Cosimo Nardi

Challenges of advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.

Motion artefacts in cone beam CT: an in vitro study about the effects on the images

OBJECTIVE In cone beam CT (CBCT), imperfect patient immobility, caused by involuntary movements, is one of the most important causes of artefacts and image quality degradation. Various works in literature address this topic, but seldom is the nature of the movement correlated with the type of artefact and the image degradation in a systematic manner, and the correlation analyzed and explained. METHODS All three types of movements that can occur during a scan-nodding, tilting and rolling-were applied to a dry skull, in various manners from abrupt to gradual through the entire scan, at different times and angles, over a wide range of displacements. 84 scans were performed, with different skull movements, and the resulting images examined by two skilled radiologists, rated in a four-point scale and statistically analyzed. A commercial CBCT machine was used, featuring supine patient positioning. RESULTS Different types of movements induce different artefacts, in different parts of the anatomy. In general, movement of short duration may lead to double contours (bilateral or monolateral depending upon the angle of the scan at which they occur), whereas gradual movements result into blurring. CONCLUSION Not all movements cause motion artefacts that equally jeopardize the image. Rolling is the type of movement that most severely affects the image diagnostic value. ADVANCES IN KNOWLEDGE These findings may help practitioners to identify the causes of motion artefacts and the resulting image degradation, and remediate them, and manufacturers to improve the patient-positioning devices.

Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up

Advanced stage hepatocellular carcinoma (HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenib treatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments (many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters (cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of sorafenib treatment. This would bring a strongly desirable help in clinical managements of these patients.

MR-diffusion imaging in assessing chronic liver diseases: does a clinical role exist?

PurposeThis study was done to evaluate whether and which of the magnetic resonance diffusion-weighted imaging (MR-DWI) parameters — apparent diffusion coefficient (ADC), diffusion (D) or perfusion fraction (f) — correlates with the degree of chronic liver disease progression.Materials and methodsTwenty-eight patients were evaluated with abdominal MR-DWI from March to November 2010: seven healthy volunteers, seven patients with chronic liver disease F0–F2 (METAVIR score), seven F3–F4 Child-Pugh A, and seven F4 Child-Pugh BC, classified as groups 1–4, respectively. DWI acquisitions were performed during breath-holding (b = 0–150 s/mm2 and 1,000) and free breathing (multi-b = 0–200–400–600–800–1,000 s/mm2). Using a double-blind control procedure, two observers estimated ADC, D, and f by applying a region of interest (ROI) in 4/12 sections in the middle-lower portion of the right hepatic lobe. Statistical analysis was done with analysis of variance (ANOVA).ResultsA reduction in the mean value of f, ADC150 and, to a lesser extent, ADC1,000 is shown to progress from healthy volunteers (group 1) to cirrhosis patients (group 4), with wide overlap among groups. There were no statistically significant changes of D.ConclusionsOur results indicate that stratifying patients with chronic liver disease for clinical purposes cannot be done with DWI. However, there is a tendency among groups for reduced perfusion-related parameters as chronic liver disease progresses.RiassuntoObiettivoScopo del nostro lavoro è stato valutare se e quale fra i parametri legati alla diffusione in risonanza magnetica (RM-DwI), coefficiente di diffusione apparente (ADC), diffusione (D), frazione di perfusione (f) correli con l’avanzare del grado dell’epatopatia cronica sclerogena.Materiali e metodiDa marzo a novembre 2010 sono stati valutati con RM 28 soggetti: 7 sani, 7 epatopatici cronici F0–F2 secondo Metavir, 7 F3–F4 Child A e 7 F4 Child B-C, denominati gruppi I–II–III–IV rispettivamente. Sono state eseguite acquisizioni DwI a respiro sospeso (b=0–150 e 1000 s/mm2) e libero (poli-b=0–200–400–600–800–1000 s/mm2). Tramite regione di interesse (ROI) in 4/12 sezioni nella porzione medio-inferiore del lobo epatico destro sono stati stimati in cieco da due osservatori i parametri ADC, D, f con statistica secondo Analysis of Variance Between Groups (ANOVA).RisultatiSi è evidenziata una riduzione del valor medio di f, dell’ADC150 e, in misura minore, dell’ADC1000 al progredire da sano (gruppo I) verso cirrotico (gruppo IV) con ampia sovrapposizione fra i vari gruppi; non è stata invece osservata variazione statisticamente significativa di D.ConclusioniI nostri risultati indicano che tramite DwI non è consentita una stratificazione ad uso clinico dei pazienti epatopatici cronici. Si riscontra tuttavia tendenza per gruppi alla riduzione dei parametri legati alla perfusione al progredire dell’epatopatia sclerogena.

Head and neck effective dose and quantitative assessment of image quality: a study to compare cone beam CT and multislice spiral CT

OBJECTIVES To evaluate the effective dose and image quality of horizontal CBCT in comparison with multislice spiral CT (MSCT) in scans of the head, cervical spine, ear and dental arches. METHODS A head and neck Alderson-Rando® phantom (The Phantom Laboratory, Salem, NY) equipped with 74 thermoluminescence dosemeters was exposed according to 5 different scans in CBCT and 4 different scans in MSCT. Spatial and contrast resolutions, in terms of modulation transfer function and contrast-to-noise ratio (CNR), were measured to obtain a quantitative assessment of image quality. RESULTS The CBCT effective dose was 248, 249, 361, 565 and 688 µSv in the cervical spine, head, ear, dental arches with small field of view and dental arches with medium field of view, respectively. The MSCT effective dose was 3409, 1892, 660 and 812 µSv in the cervical spine, head, ear and dental arches, respectively. The modulation transfer function was 0.895 vs 0.347, 0.895 vs 0.275, 0.875 vs 0.342 and 0.961 vs 0.352 for CBCT vs MSCT in the cervical spine, head, ear and dental arches, respectively. Head and cervical spine MSCT showed greater CNR than CBCT, whereas CNR of the ear and dental arches showed comparable values. CONCLUSIONS CBCT was preferable to MSCT for the ear and dental arches volumetric imaging due to its lower radiation dose and significantly higher spatial resolution. In the case of cervical spine and head imaging, MSCT should be generally recommended if a high contrast resolution is required, despite the greater radiation exposure.

Age estimation by assessment of pulp chamber volume: a Bayesian network for the evaluation of dental evidence

PurposeThe present study aimed to investigate the performance of a Bayesian method in the evaluation of dental age-related evidence collected by means of a geometrical approximation procedure of the pulp chamber volume. Measurement of this volume was based on three-dimensional cone beam computed tomography images.MethodsThe Bayesian method was applied by means of a probabilistic graphical model, namely a Bayesian network. Performance of that method was investigated in terms of accuracy and bias of the decisional outcomes. Influence of an informed elicitation of the prior belief of chronological age was also studied by means of a sensitivity analysis.ResultsOutcomes in terms of accuracy were adequate with standard requirements for forensic adult age estimation. Findings also indicated that the Bayesian method does not show a particular tendency towards under- or overestimation of the age variable. Outcomes of the sensitivity analysis showed that results on estimation are improved with a ration elicitation of the prior probabilities of age.

Role of cone-beam computed tomography with a large field of view in Goldenhar syndrome

Introduction Goldenhar syndrome is a rare disease with hemifacial microsomia and craniofacial disorders originating from the first and second branchial arches, such as ocular, auricular, and vertebral anomalies. The complexity and variety of the ways in which the disease presents itself usually need several examinations. In this study, we aimed to evaluate both craniofacial and vertebral skeletal anomalies and asymmetries between the nonaffected and affected sides in patients with Goldenhar syndrome by using cone‐beam computed tomography. Methods Ten patients (7‐14 years old; 6 boys, 4 girls) were evaluated via NewTom 5G cone‐beam computed tomography (QR srl, Verona, Italy) with a large field of view (18 × 16 cm). Ten anatomic facial landmarks were identified to measure the following distances bilaterally: sella turcica (ST)‐mandibular angle, ST‐condyle, ST‐mastoid, ST‐mental foramen, ST‐fronto zygomatic suture, ST‐zygomatic temporal suture, ST‐zygomatic facial foramen, ST‐sphenopalatine fossa, mandibular angle‐mandibular symphysis, and mandibular angle‐condyle. The following 6 volumes were calculated bilaterally: orbit, maxillary sinus, condyle, external ear canal, middle ear, and internal auditory canal. These measurements were performed to assess skeletal asymmetries to compare the nonaffected side with the affected side by the Wilcoxon test. Cervical spine anomalies were classified into fusion anomalies and posterior arch deficiencies. Results All patients showed a deficit of skeletal development on the affected side. Statistically significant differences (0.001 ≤ P value ≤ 0.043) between the nonaffected and affected sides were recorded for all measurements, except for ST‐frontozygomatic suture, mandibular angle‐mandibular symphysis, and maxillary sinus volume. Vertebral fusion anomalies and posterior arch deficiencies were found in 7 and 4 patients, respectively. Conclusions Cone‐beam computed tomography with a large field of view was able to accurately identify craniofacial and vertebral skeletal anomalies, and to quantify asymmetries between the nonaffected and affected sides for an efficient maxillofacial treatment planning. HighlightsGoldenhar syndrome is a rare disease characterized by craniofacial disorders.Patients are very young when they need several examinations and treatment planning.Head and neck multislice spiral computed tomography is usually avoided for radio‐protection reasons.CBCT can exactly identify craniofacial and vertebral skeletal anomalies at 1 time.CBCT could become the elective imaging technique for patients with Goldenhar syndrome.

Radiation dose in non-dental cone beam CT applications: a systematic review

BackgroundRadiation-induced health risks are broadly questioned in the literature. As cone beam computed tomography (CBCT) is increasingly used in non-dental examinations, its effective dose needs to be known. This study aimed to review the published evidence on effective dose of non-dental CBCT for diagnostic use by focusing on dosimetry system used to estimate dose.Materials and methodsA systematic review of the literature was performed on 12 November 2017. All the literature up to this date was included. The PubMed and web of science databases were searched. Studies were screened for inclusion based on defined inclusion and exclusion criteria according to the preferred reporting items for systematic reviews.ResultsFifteen studies met the inclusion criteria and were included in our review. Thirteen and two of them examined one and two anatomical areas, respectively. The anatomical areas were: ear (6), paranasal sinuses (4), ankle (3), wrist (2), knee (1), and cervical spine (1). Effective dose was estimated by different methods: (i) RANDO phantom associated with thermoluminescent dosimeters (6), metal oxide semiconductor field-effect transistor dosimeters (3), and optically stimulated luminescent dosimeters (1). (ii) Scanner outputs, namely computed tomography dose index (1) and dose area product (2). (iii) Monte Carlo simulations (2).ConclusionCBCT of extremities, cervical spine, ears and paranasal sinuses was found to be a low-dose volumetric imaging technique. Effective doses varied significantly because of different exposure settings of CBCT-units and different dosimetry systems used to estimate dose.

Repetition of examination due to motion artifacts in horizontal cone beam CT: Comparison among three different kinds of head support

Aims and Objectives: The aim of this study was to evaluate the repetition rate of examination due to motion artifacts in horizontal cone beam computed tomography, using three different kinds of head support, with reference to the patients age. Further purpose was to evaluate how comfortable head supports were. Materials and Methods: Seven hundred and fifty patients underwent a maxillofacial/dental arches volumetric imaging scan. They were divided into three groups depending on the head support used: foam headrest, foam headrest with head strap, and head restraint helmet. Each group was subdivided into three age groups: ≤18-year-old, 19–65-year-old, and ≥66-year-old patients. A severity index of motion artifacts, divided into four tiers from absence to remarkable artifacts, was adopted. Finally, each patient gave their judgment about the head support comfort by a questionnaire including ten yes/no questions. A three-score scale (insufficient, sufficient, and good) was used to judge the comfort. Collected data were analyzed using the SPSS® version 23.0 statistical analysis software. Results: Forty-one patients (5.4%) repeated the examination. In 16 (2.1%), 15 (2.0%), and 10 (1.3%) of them, foam headrest, foam headrest with head strap, and head restraint helmet were used, respectively. Examination was repeated in 5.3%, 3.8%, and 10.6% in ≤18-year-old, 19–65-year-old, and ≥66-year-old patients, respectively. Patients almost always judged good the comfort for each kind of support. The lowest percentage of satisfaction was observed for the headrest with head strap and was judged good in 78% of the cases. Conclusions: The repetition rate of examination showed similar values among the foam headrest, foam headrest with head strap, and head restraint helmet in under 66-year-old patients. In over 65-year-old patients, the head restraint helmet obviously decreased the repetition rate of examination. All three head supports were good comfort, especially the foam headrest.

Is Panoramic Radiography an Accurate Imaging Technique for the Detection of Endodontically Treated Asymptomatic Apical Periodontitis

Introduction This study aimed to evaluate the diagnostic accuracy of panoramic radiography (PAN) for the detection of clinically/surgically confirmed apical periodontitis (AP) in root canal–treated teeth using cone‐beam computed tomographic (CBCT) imaging as the reference standard. Methods Two hundred forty patients with endodontically treated AP (diseased group) were detected via CBCT imaging using the periapical index system. They were divided into groups of 20 each according to lesion size (2–4.5 mm and 4.6–7 mm) and anatomic area (incisor, canine/premolar, and molar) in both the upper and lower arches. Another 240 patients with root filling and a healthy periapex (healthy group) were selected. All diseased and healthy patients underwent PAN first and a CBCT scan within 40 days. The periapical index system was also used to assess AP using PAN. Sensitivity, specificity, diagnostic accuracy, positive predictive value, and negative predictive value for PAN images with respect to CBCT imaging were analyzed. The k value was calculated to assess both the interobserver reliability for PAN and the agreement between PAN and CBCT. Results PAN showed low sensitivity (48.8), mediocre negative predictive value (64.7), good diagnostic accuracy (71.3), and high positive predictive value (88.6) and specificity (93.8). Both interobserver reliability for PAN and agreement between PAN and CBCT were moderate (k = 0.58 and 0.42, respectively). The best identified AP was located in the lower canine/premolar and molar areas, whereas the worst identified AP was located in the upper/lower incisor area and upper molar area. Conclusions PAN showed good diagnostic accuracy, high specificity, and low sensitivity for the detection of endodontically treated AP.