Association between anatomic variations of extrahepatic and intrahepatic bile ducts: Do look up!

Biliary anatomic variations are usually asymptomatic, but they may cause problems in diagnostic investigations and interventional and surgical procedures, increasing both their technical difficulty and their postoperative complication rates. The aim of the present study was to evaluate the prevalence of anatomic variations in the intrahepatic biliary ducts (IHBD) in relation to demographical and clinical characteristics in a large study population requiring magnetic resonance cholangiopancreatography (MRCP) for various clinical conditions. The possible association between IHBD and extrahepatic biliary ducts (EHBD) variants was then explored. From January 2017 to May 2019, 1004 patients underwent MRCP. Demographical and clinical data were collected. IHBD and EHBD anatomy were recorded and the EHBD anatomy was classified using both qualitative and quantitative classifications. The presence of a type 3 EHBD variant (an abnormal proximal cystic duct [CD] insertion) in both qualitative and quantitative classifications and an intrapancreatic CD were associated with the presence of IHBD variants at univariate analysis (p = 0.008, p = 0.019, and p = 0.001, respectively). The presence of a posterior or medial insertion of the CD into the EHBD was a strong predictive factor of the presence of IHBD variants both at uni- and multivariate analysis (p = 0.002 and p = 0.003 for posterior insertion and p = 0.002 and p = 0.002 for medial insertion, respectively). The presence of gallstones on MRCP resulted in a strong predictor of the presence of an anatomical variant of the IHBD both at uni- and multivariate analysis (p = 0.027 and p = 0.046, respectively). In conclusion, the presence of a type 3 variant of the EHBD, an intrapancreatic CD and, especially, a posterior/medial CD insertion into the EHBD represent predictive factors of the concomitant presence of IHBD variants, thus radiologists must be vigilant when encountering these EHBD configurations and always remember to "look up" at the IHBD. Finally, the presence of an IHBD variant is a strong predictive factor of gallstones.

The power of kindness: curative treatment with metronomic combination in advanced hepatocellular carcinoma.

The administration of approved systemic treatments for advanced hepatocellular carcinoma (HCC) is limited to patients with preserved liver function (Child-Pugh A/B7) and performance status. Conversely, metronomic chemotherapy can be safely administered to patients with poor clinical conditions and severe liver impairment. The metronomic schedule demonstrated to exert different anticancer mechanisms compared to that of the same agent administered at its standard schedule, including immune stimulation and the inhibition of angiogenesis and vasculogenesis. Nevertheless, metronomic chemotherapy is a nearly neglected option for the treatment of advanced HCC patients, even among those who cannot afford standard treatments. Herein, we report the case of a 40-year-old patient affected by HBV-HDV-related cirrhosis who was diagnosed with advanced HCC. The severe liver impairment (Child-Pugh B9) did not allow to administer first-line treatment with tyrosine kinase inhibitors so that the patient received metronomic capecitabine as upfront therapy. Due to the suspect of progressive disease at the first radiologic assessment, metronomic cyclophosphamide was added to capecitabine aiming to enhance its efficacy. After 4 months of treatment, complete tumor response, alpha-fetoprotein (AFP) normalization and the recovery of a Child-Pugh A were achieved. The patient was then able to undergo liver transplantation, and, after 18 months from the diagnosis, he is still free of disease recurrence. This experience emphasizes the reliability of metronomic capecitabine as a well-tolerated and effective treatment when patient's conditions prevent the administration of standard first-line treatments. In fact, metronomic capecitabine demonstrated its effectiveness in advanced HCC in retrospective and prospective analyses, leading to median progression-free survival and overall survival of, respectively, 6.03 and 14.47 months in phase II single-arm trial. Moreover, in consideration of the raising interest in immune-checkpoint inhibition in HCC, we believe that the immunomodulating effects of metronomic chemotherapy, either capecitabine or cyclophosphamide, warrant future trials exploring its combination with immunotherapy.

Morphological, dynamic and functional characteristics of liver pseudolesions and benign lesions.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and one of the most common causes of death among patients with cirrhosis, developing in 1-8% of them every year, regardless of their cirrhotic stage. The radiological features of HCC are almost always sufficient for reaching the diagnosis; thus, histological confirmation is rarely needed. However, the study of cirrhotic livers remains a challenge for radiologists due to the developing of fibrous and regenerative tissue that cause the distortion of normal liver parenchyma, changing the typical appearances of benign lesions and pseudolesions, which therefore may be misinterpreted as malignancies. In addition, a correct distinction between pseudolesions and malignancy is crucial to allow appropriate targeted therapy and avoid treatment delays.The present review encompasses technical pitfalls and describes focal benign lesions and pseudolesions that may be misinterpreted as HCC in cirrhotic livers, providing the imaging features of regenerative nodules, large regenerative nodules, siderotic nodules, hepatic hemangiomas (including rapidly filling and sclerosed hemangiomas), segmental hyperplasia, arterioportal shunts, focal confluent fibrosis and focal fatty changes. Lastly, the present review explores the most promising new imaging techniques that are emerging and that could help radiologists differentiate benign lesions and pseudolesions from overt HCC.

Preoperative computed tomography assessment for a deep inferior epigastric perforator (DIEP) flap: a new easy technique from the Bologna experience.

BACKGROUND: Deep inferior epigastric perforator (DIEP) flap reconstruction is the gold standard reconstructive technique for women undergoing breast cancer surgery. A preoperative computed tomography angiography (CTA)-dedicated protocol and 3D reconstructions are mandatory for correct surgical planning. PURPOSE: To evaluate the diagnostic performance of a new preoperative CTA protocol and a new reconstruction method in the assessment of DIEP technique. MATERIAL AND METHODS: A total of 263 women (median age 49 years, age range 26-73 years) underwent preoperative CTA examination before DIEP flap breast reconstruction. A CTA-dedicated protocol followed by 3D-reconstructions were performed. Identification, branching pattern, and caliber at origin were assessed for each perforator. Intraoperative findings were the standard of reference. The sensitivity, positive predictive value, and diagnostic accuracy of the preoperative CTA protocol were calculated. RESULTS: In 255/263 (97%) patients, the dominant perforators assessed by CTA resulted adequate for surgical reconstruction. In 260/263 (99%) cases, the imaging localization of the dominant perforators corresponded with those seen intraoperatively (mean errors ≤1 cm). The preoperative CTA imaging sensitivity, positive predictive value, and diagnostic accuracy in determining the localization of perforators were 99% (95% CI 98-100), 100% and 99% (95% CI 98-100), respectively. No statistically significant differences were found between the CTA findings and the surgical findings for the assessment of branching pattern and caliber of the dominant perforators (P < 0.001). CONCLUSION: The present protocol has demonstrated high accuracy in the CTA imaging assessment of the perforators before DIEP flap reconstruction with high reproducibility between CT and surgical findings.

Tumor-Associated Macrophages and Inflammatory Microenvironment in Gastric Cancer: Novel Translational Implications.

Gastric cancer (GC) represents the fifth most frequently diagnosed cancer worldwide, with a poor prognosis in patients with advanced disease despite many improvements in systemic treatments in the last decade. In fact, GC has shown resistance to several treatment options, and thus, notable efforts have been focused on the research and identification of novel therapeutic targets in this setting. The tumor microenvironment (TME) has emerged as a potential therapeutic target in several malignancies including GC, due to its pivotal role in cancer progression and drug resistance. Therefore, several agents and therapeutic strategies targeting the TME are currently under assessment in both preclinical and clinical studies. The present study provides an overview of available evidence of the inflammatory TME in GC, highlighting different types of tumor-associated cells and implications for future therapeutic strategies.

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL).

BACKGROUND: Despite sensitivity to first-line chemotherapy, most small-cell lung cancer (SCLC) patients relapse. In this setting, topotecan demonstrated modest activity with significant toxicity. Paclitaxel was also active. This study was designed to evaluate activity and safety of nab-paclitaxel in relapsed SCLC. METHODS: In this multicentre prospective Phase 2 trial, patients with refractory or sensitive SCLC progressed to first-line platinum-based chemotherapy received nab-paclitaxel 100 mg/smq on days 1, 8, 15 every 4 weeks up to six cycles, progressive disease or intolerable toxicity. Primary endpoint was investigator-assessed objective tumour response. Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). RESULTS: Of the 68 patients treated, partial response was 8% in the refractory cohort and 14% in the sensitive cohort. Most common toxicities of any grade were fatigue (54%), anaemia (38%), neutropenia (29%), leukopenia (26%) and diarrhoea (21%). Median PFS was similar in both refractory (1.8 months) and sensitive cohorts (1.9 months), while median OS was longer in sensitive one (6.6 versus 3.6 months). CONCLUSIONS: Although nab-paclitaxel has shown some modest anti-tumour activity in relapsed SCLC, associated with a favourable toxicity profile, the primary end-point of the study was not met. CLINICAL TRIAL REGISTRATION: Clinical Trial registration number is ClinicalTrials.gov Identifier: NCT03219762.

An astonishing case of liver-only metastatic colorectal cancer cured by FOLFOXIRI alone.

The array of tools currently available and the aim of treatment make choosing the best therapeutic strategy in metastatic colorectal cancer (CRC) an increasing challenge worldwide. We present the case of a 53-year-old man with metachronous metastases (liver-only metastatic disease) treated with FOLFOXIRI as first-line treatment. In March 2010, a colonoscopy carried out for persistent constipation revealed a neoplastic stenosing mass. After a month, the patient underwent a low anterior rectal resection with colorectal anastomosis; no metastases were found on the computed tomography scan. Histology confirmed adenocarcinoma (pT3N0M0; stage IIA). No adjuvant treatment was given because of the absence of negative prognostic and molecular factors in stage II. After 6 months of follow-up, a computed tomography scan and F-FDG PET showed five focal hepatic lesions. We decided to start a FOLFOXIRI regimen aimed at conversion. The patient had a complete clinical and radiological response to chemotherapy after eight cycles. After 7 years, the patient is currently without any evidence of recurrence or progression of the disease. Few literature reports suggest that chemotherapy alone can cure patients with CRC liver metastases. Although regimens including oxaliplatin have never been reported as potential healing tools, the FOLFOXIRI chemotherapeutic schedule (oxaliplatin, irinotecan, and 5-fluorouracil) showed a high response rate in mCRC and can even cure the metastatic disease in sporadic cases.

New hallmark of hepatocellular carcinoma, early hepatocellular carcinoma and high-grade dysplastic nodules on Gd-EOB-DTPA MRI in patients with cirrhosis: a new diagnostic algorithm.

OBJECTIVE: Many improvements have been made in diagnosing hepatocellular carcinoma (HCC), but the radiological hallmarks of HCC have remained the same for many years. We prospectively evaluated the imaging criteria of HCC, early HCC and high-grade dysplastic nodules (HGDNs) in patients under surveillance for chronic liver disease, using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and diffusion-weighted imaging. DESIGN: Our study population included 420 nodules >1 cm in 228 patients. The MRI findings of each nodule were collected in all sequences/phases. The diagnosis of HCC was made according to the American Association for the Study of Liver Diseases (AASLD) criteria; all atypical nodules were diagnosed using histology. RESULTS: A classification and regression tree was developed using three MRI findings which were independently significant correlated variables for early HCC/HCC, and the best sequence of their application in a new diagnostic algorithm (hepatobiliary hypointensity, arterial hyperintensity and diffusion restriction) was suggested. This algorithm demonstrated, both in the entire study population and for nodules ≤2 cm, higher sensitivity (96% [95% CI 93.5% to 97.6%] and 96.6% [95% CI 93.9% to 98.5%], P<0.001, respectively) and slightly lower specificity (91.8% [95% CI 88.6% to 94.1%], P=0.063, and 92.7% [95% CI 88.9% to 95.4%], P=0.125, respectively) than those of the AASLD criteria. Our new diagnostic algorithm also showed a very high sensitivity (94.7%; 95% CI 92% to 96.6%) and specificity (99.3%; 95% CI 97.7% to 99.8%) in classifying HGDN. CONCLUSION: Our new diagnostic algorithm demonstrated significantly higher sensitivity and comparable specificity than those of the AASLD imaging criteria for HCC in patients with cirrhosis evaluated using Gd-EOB-DTPA MRI, even for lesions ≤2 cm. Moreover, this diagnostic algorithm allowed evaluating other lesions which could arise in a cirrhotic liver, such as early HCC and HGDN.

Imaging features of microvascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy in HCV-related cirrhosis.

OBJECTIVES: To evaluate imaging features of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) developed after direct-acting antiviral (DAA) therapy in HCV-related cirrhosis. METHODS: Retrospective cohort study on 344 consecutive patients with HCV-related cirrhosis treated with DAA and followed for 48-74 weeks. Using established imaging criteria for MVI, HCC features were analysed and compared with those in nodules not occurring after DAA. RESULTS: After DAA, HCC developed in 29 patients (single nodule, 18 and multinodular, 11). Median interval between therapy end and HCC diagnosis was 82 days (0-318). Forty-one HCC nodules were detected (14 de novo, 27 recurrent): maximum diameter was 10-20 mm in 27, 20-50 mm in 13, and > 50 mm in 1. Imaging features of MVI were present in 29/41 nodules (70.7%, CI: 54-84), even in 17/29 nodules with 10-20 mm diameter (58.6%, CI: 39-76). MVI was present in only 17/51 HCC nodules that occurred before DAA treatment (33.3%, CI: 22-47) (p= 0.0007). MVI did not correlate with history of previous HCC. CONCLUSIONS: HCC occurs rapidly after DAA therapy, and aggressive features of MVI characterise most neoplastic nodules. Close imaging evaluations are needed after DAA in cirrhotic patients. KEY POINTS: • In HCV cirrhosis, hepatocellular carcinoma develops soon after direct-acting antiviral therapy. • HCC presents imaging features of microvascular invasion, predictive of more aggressive progression. • Cirrhotic patients need aggressive and close monitoring after direct-acting antiviral therapy.

Inter-operator variability and source of errors in tumour response assessment for hepatocellular carcinoma treated with sorafenib.

OBJECTIVES: To assess the inter-operator concordance and the potential sources of discordance in defining response to sorafenib in hepatocellular carcinoma (HCC). METHODS: All patients who received sorafenib between September 2008 and February 2015 were scrutinised for this retrospective study. Images were evaluated separately by three radiologists with different expertise in liver imaging (operator 1, >10 years; operator 2, 5 years; operator 3, no specific training in liver imaging), according to: response evaluation radiological criteria in solid tumours (RECIST) 1.1, modified RECIST (mRECIST) and response evaluation criteria in cancer of the liver (RECICL). RESULTS: The overall response concordance between the more expert operators was good, irrespective of the criteria (RECIST 1.1, ĸ = 0.840; mRECIST, ĸ = 0.871; RECICL, ĸ = 0.819). Concordance between the less expert operator and the other colleagues was lower. The most evident discordance was in target lesion response assessment, with expert operators disagreeing mostly on lesion selection and less expert operators on lesion measurement. As a clinical correlate, overall survival was more tightly related with "progressive disease" as assessed by the expert compared to the same assessment performed by operator 3. CONCLUSIONS: Decision on whether a patient is a responder or progressor under sorafenib may vary among different operators, especially in case of a non-specifically trained radiologist. Regardless of the adopted criteria, patients should be evaluated by experienced radiologists to minimise variability in this critical instance. KEY POINTS: • Inter-operator variability in the assessment of response to sorafenib is poorly known. • The concordance between operators with expertise in liver imaging was good. • Target lesions selection was the main source of discordance between expert operators. • Concordance with non-specifically trained operator was lower, independently from the response criteria. • The non-specifically trained operator was mainly discordant in measurements of target lesions.

Can Current Preoperative Imaging Be Used to Detect Microvascular Invasion of Hepatocellular Carcinoma?

PURPOSE: To determine the accuracy of imaging features, such as tumor dimension, multinodularity, nonsmooth tumor margins, peritumoral enhancement, and radiogenomic algorithm based on the association between imaging features (internal arteries and hypoattenuating halos) and gene expression that the authors called two-trait predictor of venous invasion (TTPVI), in the prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This single-center retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. One hundred twenty-five patients (median age, 63 years; interquartile range, 53-71 years) with a diagnosis of HCC and indications for hepatic resection were included. Two observers independently reviewed radiologic images to evaluate the following features for MVI: maximum diameter, number of lesions, tumor margins, TTPVI, and peritumoral enhancement. Interobserver agreement was checked, and diagnostic accuracy of radiologic features was investigated. RESULTS: The total number of HCC nodules was 140. Large tumor size, nonsmooth tumor margins, TTPVI, and peritumoral enhancement were significantly related to the presence of MVI (P < .05 in all cases and for both observers). Multinodularity was not significantly related (P = .158). Moreover, the diagnostic accuracy of the three "worrisome" radiologic features (nonsmooth tumor margins, peritumoral enhancement, and TTPVI) was associated with tumor size: The negative predictive value of the absence of worrisome features decreased from 0.84 for observer 1 and 0.91 for observer 2 for tumors smaller than 2 cm to 0.56 and 0.71, respectively, for tumors larger than 5 cm, whereas the presence of all three worrisome features returned to a positive predictive value of 0.95 for observer 1 and 0.96 for observer 2 independent of tumor size, with no significant interobserver differences (P > .10). CONCLUSION: "Worrisome" imaging features, such as tumor dimension, nonsmooth tumor margins, peritumoral enhancement, and TTPVI, have high accuracy in the prediction of MVI in HCC.

Actionable imaging findings in the daily PET/CT scenario.

Background and aim: The American College of Radiology (ACR) defines "actionable findings" the ones requiring a special communication between radiologists and referring clinicians, suggesting to organize their categorization in a three-degree scale on the basis of the risk for the patient to develop complications. These cases may fall in a grey-zone communication between different care figures with the risk of being underestimated or even not being considered at all. In this paper, our aim is to adapt the ACR categorization to the most frequent actionable findings encountered when reporting PET/CT images in a Nuclear Medicine Department, describing the most frequent and relevant imaging features and presenting the modalities of communication and the related clinical interventions that can be modulated by the prognostic severity of the clinical cases. Materials and methods: We performed a descriptive, observational and critical analysis of the most relevant literature on the topic of "actionable findings", in particular, starting from the reports of the ACR Actionable Reporting Work Group, we categorised and described, in a narrative review, the most relevant "actionable findings" encountered in the Nuclear Medicine PET/CT daily practice. Results: To the best of our knowledge, to date there are no clear indications on this selective PET/CT topic, considering that the current recommendations target mainly radiologists and assume a certain level of radiological expertise. We resumed and classified the main imaging conditions under the term of "actionable findings" according to the corresponding anatomical districts, and we described their most relevant imaging features (independently of PET avidity or not). Furthermore, a different communication timing and strategy was suggested on the basis of the findings' urgency. Conclusion: A systematic categorization of the actionable imaging findings according to their prognostic severity may help the reporting physician to choose how and when to communicate with the referring clinician or to identify cases requiring a prompt clinical evaluation. Effective communication is a critical component of diagnostic imaging: timely receipt of the information is more important than the method of delivery.

Prognostic value of integrated morphofunctional imaging methods in inoperable intrahepatic cholangiocarcinoma.

Introduction and aim: Intrahepatic cholangiocarcinoma (iCCA) is a disease characterized by rarity, heterogeneity, and high mortality, where surgical resection is often not possible. Nowadays, due to the recent introduction of new therapeutic options such as trans-arterial radioembolization (TARE), it is increasingly important to define the role of morphofunctional imaging methods for the prognostic stratification of patients affected by iCCA. The aim of the study was to verify the prognostic value of morphofunctional imaging methods at the baseline in patients with inoperable iCCA. Methods: In total, 45 patients with iCCA were sent to our center between January 2016 and March 2021 for being evaluated to be treated with TARE. All of them underwent both [18F]-FDG-PET/CT and contrast-enhanced CT (ceCT) in a single procedure and were included in our study. The inclusion criteria were as follows: a diagnosis of inoperable iCCA; both [18F]-FDG-PET/CT and ceCT scans; and washout from therapy for at least 2 months before baseline [18F]-FDG-PET/CT and ceCT scans. Both clinical and laboratory data and baseline imaging data (ceCT and [18F]-FDG-PET/CT) were collected. In particular, regarding clinical and laboratory data, we collected overall survival (OS), gender, age, prior therapies, liver function indices, and tumor markers. Regarding ceCT, we collected TNM staging, lesion diameter, volume, vascularization, and presence of intravascular necrosis. Regarding [18F]-FDG-PET/CT, we collected TNM staging, Standard-Uptake-Value max (SUVmax), Metabolic-Tumor-Volume (MTV), and Total-Lesion-Glycolysis (TLG=MTV*lesions SUVmean). Philips-Vue-PACS software was used, setting hepatic SUVmean as TLG threshold. Results: A statistically significant correlation was found between some examined parameters at morphofunctional investigations at the baseline and OS. [18F]-FDG-PET/CT parameters statistically correlated with OS were the stage of disease greater than M0 (p = 0.037), major lesion SUVmax (p = 0.010), MTV (p ≤ 0.001), and TLG (p < 0.001). Other parameters at ceCT correlated with OS were the stage of disease greater than T2 (p = 0.038), maximum lesion diameter (p = 0.07), volume of the major lesion (p = 0.016), and total volume of lesions (p = 0. 009). Biochemical parameters correlated with OS were gamma glutamyl transferase (GGT, p = 0.014), alkaline phosphatase (ALP, p = 0.019), carcinoembryonic antigen (CEA, p = 0.004), and carbohydrate antigen 19-9 (CA 19-9, p < 0.001). From the parameters estimated by the multivariate model, we derived a four-variable score for OS combining nodal involvement and SUVmax at [18F]-FDG-PET/CT, GGT, and CA 19-9 levels. Conclusion: Considering our data, performing integrated pre-therapy imaging is critical for the prognostic stratification of patients with iCCA.

Optimization of pineapple juice amount used as a negative oral contrast agent in magnetic resonance cholangiopancreatography.

To evaluate the potential variability of Manganese (Mn2+) in commercial pineapple juice (PJ) produced in different years and to identify the optimal Mn2+ concentration in the correct amount of PJ to be administered prior to Magnetic Resonance Cholangiopancreatography (MRCP) in order to suppress the gastroduodenal (GD) liquid signal. The Mn2+ concentration in PJ produced in different years was defined using Atomic Absorption Spectrometry. The optimal Mn2+ concentration and the amount of PJ, were estimated in an in-vitro analysis, and were then prospectively tested in a population of patients who underwent MRCP. The results were compared with those achieved with the previous standard amount of PJ used in a similar population. The concentrations of Mn2+ in commercial PJ produced in different years did not differ. A total amount of 150 ml (one glass) of PJ having a high Mn2+ content (2.37 mg/dl) was sufficient for the suppression of the GD liquid signal, despite the additional dilution caused by GD liquids since it led to a final concentration of Mn2+ of 0.5-1.00 mg/dl. The optimized single-dose oral administration of 150 ml (approximately one glass) of PJ having a high Mn2+ concentration prior to MRCP was adequate to guarantee the correct amount of Mn2+ to suppress the GD signal.

The Feasibility of Liver Biopsy for Undefined Nodules in Patients under Surveillance for Hepatocellular Carcinoma: Is Biopsy Really a Useful Tool?

Background: The aim of the present study is to determine the feasibility of biopsy for atypical liver nodules in patients under surveillance for hepatocellular carcinoma (HCC), assessing which factors influence the decision to perform it. Methods: A total of 128 atypical liver nodules in 108 patients under surveillance for HCC, who underwent CT between September 2018 and September 2019, were included. All the images were saved digitally (on CD-ROM) and the two most representative images in the arterial and delayed phases were selected for each lesion and inserted into a digital atlas (on PDF). Two experienced radiologists (Readers 1 and 2) reviewed both the CD-ROM and the PDF to define the feasibility of biopsy in both scenarios, specifying the reasons for the unfeasibility of biopsy. The intra-observer variability and inter-observer variability were assessed. Results: When reviewing the PDF, 76 (59.4%) and 68 (53.1%) nodules were deemed unfeasible for biopsy by the less experienced radiologist (Reader 1) and the more experienced radiologist (Reader 2), respectively (p = 0.604). When reviewing the entire CT study, both percentages decreased slightly (Reader 1 = 70/128 (54.7%); Reader 2 = 61/128 (47.6%); p = 0.591). The intra-reader agreement on the PDF was substantial (k = 0.648 (95% CI = 0.513-0.783)). The inter-reader agreement on the PDF was slight (k = 0.185 (95% CI = 0.021-0.348)) and moderate on the entire CT study (k = 0.424 (95% CI = 0.269-0.579)). When assessing the PDF, the nodule size (10-20 mm) and location in segments six and eight were negatively and positively associated with the feasibility of liver biopsy, respectively. When assessing the CD-ROM, only the nodule dimension was associated with the unfeasibility of liver biopsy. Conclusions: The unfeasibility of liver biopsy is mainly due to the small size of the lesions and their location.

Monitoring tumor growth rate to predict immune checkpoint inhibitors' treatment outcome in advanced NSCLC.

INTRODUCTION: Radiological response assessment to immune checkpoint inhibitor is challenging due to atypical pattern of response and commonly used RECIST 1.1 criteria do not take into account the kinetics of tumor behavior. Our study aimed at evaluating the tumor growth rate (TGR) in addition to RECIST 1.1 criteria to assess the benefit of immune checkpoint inhibitors (ICIs). METHODS: Tumor real volume was calculated with a dedicated computed tomography (CT) software that semi-automatically assess tumor volume. Target lesions were identified according to RECIST 1.1. For each patient, we had 3 measurement of tumor volume. CT-1 was performed 8-12 weeks before ICI start, the CT at baseline for ICI was CT0, while CT + 1 was the first assessment after ICI. We calculated the percentage increase in tumor volume before (TGR1) and after immunotherapy (TGR2). Finally, we compared TGR1 and TGR2. If no progressive disease (PD), the group was disease control (DC). If PD but TGR2 < TGR1, it was called LvPD and if TGR2 ⩾ TGR1, HvPD. RESULTS: A total of 61 patients who received ICIs and 33 treated with chemotherapy (ChT) were included. In ICI group, 18 patients were HvPD, 22 LvPD, 21 DC. Median OS was 4.4 months (95% CI: 2.0-6.8, reference) for HvPD, 7.1 months (95% CI 5.4-8.8) for LvPD, p = 0.018, and 20.9 months (95% CI: 12.5-29.3) for DC, p < 0.001. In ChT group, 7 were categorized as HvPD, 17 as LvPD and 9 as DC. No difference in OS was observed in the ChT group (p = 0.786). CONCLUSION: In the presence of PD, a decrease in TGR may result in a clinical benefit in patients treated with ICI but not with chemotherapy. Monitoring TGR changes after ICIs administration can help physician in deciding to treat beyond PD.

Transient asymptomatic pulmonary opacities and interstitial lung disease in EGFR-mutated non-small cell lung cancer treated with osimertinib.

INTRODUCTION: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Some osimertinib-related interstitial lung diseases (ILDs) were shown to be transient, called transient asymptomatic pulmonary opacities (TAPO)-clinically benign pulmonary opacities that resolve despite continued osimertinib treatment-and are not associated with the clinical manifestations of typical TKI-associated ILDs. METHODS: In this multicentric study, we retrospectively analyzed 92 patients with EGFR-mutated NSCLC treated with osimertinib. Computed tomography (CT) examinations were reviewed by two radiologists and TAPO were classified according to radiologic pattern. We also analyzed associations between TAPO and patients' clinical variables and compared clinical outcomes (time to treatment failure and overall survival) for TAPO-positive and TAPO-negative groups. RESULTS: TAPO were found in 18/92 patients (19.6%), with a median follow-up of 114 weeks. Median onset time was 16 weeks (range 6-80) and median duration time 14 weeks (range 8-37). The most common radiologic pattern was focal ground-glass opacity (54.5%). We did not find any individual clinical variable significantly associated with the onset of TAPO or significant difference in clinical outcomes between TAPO-positive and TAPO-negative groups. CONCLUSIONS: TAPO are benign pulmonary findings observed in patients treated with osimertinib. TAPO variability in terms of CT features can hinder the differential diagnosis with either osimertinib-related mild ILD or tumor progression. However, because TAPO are asymptomatic, it could be reasonable to continue therapy and verify the resolution of the CT findings at follow-up in selected cases.

Critical diagnostic delay associated with unusual presentation of hepatocellular carcinoma (HCC) with orbital metastases: a case report.

Orbital metastases are an extremely rare finding in patients with hepatocarcinoma (HCC), especially as its first presentation. Therefore, the risk of misdiagnosis is high, as well as that of drastic delays of the therapeutic algorithm. Here we report a 71-year-old man presenting with orbital metastases as the initial sign of HCC, whose initial misdiagnosis led to the impossibility to start life-saving cancer treatment. The patient's history has begun on March 2018 with a growing tumefaction of the right orbit initially treted with antibiotics and corticosteroids without benefit. Subsequently, a facial CT scan showed a voluminous right intra-orbital mass, eroding the orbital roof. Tissue biopsy documented well differentiated malignant epithelial tumor cells. Under the suspect of primitive lachrymal gland tumor, the patient was admitted to the head and neck Unit with surgical intent. However, a subsequent 18F-FDG-PET documented the presence of liver lesions and multiple sites of metastasis. A new biopsy, this time on liver nodules, was carried out and the diagnosis of HCC was finally made. Samples from the first biopsy were then reviewed and judged consistent with HCC metastasis. Unfortunately, the initial misdiagnosis resulted in a six-month delay of the start of a therapeutic approach. During that time, patient's general conditions got extremely worse, making him unable to afford an antiblastic treatment. The patient died three months after the definitive diagnosis. This case suggests that the presence of intraorbital lesion requires a multimodal approach starting from the initial presentation. Performing a complete staging since tumor's clinical onset is mandatory, preferably before carrying out a tissue biopsy. Even though HCC represents a rare cause of intraocular metastasis, it needs to be ruled out when an orbital mass is documented, as the short median survival and the frequently poor conditions of HCC patients make a timely diagnosis crucial.

Expected and non-expected immune-related adverse events detectable by CT.

PURPOSE: Cancer treatments with immune checkpoint inhibitors (ICI) are associated with a unique set of drug toxicities called immune-related adverse events (irAES). The aim of the present study was to describe the radiological manifestation of irAES detectable by CT. METHOD: Retrospective analysis of 284 patients treated with ICI for various types of advanced cancer; of them, 129 patients were selected, all having been treated with single-agent ICI, and all with a baseline CT scan and follow-up scans available at our Institute. CT examinations were reviewed by two radiologists involved in the study with a consensus reading. Imaging findings consistent with irAES were reported and correlated with clinical-laboratory data. RESULTS: Immune-related adverse events were found in 25/129 (19.4 %) patients. No statistically significant differences were found in either the prevalence of irAES or in the time of onset of tumour type. Thoracic complications were detected in 14/25 (56.0 %) patients consisting in: 3 radiation recall pneumonia, 3 Transient Asymptomatic Pulmonary Opacities (TAPOs), 3 hypersensitivity pneumonia, 2 diffuse alveolar damage, 2 organizing pneumonia, 1 sarcoid-like reaction. In the remaining 11/25 (44.0 %), there were extra-pulmonary complications: 3 colitis, 4 cholecystitis, 2 pancreatitis and 2 cases of visceral ischemia. CONCLUSIONS: Radiologists should be aware of the wide spectrum of irAES as they could affect the outcome. Pneumonia is the most frequent irAES; however, the international classification for interstitial lung disease does not seem to be capable of describing all possible drug-related pulmonary toxicities. Additional findings included TAPOs, radiation recall pneumonia and sarcoid-like reaction.