Case Report: A Peculiar Case of Inflammatory Colitis After SARS-CoV-2 Infection.

We report a case of inflammatory colitis after SARS-CoV-2 infection in a patient with no additional co-morbidity who died within three weeks of hospitalization. As it is becoming increasingly clear that SARS-CoV-2 infection can cause immunological alterations, we investigated the expression of the inhibitory checkpoint PD-1 and its ligand PD-L1 to explore the potential role of this axis in the break of self-tolerance. The presence of the SARS-CoV-2 virus in colon tissue was demonstrated by qRT-PCR and immunohistochemical localization of the nucleocapsid protein. Expression of lymphocyte markers, PD-1, and PD-L1 in colon tissue was investigated by IHC. SARS-CoV-2-immunoreactive cells were detected both in the ulcerated and non-ulcerated mucosal areas. Compared to healthy tissue, where PD-1 is weakly expressed and PD-L1 is absent, PD-1 and PD-L1 expression appears in the inflamed mucosal tissue, as expected, but was mainly confined to non-ulcerative areas. At the same time, these markers were virtually undetectable in areas of mucosal ulceration. Our data show an alteration of the PD-1/PD-L1 axis and suggest a link between SARS-CoV-2 infection and an aberrant autoinflammatory response due to concomitant breakdown of the PD-1/PD-L1 interaction leading to early death of the patient.

Rare anti-VEGFR therapy-induced toxicity and long-term response to immunotherapy in a rare non-clear cell renal cell carcinoma patient.

Advanced non-clear cell renal cell carcinoma (nccRCC) has a poor prognosis and clinical data on the therapeutic options currently available, including immunotherapy, are generally limited highlighting an unmet clinical need. Moreover, the onset of rare adverse events raises the need of a better therapeutic management of limited treatment options. We report the clinical case of a 63-year-old man with the diagnosis of metastatic mucinous tubular and spindle cell carcinoma, a rare nccRCC, with sarcomatoid differentiation who developed two episodes of posterior reversible encephalopathy syndrome (PRES) to first-line sunitinib. It appeared after 5 months the start of the targeted therapy and reappeared at the reintroduction of the therapy. PRES is a rare and unusual adverse event to anti-vascular endothelial growth factor receptor (VEGFR) therapies, which is characterized by acute neurological disorders along with typical changes on neurological imaging, especially MRI. Moreover, this rare histotype of RCC experienced a long-term response to immunotherapy which is lasting more than 2 years. This clinical case is interesting for its rarity as a rare neurological adverse event developed twice in a rare type of RCC which also experienced an unusual long-term benefit to immunotherapy.

Percutaneous trans-hepatic rescue and neo-creation of a post-surgical complete hepaticojejunostomy dehiscence.

Biliary leakage complicating hepaticojejunostomy is a therapeutic dilemma for surgeons, gastroenterologist, and interventional radiologist. It is a major cause of postoperative morbidity. Percutaneous biliary intervention techniques have been developed for treating benign post-surgical biliary disease in patients not having severely compromised clinical conditions. Interventional radiology manoeuvres are especially indicated as the first line of treatment if endoscopic procedures are unfeasible for patients due to postsurgical anatomical modifications. We present a case of post-surgical complete hepaticojejunostomy dehiscence that was treated totally by percutaneous techniques with trans-hepatic rescue and hepaticojejunostomy neo-creation.

Heterogeneity of bone metastases as an important prognostic factor in patients affected by oestrogen receptor-positive breast cancer. The role of combined [18F]Fluoroestradiol PET/CT and [18F]Fluorodeoxyglucose PET/CT.

PURPOSE: To assess the prognostic role of different inter and intralesional expression (heterogeneity) of oestrogen receptor (ER) in bone metastases, as identified by the combined use of [18F]FES PET/CT and [18F]FDG PET/CT in patients with oestrogen receptor-positive (ER+) metastatic breast cancer (BC). METHODS: We analysed patients with a new diagnosis of bone metastases who were candidates for first-line systemic endocrine therapy. Before starting therapy, patients underwent baseline [18F]FES PET/CT and [18]FDG PET/CT. Semi-quantitative evaluation of whole-body bone metabolic burden (WB-B-MB) was performed on [18F]FES and [18F]FDG PET/CT in order to evaluate disease extent, tumour metabolism and ER heterogeneity. We used time-to-event analyses (Kaplan-Meier and Cox proportional-hazards methods) to estimate progression-free (PFS) and overall survival (OS), in order to assess the independent prognostic value of [18F]FES PET/CT and [18F]FDG PET/CT, alone and in combination. RESULTS: According to our criteria, we enrolled 49 patients. Over a median follow-up of 44.7 months, 35 patients suffered disease progression (71.4 %) and 15 died of disease (30.6 %). When the risk of disease progression was calculated by means of the Cox model, only [18F]FDG WB-B-MB was independently and directly associated to PFS (p = 0.02). On analysing the association between all prognostic parameters and survival, the Cox model showed that the only parameter associated with OS was the WB-B-MB FES/FDG ratio (p = 0.01). CONCLUSION: The combined use of [18F]FES-PET/CT and [18F]FDG-PET/CT can identify ER heterogeneity in BC bone metastases. This heterogeneity is significantly associated with survival. Moreover, the extension of the FDG-avid component correlates with the risk of disease progression.

Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia.

BACKGROUND: IL-1 plays a pivotal role in the inflammatory response during cytokine storm syndromes. OBJECTIVE: Our aim was to analyze the efficacy and safety of early anti-inflammatory treatment (AIT) with intravenous anakinra with or without glucocorticoids in coronavirus disease 2019 (COVID-19) pneumonia. METHODS: We performed a retrospective single-center cohort study of patients admitted for COVID-19 pneumonia from February 26 to April 29, 2020, to assess the efficacy of early AIT with intravenous anakinra (100 mg every 8 hours for 3 days, with tapering) alone or in combination with a glucocorticoid (intravenous methylprednisolone, 1-2 mg/kg daily, with tapering). The standard of care (SOC) treatment was hydroxychloroquine and/or azithromycin with or without antivirals and anticoagulants. Late rescue AIT with anakinra or tocilizumab was also evaluated. Treatment effect on overall survival was assessed by a propensity score-adjusted Cox model. RESULTS: A total of 128 patients were analyzed; 63 patients received early AIT (30 received anakinra alone and 33 received anakinra plus a glucocorticoid) at admission, and 65 patients did not receive early AIT and were used as controls; of the latter 65 patients, 44 received the SOC treatment alone and 21 received the SOC treatment plus late rescue AIT. After adjustment for all the unbalanced baseline covariates, early AIT reduced the hazard of mortality by 74% (adjusted hazard ratio [HR] = 0.26; P < .001). The effect was similar in patients receiving anakinra alone (adjusted HR = 0.28; P = .04) and anakinra plus a glucocorticoid (adjusted HR = 0.33; P = .07). Late rescue treatment did not show a significant advantage over SOC treatment alone (adjusted HR = 0.82; P = .70). CONCLUSIONS: This study suggests, on a larger series of patients with COVID-19 pneumonia, the potential efficacy and safety of the early use of high doses of intravenous anakinra with or without glucocorticoids.

ERANET JTC 2011: Submission and Activation of an International Academic Translational Project in Advanced Breast Cancer. Experience From the ET-FES Study.

Background: Academic research is important to face unmet medical needs. The Oncological community encounters many hurdles in setting up multicenter investigator-driven trials mainly due to administrative complexity. The purpose of a network organization at a multinational level is to facilitate clinical trials through standardization, coordination, and education for drug development and regulatory approval. Methods: The application of an European grant foresees the creation of a consortium which aims at facilitating multi-center academic clinical trials. Results: The ERA-NET TRANSCAN Call 2011 on "Validation of biomarkers for personalized cancer medicine" was released on December 2011. This project included Italian, Spanish, French and German centers. The approval process included Consortium constitution, project submission, Clinical Trial Submission, and activation on a national level. The different timescales for submitting study documents in each Country and the misalignment of objections by each Competent Authority CA, generated several requests for changes to the study documents which meant amendments had to be made; as requested by the 2001/20/EC Directive, the alignment of core documents is mandatory. This procedure impacted significantly on study activation timelines. Time to first patient in was 14, 10, 28, and 31 months from the date of submission in Italy, France, Spain, and Germany, respectively. Accrual was stopped on 22nd January 2021 due to an 18F FES shortage as the primary reason but also for having exceeded the project deadlines with consequent exhaustion of the funds allocated for the project. Conclusions: Pharmaceutical companies might be reluctant to fund research projects aimed at treatment individualization if the approval for a wider indication has already been achieved. Academic trials therefore become fundamental for promoting trials which are not attractive to big pharma. It was very difficult and time consuming to activate an academic clinical trial, for this reason, a study may become "old" as new drugs entered into the market. National institutions should promote the development of clinical research infrastructures and network with competence in regulatory, ethical, and legal skills to speed up academic research.

Contamination inside CT gantry in the SARS-CoV-2 era.

We investigated whether the internal gantry components of our computed tomography (CT) scanner contain severe acute respiratory syndrome 2 (SARS-CoV-2) ribonucleic acid (RNA), bacterial or fungal agents. From 1 to 27 March 2020, we performed 180 examinations of patients with confirmed SARS-CoV-2 infection using a dedicated CT scanner. On 27 March 2020, this CT gantry was opened and sampled in each of the following components: (a) gantry case; (b) inward airflow filter; (c) gantry motor; (d) x-ray tube; (e) outflow fan; (f) fan grid; (g) detectors; and (h) x-ray tube filter. To detect SARS-CoV-2 RNA, samples were analysed using reverse transcriptase-polymerase chain reaction (RT-PCR). To detect bacterial or fungal agents, samples have been collected using "replicate organism detection and counting" contact plates of 24 cm2, containing tryptic soy agar, and subsequently cultured. RT-PCR detected SARS-CoV-2 RNA in the inward airflow filter sample. RT-PCR of remaining gantry samples did not reveal the presence of SARS-CoV-2 RNA. Neither bacterial nor fungal agents grew in the agar-based growth medium after the incubation period. Our data showed that SARS-Cov-2 RNA can be found inside the CT gantry only in the inward airflow filter. All remaining CT gantry components were devoid of SARS-CoV-2 RNA.

Evaluation of novel coronavirus disease (COVID-19) using quantitative lung CT and clinical data: prediction of short-term outcome.

BACKGROUND: Computed tomography (CT) enables quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, helping in outcome prediction. METHODS: From 1 to 22 March 2020, patients with pneumonia symptoms, positive lung CT scan, and confirmed SARS-CoV-2 on reverse transcription-polymerase chain reaction (RT-PCR) were consecutively enrolled. Clinical data was collected. Outcome was defined as favourable or adverse (i.e., need for mechanical ventilation or death) and registered over a period of 10 days following CT. Volume of disease (VoD) on CT was calculated semi-automatically. Multiple linear regression was used to predict VoD by clinical/laboratory data. To predict outcome, important features were selected using a priori analysis and subsequently used to train 4 different models. RESULTS: A total of 106 consecutive patients were enrolled (median age 63.5 years, range 26-95 years; 41/106 women, 38.7%). Median duration of symptoms and C-reactive protein (CRP) was 5 days (range 1-30) and 4.94 mg/L (range 0.1-28.3), respectively. Median VoD was 249.5 cm3 (range 9.9-1505) and was predicted by lymphocyte percentage (p = 0.008) and CRP (p < 0.001). Important variables for outcome prediction included CRP (area under the curve [AUC] 0.77), VoD (AUC 0.75), age (AUC 0.72), lymphocyte percentage (AUC 0.70), coronary calcification (AUC 0.68), and presence of comorbidities (AUC 0.66). Support vector machine had the best performance in outcome prediction, yielding an AUC of 0.92. CONCLUSIONS: Measuring the VoD using a simple CT post-processing tool estimates SARS-CoV-2 burden. CT and clinical data together enable accurate prediction of short-term clinical outcome.

Diagnostic value of retrospectively fused 64CuCl2 PET/MRI in biochemical relapse of prostate cancer: comparison with fused 18F-Choline PET/MRI, 64CuCl2 PET/CT, 18F-Choline PET/CT, and mpMRI.

PURPOSE: To assess the diagnostic value of retrospectively fused PET/MRI by comparing the detection rates (DRs) of fused 64CuCl2 PET/MRI vs. fused 18F-Choline PET/MRI in patients with suspected prostatic cancer (PCa) recurrence. The secondary objective was to compare the DRs of fused PET/MRI vs. those of the separate imaging modalities. METHODS: We retrospectively evaluated 50 PCa patients with biochemical relapse after radical prostatectomy (RP) or radiotherapy (RT). All patients underwent 64CuCl2 PET/CT, 18F-Choline PET/CT, and multiparametric magnetic resonance imaging (mpMRI) within 15 days. Fused 64CuCl2-PET/MRI and fused 18F-Choline PET/MRI images were obtained by retrospective co-registration of MRI and PET images. Experienced readers interpreted the images, and the DRs of each imaging modality were assessed. RESULTS: In the patient-based analysis, overall DRs of fused 64CuCl2 PET/MRI, fused 18F-Choline PET/MRI, 64CuCl2 PET/CT, 18F-Choline PET/CT, and mpMRI were 88%, 68%, 82%, 56%, and 74%, respectively. In the lesion-based analysis, overall DRs of fused 64CuCl2 PET/MRI, fused 18F-Choline PET/MRI, 64CuCl2 PET/CT, 18 F-Choline PET/CT, and mpMRI were 95%, 66%, 87%, 58%, and 71%, respectively. CONCLUSIONS: Retrospectively fused PET/MRI is able to overcome the limitations of the separate interpretation of the individual imaging modalities. Fused 64CuCl2 PET/MRI provided the highest diagnostic performance in the detection of PCa local relapse.

Solitary Fibrous Tumor of the Prostate.

Even though most tumors located in the prostate derive from prostatic glands, there is a long list of malignant and nonmalignant causes for prostatic growths that clinicians should be aware of. Tumors of the prostate can be grouped in epithelial, neuroendocrine, stromal, mesenchymal, hematolymphoid, and miscellaneous. Solitary fibrous tumor of the prostate (SFT), is an extremely rare mesenchymal tumor (only about 20 cases reported in the literature). Histologic features resemble those of the more common variant pleural SFT. Of all, 10%-20% of SFTs, also known as malignant SFTs, behave aggressively. Herein, we describe a case of prostatic SFT in a 66-year-old patient that presented with obstructive urinary symptoms and normal prostate-specific antigen levels.

Horseshoe adrenal gland associated with spinal and vascular anomalies.

Horseshoe (or butterfly) adrenal gland (HAG) is an exceedingly rare congenital abnormality compared to horseshoe kidney. Here we present computed tomography findings of HAG in a 70-year-old man, associated with some spinal and vascular abnormalities; in addition, a brief review of HAG in adult people is presented. In our case, spinal anomalies included a severe scoliosis, a "butterfly" deformation of Th9 vertebra and the presence of a "split lumbosacral thecal sac" at L5 level. As regards, vascular anomalies, they were noted: the origin of the left common carotid artery from the innominate artery and the absence of celiac trunk with separate origin of three branches directly off the aorta (a splenic artery, a left gastrohepatic trunk and a right hepatic-pancreaticoduodenal artery).

Noninvasive liver fibrosis assessment in chronic viral hepatitis C: agreement among 1D transient elastography, 2D shear wave elastography, and magnetic resonance elastography.

PURPOSE: To assess the agreement of one-dimensional transient elastography (1D-TE), two-dimensional shear wave elastography (2D-SWE), and magnetic resonance elastography (MRE) in a consecutive cohort of patients affected by hepatitis C virus (HCV) and to understand which patient-related factors are associated with disagreement. METHODS: Ninety-one consecutive patients with current or previous chronic HCV infection were enrolled between March 2017 and September 2018. We assessed the correlation between stiffness measurements expressed in kilopascals (kPa). After converting kPa values in three groups of increasing fibrosis burden using validated cut-off values, we assessed the agreement among the different techniques. Factors influencing inter-modality disagreement were examined by employing multivariate logistic regression analysis. RESULTS: Seventy-seven patients met the inclusion criteria and had reliable measurements by all stiffness imaging techniques. At the quantitative analysis, a strong correlation between stiffness measurements was found (Spearman's rho values ranging from 0.7 to 0.89 in all pairs of techniques). Complete concordance among MRE, 1D-TE, and 2D-SWE was found in 64.9% of patients, and the agreement was highest between MRE and 1D-TE, with κ value of 0.801. In only 2/77 patients (2.6%), there was complete disagreement. High body mass index (BMI) was the only factor significantly associated with inter-modality discordance. CONCLUSIONS: MRE, 1D-TE, and 2D-SWE assigned the majority of patients to the same fibrosis group. The agreement was at least good, and there was a strong correlation between kPa values in all three pairs of techniques. Highest agreement was found between MRE and 1D-TE. High BMI was associated with discordance among the techniques.

Thoracic Renal Artery.

We report a case of right renal artery originating from the thoracic aorta with normal position of the right kidney. Although this anomaly is rare, vascular, thoracic, and urological surgeons should be aware about this vascular variant before planning their surgical intervention.

Spontaneous hepatic haemangioma rupture and hemoperitoneum: a double problem with a single stage interventional radiology solution.

Hepatic haemangioma is a congenital vascular malformation, considered the most common benign mesenchymal hepatic tumour. Spontaneous or traumatic rupture is the most severe complication. In case of rupture, surgical resection and enucleation, as a single therapy or after trans-arterial embolization are considered the treatments of choice. We report a case of spontaneous rupture of a hepatic haemangioma with massive hemoperitoneum successfully treated by percutaneous hepatic trans-arterial embolization and pelvic drainage alone.

Imaging findings of ovarian leiomyosarcoma with histopathologic correlations.

Leiomyosarcoma (LMS) is a malignant mesenchymal tumor deriving from smooth muscle. Ovarian LMS is exceedingly rare and only few reports have been reported in literature. The article illustrates a case of ovarian leiomyosarcoma in a 61-year-old woman, describing CT and MRI features correlated to histopathologic findings. LMS should be included in the differential diagnosis of solid and multiloculated ovarian lesions, in particular in post-menopausal women.

Mechanical aspiration thrombectomy in the treatment of acute intrastent renal artery thrombosis.

Chimney-and-periscope technique for thoraco-abdominal aneurysm repair is a valuable treatment option in selected patients. Acute renal artery occlusion is a serious complication after this technique. We report a case of acute right renal artery occlusion, consequent to a previous chimney-and-periscope technique that was treated urgently by mechanical aspiration thrombectomy.