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Purpose: To evaluate the role of apparent diffusion coefficient (ADC) value measurement in the diagnosis of meta-static lymph nodes (LNs) in patients with locally advanced cervical cancer (LACC) and to present a systematic review of the literature., Material and Methods: Magnetic resonance imaging (MRI) exams of patients with LACC were retrospectively eva-luated. Mean ADC, relative ADC (rADC), and correct ADC (cADC) values of enlarged LNs were measured and compared between positron emission tomography (PET)-positive and PET-negative LNs. Comparisons were made using the Mann-Whitney U -test and Student's t -test. ROC curves were generated for each parameter to identify the optimal cut-off value for differentiation of the LNs. A systematic search in the literature was performed, exploring several databases, including PubMed, Scopus, the Cochrane library, and Embase., Results: A total of 105 LNs in 34 patients were analysed. The median ADC value of PET-positive LNs (0.907 × 10 -3 mm 2 /s [0.780-1.080]) was lower than that in PET-negative LNs (1.275 × 10 -3 mm 2 /s [1.063-1.525]) ( p < 0.05). rADC and cADC values were lower in PET-positive LNs (rADC: 0.120 × 10 -3 mm 2 /s [-0.060-0.270]; cADC: 1.130 [0.980-1.420]) than in PET-negative LNs (rADC: 0.435 × 10 -3 mm 2 /s [0.225-0.673]; cADC: 1.615 [1.210-1.993]) LNs ( p < 0.05). ADC showed the highest area under the curve (AUC 0.808)., Conclusions: Mean ADC, rADC, and cADC were significantly lower in the PET-positive group than in the PET-negative group. The ADC cut-off value of 1.149 × 10-3 mm 2 /s showed the highest sensitivity. These results confirm the usefulness of ADC in differentiating metastatic from non-metastatic LNs in LACC., Competing Interests: The authors report no conflict of interest., (© Pol J Radiol 2022.)

Parathyroid carcinoma (PC) is an extremely rare disease. Although it may occasionally occur in genetic syndromes, it is more often sporadic. It is usually associated with a consistent secretion of PTH, causing severe hypercalcemia and potentially all clinical conditions due to primary hyperparathyroidism. Management of PC can be challenging: some clinical, biochemical, and radiological features may be useful, but the final diagnosis of malignancy strictly relies on histological criteria. To date, radical surgery is the first-choice treatment and is the only effective therapy to control hypercalcemia and other clinical manifestations. On the other hand, chemo- or radiotherapy, local treatments, or novel drugs should be reserved for selected cases. We report an exceptionally unusual case of life-threatening PC, associated with several systemic manifestations: moderate pancreatitis, portal thrombosis, kidney stones, brown tumors, osteoporosis, hungry bone syndrome (HBS), chondrocalcinosis, neuropathy, and depression. The clinical case also represents an opportunity to provide a review of the recent literature, associated with a complete evaluation of the main diagnostic and therapeutic approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zelano, Locantore, Rota, Policola, Corsello, Rossi, Rufini, Zagaria, Raffaelli and Pontecorvi.)

Adrenal masses are a frequent finding in clinical practice. Many of them are incidentally discovered with a prevalence of 4% in patients undergoing abdominal anatomic imaging and require a differential diagnosis. Biochemical tests, evaluating hormonal production of both adrenal cortex and medulla (in particular, mineralocorticoids, glucocorticoids and catecholamines), have a primary importance in distinguishing functional or non-functional lesions. Conventional imaging techniques, in particular computerized tomography (CT) and magnetic resonance imaging (MRI), are required to differentiate between benign and malignant lesions according to their appearance (size stability, contrast enhanced CT and/or chemical shift on MRI). In selected patients, functional imaging is a non-invasive tool able to explore the metabolic pathways involved thus providing additional diagnostic information. Several single photon emission tomography (SPET) and positron emission tomography (PET) radiopharmaceuticals have been developed and are available, each of them suitable for studying specific pathological conditions. In functional masses causing hypersecreting diseases (mainly adrenal hypercortisolism, primary hyperaldosteronism and pheochromocytoma), functional imaging can lateralize the involvement and guide the therapeutic strategy in both unilateral and bilateral lesions. In non-functioning adrenal masses with inconclusive imaging findings at CT/MR, [ 18 F]-FDG evaluation of tumor metabolism can be helpful to characterize them by distinguishing between benign nodules and primary malignant adrenal disease (mainly adrenocortical carcinoma), thus modulating the surgical approach. In oncologic patients, [ 18 F]-FDG uptake can differentiate between benign nodule and adrenal metastasis from extra-adrenal primary malignancies.

Congenital hyperinsulinism (HI) is a life-threatening condition characterized by severe and recurrent episodes of hypoglycaemia due to defects in key genes involved in regulating insulin secretion. The delay in diagnosis and inappropriate management of HI lead to high risk of permanent hypoglycemic brain injury. The management of HI is challenging as each form of HI (focal, diffuse, and atypical) requires its own therapeutic strategy. In HI diagnostic work-up, integrated PET/CT scan is currently the first-line imaging technique allowing to differentiate between diffuse and focal form and, in the latter case, to localize the focus within the pancreas with high precision. Only in focal HI partial pancreatectomy is the treatment of choice and a curative surgical treatment means a real chance of transforming patient's lives and HI patient's future. The aim of this review is to discuss the role of PET/CT imaging in HI scenario, its technical advantages and limitations and how successful surgery is strongly dependent on accurate preoperative assessment (genetic analysis and PET/CT scan). A multidisciplinary approach in HI diagnosis and treatment inside a single team (involving different expertise) allows to manage children safely and properly, supporting their families in an organized care network., Competing Interests: None., (AJNMMI Copyright © 2022.)

Purpose: To investigate whether the COVID-19 pandemic and national lockdown had an impact on the extent of cancer disease at FDG PET/CT staging as surrogate marker., Methods: Retrospective observational study including cancer patients submitted to FDG PET/CT staging from June 1 to October 31, 2020, and June 1 to October 31, 2019, respectively. Data regarding primary tumour, nodal (N) status and number of involved nodal stations, and presence and number of distant metastases (M) were collected. Each scan was classified in limited vs advanced status. Data were aggregated across the study population and tumour type. Bi-weekly frequencies of the observed events were analysed., Results: Six hundred eleven patients were included (240 in 2019 vs 371 in 2020, respectively). A significant increase of advanced disease patients (rate 1.56, P < 0.001), N + or M + patients (rate 1.84 and 2.09, respectively, P < 0.001), and patients with a greater number of involved N stations or M (rate 2.01 and 2.06, respectively, P < 0.001) were found in 2020 compared with data of 2019. Analysis by tumour type showed a significant increase of advanced disease in lymphoma and lung cancer in 2020 compared with 2019 (P < 0.001). In addition, a significant increase of nodal involvement was found in lung, gastro-intestinal, and breast cancers, as well as in lymphoma patients (P < 0.02). A significant increase of distant metastases was found in lung cancers (P = 0.002)., Conclusion: Cancer patients with advanced disease at FDG PET/CT staging increased in 2020 compared with 2019, following the national lockdown due to the COVID-19 pandemic, 1.5-fold with a significant increase of patients with N or M involvement. Targeted health interventions are needed to mitigate the effects of the pandemic on patient outcome., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: 'Severe acute respiratory syndrome coronavirus-2' (SARS-CoV-2) infection has dramatically affected the management of patients with cancer, who are most vulnerable to the consequences of the infection. Patients with vulvar cancer are frequently elderly and affected by multiple co-morbidities, thus representing a particularly frail population., Objective: To assess the clinical impact of the SARS-CoV-2 infection among patients scheduled for treatment for active vulvar cancer., Methods: Data on patients with vulvar tumors referred to Fondazione Policlinico Universitario Agostino Gemelli IRCCS between February 2020 and July 2021 were retrospectively analyzed. Patients with a positive reverse transcription polymerase chain reaction in nasopharyngeal swab were considered as positive for SARS-Cov-2., Results: One hundred and ninety-one patients with vulvar cancer were evaluated and scheduled for treatment. The median age was 72 years (range 35-94). Seven (3.7%) patients were diagnosed with SARS-Cov-2 infection: three (42.9%) had their treatment delayed, with no apparent consequences, two (28.6%) had their treatment delayed and later abandoned because of clinical worsening due to oncologic disease progression, and two (28.6%) contracted the infection in the post-operative period and died due to respiratory complications., Conclusions: In most cases the infection had major clinical implications, being associated with significant delays in oncologic treatments and extremely high mortality when contracted in the post-operative period., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The first prototype of the "Multidisciplinary Tumor Board Smart Virtual Assistant" is presented, aimed to (i) Automated classification of clinical stage starting from different free-text diagnostic reports; (ii) Resolution of inconsistencies by identifying controversial cases drawing the clinician's attention to particular cases worthy for multi-disciplinary discussion; (iii) Support environment for education and knowledge transfer to junior staff; (iv) Integrated data-driven decision making and standardized language and interpretation., Patients and Method: Data from patients affected by Locally Advanced Cervical Cancer (LACC), FIGO stage IB2-IVa, treated between 2015 and 2018 were extracted. Magnetic Resonance (MR), Gynecologic examination under general anesthesia (EAU), and Positron Emission Tomography-Computed Tomography (PET-CT) performed at the time of diagnosis were the items from the Electronic Health Records (eHRs) considered for analysis. An automated extraction of eHR that capture the patient's data before the diagnosis and then, through Natural Language Processing (NLP), analysis and categorization of all data to transform source information into structured data has been performed., Results: In the first round, the system has been used to retrieve all the eHR for the 96 patients with LACC. The system has been able to classify all patients belonging to the training set and - through the NLP procedures - the clinical features were analyzed and classified for each patient. A second important result was the setup of a predictive model to evaluate the patient's staging (accuracy of 94%). Lastly, we created a user-oriented operational tool targeting the MTB who are confronted with the challenge of large volumes of patients to be diagnosed in the most accurate way., Conclusion: This is the first proof of concept concerning the possibility of creating a smart virtual assistant for the MTB. A significant benefit could come from the integration of these automated methods in the collaborative, crucial decision stages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Macchia, Ferrandina, Patarnello, Autorino, Masciocchi, Pisapia, Calvani, Iacomini, Cesario, Boldrini, Gui, Rufini, Gambacorta, Scambia and Valentini.)

Purpose: This retrospective study aimed to assess the diagnostic performance of preoperative [ 18 F]FDG-PET/CT in predicting the groin and pelvic lymph node (LN) status in a large single-centre series of vulvar cancer patients., Methods: Between January 2013 and October 2018, among all consecutive women with proven vulvar cancer submitted to [ 18 F]FDG-PET/CT, 160 patients were included. LNs were analysed by two qualitative methods assessing PET information (defined as visual assessment) and a combination of PET and low-dose CT information (defined as overall assessment), respectively, as well as semi-quantitative analysis (LN-SUV max ). Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) in predicting the groin and pelvic LN status were calculated in the overall study population; a subset analysis of groin parameters in clinically/ultrasonography negative patients was also performed. Histopathology was the reference standard., Results: All patients underwent vulvar and inguinofemoral LN surgery, and 35 pelvic LN surgery. Overall, 338 LN sites (296 groins and 42 pelvic sites) were histologically examined with 30.4% prevalence of metastatic groins and 28.6% for metastatic pelvic sites. In the overall study population, sensitivity (95% confidence interval, CI), specificity (95% CI), accuracy (95% CI), PPV (95% CI) and NPV (95% CI) at the groin level were 85.6% (78.3-92.8), 65.5% (59.0-72.0), 71.6% (66.5-76.8), 52.0% (44.0-60.1) and 91.2% (86.7-95.8) for visual assessment; 78.9% (70.5-87.3), 78.2% (72.5-83.8), 78.4% (73.7-83.1), 61.2% (52.3-70.1) and 89.4% (85.0-93.9) for overall assessment; and 73.3% (64.2-82.5), 85.0% (80.1-89.8), 81.4% (77.0-85.8), 68.0% (58.8-77.3) and 87.9% (83.4-92.5) for semi-quantitative analysis (SUV max cut-off value 1.89 achieved by ROC analysis). Similar results were observed in the pelvis-based analysis., Conclusion: In this large single-centre series of vulvar cancer patients, [ 18 F]FDG-PET/CT showed good values of sensitivity and NPV in discriminating metastatic from non-metastatic LNs. In routine clinical practice, qualitative analysis is a reliable interpretative criterion making unnecessary commonly used semi-quantitative methods such as SUV max ., (© 2021. The Author(s).)

Abstract: Solitary fibrous tumor of the pleura (SFTP) is a rare mesenchymal neoplasm. Preoperative diagnosis is usually difficult and based on radiological findings only. We report the imaging results observed in 5 patients with SFTP (2 malignant) obtained by 68Ga-DOTATOC PET/CT. At qualitative analysis, all tumors showed uptake of 68Ga-DOTATOC. Mean tumor SUVmax was 9.9 ± 5.7. The expression of SST2 (somatostatin receptors subtype 2) was confirmed by immunohistochemistry in 2 tumor samples, and by gene amplification of SST2 mRNA in all cases. These data suggest a diagnostic role of radioreceptor PET/CT in SFTP, and open novel potential treatment options in unresectable/metastatic disease., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: The aims of this study were to determine the role of 18F-FDG PET/CT in vulvar cancer patients and to extract summary estimates of its diagnostic performance for preoperative lymph node staging., Patients and Methods: PubMed/Medline and Embase databases were searched to identify studies evaluating 18F-FDG PET/CT in vulvar cancer patients. The assessment of methodological quality of the included articles was performed. Per-patient and per-groin pooled estimates, with 95% confidence intervals (CIs), of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (DOR) were calculated., Results: Ten articles were included in the systematic review, 7 among which evaluated the diagnostic performance of preoperative 18F-FDG PET/CT for lymph node staging. Qualitative per-patient analysis (72 patients from 4 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.70 (95% CI, 0.44-0.95), 0.90 (95% CI, 0.76-1.04), 0.86 (95% CI, 0.66-1.06), 0.77 (95% CI, 0.56-0.97), and 10.49 (95% CI, 1.68-65.50), respectively. Qualitative per-groin analysis (245 groins from 5 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.76 (95% CI, 0.57-0.94), 0.88 (95% CI, 0.82-0.94), 0.70 (95% CI, 0.55-0.85), 0.92 (95% CI, 0.86-0.97), and 19.43 (95% CI, 6.40-58.95), respectively., Conclusions: Despite limited literature data, this systematic review and meta-analysis revealed that a negative preoperative PET/CT scan may exclude groin metastases in at least early-stage vulvar cancer patients currently unfit for sentinel node biopsy and select those eligible for a less invasive surgical treatment. A positive PET/CT result should otherwise be interpreted with caution. Larger prospective studies are needed to confirm these results and to evaluate the diagnostic value of standardized semiquantitative analysis compared with the qualitative one., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This prospective study aimed to evaluate whether 18 F-FDG-PET/CT performed before, during and after neoadjuvant chemo-radiotherapy (CRT) could predict histopathological response in patients with locally advanced cervical cancer (LACC) treated with CRT followed by radical surgery., Methods: Between October 2010 and June 2014, 88 patients with LACC were enrolled. For each patient, three 18 F-FDG-PET/CT scans (baseline, early and final) were acquired and evaluated by qualitative and quantitative analysis. Maximum standardized uptake value (SUV max ), SUV mean , metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured as absolute values and their percentage variation (delta) (early vs. baseline and final vs. baseline). The role of 18 F-FDG-PET/CT in predicting lymph node (LN) residual disease was evaluated by qualitative analysis only. Histopathology was the reference standard., Results: At histopathology, 40 patients had complete response (CR, pR0), 48 had partial response (PR: 21 microscopic [pR1] and 27 macroscopic [pR2]). At baseline, SUV max and SUV mean were significantly higher in pR0 than in pR1-pR2 patients. At early evaluation, MTV and TLG were significantly higher in pR1-pR2 than in pR0 patients. At final evaluation, SUV max , SUV mean and TLG were significantly higher in pR1-pR2 than in pR0 patients. Delta SUV parameters and delta TLG were significantly lower in PR group both during and after CRT. Delta MTV was significantly lower in patients with PR in the early phase only. In receiver operating characteristic (ROC) curve analysis, baseline SUV mean , early delta TLG, and final delta SUV max better discriminated PR, providing 83.3%, 67.6% and 85% positive predictive value (PPV) and 60.3%, 90% and 70.8% negative predictive value (NPV), respectively. For LN assessment, high NPV was observed at early and final 18 F-FDG-PET/CT (93.5% and 92.3%, respectively)., Conclusion: In LACC patients treated with CRT followed by surgery, early variations in metabolic parameters effectively discriminate histopathological PR of the primary tumor, suggesting the potential role of 18 F-FDG-PET/CT in early personalized treatment. The high NPV of early and final PET/CT could enable "tailored surgery" by avoiding lymphadenectomy in selected patients.

Purpose: The aim of this retrospective study was to determine, by dynamic acquisition, the optimal scan time of F-DOPA PET/CT in patients with recurrent medullary thyroid carcinoma (MTC)., Methods: Twenty-one patients with suspected recurrent MTC underwent dynamic F-DOPA PET/CT (lasting 45 minutes) followed by whole-body scan. Three different time intervals of dynamic acquisition were evaluated: ultra-early phase (2-5 minutes), early phase (5-10 minutes), and late phase (40-45 minutes). The number and SUVmax of all detected lesions among the 3 dynamic acquisition phases were compared on qualitative and semiquantitative analyses. Time-activity curves, SUVmax washout rate between ultra-early or early phase and late phase, and signal-to-noise ratio (SNR) between lesion and background activity were also calculated., Results: At dynamic acquisition, 15 of 21 patients were classified as PET-positive and 6 of 21 as PET-negative, with overall 21 detected lesions. Ultra-early and early imaging provided a better lesion visualization than late phase in more than 70% of cases, as also reflected by SNR (mean SNR reduction between 2 and 45 minutes, -45% ± 19%). Time-activity curves showed a rapid tracer accumulation in MTC lesions, with an average maximum uptake at 2 minutes after injection. Mean lesion SUVmax was 2-fold higher in ultra-early frames compared with last frames (mean washout rate, -44% ± 33%). Finally, compared with whole-body imaging in the same field of view, dynamic acquisition identified 1 additional positive patient and 3 additional lesions in 2 patients., Conclusions: Our study, showing a very fast F-DOPA uptake in MTC lesions, suggests the utility to obtain early PET/CT images, already at 2 to 5 minutes after tracer injection, when maximum lesion tracer uptake is reached.

Objective: We assessed the prognostic value of several FDG PET/CT parameters, measured within the primary tumor and the involved lymph nodes, before definitive radio-chemotherapy (RCT) in anal cancer patients., Methods: Anal cancer patients with positive baseline FDG PET/CT who underwent definitive RCT from May 2011 to February 2018 were retrospectively assessed. Primary tumour (T)-SUVmax, T-SUVpeak, T-SUVmean, T-MTV, T-TLG, whole-body (WB) MTV, and WB-TLG were measured. Kaplan-Meier curves, Cox-regression analysis, and logistic regression machine-learning technique were used to test for associations between clinical data, metabolic parameters, and outcomes as overall survival (OS), disease-specific survival (DSS), metastatic-free survival (MFS), disease-free survival (DFS), local relapse-free survival (LRFS), and colostomy-free survival (CFS)., Results: Fifty-nine patients were included in the study. Median follow-up was 28 months. Higher pre-treatment WB-MTV, T-TLG, and WB-TLG were associated with worse OS (p = 0.025, 0.021, and 0.02, respectively). PET parameters resulted also statistically significant for DSS, DFS, and CFS (p = 0.032, 0.043, 9 × 10 -4 for WB-TLG). Cox analysis showed that PET parameters are significant predictors of OS, DSS, DFS, CFS, and LRFS. On multivariate analysis, age, stage, T-SUVpeak, WB-MTV, and T-TLG resulted significantly related to OS. A further stratification for patients with advanced stage (cT3-4 any N or any cT, N + ) showed that MTV and TLG, measured within the primary tumor and the involved nodes, are significantly higher in patients with a worse prognosis. In this subgroup, cut-off values of T- and WB-TLG as well as T- and WB-MTV showed a statistically significant correlation with clinical outcomes., Conclusions: Pre-treatment metabolic parameters measured within the primary tumor and the involved nodes may represent additional new biomarkers for estimating prognosis in anal cancer patients, especially in advanced stage patients.

Background: Metastatic spreading to the lungs is a negative prognostic factor in patients with prostate cancer (PC). Aim of our study was to assess the prevalence of lung PC metastases in patients with fluorine-18 fluoroethyl-choline (F-18-FECh) PET-CT positive lung lesions and the role of Gleason Score (GS) and common biochemical markers in predicting metastatic spreading to the lungs., Methods: We retrospectively evaluated the scans of 1283 patients ongoing (F-18-FECh) PET-CT for PC between May 2010 and July 2014. Patients with lung lesion with F-18-FECh uptake were included. Data concerning GS at diagnosis, "trigger" prostate-specific antigen (PSAtr), PSA doubling time (PSAdt), PSA velocity (PSAvel) and ongoing androgen deprivation therapy were collected. PET-CT findings were confirmed by histology or follow-up (FU) and classified as follows: inflammation, primary lung cancer or metastases from tumor other than PC, and lung metastases from PC., Results: Twenty-two patients with F-18-FECh positive lung lesion and available histology or FU were identified. PSAdt was significantly (P=0.029) shorter in patients with lung metastases from PC (median PSAdt 1.7 months, interquartile range [IQR] 1.5-4.1 months) than in patients without lung PC relapse (median PSAdt 6.7 months, IQR 3.9-7.8); PSAvel was significantly (P=0.019) higher in patients with lung metastases from PC (median PSAvel 3.2 ng/mL/month, IQR 0.65-6.65 ng/mL/month) than in patients without lung PC relapse (median PSAvel 0.3 ng/mL/month, IQR 0.2-0.5 ng/mL/month). Patients with lung metastases from PC had significantly (P=0.006) higher GS at diagnosis (median GS 8) than the other ones (median GS 7)., Conclusions: Our analysis shows that the prevalence of F-18-FECh positive lung metastases in patients with PC, especially with higher GS at diagnosis, is higher in presence of a steady increase in PSA values, confirmed by higher PSAvel and shorter PSAdt.

A 75-year-old man, who had been diagnosed with small lymphocytic lymphoma with cervical localization, underwent F-FDG PET/CT with iodinated contrast medium due to the appearance of cervical swelling suspected of illness relapse. PET/CT revealed intense F-FDG uptake in multiple cervical and subdiaphragmatic lymph nodes and in the left parotid. Moreover, diffuse uptake and wall thickening of the colon were evident; endoscopy with biopsy revealed a diffuse large B-cell lymphoma. Transformation into a more aggressive lymphoma occurs in 2% to 8% of small lymphocytic lymphoma, the so-called Richter syndrome. Extranodal localization in the sigmoid colon is an extremely rare site for transformed lymphoma.

We report the case of a 43-year-old man with a history of lung carcinoid and a recent detection of thyroid nodules by ultrasound. The cytological analysis raised the suspicion of medullary thyroid carcinoma; however, calcitonin and carcinoembryonic antigen levels were in reference range. Considering the previous diagnosis of lung carcinoid, the patient underwent whole-body Ga-DOTATOC PET/CT. The images showed focal radiopharmaceutical uptake in both thyroid lobes. After thyroidectomy, the histology and immunohistochemistry (negative for calcitonin and positive for chromogranin A) confirmed the neuroendocrine origin of the thyroid nodules, possibly referable to previous lung carcinoid.

Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor. Currently, 18 F-fluoro-deoxy-glucose ( 18 F-FDG) PET/CT is the functional imaging modality of choice. Few data are available on the use of 68 Ga-somatostatin analogs. The aim of our study was to evaluate and compare the diagnostic performance of 18 F-FDG and 68 Ga-somatostatin analog PET/CT in MCC patients., Results: Fifteen patients (12 males, 3 females; median age 73 years; range 41-81 years) with histologically proven MCC (4 with unknown primary lesion) who underwent both 18 F-FDG and 68 Ga-somatostatin analog PET/CT for staging, re-staging, or treatment response assessment were retrospectively evaluated. Results of both studies were qualitatively analyzed and compared on a patient- and lesion-based analysis, using histology or clinical/radiological follow-up as reference standard for final diagnosis. According to final diagnosis, 8/15 patients had at least one MCC lesion and 7/15 had no evidence of disease. On a patient-based analysis, 18 F-FDG and 68 Ga-somatostatin analogs correctly classified as positive 8/8 (100% sensitivity) patients and as negative 6/7 (85.7% specificity) and 5/7 (71.4% specificity) patients, respectively, with no significant difference. On a lesion-based analysis, 18 F-FDG detected 67/75 lesions (89%) and 68 Ga-somatostatin analogs 69/75 (92%), with no significant difference. In four patients with unknown primary MCC, both tracers failed to identify the primary MCC site., Conclusions: Our preliminary data suggest that 18 F-FDG and 68 Ga-somatostatin analog PET/CT provide good and equivalent diagnostic performance, adding interesting insights into the complex MCC biology. However, these results do not suggest that 18 F-FDG PET/CT should be replaced by 68 Ga-somatostatin receptor imaging, which should be performed in addition, according to clinical indication, to the perspective of "personalized medicine."

This study investigates whether radiomic features derived from preoperative positron emission tomography (PET) images could predict both tumor biology and prognosis in women with invasive squamous cell carcinoma of the vulva. Methods: Patients were retrospectively included when they had a unifocal primary cancer of ≥ 2.6 cm in diameter, had received a preoperative 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/computed tomography (CT) scan followed by surgery and had at least six months of follow-up data. 18 F-FDG-PET images were analyzed by semi-automatically drawing on the primary tumor in each PET image, followed by the extraction of 83 radiomic features. Unique radiomic features were identified by principal component analysis (PCA), after which they were compared with histopathology using non-pairwise group comparison and linear regression. Univariate and multivariate Cox regression analyses were used to correlate the identified features with progression-free survival (PFS) and overall survival (OS). Survival curves were estimated using the Kaplan-Meier method. Results: Forty women were included. PCA revealed four unique radiomic features, which were not associated with histopathologic characteristics such as grading, depth of invasion, lymph-vascular space invasion and metastatic lymph nodes. No statistically significant correlation was found between the identified features and PFS. However, Moran's I, a feature that identifies global spatial autocorrelation, was correlated with OS ( P = 0.03). Multivariate Cox regression analysis showed that extracapsular invasion of the metastatic lymph nodes and Moran's I were independent prognostic factors for PFS and OS. Conclusion: Our data show that PCA is usable to identify specific radiomic features. Although the identified features did not correlate strongly with tumor biology, Moran's I was found to predict patient prognosis. Larger studies are required to establish the clinical relevance of the observed findings., (Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: The aim of this study was to verify the feasibility, in clinical practice, of three simplified methods (Hunter, Sadato and another one proposed by our group) to calculate Ki and MRglu of 18F-FDG, comparing the results with those derived by the linear regression (LR) method (considered the golden standard), and also with SUV., Methods: Forty-five patients (32males, mean age 69±9years) with non-small-cell-lung cancer prospectively enrolled, underwent dynamic 18F-FDG PET-CT over the thorax. Ki was estimated as follows: from a static acquisition and performing one venous blood sampling using the Hunter method; multiplying the SUV for the average plasma clearance rate (kP(T)) and for the initial distribution volume (V0bw) without performing any blood sampling using the Sadato method; multiplying the SUV for a factor F (which encompasses the mean value of haematocrit and plasma volume, both according to patient's sex) without performing any blood sample using ours method. Wilcoxon signed rank and coefficient of determination (R2) were used for statistical analysis., Results: No significant difference was observed between the Ki and MRglu estimated by all three simplified methods and the Ki and MRglu estimated by LR. The highest P values and the lower values of mean differences were observed with our method compared with LR: Ki=0.0392±0.0178 min-1 vs. Ki=0.0392±0.0202 min-1 (P=0.897, MD=0.0001 min-1), respectively; MRglu= 4.47±2.23 ml/min/100g vs. MRglu= 4.43±2.38 ml/min/100g (P=0.839, MD= -0.0373 mL/min/100g), respectively. The highest correlation was observed between the Ki estimated by both Hunter and our methods and the Ki estimated by LR: R2=0.87, R2=0.86, respectively. A good correlation (R2=0.83) was observed between SUV and Ki estimated by LR., Conclusions: These three simplified methods represent a valid alternative to the more invasive and complex full kinetic analysis. Their "pros" are: the non-invasiveness, the feasibility, the good correlation with the golden standard; their "cons" is that full kinetic analysis provides highest accuracy in Ki determination. Therefore, in clinical oncology routine, the nuclear physicians can choose among different simplified methods especially for monitoring the response to treatment, for tumour grading, and for prognostic stratification, letting the full kinetic analysis to specific centre/studies.

Aim: To retrospectively investigate the prognostic role of the ratio between target lesion and liver SUV max (rPET) in patients with follicular lymphoma (FL) submitted to FDG-PET/CT at the end of immuno-chemotherapy (PI-PET), and to compare rPET with International Harmonization Project criteria (IHP), Deauville Score (5p-DS) and FL International Prognostic Index at diagnosis (FLIPI)., Methods: Eighty-nine patients with FL undergoing PI-PET were evaluated. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point of rPET with respect to 5-years progression free survival (PFS). The prognostic significance of rPET was compared with IHP, DS and FLIPI. Positive predictive value (PPV) and negative predictive value (NPV) were calculated using the presence of adverse events as gold standard., Results: The ROC analysis for rPET as predictor of progression showed an optimal rPET cut-point of 0.98. Patients with positive values of IHP, DS and rPET had a PFS of 50, 30 and 31%. PPV were of 56, 80 and 80%, NPV of 83, 86 and 88%, respectively. DS and rPET differed only in two patients. FLIPI was not predictive of progression and relapse., Conclusions: rPET is a prognostic factor in patients with FL submitted to PI-PET. Although it has a similar prognostic power as DS, it can have methodological advantages over visual analysis. PI-PET with different evaluation systems has a stronger prognostic power than FLIPI at diagnosis, so it could be useful to identify patients with FL at risk for early relapse after immuno-chemotherapy.

The rarity of neoplastic cells in the biopsy imposes major technical hurdles that have so far limited genomic studies in classical Hodgkin lymphoma (cHL). By using a highly sensitive and robust deep next-generation sequencing approach for circulating tumor DNA (ctDNA), we aimed to identify the genetics of cHL in different clinical phases, as well as its modifications on treatment. The analysis was based on specimens collected from 80 newly diagnosed and 32 refractory patients with cHL, including longitudinal samples collected under ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy and longitudinal samples from relapsing patients treated with chemotherapy and immunotherapy. ctDNA mirrored Hodgkin and Reed-Sternberg cell genetics, thus establishing ctDNA as an easily accessible source of tumor DNA for cHL genotyping. By identifying STAT6 as the most frequently mutated gene in ∼40% of cases, we refined the current knowledge of cHL genetics. Longitudinal ctDNA profiling identified treatment-dependent patterns of clonal evolution in patients relapsing after chemotherapy and patients maintained in partial remission under immunotherapy. By measuring ctDNA changes during therapy, we propose ctDNA as a radiation-free tool to track residual disease that may integrate positron emission tomography imaging for the early identification of chemorefractory patients with cHL. Collectively, our results provide the proof of concept that ctDNA may serve as a novel precision medicine biomarker in cHL., (© 2018 by The American Society of Hematology.)

This study aimed to assess the value of dual-timepoint 18 F-FDG PET/CT in the prediction of lymph node (LN) status in patients with invasive vulvar cancer (VC) scheduled for inguinofemoral LN dissection. Methods: From April 2013 to July 2015, all consecutive patients with VC scheduled for inguinofemoral LN dissection were prospectively enrolled. All patients underwent a preoperative whole-body 18 F-FDG PET/CT scan at 1 h (standard examination) and an additional scan from T11 to the groins at 3 h (delayed examination) after 18 F-FDG injection. On both scans, each groin was visually scored 0 or 1 concerning 18 F-FDG LN uptake relative to background. Semiquantitative analysis included SUV max and the corresponding retention index of SUV max , measured on both scans. The optimal cutoff value of these parameters was defined using a receiver-operating-characteristic analysis. Histopathology was the standard of reference. Results: Thirty-three patients were included, with a total of 57 groins dissected and histologically evaluated. At histopathology, 21 of 57 (37%) groins contained metastatic LNs. Concerning visual score, sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 95.2%, 75%, 96.4%, 69%, and 82.5% on standard scanning and 95.2%, 77.8%, 96.6%, 71.4%, and 84.2% on delayed scanning, respectively. At receiver-operating-characteristic analysis, sensitivity and specificity were 95.2% and 77.8% on standard and delayed 18 F-FDG PET/CT for an SUV max cutoff of greater than 1.32 and 1.88, respectively, and 95.2% and 80% for a retention index of SUV max cutoff of greater than 0. Conclusion: Standard 18 F-FDG PET/CT is an effective preoperative imaging method for the prediction of LN status in VC, allowing the prediction of pathologically negative groins and thus the selection of patients suitable for minimally invasive surgery. Delayed 18 F-FDG PET/CT did not improve the specificity and the positive predictive value in our series. Larger studies are needed for a further validation., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: The study aims were: 1) to verify the role of sentinel node biopsy (SNB) in a subset of patients with clinical N0 (cN0) invasive vulvar cancer (VC) who were still candidates for radical inguinal surgery according to the current guidelines; 2) to investigate whether a preoperative 18 F-FDG PET/CT (PET/CT) evaluation could improve the selection of node negative patients., Methods: From July 2013 to July 2016, all patients with VC admitted to our Division were evaluated by standard imaging and clinical exam. Among the patients assessed as cN0 we enrolled those unsuitable for SNB, due to: T > 4 cm, multifocal tumors, complete tumor diagnostic excision, contralateral nodal involvement and local recurrence. A preoperative PET/CT was performed. For each patient surgery included SNB, performed using a combined technique (radiotracer plus blue dye), followed by standard inguino-femoral lymphadenectomy. The reference standard was histopathology., Results: Forty-seven patients entered the study for a total of 73 groins. Histopathology revealed 12 metastatic SNs in 9 groins. No false negative SNs were found (NPV 100%). PET/CT showed a negative predictive value of 93%., Conclusions: Our data suggest that SNB is accurate and safe even in cN0 patients currently excluded from this procedure, providing that a careful preoperative selection is performed. PET/CT allows a reliable assessment of LN status and may be an effective support for the selection of patients who are safe candidates for SNB., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Hodgkin Lymphoma (HL) is a tumor of B-cell origin characterized by Hodgkin and Reed-Stenberg (H/RS) cells embedded in an inflammatory tissue where numerous cytokines/chemokines contribute to shape the microenvironment, leading to the typical clinical symptoms. We investigated: i) the expression of Interleukin-IL-31 (IL-31) and Thymic Stromal Lymphopoietin (TSLP), two Th2-related cytokines with tumor-promoting and pruritogenic functions, and of the respective receptors in HL invaded lymph nodes by flow cytometry, and ii) the potential association of IL-31/TSLP plasma concentrations with clinical characteristics by ELISA. H/RS cells and the major immune cell types infiltrating HL lymph nodes expressed intracytoplasmic and surface IL-31/TSLP, and their receptors. A subgroup of patients showing at diagnosis elevated IL-31 and TSLP plasma levels had an International Prognostic Score>2, indicative of high risk of relapse, and a subsequent positive interim PET-scan, indicative of insufficient response to chemotherapy. No correlation was found between IL-31/TSLP plasma levels and overall or event-free survival. In conclusion, IL-31/TSLP and their receptors are expressed in HL cells and in immune cells infiltrating affected lymph nodes, where both cytokines may contribute to local immune suppression. The clinical impact of IL-31 and TSLP plasma levels has to be further defined in larger patient cohorts., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing financial interests in relation to the work described.

Objective: The aim of the study was to assess the value and potential pitfalls of Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) in patients with suspected pancreatic neuroendocrine neoplasms (pNEN)., Methods: Consecutive patients referred for Ga-DOTANOC PET/CT for suspected pNEN between May 1, 2011, and October 31, 2014, were retrospectively assessed. Scan data were compared with cytological/histological final diagnosis. Pancreatic neuroendocrine neoplasm detection rate was determined on per-patient and per-lesion basis. Maximum standardized uptake values of lesions were determined., Results: Fifty-eight patients with 65 lesions were enrolled. Twelve patients had nonconfirmed diagnosis; of these, 7 were positive and 5 negative at PET/CT. Of 46 patients with confirmed diagnosis, 36 had pNEN; of these, 33 were positive, 1 negative, and 2 nonevaluable at PET/CT. Ten patients had non-NE lesions, of which 8 were positive, 1 negative, and 1 nonevaluable at PET/CT. Of 48 patients with positive PET/CT, 8 proved to have non-NE lesions, of which 6 were intrapancreatic accessory spleen. No significant maximum standardized uptake values difference was found between pNEN and non-NE lesions., Conclusions: Intrapancreatic accessory spleen is an important pitfall in Ga-DOTANOC PET/CT for suspected pNEN. Cytological/histological confirmation is mandatory before any surgical procedure is undertaken.

Extramedullary relapse of multiple myeloma (MM) is uncommon. A 40-year-old woman with history of MM underwent PET/CT using C-methionine (C-MET) after the detection of a vulvar lesion on MRI, biopsy proven to be extramedullary relapse of MM. The vulvar lesion was negative at the F-FDG PET/CT but showed high uptake of C-MET; focal uptake of both F-FDG and C-MET was shown within the muscles of the left leg, histologically confirmed as extramedullary relapse of MM. F-FDG PET/CT performed after chemotherapy showed no uptake in both sites, whereas posttreatment C-MET PET/CT showed persistence of residual uptake within the vulvar lesion.

Objective: To evaluate the prognostic role of the ratio between target lesion and liver SUVmax (rPET) in patients with Hodgkin lymphoma (HL) undergoing interim FDG-PET/CT and to compare rPET with the 5-point Deauville Score (5p-DS)., Methods: Sixty-eight patients with HL undergoing interim FDG-PET/CT after first courses of chemotherapy were evaluated. The receiver operating characteristic (ROC) approach was applied to identify the optimal cutpoint of rPET with respect to progression free survival (PFS). The prognostic significance of rPET was compared with 5p-DS (scores 4 and 5 considered as positive). Positive predictive value (PPV) and negative predictive value (NPV) were calculated using the presence of an adverse event as the gold standard., Results: The ROC analysis for rPET as a predictor of progression showed an optimal rPET cutpoint of 1.14. Both 5p-DS and rPET were strong outcome predictors (p < 0.001). Patients with negative 5p-DS and patients with rPET <1.14 had a similar two-year PFS (86 and 87 %, respectively). Patients with a positive 5p-DS had a 2-year PFS of 27 %, while patients with rPET >1.14 had a 2-year PFS of 15 %. 5p-DS and rPET cutoff of 1.14 showed a PPV of 58 versus 70 %, and a NPV of 85 versus 86 %, respectively., Conclusions: rPET could be considered an accurate prognostic factor in patients with HL undergoing interim FDG-PET/CT. Larger prospective studies are needed to confirm these data.

Objectives: The aims of this study were to investigate the added value of diffusion-weighted imaging (DWI) in pancreatic neuroendocrine tumor (pNET) evaluation and to compare magnetic resonance imaging (MRI) to Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) results., Methods: Morphological MRI (T2-weighted [T2-w] + contrast-enhanced [CE] T1-w) and DWI (T2-w + DWI) and Ga-DOTANOC PET/CT in 25 patients/30 pNETs were retrospectively evaluated. Per-patient and per-lesion detection rates (pDR and lDR, respectively) were calculated. Apparent diffusion coefficient values were compared among pNET and surrounding and normal pancreas (control group, 18 patients). Apparent diffusion coefficient and standardized uptake value (SUV) values were compared among different grading and staging groups., Results: No statistically significant differences in PET/CT and MRI session detection rates were found (morphological MRI and DW-MRI, 88% pDR and 87% lDR; combined evaluation, 92% pDR and 90% lDR; Ga-DOTANOC PET/CT, 88% pDR and 80% lDR). Consensus reading (morphological/DW-MRI + PET/CT) improved pDR and lDR (100%). Apparent diffusion coefficient mean value was significantly lower compared with surrounding and normal parenchyma (P < 0.01). The apparent diffusion coefficient and SUV values of pNETs among different grading and staging groups were not statistically different., Conclusions: Conventional MRI, DW-MRI + T2-w sequences, and Ga-DOTANOC PET/CT can be alternative tools in pNET detection. Diffusion-weighted MRI could be valuable in patients with clinical suspicion but negative conventional imaging findings. However, the consensus reading of the 3 techniques seems the best approach.

Early response evaluation with [(18) F]fluordeoxyglucose (FDG) positron emission tomography after 2 cycles of chemotherapy (interim PET) has been indicated as the strongest predictor for outcome in classical Hodgkin lymphoma (HL). We studied the prognostic role of the number of tumor-infiltrating CD68+ cells and of the plasma levels of TARC (thymus and activation-regulated chemokine) in the context of interim PET in 102 patients with classical HL treated with Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD). After 2 ABVD cycles, interim PET according to Deauville criteria was negative (score 0-3) in 85 patients and positive (score 4-5) in 15 patients (2 patients technically not evaluable). TARC levels were elevated in 89% of patients at diagnosis, and decreased after 2 cycles in 82% of patients. Persistently elevated TARC levels in 18% of patients were significantly associated with a positive PET result (P = 0.007). Strong predictors for progression-free survival (PFS) were a negative interim PET (85% vs. 28%, P < 0.0001) and CD68+ cell counts <5% (89% vs. 67%, P = 0.006), while TARC levels at diagnosis and at interim evaluation had no prognostic role. In multivariate analysis, interim PET, CD68+ cell counts and presence of B-symptoms were independently associated with PFS. We conclude that although TARC levels are a biomarker for early response evaluation, they cannot substitute for interim PET as outcome predictor in HL. The evaluation of CD68 counts and B-symptoms at diagnosis may help to identify low-risk patients regardless positive interim PET., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

In recent years, 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has emerged as an important tool for the postoperative management of patients with differentiated thyroid cancer (DTC) and it is widely used in selected clinical situations. The most valuable role that FDG-PET/CT plays in clinical practice is that it can be used to obtain prognostic information in patients with increasing thyroglobulin (Tg) levels and negative (131)I whole-body scan post-thyroidectomy and radioiodine (RAI) ablation. FDG-PET/CT may also have a potential role in the initial staging and follow-up of high-risk patients with aggressive histological subtypes, in the identification of patients who are at the highest risk of disease-specific mortality, in the management of patients with RAI-refractory disease, in clinical trials of novel targeted therapies in patients with advanced metastatic disease, and in the evaluation of thyroid nodules with indeterminate fine-needle aspiration for cytology. However, several controversies remain to be resolved, namely: the cutoff value of Tg in the selection of DTC patients for FDG-PET/CT, whether FDG-PET/CT scanning should be performed under thyrotropin stimulation or suppression, and the clinical significance of thyroid FDG-PET/CT incidentalomas. The aim of the present article is to provide an overview of the data about the molecular basis for, clinical indications of, and controversies related to the use of FDG-PET/CT in patients with DTC., (© 2015 European Society of Endocrinology.)

Study Design: Retrospective study., Objective: To evaluate, in a pediatric population, F-Fluoro-deoxy-glucose (F-FDG) metabolic activity of normal spinal cord and to assess the correlation with demographic, clinical, and environmental variables., Summary of Background Data: F-FDG uptake of normal spinal cord is variable in children. The knowledge of physiological metabolism of spinal cord is essential to distinguish normal from pathological findings by positron emission tomography-computed tomography (PET-CT)., Methods: We retrospectively evaluated F-FDG positron emission tomography-computed tomography scans from a total of 167 pediatric patients (97 males; 3.9-18.9 yr) divided into 4 age groups (0-4.9 yr, 5-9.9 yr, 10-14.9 yr, and 15-18.9 yr), excluding those submitted to previous or recent therapeutic procedures influencing spinal cord metabolism or with central nervous system diseases. Spinal cord was divided into 3 levels (C1-C7; D1-D6; and D7-L1), and maximum standardized uptake value (SUVmax) of each cord level was measured. Correlations between SUVmax and spinal cord level, age, body weight, sex, type of disease, and season were statistically assessed., Results: Median SUVmax was similar and significantly (P < 0.01) higher at C1-C7 and D7-L1 levels than at D1-D6 level and it significantly (P < 0.01) increased with age in all spinal cord levels. A positive and significant association between SUVmax and body weight, female sex, and Hodgkin lymphoma was found. No significant association with season was observed. By multivariate analysis, only weight and female sex remained significant., Conclusion: Knowledge of physiological F-FDG spinal cord activity in children is essential for a correct interpretation of positron emission tomography-computed tomography, especially in oncologic pediatric patients to avoid potential pitfalls., Level of Evidence: N/A.

A 77-year-old man was referred to our center for a suspected neuroendocrine neoplasm in the pancreatic tail, incidentally detected at CT. Ga DOTANOC PET/CT showed intense tracer uptake in the pancreatic lesion. At MRI, the lesion was similar to the spleen on all sequences, suggesting the presence of intrapancreatic accessory spleen. A Tc-colloid SPECT/CT scan performed to differentiate spleen tissue from neuroendocrine tumor revealed a focal uptake in the pancreatic lesion, thus confirming the presence of ectopic spleen and avoiding unnecessary surgery.

Purpose: The aims of this study were to retrospectively evaluate and compare the detection rate (DR) of 68Ga-DOTA-peptide and 18F-FDG PET/CT in the preoperative workup of patients with pulmonary carcinoid (PC) and to assess the utility of various functional indices obtained with the 2 tracers in predicting the histological characterization of PC, that is, typical versus atypical., Methods: Thirty-three consecutive patients with confirmed PC referred for 18F-FDG and 68Ga-DOTA-peptide PET/CT in 2 centers between January 2009 and April 2013 were included. The semiquantitative evaluation included the SUV max, the SUV of the tumor relative to the maximal liver uptake for 18F-FDG (SUV T/L) or the maximal spleen uptake for 68Ga-DOTA-peptides (SUV T/S), the ratio between SUV max of 68Ga-DOTA-peptides PET/CT, and the SUV max of 18F-FDG PET/CT (SUV max ratio). Histology was used as reference standard., Results: Definitive diagnosis consisted of 23 typical carcinoids (TCs) and 10 atypical carcinoids. 18F-FDG PET/CT was positive in 18 cases and negative in 15 (55% DR). 68Ga-DOTA-peptide PET/CT was positive in 26 cases and negative in 7 (79% DR). In the subgroup analysis, 68Ga-DOTA-peptide PET/CT was superior in detecting TC (91% DR; P < 0.001), whereas 18F-FDG PET/CT was superior in detecting atypical carcinoid (100% DR; P = 0.04). The SUV max ratio was the most accurate semiquantitative index in identifying TC., Conclusions: Overall diagnostic performance of PET/CT in detecting PC is optimal when integrating 18F-FDG and 68Ga-DOTA-peptide PET/CT findings. In the subgroup analysis, the SUV max ratio seems to be the most accurate index in predicting TC. Both methods should be performed when PC is suspected or when the histological subtype is undefined.

Introduction: Primary lymphomas of peripheral nerves are extremely rare, and only a few cases have been reported., Methods: We describe the clinical, neurophysiological, radiological, and pathological findings in a 61-year-old woman affected by primary multifocal lymphoma of the peripheral nervous system without systemic involvement., Results: Fascicular left femoral nerve biopsy was decisive for the diagnosis of diffuse large B-cell non-Hodgkin lymphoma. Magnetic resonance imaging, fluorine-18 fluorodeoxyglucose positron emission tomography computed tomography, and nerve ultrasound contributed to the diagnosis., Conclusions: Primary lymphoma of peripheral nerves (PLPNs) is a rare but potentially treatable condition, which is frequently misdiagnosed. In the literature, there are very few descriptions of PLPNs, most of which are mononeuropathies. The possibility of a neuropathy associated with lymphoma should be considered in patients with poor response to treatment and severe pain symptoms., (© 2014 Wiley Periodicals, Inc.)

Objective: Congenital hyperinsulinism (CHI) requires rapid diagnosis and treatment to avoid irreversible neurological sequelae due to hypoglycaemia. Aetiological diagnosis is instrumental in directing the appropriate therapy. Current diagnostic algorithms provide a complete set of diagnostic tools including (i) biochemical assays, (ii) genetic facility and (iii) state-of-the-art imaging. They consider the response to a therapeutic diazoxide trial an early, crucial step before proceeding (or not) to specific genetic testing and eventually imaging, aimed at distinguishing diffuse vs focal CHI. However, interpretation of the diazoxide test is not trivial and can vary between research groups, which may lead to inappropriate decisions. Objective of this report is proposing a new algorithm in which early genetic screening, rather than diazoxide trial, dictates subsequent clinical decisions., Patients, Methods and Results: Two CHI patients weaned from parenteral glucose infusion and glucagon after starting diazoxide. No hypoglycaemia was registered during a 72-h continuous glucose monitoring (CGMS), or hypoglycaemic episodes were present for no longer than 3% of 72-h. Normoglycaemia was obtained by low-medium dose diazoxide combined with frequent carbohydrate feeds for several years. We identified monoallelic, paternally inherited mutations in KATP channel genes, and (18) F-DOPA PET-CT revealed a focal lesion that was surgically resected, resulting in complete remission of hypoglycaemia., Conclusions: Although rare, some patients with focal lesions may be responsive to diazoxide. As a consequence, we propose an algorithm that is not based on a 'formal' diazoxide response but on genetic testing, in which patients carrying paternally inherited ABCC8 or KCNJ11 mutations should always be subjected to (18) F-DOPA PET-CT., (© 2014 John Wiley & Sons Ltd.)

Follow-up routines after gynaecological cancer vary. The optimal approach is unknown, and no randomised-controlled trials comparing surveillance protocols have been published. In this chapter, we summarise the diagnostic performance of ultrasound, computed tomography, and magnetic resonance imaging in the follow up of women treated for ovarian or uterine cancers. Computed tomography is today the standard imaging method for the follow up of women treated for endometrial, cervical, or ovarian cancer. Six-monthly or annual follow-up examinations have not been shown to positively affect survival. Instead, a combination of transvaginal and transabdominal ultrasound examination with clinical examination might be a more cost-effective strategy for early detection of recurrence. Positron-emission tomography might play a role in women with clinical or serological suspicion of recurrence but without evidence of disease at conventional diagnostic imaging. To create guidelines, more studies, preferably randomised-controlled trials, on follow-up strategies are needed., (Copyright © 2014. Published by Elsevier Ltd.)

Improvements in the treatment of cervical carcinoma have made it possible to offer optimal and personalised treatment. Cervical cancer staging is based on clinical examination and histological findings. Many diagnostic methods are used in clinical practice. Magnetic resonance imaging is considered the optimal method for staging cervical carcinoma because of its high accuracy in assessing local extension of disease and distant metastases. Ultrasound has gained increased attention in recent years; it is faster, cheaper, and more widely available than other imaging techniques, and is highly accurate in detecting tumour presence and evaluating local extension of disease. Magnetic resonance imaging and ultrasound are often used together with computed tomography or positron emission tomography combined with computed tomography to assess the whole body, a more accurate detection of pathological lymph nodes and metabolic information of the disease., (Copyright © 2014. Published by Elsevier Ltd.)

A 33-year old man underwent an F-FDG PET/CT searching for the cause of a fever of unknown origin. F-FDG PET/CT incidentally detected a focal area of markedly increased radiopharmaceutical uptake corresponding to a 2.5-cm nodule in the right adrenal gland. Laboratory data ruled out the presence of a functioning adrenal lesion. All these findings were suggestive of adrenal malignancy. After right adrenalectomy, histology showed a benign solitary fibrous tumor of the adrenal gland. This case highlights that benign solitary fibrous tumor should be considered as possible false-positive F-FDG PET/CT finding for malignancy in evaluating adrenal incidentalomas.

Context: The ectopic production of ACTH is responsible for approximately 10% of cases of Cushing's syndrome. Whenever possible, once hypercortisolemia is under control with medical therapy, the final treatment consists of surgical excision of the tumor. We report a case of a patient with high surgical risk and poor response to medical therapy in which hypercortisolemia has been successfully treated with radiofrequency ablation of the bronchial carcinoid tumor., Case Presentation: A 43-year-old woman came to our hospital because of severe and rapidly worsening signs and symptoms of hypercortisolism over the previous 3 months. Hormonal tests suggested the presence of Cushing's syndrome due to ectopic ACTH production. Imaging studies detected an 8-mm pulmonary nodule with fluorine-18-fluorodeoxyglucose uptake localized in the middle right lobe. The patient started therapy with ketoconazole with poor response. Middle right lobectomy was indicated but, due to the patient's very high surgical risk, a thermal ablation with radiofrequency of the bronchial nodule was performed., Outcomes and Results: After the procedure, ACTH and cortisol levels dropped and fluorine-18-fluorodeoxyglucose positron emission tomography showed complete response to treatment. Clinical conditions progressively improved, and 6 weeks later, the patient underwent middle lobectomy without complications. Histology showed a 0.7-cm ACTH-producing typical bronchial carcinoid tumor., Conclusions: Thermal ablation with radiofrequency allows achieving a rapid control of hypercortisolism with subsequent improvement of symptoms. This procedure should therefore be considered as a viable therapeutic option in those cases of bronchial ACTH-secreting tumors in which the surgical approach is initially contraindicated.

A 40-year-old female patient with suspected multifocal extra-adrenal paraganglioma, on the basis of biochemical, genetic, and conventional imaging data, underwent 18F-FDG, 18F-DOPA and 68Ga DOTANOC PET/CT. FDOPA- and FDG-PET/CT detected a multifocal mediastinal and cervical paraganglioma. 68Ga-DOTANOC PET/CT detected 2 additional lesions compared to the other PET/CT methods. In our case, somatostatin receptor PET/CT with 68Ga-DOTANOC correctly assessed the extent of the disease in a patient with multifocal paraganglioma.

Purpose: To evaluate whether standardized uptake value (SUV) and/or metabolic rate of glucose (MRglu) are different among epithelioid, mixed, and spindle cell uveal melanomas, as well as between low and high risk melanomas; to correlate ultrasonographic data and metabolic parameters with histopathological features; and to assess the role of (18)F-FDG PET/CT for evaluating prognosis., Methods: Of 34 eligible patients prospectively enrolled with clinical suspicion of medium/large uveal melanoma, 26 (15 men, mean age 62.8 ± 11.8 years) were evaluated. All patients underwent metastatic work-up, 3-D dynamic brain and whole-body (18)F-FDG PET/CT, and surgery., Results: Of the 26 ocular lesions, 23 showed (18)F-FDG uptake, with a sensitivity of 88 %. MRglu was significantly higher in the epithelioid cell melanomas than in the spindle cell melanomas, as well as in high-risk lesions than in low-risk lesions (p = 0.01, p = 0.02, respectively). SUV and MRglu were correlated with histopathological features while ultrasonographic data were not., Conclusion: MRglu is useful for distinguishing the different cell types in uveal melanoma, as well as high-risk from low-risk lesions, while SUV is not. MRglu provides a more accurate evaluation of glucose consumption, whereas SUV provides only an estimation. In addition, the metabolic parameters correlate with histopathological features, well also reflecting cellular behaviour in ocular malignancy. A longer follow-up is needed to assess the role of (18)F-FDG in evaluating prognosis.

Background: In 2007, sorafenib was the first drug able to improve overall survival in patients with advanced hepatocellular carcinoma., Aim: In 2005 we designed a phase II study to assess safety and efficacy of sunitinib., Methods: This is a single arm, open-label, single-centre phase II trial. Eligibility criteria were advanced hepatocellular carcinoma; no prior chemotherapy, performance status 0-1; and Child≤B8. The treatment schedule was 50mg each day orally, 4 weeks on, 2 weeks off., Results: Between 10/2007 and 10/2010, 34 patients were enrolled. A significant worsening of liver functional reserve after sunitinib was observed. Grade 3/4 adverse effects occurred in 80% of patients and included fatigue (47%), nausea (15%), liver failure (15%), encephalopathy (12%) and upper gastrointestinal bleeding (12%). Six patients (18%) died within 60 days of enrolment. A partial response was observed in 4 patients (12%). Median time to tumour progression was 2.8 months and median overall survival was 5.8 months., Conclusion: A dose of 50mg/d induces a high rate of severe adverse events. Toxicity remains a key concern also at the dose of 37.5mg/d. However, sunitinib is able to induce a prolonged response in some patients. Positron Emission Tomography/Computed Tomography scans may select good responders., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

A 63-year-old woman underwent (18)F-FDG PET/CT searching for the cause of a fever of unknown origin. (18)F-FDG PET/CT incidentally detected a focal area of markedly increased radiopharmaceutical uptake in the right adrenal gland; this finding was suspicious for an adrenal malignancy or a functioning adenoma. Nevertheless, histology and laboratory data demonstrated the presence of a nonfunctioning adenoma. This case highlights that nonfunctioning adrenal adenomas should be considered as possible false-positive (18)F-FDG PET/CT findings for malignancy in the evaluation of adrenal incidentalomas, even when marked (18)F-FDG uptake is revealed.

Positron emission tomography (PET) and PET/computed tomography (PET/CT) with different tracers are imaging methods increasingly used in patients with thyroid and adrenal diseases. The aim of this article is to provide an overview based on literature data about the usefulness of PET imaging in this setting. PET and PET/CT with different tracers have been used in patients with thyroid diseases including differentiated thyroid carcinoma, medullary thyroid carcinoma, and poorly differentiated and anaplastic thyroid carcinoma. The usefulness of 18F-FDG-PET and PET/CT in assessing indeterminate thyroid nodules at fine needle aspiration biopsy and the clinical relevance of thyroid incidental 18F-FDG uptake has also been evaluated. Currently, great interest is being shown in a variety of PET tracers that target specific characteristics of adrenal gland function, allowing a more accurate characterization of adrenal masses and staging of adrenal tumors. Since PET/CT using different tracers is an expensive diagnostic tool which necessitates ionizing radiation exposure, cost-effectiveness studies are needed in order to define the appropriate use of this diagnostic method in various endocrine disorders.

We report a rare case of ectopic adrenocorticotropic hormone (ACTH) syndrome caused by a metastatic neuroendocrine tumor (NET) of the pancreas detected by PET/CT using different tracers. A 43-year-old female patient with Cushing syndrome (CS) by suspected ectopic ACTH secretion underwent a 68Ga-DOTANOC and a 18F-FDG PET/CT. Both these functional imaging techniques revealed increased tracer uptake in a pancreatic mass and multiple liver metastases. Histology showed the presence of a mildly differentiated pancreatic NET. 68Ga-DOTANOC PET/CT may be a useful functional imaging method, complementary to 18F-FDG PET/CT, in detecting ACTH-secreting pancreatic NETs.

A 65-year-old woman with suspected insulinoma on the basis of clinical, biochemical, and conventional imaging data underwent F-dihydroxyphenylalanine (DOPA) PET/CT and Ga-DOTANOC PET/CT. F-DOPA PET/CT did not show any focal uptake in the pancreas, whereas Ga-DOTANOC PET/CT showed a focal area of intense uptake in the pancreatic tail. The patient underwent surgery and an insulinoma of about 20 mm in diameter was detected in the pancreatic tail. F-DOPA PET may fail in localizing insulin secreting tumors in adults; in these cases, the use of Ga-somatostatin analogs may lead to the correct diagnosis.