging Score Derived from Gadoxetic Acid-enhanced MRI Predict Outcomes in Chronic Liver Disease?

Background Gadoxetic acid-enhanced MRI enables estimation of liver function in patients with chronic liver disease (CLD). The functional liver imaging score (FLIS), derived from gadoxetic acid-enhanced MRI, has been shown to predict transplant-free survival in liver transplant patients. Purpose To investigate the accuracy of the FLIS for predicting hepatic decompensation and transplant-free survival in patients with CLD. Materials and Methods Patients with CLD who had undergone gadoxetic acid-enhanced liver MRI, including T1-weighted volume-interpolated breath-hold examination sequences with fat suppression, performed between 2011 and 2015 were included. FLIS was assigned on the basis of the sum of three hepatobiliary phase features, each scored on an ordinal 0-2 scale: hepatic enhancement, biliary excretion, and the signal intensity in the portal vein. Patients were stratified into the following three groups according to fibrosis stage and a presence or history of hepatic decompensation: nonadvanced CLD, compensated advanced CLD (CACLD), and decompensated advanced CLD (DACLD). The predictive value of FLIS for first and/or further hepatic decompensation and for transplant-free survival was investigated by using Kaplan-Meier analysis, log-rank tests, and Cox regression analysis. Results This study evaluated 265 patients (53 years ± 14 [standard deviation]; 164 men). Intraobserver (κ = 0.98; 95% confidence interval: 0.97, 0.99) and interobserver (κ = 0.93; 95% confidence interval: 0.90, 0.95) agreement for FLIS were excellent. In patients with CACLD, the FLIS was independently predictive of a first hepatic decompensation (adjusted hazard ratio, 3.7; 95% confidence interval: 1.1, 12.6; P = .04), but not for further hepatic decompensations in patients with DACLD (adjusted hazard ratio, 1.4; 95% confidence interval: 0.9, 1.9; P = .17). The FLIS was an independent risk factor for mortality in both patients with CACLD (adjusted hazard ratio, 7.4; 95% confidence interval: 2.7, 20.2; P < .001) and those with DACLD (adjusted hazard ratio, 3.8; 95% confidence interval: 1.7, 9.5; P = .004). Conclusion The functional liver imaging score derived from gadoxetic acid-enhanced MRI identified patients with advanced chronic liver disease who are at increased risk for a first hepatic decompensation and for mortality. © RSNA, 2019 Online supplemental material is available for this article.

Predicting Postoperative Liver Dysfunction Based on Blood-Derived MicroRNA Signatures.

There is an urgent need for an easily assessable preoperative test to predict postoperative liver function recovery and thereby determine the optimal time point of liver resection, specifically as current markers are often expensive, time consuming, and invasive. Emerging evidence suggests that microRNA (miRNA) signatures represent potent diagnostic, prognostic, and treatment-response biomarkers for several diseases. Using next-generation sequencing as an unbiased systematic approach, 554 miRNAs were detected in preoperative plasma of 21 patients suffering from postoperative liver dysfunction (LD) after liver resection and 27 matched controls. Subsequently, we identified a miRNA signature-consisting of miRNAs 151a-5p, 192-5p, and 122-5p-that highly correlated with patients developing postoperative LD after liver resection. The predictive potential for postoperative LD was subsequently confirmed using real-time PCR in an independent validation cohort of 98 patients. Ultimately, a regression model of the two miRNA ratios 151a-5p to 192-5p and 122-5p to 151a-5p was found to reliably predict postoperative LD, severe morbidity, prolonged intensive care unit and hospital stays, and even mortality before an operation with a remarkable accuracy, thereby outperforming established markers of postoperative LD. Ultimately, we documented that miRNA ratios closely followed liver function recovery after partial hepatectomy. Conclusion: Our data demonstrate the clinical utility of an miRNA-based biomarker to support the selection of patients undergoing partial hepatectomy. The dynamical changes during liver function recovery indicate a possible role in individualized patient treatment. Thereby, our data might help to tailor surgical strategies to the specific risk profile of patients.

PET/MRI versus PET/CT in oncology: a prospective single-center study of 330 examinations focusing on implications for patient management and cost considerations.

PURPOSE: PET/MRI has recently been introduced into clinical practice. We prospectively investigated the clinical impact of PET/MRI compared with PET/CT, in a mixed population of cancer patients, and performed an economic evaluation of PET/MRI. METHODS: Cancer patients referred for routine staging or follow-up by PET/CT underwent consecutive PET/CT and PET/MRI, using single applications of [18F]FDG, [68Ga]Ga-DOTANOC, or [18F]FDOPA, depending on tumor histology. PET/MRI and PET/CT were rated separately, and lesions were assessed per anatomic region; based on regions, per-examination and per-patient accuracies were determined. A simulated, multidisciplinary team meeting served as reference standard and determined whether differences between PET/CT and PET/MRI affected patient management. The McNemar tests were used to compare accuracies, and incremental cost-effectiveness ratios (ICERs) for PET/MRI were calculated. RESULTS: Two hundred sixty-three patients (330 same-day PET/CT and PET/MRI examinations) were included. PET/MRI was accurate in 319/330 examinations and PET/CT in 277/330 examinations; the respective accuracies of 97.3% and 83.9% differed significantly (P < 0.001). The additional findings on PET/MRI-mainly liver and brain metastases-had implications for patient management in 21/263 patients (8.0%). The per-examination cost was 596.97 EUR for PET/MRI and 405.95 EUR for PET/CT. ICERs for PET/MRI were 14.26 EUR per percent of diagnostic accuracy and 23.88 EUR per percent of correctly managed patients. CONCLUSIONS: PET/MRI enables more appropriate management than PET/CT in a nonnegligible fraction of cancer patients. Since the per-examination cost is about 50% higher for PET/MRI than for PET/CT, a histology-based triage of patients to either PET/MRI or PET/CT may be meaningful.

Protocol analysis of dual-energy CT for optimization of kidney stone detection in virtual non-contrast reconstructions.

OBJECTIVES: Previous studies have shown that split-bolus protocols in virtual non-contrast (VNC) reconstructions of dual-energy computed tomography (DE-CT) significantly decrease radiation dose in patients with urinary stone disease. To evaluate the impact on kidney stone detection rate of stone composition, size, tube voltage, and iodine concentration for VNC reconstructions of DE-CT. METHODS: In this prospective study, 16 kidney stones of different sizes (1.2-4.5 mm) and compositions (struvite, cystine, whewellite, brushite) were placed within a kidney phantom. Seventy-two scans with nine different iodine contrast agents/saline solutions with increasing attenuation (0-1400 HU) and different kilovoltage settings (70 kV/150 kV; 80 kV/150 kV; 90 kV/150 kV; 100 kV/150 kV) were performed. Two experienced radiologists independently rated the images for the presence and absence of stones. Multivariate classification tree analysis and descriptive statistics were used to evaluate the diagnostic performance. RESULTS: Classification tree analysis revealed a higher detection rate of renal calculi > 2 mm in size compared with that of renal calculi < 2 mm (84.7%; 12.7%; p < 0.001). For stones with a diameter > 2 mm, the best results were found at 70 kV/Sn 150 kV and 80 kV/Sn 150 kV in scans with contrast media attenuation of 600 HU or less, with sensitivity of 99.6% and 96.0%, respectively. A higher luminal attenuation (> 600 HU) resulted in a significantly decreased detection rate (91.8%, 0-600 HU; 70.7%, 900-1400 HU; p < 0.001). In our study setup, the detection rates were best for cystine stones. CONCLUSION: Scan protocols in DE-CT with lower tube current and lower contrast medium attenuation show excellent results in VNC for stones larger than 2 mm but have limitations for small stones. KEY POINTS: • The detection rate of virtual non-contrast reconstructions is highly dependent on the surrounding contrast medium attenuation at the renal pelvis and should be kept as low as possible, as at an attenuation higher than 600 HU the VNC reconstructions are susceptible to masking ureteral stones. • Protocols with lower tube voltages (70 kV/Sn 150 kV and 80 kV/Sn 150 kV) improve the detection rate of kidney stones in VNC reconstructions. • The visibility of renal stones in virtual non-contrast of dual-energy CT is highly associated with the size, and results in a significantly lower detection rate in stones below 2 mm.

The Efficacy of MRI in the diagnostic workup of cystic fibrosis-associated liver disease: A clinical observational cohort study.

PURPOSE: To identify independent imaging features and establish a diagnostic algorithm for diagnosis of cystic fibrosis (CF)-associated liver disease (CFLD) in CF patients compared to controls using gadoxetic acid-enhanced MRI. METHODS: A total of 90 adult patients were enrolled: 50 with CF, 40 controls. The CF group was composed of two subgroups: a retrospective test subgroup (n = 33) and a prospective validation subgroup (n = 17). Controls (patients with normal liver enzymes and only benign focal liver lesions) were divided accordingly (27:13). MRI variables, including quantitative and qualitative parameters, were used to distinguish CFLD from controls using clinical symptoms, laboratory tests and Debray criteria. Disease severity was classified according to Child-Pugh and Albumin-Bilirubin (ALBI) scores. Fifteen qualitative single-lesion CF descriptors were defined. Two readers independently evaluated the images. Univariate statistical analysis was performed to obtain significant imaging features that differentiate CF patients from controls. Through multivariate analysis using chi-squared automatic interaction detector (CHAID) methodology the most important descriptors were identified. Diagnostic performance was assessed by receiver-operating characteristic (ROC) analysis. RESULTS: Three independent imaging descriptors distinguished CFLD from controls: (1) presence of altered gallbladder morphology; (2) periportal tracking; and (3) periportal fat deposition. Prospective validation of the classification algorithm demonstrated a sensitivity of 94.1% and specificity of 84.6% for discriminating CFLD from controls. Disease severity was well associated with the imaging features. CONCLUSIONS: A short unenhanced MRI protocol can identify the three cardinal imaging features of CFLD. The hepatobiliary phase of gadoxetic acid-enhanced MRI can define CFLD progression. KEY POINTS: • Using a multivariate classification analysis, we identified three independent imaging features, altered gallbladder morphology (GBAM), periportal tracking (PPT) and periportal fat deposition (PPFD), that could diagnose CFLD with high sensitivity, 94.1 % (95% CI: 71.3-99.9) and moderate specificity, 84.6 % (95% CI: 54.6-98.1). • Based upon the results of this study, gadoxetic acid-enhanced MRI with DWI is able to diagnose early-stage CFLD, as well as its progression.

Inter- and intra-reader agreement for gadoxetic acid-enhanced MRI parameter readings in patients with chronic liver diseases.

OBJECTIVES: To examine inter- and intra-observer agreement for four simple hepatobiliary phase (HBP)-based scores on gadoxetic acid (GA)-enhanced MRI and their correlation with liver function in patients with mixed chronic liver disease (CLD). METHODS: This single-center, retrospective study included 287 patients (62% male, 38% female, mean age 53.5 ± 13.7 years) with mixed CLD (20.9% hepatitis C, 19.2% alcoholic liver disease, 8% hepatitis B) who underwent GA-enhanced MRI of the liver for clinical care between 2010 and 2015. Relative liver enhancement (RLE), contrast uptake index (CUI), hepatic uptake index (HUI), and liver-to-spleen contrast index (LSI) were calculated by two radiologists independently using unenhanced and GA-enhanced HPB (obtained 20 min after GA administration) images; 50 patients selected at random were reviewed twice by one reader to assess intra-observer reliability. Agreement was assessed by intraclass correlation coefficient (ICC). The albumin-bilirubin (ALBI) score, the model of end-stage liver disease (MELD), and the Child-Turcotte-Pugh (CTP) score were calculated as standards of reference for hepatic function. RESULTS: Intra-observer ICCs ranged from 0.814 (0.668-0.896) for CUI to 0.969 (0.945-0.983) for RLE. Inter-observer ICCs ranged from 0.777 (0.605-0.874) for HUI to 0.979 (0.963-0.988) for RLE. All HBP-based scores correlated significantly (all p < 0.001) with the ALBI, MELD, and CTP scores and were able to discriminate patients with a MELD score ≥ 15 versus ≤ 14, with area under the curve values ranging from 0.760 for RLE to 0.782 for HUI. CONCLUSION: GA-enhanced, MRI-derived, HBP-based parameters showed excellent inter- and intra-observer agreement. All HBP-based parameters correlated with clinical and laboratory scores of hepatic dysfunction, with no significant differences between each other. KEY POINTS: • Radiological parameters that quantify the hepatic uptake of gadoxetic acid are highly reproducible. • These parameters can be used interchangeably because they correlate with each other and with scores of hepatic dysfunction. • Assessment of these parameters may be helpful in monitoring disease progression.

Circulating Free Methylated Tumor DNA Markers for Sensitive Assessment of Tumor Burden and Early Response Monitoring in Patients Receiving Systemic Chemotherapy for Colorectal Cancer Liver Metastasis.

BACKGROUND: Neoadjuvant chemotherapy (neoCTx) followed by hepatic resection is the treatment of choice for patients with colorectal cancer liver metastasis (CLM). Treatment response is generally assessed using radiologic imaging after several cycles of chemotherapy. However, earlier assessment of response would be desirable since nonresponders could be switched early to an alternative chemotherapy regimen. Recent evidence suggests that circulating free methylated tumor DNA is a highly sensitive biomarker and may more accurately reflect tumor burden and treatment response than conventional markers for CRC. PATIENTS AND METHODS: Thirty-four patients with CLM who received neoCTx prior to intended hepatic resection were included in this prospective nonrandomized study. Peripheral blood plasma was collected at baseline and before each cycle of neoCTx and was then analyzed for aberrant methylation of 48 CRC-associated genes. Methylation marker levels were correlated with baseline tumor volume and treatment response and compared with the standard tumor markers CEA and CA 19-9. RESULTS: The methylation markers SEPT9, DCC, BOLL, and SFRP2 were present in all patients at baseline and displayed a stronger correlation with tumor volume than CEA and CA 19-9. Serial measurement of these methylation markers allowed for discrimination between operated and nonoperated patients already after 1 cycle of neoCTx with high sensitivity and specificity. The early dynamic changes of SEPT9 and DCC also seemed to correlate with pathohistological response. CONCLUSION: Our data suggest that serial measurements of CRC-associated methylation markers could be a particularly valuable tool for early response assessment in patients receiving neoCTx for CLM.

Impact of Neoadjuvant Chemotherapy on Clinical Risk Scores and Survival in Patients with Colorectal Liver Metastases.

BACKGROUND: Several clinical risk scores for patients with colorectal liver metastases (CLM) were established in cohorts of patients undergoing liver resection (LR) without neoadjuvant chemotherapy (NAC). The purpose of the study was to evaluate the predictive values of four common risk scores in the setting of NAC and the impact of score changes during NAC. METHODS: Risk scores (Fong, Nordlinger, Nagashima, and Konopke) were retrospectively calculated for 336 patients undergoing LR for CLM, including 109 patients without and 227 patients with NAC. In patients with NAC, the scores were calculated before and after NAC. RESULTS: In patients without NAC (n = 109), all risk scores except the Konopke score showed a significant correlation with disease-free survival (DFS). Only the Nagashima score also was predictive for overall survival (OS). In patients with NAC (n = 227), all scores except the Konopke score were predictive for DFS and OS before and after NAC. Score changes in the Fong and the Nagashima score showed a significant correlation with DFS and OS. CONCLUSIONS: Nagashima score was the most universally applicable score and predicted prognosis in all tested scenarios.

Markers of sarcopenia quantified by computed tomography predict adverse long-term outcome in patients with resected oesophageal or gastro-oesophageal junction cancer.

OBJECTIVES: To assess the impact of sarcopenia and alterations in body composition parameters (BCPs) on survival after surgery for oesophageal and gastro-oesophageal junction cancer (OC). METHODS: 200 consecutive patients who underwent resection for OC between 2006 and 2013 were selected. Preoperative CTs were used to assess markers of sarcopenia and body composition (total muscle area [TMA], fat-free mass index [FFMi], fat mass index [FMi], subcutaneous, visceral and retrorenal fat [RRF], muscle attenuation). Cox regression was used to assess the primary outcome parameter of overall survival (OS) after surgery. RESULTS: 130 patients (65%) had sarcopenia based on preoperative CT examinations. Sarcopenic patients showed impaired survival compared to non-sarcopenic individuals (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.15-3.03, p = 0.011). Furthermore, low skeletal muscle attenuation (HR 1.91, 95% CI 1.12-3.28, p = 0.019) and increased FMi (HR 3.47, 95% CI 1.27-9.50, p = 0.016) were associated with impaired outcome. In the multivariate analysis, including a composite score (CSS) of those three parameters and clinical variables, only CSS, T-stage and surgical resection margin remained significant predictors of OS. CONCLUSION: Patients who show signs of sarcopenia and alterations in BCPs on preoperative CT images have impaired long-term outcome after surgery for OC. KEY POINTS: • Sarcopenia is associated with impaired OS after surgery for oesophageal cancer. • Other body composition parameters are also associated with impaired survival. • This influence on survival is independent of established clinical parameters. • Sarcopenia provides a better estimation of cachexia than BMI. • Sarcopenia assessment could be considered in risk/benefit stratification before oesophagectomy.