Heterogeneous response to target therapy in metastatic papillary renal cell carcinoma evaluated by morphologic and metabolic multimodality imaging

Papillary renal cell carcinoma (PRCC) accounts for about 15% to 20% of renal cell carcinoma and is histologically distinguished in type I and type II. The last one is associated with poorer prognosis. Treatment options for PRCC patients are surgery, immunotherapy, revolutionized by Nivolumab, and other target-therapy with an improvement in overall survival. Heterogenous response and a pseudo-progression may be observed in the initial phase of biological treatment that could induce premature discontinuation. Patient concerns: We present the case of a 44-year-old woman with left cervical palpable mass increased in size and without concomitant disease or previous surgery. Diagnosis: Neck ultrasonography, contrast-enhanced Computed Tomography, and 18F-FDG PET/CT were performed with the detection of lymph nodes involvement and a left renal lesion. Interventions: The patients underwent left radical nephrectomy and homolateral cervical and para-aortic lymphadenectomy, with histological diagnosis of PRCC, type II. After disease relapse, the inter-aortocaval lymph node was laparoscopically removed. Following the detection of further disease relapse in several lymph nodes and the lung, several lines of target-therapy were started; then disease progression and worsening of clinical and hematological status led us to start Nivolumab as last-line therapy. Outcomes: A heterogeneous response to therapies was documented with morphological and nuclear medicine imaging, however the concomitant deterioration of performance status and liver function led to discontinuation of Nivolumab; then the patient died, 30 months after diagnosis. Lessons: Here we describe the clinical case and radiological and nuclear medicine imaging investigations performed by our patient, highlighting that 18F-FDG PET/CT shows greater adequacy in assessing the response to therapy, avoiding premature drug discontinuation, and ensuring better management of a patient with advanced PRCC

Copper-64 Dichloride as Theranostic Agent for Glioblastoma Multiforme: A Preclinical Study

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a median survival time less than one year. To date, there are only a limited number of effective agents available for GBM therapy and this does not seem to add much survival advantage over the conventional approach based on surgery and radiotherapy. Therefore, the development of novel therapeutic approaches to GBM is essential and those based on radionuclide therapy could be of significant clinical impact. Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the nucleus compared to normal cells. This behavior can be conveniently exploited both for diagnosis and for delivering therapeutic payloads (theranostic) of the radionuclide copper-64 into the nucleus of cancerous cells by intravenous administration of its simplest chemical form as dichloride salt [64Cu]CuCl To evaluate the potential theranostic role of [64Cu]CuClin GBM, the present work reports results from a preclinical study carried out in a xenografted GBM tumor mouse model. Biodistribution data of this new agent were collected using a small-animal PET tomograph. Subsequently, groups of tumor implanted nude mice were treated with [64Cu]CuClto simulate single-and multiple-dose therapy protocols, and results were analyzed to estimate therapeutic efficacy

Clinical impact of routine angiographic follow-up after percutaneous coronary interventions on unprotected left main

Background: Patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES) on unprotected left main (ULM) represent a complex subset. The role of routine coronary angiography at follow up in this subset remains debated. Methods: At the documented center, all patients undergoing successful PCI on ULM lesions performing angiographic follow-up is suggested, but adherence to such a recommendation is inhomogeneous. Consecutive patients undergoing DES PCI on ULM were enrolled and experienced no adverse events during the first 6 months. Patients were then allocated to two groups: those undergoing routine control angiography (CA) and those undergoing clinical follow-up (CF). Primary endpoint was major adverse cardiac events (MACE) defined as cardiac death, myocardial infarction and urgent repeat target vessel revascularization. Results: A total of 190 patients underwent successful DES implantation on ULM and the study population was without early events. CA was performed at 6 months after the index procedure in 91 (48%) patients. After 35 \ub1 21 months, MACE rates were significantly more common in the CF group as compared with the CA group (16.2% vs. 4.3%, p = 0.009). At multivariable analysis, CA was associated with reduced MACE risk (HR 0.13, 95% CI 0.1\u20130.7, p = 0.028). Of note, this was mainly driven by higher cardiac death rate in those undergoing CF than in those undergoing CA (p = 0.01). Conclusions: CA after complex PCI, such as ULM PCI, is associated with reduced MACE. Such an observation calls for appropriately designed randomized trials

Clinical impact of routine angiographic follow-up after percutaneous coronary interventions on unprotected left main

Background: Patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES) on unprotected left main (ULM) represent a complex subset. The role of routine coronary angiography at follow up in this subset remains debated. Methods: At the documented center, all patients undergoing successful PCI on ULM lesions performing angiographic follow-up is suggested, but adherence to such a recommendation is inhomogeneous. Consecutive patients undergoing DES PCI on ULM were enrolled and experienced no adverse events during the first 6 months. Patients were then allocated to two groups: those undergoing routine control angiography (CA) and those undergoing clinical follow-up (CF). Primary endpoint was major adverse cardiac events (MACE) defined as cardiac death, myocardial infarction and urgent repeat target vessel revascularization. Results: A total of 190 patients underwent successful DES implantation on ULM and the study population was without early events. CA was performed at 6 months after the index procedure in 91 (48%) patients. After 35 ± 21 months, MACE rates were significantly more common in the CF group as compared with the CA group (16.2% vs. 4.3%, p = 0.009). At multivariable analysis, CA was associated with reduced MACE risk (HR 0.13, 95% CI 0.1–0.7, p = 0.028). Of note, this was mainly driven by higher cardiac death rate in those undergoing CF than in those undergoing CA (p = 0.01). Conclusions: CA after complex PCI, such as ULM PCI, is associated with reduced MACE. Such an observation calls for appropriately designed randomized trials

18F-FDG PET/CT role in staging of gastric carcinomas: comparison with conventional contrast enhancement computed tomography

The purpose of the report was to evaluate the role of fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) in staging gastric cancer comparing it with contrast enhancement computed tomography (CECT).This retrospective study included 45 patients who underwent performed whole body CECT and F-FDG PET/CT before any treatment. We calculated CECT and F-FDG PET/CT sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) for gastric, lymphnode, and distant localizations; furthermore, we compared the 2 techniques by McNemar test. The role of F-FDG PET/CT semiquantitative parameters in relation to histotype, grading, and site of gastric lesions were evaluated by ANOVA test.Sensitivity, specificity, accuracy, PPV and NPV of CECT, and F-FDG PET/CT for gastric lesion were, respectively, 92.11%, 57.14%, 86.66%, 92.11%, 57.14% and 81.58%, 85.71%, 82.22%, 96.88%, 46.15%. No differences were identified between the 2 techniques about sensitivity and specificity. No statistical differences were observed between PET parameters and histotype, grading, and site of gastric lesion. The results of CECT and F-FDG PET/CT about lymphnode involvement were 70.83%, 61.90%, 66.66%, 68%, 65% and 58.33%, 95.24%, 75.55%, 93.33%, 66.67%. The results of CECT and F-FDG PET/CT about distant metastases were 80%, 62.86%, 66.66%, 38.10%, 91.67% and 60%, 88.57%, 82.22%, 60%, 88.57%. FDG PET/CT specificity was significantly higher both for lymphnode and distant metastases.The F-FDG PET/CT is a useful tool for the evaluation of gastric carcinoma to detect primary lesion, lymphnode, and distant metastases using 1 single image whole-body technique. Integration of CECT with F-FDG PET/CT permits a more valid staging in these patients

Comparison of the Diagnostic Value of MRI and Whole Body 18F-FDG PET/CT in Diagnosis of Spondylodiscitis

Spondylodiscitis is a spine infection for which a diagnosis by a magnetic resonance imaging (MRI) is considered the most appropriate imaging technique. The aim of this study was to compare the role of an F-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) and an MRI in this field. For 56 patients with suspected spondylodiscitis for whom MRI and F-18-FDG PET/CT were performed, we retrospectively analyzed the results. Cohen's kappa was applied to evaluate the agreement between the two techniques in all patients and in subgroups with a different number of spinal districts analyzed by the MRI. Sensitivity, specificity, and accuracy were also evaluated. The agreements of the F-18-FDG PET/CT and MRI in the evaluation of the entire population, whole-spine MRI, and two-districts MRI were moderate (kappa = 0.456, kappa = 0.432, and kappa = 0.429, respectively). In patients for whom one-district MRI was performed, F-18-FDG PET/CT and MRI were both positive and completely concordant (kappa = 1). We also separately evaluated patients with suspected spondylodiscitis caused by Mycobacterium tuberculosis for whom the MRI and F-18-FDG PET/CT were always concordant excepting in 2 of the 18 (11%) patients. Sensitivity, specificity, and accuracy of the MRI and F-18-FDG PET/CT were 100%, 60%, 97%, and 92%, 100%, and 94%, respectively. Our results confirmed the F-18-FDG PET/CT diagnostic value in the diagnosis of spondylodiscitis is comparable to that of MRI for the entire spine evaluation. This could be considered a complementary technique or a valid alternative to MRI

Prognostic role of TPL2 in early‑stage non‑small cell lung cancer

Non‑small cell lung cancer (NSCLC) accounts for ~70% of all lung cancer‑associated mortalities worldwide. The serine/threonine protein kinase tumor progression locus 2 [TPL2/MAP3 kinase 8 (MAP3K8)] may impact oncogenic events; however the role of TPL2 in lung carcinogenesis remains unclear. The present study was focused on the potential prognostic role of TPL2 in 101 patients with early‑stage NSCLC. Since TPL2 is a potential target of miR‑21, the association between TPL2 and miR‑21 expression was also examined. TPL2 and miR‑21 mRNA expression was quantified using reverse transcription quantitative polymerase chain reaction (RT‑qPCR). TPL2 protein levels were evaluated by immunohistochemistry (IHC). The present study identified that the mRNA expression of TPL2 was low in 52/101 (51%) cases and high in 49/101 (49%) cases. IHC analysis of TPL2 protein expression often demonstrated identical mRNA results. No statistically significant associations were observed between the mRNA expression of TPL2 and the predominant clinicopathological characteristics of the patients with NSCLC, as well as identifying no association between TPL2 and miR‑21. TPL2 mRNA expression was significantly higher in patients with NSCLC with good prognosis (disease‑free interval P=0.009; overall survival P=0.024), when compared with those of poor prognosis. Focusing on the difference in mRNA expression of TPL2 among the adenocarcinomas in affected patients, TPL2 was more highly expressed in lepidic adenocarcinomas compared with in the other subtypes (P=0.012). The present study is the first examination, to the best of our knowledge, of TPL2 in early‑stage NSCLC in relation to miR‑21, and in different adenocarcinoma subtypes. Future studies must clarify the mechanism by which TPL2 is involved in lung carcinogenesis due to its important translational implications

Identification of two distinct molecular subtypes by digital RNA counting of "non-invasive follicular tumour with papillary-like nuclear features (NIFTP)"

Backgound. The follicular variant (FV) is one of the most common variants of papillary thyroid carcinoma (PTC). Clinically, the FVPTC is considered a low-risk variant of PTC, and the encapsulated forms of FVPTC represent a group of thyroid tumours with an overall good prognosis. Consequently, these neoplasms were very recently reclassified as "non-invasive follicular tumour with papillary-like nuclear features (NIFTP)". From a molecular standpoint, NIFTP appears similar to the follicular pattern thyroid neoplasm; however, limited data are currently available regarding their gene expression profile

Pediatric Hodgkin Lymphoma: Predictive value of interim 18F-FDG PET/CT in therapy response assessment

We investigated the prognostic value of interim 18F-FDG PET/CT (PET-2) in pediatric Hodgkin lymphoma (pHL), evaluating both visual and semiquantitative analysis. Thirty pHL patients (age ⠤16) underwent serial 18F-FDG PET/CT: At baseline (PET-0), after 2 cycles of chemotherapy (PET-2) and at the end of first-line chemotherapy (PET-T). PET response assessment was carried out visually according to the Deauville Score (DS), as well as semiquantitatively by using the semiquantitative parameters reduction from PET-0 to PET-2 (ΠΣSUVmax0-2, ΠΣSUVmean0-2). Final clinical response assessment (outcome) at the end of first-line chemotherapy was the criterion standard, considering patients as responders (R) or nonresponders (NR). Disease status was followed identifying patients with absence or relapsed/progression disease (mean follow-up: 24 months, range 3-78). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of visual and semiquantitative assessment were calculated; furthermore, Fisher exact test was performed to evaluate the association between both visual and semiquantitative assessment and outcome at the end of the first-line chemotherapy. The prognostic capability of PET-2 semiquantitative parameters was calculated by ROC analysis and expressed as area under curve (AUC). Finally, progression-free survival (PFS) was analyzed according to PET-2 results based on the 5-point scale and semiquantitative criteria, using the Kaplan-Meier method. Based on the outcome at the end of first-line chemotherapy, 5 of 30 patients were NR, the remnant 25 of 30 were R. Sensitivity, specificity, PPV, NPV, and accuracy of visual analysis were 60%,72%,30%,90%,70%; conversely, sensitivity, specificity, PPV, NPV, and accuracy of semiquantitative assessment were 80%, 92%, 66.7%, 95.8%, 90%. The highest AUC resulted for ΠΣSUVmax0-2 (0.836; cut-off <12.5; sensitivity 80%; specificity 91%). The association between ΠΣSUVmax0-2 and outcome at the end of first-line chemotherapy resulted to have a strong statistical significance (P=0.0026). Both methods demonstrated to influence PFS, even if the semiquantitative assessment allowed a more accurate identification of patients with a high risk of treatment failure (P=0.005). Our preliminary results showed that PET-2 visual assessment, by using Deauville criteria, can be improved by using the semiquantitative analysis. The SUV max reduction (ΠΣSUVmax0-2) evaluation might provide a support for the interpretation of intermediate scores, predicting with good confidence those patients who will have a poor outcome and require alternative therapies

Vasculitis Diagnosed on Fluorine-18 Labelled-2-Deoxy-2-Fluoro-D-Glucose Uptake in A Patient With Fever of Unknown Origin and A History of Non Hodgkin’s Lymphoma

There are increasing data demonstrating the role of 18F-flourodeoxyglucose positron emission tomography with computerized tomography fusion (18F-FDG PET/CT) in the diagnosis of large vessel vasculitis, including Takayasu arteritis and giant cell arteritis. We report a case of large vessel vasculitis detected on 18F-FDG PET/CT; a 32-year-old woman with history of Non Hodgkin Lymphoma, admitted with fever of unknown origin (FUO) of 2-months duration and asthenia. To exclude FUO of malignancy, in the suspect of NHL relapse, 18F-FDG PET/CT imaging was performed. The images demonstrated significant 18F-FDG uptake in aortic arch and no signs of NHL relapse. This case report supports the role of 18F-FDG PET/CT as a useful and noninvasive tool in diagnostic evaluation of patient with FUO, both by excluding a malignant etiology and providing information about other possible causes such as inflammation, including vasculitis. 18F-FDG PET/CT is very useful in the early diagnosis of active inflammation including vasculitis and provides timely information for appropriate therapy