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Simple Summary: Recent advances in PET/CT technology led to the development of long-axial field-of-view (LAFOV) PET/CT with the possibility of simultaneously scanning a large portion of the body with reduced acquisition time, reduced radiation burden, and improved spatial resolution. This article explores the potential applications of LAFOV PET/CT imaging in gynecological malignancies. Patients affected by these diseases are expected to gain multiple and major benefits from this technology and have some of their unmet needs answered in all phases of management, from initial staging to surgery and radiotherapy planning, assessment of treatment response, and restaging, with improved patient-tailored care. Gynecological malignancies currently affect about 3.5 million women all over the world. Imaging of uterine, cervical, vaginal, ovarian, and vulvar cancer still presents several unmet needs when using conventional modalities such as ultrasound, computed tomography (CT), magnetic resonance, and standard positron emission tomography (PET)/CT. Some of the current diagnostic limitations are represented by differential diagnosis between inflammatory and cancerous findings, detection of peritoneal carcinomatosis and metastases <1 cm, detection of cancer-associated vascular complications, effective assessment of post-therapy changes, as well as bone metabolism and osteoporosis assessment. As a result of recent advances in PET/CT instrumentation, new systems now offer a long-axial field-of-view (LAFOV) to image between 106 cm and 194 cm (i.e., total-body PET) of the patient's body simultaneously and feature higher physical sensitivity and spatial resolution compared to standard PET/CT systems. LAFOV PET could overcome the forementioned limitations of conventional imaging and provide valuable global disease assessment, allowing for improved patient-tailored care. This article provides a comprehensive overview of these and other potential applications of LAFOV PET/CT imaging for patients with gynecological malignancies. [ABSTRACT FROM AUTHOR]

Purpose : To correlate somatostatin receptor (SSTR) and proliferative activity profile (SSTR2, SSTR5, Ki-67) at immunohistochemistry (IHC) with SSTR-PET/CT imaging features in a retrospective series of lung neuroendocrine tumors (NET). Proliferative activity by Ki-67 and 18F-FDG-PET/CT parameters (when available) were also correlated. Methods: Among 551 patients who underwent SSTR-PET/CT with 68Ga-DOTA-somatostatin analogs (SSA) between July 2011 and March 2020 for lung neuroendocrine neoplasms, 32 patients with a confirmed diagnosis of NET were included. For 14 of them, 18F-FDG-PET/CT was available. PET/CT images were reviewed by qualitative and semi-quantitative analyses. Immunohistochemistry for SSTR2, SSTR5, and Ki-67 was assessed. Inferential analysis was performed including kappa statistics and Spearman's rank correlation test. Results: Definitive diagnosis consisted of 26 typical carcinoids-G1 and six atypical carcinoids-G2. Positive SSTR2-IHC was found in 62.5% of samples while SSTR5-IHC positivity was 19.4%. A correlation between SSTR2-IHC and SSTR-PET/CT was found in 24/32 cases (75.0%, p = 0.003): 20 were concordantly positive, 4 concordantly negative. For positive IHC, 100% concordance with SSTR-PET/CT (both positive) was observed, while for negative IHC concordance (both negative) was 33.3%. In 8 cases, IHC was negative while SSTR-PET/CT was positive, even though with low-grade uptake in all but one. A significant correlation between SUVmax values at SSTR-PET/CT and the SSTR2-IHC scores was found, with low SUVmax values corresponding to negative IHC and higher SUVmax values to positive IHC (p = 0.002). Conclusion: This retrospective study showed an overall good agreement between SSTR2-IHC and tumor uptake at SSTR-PET/CT in lung NETs. SSTR-PET/CT SUVmax values can be used as a parameter of SSTR2 density. Within the limits imposed by the relatively small cohort, our data suggest that SSTR2-IHC may surrogate SSTR-PET/CT in selected lung NET patients for clinical decision making when SSTR-PET/CT is not available. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study aimed to assess the diagnostic performance of preoperative [18F]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 [18F]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-SUVmax). 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 (SUVmax 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, [18F]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 SUVmax. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study aimed to evaluate whether 18F-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 18F-FDG-PET/CT scans (baseline, early and final) were acquired and evaluated by qualitative and quantitative analysis. Maximum standardized uptake value (SUVmax), SUVmean, 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 18F-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, SUVmax and SUVmean 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, SUVmax, SUVmean 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 SUVmean, early delta TLG, and final delta SUVmax 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 18F-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 18F-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. [ABSTRACT FROM AUTHOR]

Purpose: Although multiple radiopharmaceuticals are currently available for sentinel node (SN) biopsy, 99mTc-tilmanocept is of particular interest due to its low molecular weight and specific binding capability for the mannose receptors of lymphatic reticuloendothelial cells. In the current systematic review and meta-analysis, we aimed to provide an update from a European expert panel on the performance of 99mTc-tilmanocept for SN biopsy. Methods: A systematic literature search of the PubMed/Medline and Embase databases was performed to identify studies on the use of 99mTc-tilmanocept for SN identification in oncological patients. The articles' methodological quality was assessed before inclusion. The pooled estimates of the pre-/intraoperative detection rates (DR; proportion of patients with ≥ 1 SN identified) and/or pN + sensitivity (SN + /pN + patients ratio), with 95% confidence intervals (CIs), were calculated for breast cancer, melanoma, and head and neck cancer. Results: Twenty-four articles were included in the systematic review, and twenty-one provided data for the meta-analysis. According to data availability, the 99mTc-tilmanocept-estimated pooled preoperative and intraoperative DRs were 0.94 (95%CI, 0.88–1.01) and 0.99 (0.98–1.00) for breast cancer, 0.98 (0.96–0.99) and 1.00 (0.99–1.00) for melanoma, and 0.97 (0.93–1.02) and 0.99 (0.96–1.01) for head and neck carcinoma. Finally, the pooled sensitivity for nodal metastasis in melanoma was 0.97 (95% CI, 0.92–1.03). Conclusion: 99mTc-tilmanocept is a promising radiotracer for SN mapping in patients with breast cancer, melanoma, or head and neck cancer. We strongly believe that multicenter trials are still needed to assess if 99mTc-tilmanocept is superior to other radiotracers used in clinical routine. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "European Journal of Nuclear Medicine and Molecular Imaging" which appeared in the 14 June 2022 issue.

Endocrine pancreatic tumors (EPTs) are a heterogeneous group of neoplasms with variable clinical and biological features and prognosis, ranging from very slow-growing tumors to highly aggressive and very malignant ones. As other neuroendocrine tumors, EPTs are characterized by the presence of neuroamine uptake mechanisms and/or peptide receptors at the cell membrane and these features constitute the basis of the clinical use of specific radiolabeled ligands, both for imaging and therapy. The more widespread use of hybrid machines, i.e., positron emission tomography/computed tomography (PET/CT), allows to perform imaging with high resolution and high diagnostic accuracy especially for small lesions, and to correlate anatomic location with function. The recent WHO recommendations for classification and prognostic factors help the selection of tracers likely to show a positive image on PET; therefore, tracers exploiting specific metabolic patterns (F-DOPA and C-5-HTP) or specific receptor expression (Ga-DOTA-peptides) are suited to well-differentiated tumors, while the use of F-FDG is preferred for poorly-differentiated neoplasms with high proliferative activity and loss of neuroendocrine features. In differentiated EPTs, C-5-HTP performs better than F-DOPA even though its use is hampered by its complex production and limited availability and experience; Ga-peptides are indicated for all type of gastroenteropancreatic (GEP) neuroendocrine tumors, regardless of their functional activity. In addition, Ga-DOTA-peptides play a distinctive role in planning peptide receptor radionuclide therapy. [ABSTRACT FROM AUTHOR]

The assessment of hepatobiliary and pancreatic tumors is commonly achieved by ultrasound, computed tomography (CT), and magnetic resonance. The 2-[fluorine-18]fluoro-2-deoxy- d-glucose (FDG) positron emission tomography (PET) detects increased glucose metabolism associated with neoplastic lesions, provides high accuracy in most cancer imaging applications and is now widely used in clinical practice. However, PET is not always useful and accurate knowledge of appropriate indications is essential for a proper clinical management. F-FDG is transported into cells and phosphorylated by the enzyme hexokinase to F-FDG-6-phosphate, which cannot proceed down the glycolytic pathway and therefore is accumulated in the malignant tissue. PET allows accurate quantification of FDG uptake in tissue, and previous studies have demonstrated that standardized uptake values provide highly reproducible parameters of tumor glucose use (Weber et al., J Nucl Med 40:1771-1777, ). The recent development and diffusion of hybrid PET-CT scanners allows functional and anatomic data to be obtained in a single examination, improving lesion localization and resulting in significant diagnostic improvement (Wahl, J Nucl Med 45:82S-95S, ). Moreover, CT can be performed diagnostically with the use of intravenous and oral contrast and simultaneous PET-contrast-enhanced CT scanning appears to be an efficient method in cancer evaluation. However, in most centers, a low-dose CT is routinely performed without contrast media infusion. Proper patient preparation, scanning protocol, combined assessment of PET and CT data, and the evaluation of conventional imaging findings are essential to define disease and to avoid diagnostic pitfalls. The role of PET and PET-CT in malignancies of the liver, biliary tract, and pancreas is here reviewed; normal patterns, representative cases, and common pitfalls are also presented. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate the prognostic value of “early” and “late” Fluorine-18-Fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET–CT) in patients with head and neck squamous cell carcinoma (HNSCC) treated with radio-chemotherapy (RTCT). Materials and methods: Twenty-six patients treated with RTCT for HNSCC were included. All patients underwent 18F-FDG PET–CT at baseline (“staging” PET–CT), after 2weeks of treatment (“early” PET–CT) and 8–12weeks after treatment (“late” PET–CT). Changes in FDG uptake in the primary tumor (T) and lymph nodes (N) were correlated with local and regional control, respectively; overall metabolic response was correlated with relapse free survival (RFS) and disease specific survival (DSS). Results: After a median follow-up of 29.2months, 19/26 patients were living and 17/19 had no evidence of disease. When comparing “staging”, “early” and “late” PET results, a significant decrease of FDG SUVmax in T and N was documented. When correlating changes in FDG uptake in T and N with local and regional control, a statistically significant correlation only with the “late” reduction was found. Statistical analysis failed to demonstrate any correlation between the “early” metabolic response and the patient clinical outcome while the “late” metabolic response revealed a strong correlation with RFS (p =0.01) and DSS (p =0.009). Conclusions: In patients with HNSCC, PET–CT performed after RTCT predicts the clinical outcome, since it strongly correlates with RFS and DSS. On the other hand, the predictive role of “early” metabolic response was not confirmed by this study. [Copyright &y& Elsevier]

Purpose. To perform an overview about the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using different radiopharmaceuticals in recurrent medullary thyroid carcinoma (MTC) based on biochemical findings (increased tumor marker levels after primary surgery). Methods. A comprehensive literature search of studies published in PubMed/MEDLINE, Scopus, and Embase databases through February 2012 regarding PET or PET/CT in patients with recurrent MTC was performed. Results. Twenty-nine studies comprising 714 patients with suspected recurrent MTC were retrieved. Twentyseven articles evaluated the role of fluorine-18-fluorodeoxyglucose (FDG) PET or PET/CT in recurrent MTC with conflicting results. Diagnostic accuracy of FDG-PET and PET/CT increased in MTC patients with higher calcitonin and carcinoembryonic antigen values, suggesting that these imaging methods could be very useful in patients with more advanced and aggressive disease. Eight articles evaluated the role of fluorine-18-dihydroxyphenylalanine (FDOPA) PET or PET/CT in recurrent MTC reporting promising results. Overall, FDOPA seems to be superior but complementary compared to FDG in detecting recurrent MTC. Few studies evaluating other PET tracers are also discussed. Conclusions. PET radiopharmaceuticals reflect differentmetabolic pathways in MTC. FDOPA seems to be the most useful PET tracer in detecting recurrentMTC based on rising levels of tumor markers. FDG may complement FDOPA in patients with more aggressive MTC. [ABSTRACT FROM AUTHOR]

Abstract: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating in the parafollicular cells (C cells) of the thyroid and secretes both calcitonin and carcino-embryonic antigen (CEA). Genetic and biochemical testing allow early pre-clinical identification of familial forms. Sporadic MTC usually presents as a solitary thyroid nodule; the diagnosis can be made preoperatively by fine-needle aspiration or by calcitonin assay, though it is usually established at the time of surgery. In the diagnostic assessment of MTC, nuclear medicine imaging provides its contribution mainly in the post-operative work-up to detect residual/recurrent tumor. For such purpose a number of radiopharmaceuticals, which take advantage of the specific expression of receptors (the somatostatin analogue 111In-octreotide), hormone transporters (radiolabelled MIBG) or molecular targets (radiolabelled anti-CEA monoclonal antibodies) by MTC lesions are available; these tracers may be used also for the palliative treatment of advanced MTC. Interesting perspectives for MTC imaging are offered by PET radiopharmaceuticals. [Copyright &y& Elsevier]

This article discusses the findings of a study, which determined whether a greater extension of the insular component (IC) influences different clinical and histologic features at diagnosis, and a different tumor aggressiveness in terms of frequency in the occurrence of metastases and survival. First described in 1984, insular thyroid carcinoma refers to a characteristic appearance consisting of nests or insulae of tumor cells with round dark and monomorphic nuclei and scant cytoplasm.

The objectives of this study were to assess the reliability of radioiodine (131I) and a gamma probe for radio-guided surgery (RGS) to detect and then radically dissect lymph node recurrences (LNRs) in 10 patients with differentiated thyroid cancer (DTC). The major inclusion criterion was the presence of an iodine-positive LNR after previous total thyroidectomy and at least two ineffective 131I treatments. The protocol was designed as follows. Day 0: all patients were hospitalized and received 3.7 GBq of 131I in the hypothyroid condition. Day 3: presurgery whole-body scan with a therapeutic dose (TxWBS). Day 5: neck surgery using a gamma probe (Navigator GPS, AutoSuture, Italy), recording the absolute counts and the lesion/background (L/B) counts ratio. Day 7: post-surgery TxWBS performed using the remaining radioactivity. The presurgery TxWBS was positive in all patients, and the post-surgery TxWBS showed a negative pattern in 7 of 10 patients, suggesting the efficacy of the surgical procedure in most of the patients. After RGS the mean decrease in the absolute counts and the L/B counts ratio were 77.6% (52.7% minimum, 94.6% maximum) and 77.4% (52.3% minimum, 94.8% maximum), respectively. After operation the surgeon judged the procedure to be decisive in two patients, favorable in six, and irrelevant in two. The final histologic examination showed the presence of 78 lymph node metastases (mean of 8 per patient). There were 33 neoplastic lesions found by both TxWBS and gamma probe evaluations; 41 were shown only by gamma probe, and 4 were negative by both TxWBS and gamma probe evaluations. This protocol permitted us to look for neoplastic foci with high sensitivity and specificity, and we were able to remove lymph node metastases resistant to radioiodine therapy at a single session. The protocol also allowed detection of some additional tumoral foci in sclerotic areas or behind vascular structures that are difficult to identify and were not seen at the presurgery TxWBS evaluation. However, because of the possible false-negative results, complete excision must be undertaken in high risk patients with a local recurrence to eradicate the largest number of lymph nodes, independent of the counts measured by the gamma probe. [ABSTRACT FROM AUTHOR]

Simple Summary: Among head–neck tumors, squamous cell carcinoma is the most frequent histotype and includes a range of malignancies with different sites of origin as well as different therapeutic strategies and clinical outcomes. In daily practice, patients with head–neck squamous cell carcinoma are seen in various clinical settings, requiring a multidisciplinary approach to therapeutic decisions and clinical care. 18F-FDG PET/CT plays a well-defined role in the management of these tumors for pre-treatment staging and radiotherapy planning as well as treatment-response assessment and post-therapy follow-up. This paper is an overview of the standard use of 18F-FDG PET/CT in the various clinical scenarios of head–neck squamous cell carcinoma. Also, emerging applications will be reviewed, including the use of radiopharmaceuticals other than 18F-FDG, PET/MRI implementation in clinical practice, and the use of radiomics and machine learning. This article provides an overview of the use of 18F-FDG PET/CT in various clinical scenarios of head–neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications. Methodological aspects and the most frequent pitfalls in head–neck imaging interpretation are described. In the initial work-up, 18F-FDG PET/CT is recommended in patients with metastatic cervical lymphadenectomy and occult primary tumor; moreover, it is a well-established imaging tool for detecting cervical nodal involvement, distant metastases, and synchronous primary tumors. Various 18F-FDG pre-treatment parameters show prognostic value in terms of disease progression and overall survival. In this scenario, an emerging role is played by radiomics and machine learning. For radiation-treatment planning, 18F-FDG PET/CT provides an accurate delineation of target volumes and treatment adaptation. Due to its high negative predictive value, 18F-FDG PET/CT, performed at least 12 weeks after the completion of chemoradiotherapy, can prevent unnecessary neck dissections. In addition to radiomics and machine learning, emerging applications include PET/MRI, which combines the high soft-tissue contrast of MRI with the metabolic information of PET, and the use of PET radiopharmaceuticals other than 18F-FDG, which can answer specific clinical needs. [ABSTRACT FROM AUTHOR]

Purpose: Asymptomatic patients with follicular lymphoma (FL) and a low tumour burden can be followed without initial therapy, a strategy called watchful waiting (WW). Prediction of the time to treatment (TTT) is still a challenge. We investigated the prognostic value of baseline total metabolic tumour volume (TMTV) and whole-body total lesion glycolysis (WB-TLG) to predict TTT in patients with FL on WW. Methods: We conducted a retrospective study of 54 patients with FL (grade 1–3a) diagnosed between June 2013 and December 2019, staged with FDG PET/CT, and managed on WW. Median age was 62 years (range 34–85), stage was advanced (III–IV) in 57%, and FLIPI score was intermediate to high (≥ 2) in 52% of the patients. Results: The median TMTV and WB-TLG were 7.1 and 43.3, respectively. With a median follow-up of 59 months, 41% of patients started immuno-chemotherapy. The optimal cut-points to identify patients with TTT within 24 months were 14 for TMTV (AUC 0.70; 95% CI 51–88) and 64 for WB-TLG (AUC 0.71; 95% CI 52–89) (p < 0.005). The probability of not having started treatment within 24 months was 87% for TMTV < 14 and 53% for TMTV ≥ 14 (p < 0.005). TMTV was independent of the FLIPI score for TTT prediction. Patients with both FLIPI ≥ 2 and TMTV ≥ 14 had only an 18% probability of not having started treatment at 36 months, while this probability was 75% in patients with TMTV < 14. Conclusion: Metabolic tumour volume parameters may add information to clinical scores to better predict TTT and better stratify patients for interventional studies. [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with locally advanced cervical cancer, the availability of imaging techniques for accurately defining the residual tumor would be clinically relevant for selecting patients who could be offered a more tailored surgery. The novelty of this prospective study is the development of multiparametric predictive models of histopathological response using a unique data set with three imaging modalities (transvaginal ultrasound, magnetic resonance (MRI) and 18F-FDG-PET/CT) evaluated at three time points ("baseline", two ("early") and five ("final") weeks after treatment). In a cohort of 88 patients, the predictive models retrieved integrating morphometric, vascular, perfusion and metabolic parameters, demonstrated that two imaging approaches (MRI and PET/CT at "final" evaluation or PET/CT at "baseline" and "final" evaluation) are sufficient to identify possible residual disease after chemotherapy. These findings could be useful in selecting patients with residual disease, helping clinicians to tailor the radicality of the surgical approach. Purpose: This study aimed to develop predictive models for pathological residual disease after neoadjuvant chemoradiation (CRT) in locally advanced cervical cancer (LACC) by integrating parameters derived from transvaginal ultrasound, MRI and PET/CT imaging at different time points and time intervals. Methods: Patients with histologically proven LACC, stage IB2–IVA, were prospectively enrolled. For each patient, the three examinations were performed before, 2 and 5 weeks after treatment ("baseline", "early" and "final", respectively). Multivariable logistic regression models to predict complete vs. partial pathological response (pR) were developed and a cost analysis was performed. Results: Between October 2010 and June 2014, 88 patients were included. Complete or partial pR was found in 45.5% and 54.5% of patients, respectively. The two most clinically useful models in pR prediction were (1) using percentage variation of SUVmax retrieved at PET/CT "baseline" and "final" examination, and (2) including high DWI signal intensity (SI) plus, ADC, and SUVmax collected at "final" evaluation (area under the curve (95% Confidence Interval): 0.80 (0.71–0.90) and 0.81 (0.72–0.90), respectively). Conclusion: The percentage variation in SUVmax in the time interval before and after completing neoadjuvant CRT, as well as DWI SI plus ADC and SUVmax obtained after completing neoadjuvant CRT, could be used to predict residual cervical cancer in LACC patients. From a cost point of view, the use of MRI and PET/CT is preferable. [ABSTRACT FROM AUTHOR]

Objective. This multicenter study aimed to investigate the role of preoperative lymphatic mapping and sentinel node biopsy (SNB) as well as the impact of negative SNB on loco-regional control and survival in vulvar melanoma patients with clinically negative nodes (cN0). Methods. Patients who had a proven vulvar melanoma with a Breslow thickness of 1–4 mm, cN0 and underwent a preoperative lymphatic mapping followed by SNB between July 2013 and March 2021 were retrospectively included. Groin recurrence and mortality rate were calculated as absolute and relative frequency. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. We provided a systematic review, searching among PubMed/Medline and Embase libraries. A total of 6 studies were identified (48 patients). Results. A total of 18 women were included. Preoperative planar images showed 51 SNs in 28 groins. Additional SPECT/CT images were acquired in 5/18 cases; SNs were identified pre- and intra-operatively in all cases. A total of 65 SNs were excised from 28 groins. A total of 13/18 (72.2%) patients (21/28 groins, 75%) had negative SNs with no groin recurrences and 12/13 (92.3%) were still alive at last follow-up. Five out of the 18 (27.8%) patients (7/28 groins, 25%) had positive SNs, 2/5 (40%) patients died of cancer after 26.2 and 33.8 months, respectively. The median DFS and OS for the entire cohort were 17.9 months (95% CI, 10.3–19.9) and 65.0 months (95% CI, 26.2-infinite), respectively. The probability of DFS and OS at 3 years were 15.5% (95% CI, 2.6–38.7) and 64.3% (95% CI, 15.5–90.2), respectively. Conclusions. The use of preoperative lymphatic mapping followed by SNB permits a precise and minimally invasive surgical approach in cN0 vulvar melanoma patients. Negative SNB is associated with low risk of groin relapse and good survival. • Lymphoscintigraphy and sentinel node biopsy allow a personalized surgical approach in cN0 vulvar melanoma patients. • This technique could be a valid alternative to radical surgery, thus avoiding post-operative complications. • A negative sentinel node biopsy is associated with low risk of groin relapse and good survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Inguinal node status represents one of the key elements in defining prognosis and treatment strategies in vulvar cancer patients. Preoperative lymph node staging is still a challenging topic. Several imaging methods are currently recommended in the guidelines (CT, PET/CT, MRI, US) based on performance data that are still not conclusive in the literature. Recently, ultrasound is emerging as the method of choice for preoperative evaluation of the inguinofemoral LN, but only when performed by experienced operators, given the limited reliability of subjective evaluation by unskilled operators. The morphonode predictive model represents an artificial intelligence tool that aims to overcome this limitation by supporting the standard ultrasound in adequately predicting the presence of lymph node metastases for improving preoperative surgical planning. We plan to proceed with further multicenter prospective validation and further develop the actual model, including both clinical and biological data. Ultrasound examination is an accurate method in the preoperative evaluation of the inguinofemoral lymph nodes when performed by experienced operators. The purpose of the study was to build a robust, multi-modular model based on machine learning to discriminate between metastatic and non-metastatic inguinal lymph nodes in patients with vulvar cancer. One hundred and twenty-seven women were selected at our center from March 2017 to April 2020, and 237 inguinal regions were analyzed (75 were metastatic and 162 were non-metastatic at histology). Ultrasound was performed before surgery by experienced examiners. Ultrasound features were defined according to previous studies and collected prospectively. Fourteen informative features were used to train and test the machine to obtain a diagnostic model (Morphonode Predictive Model). The following data classifiers were integrated: (I) random forest classifiers (RCF), (II) regression binomial model (RBM), (III) decisional tree (DT), and (IV) similarity profiling (SP). RFC predicted metastatic/non-metastatic lymph nodes with an accuracy of 93.3% and a negative predictive value of 97.1%. DT identified four specific signatures correlated with the risk of metastases and the point risk of each signature was 100%, 81%, 16% and 4%, respectively. The Morphonode Predictive Model could be easily integrated into the clinical routine for preoperative stratification of vulvar cancer patients. [ABSTRACT FROM AUTHOR]

In recent years, 2-[18F]-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 131I 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of apparent diffusion coefficient (ADC) value measurement in the diagnosis of metastatic 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 evaluated. 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 mm²/s [0.780-1.080]) was lower than that in PET-negative LNs (1.275 × 10-3 mm²/s [1.063-1.525]) (p < 0.05). rADC and cADC values were lower in PET-positive LNs (rADC: 0.120 × 10-3 mm²/s [–0.060-0.270]; cADC: 1.130 [0.980-1.420]) than in PET-negative LNs (rADC: 0.435 × 10-3 mm²/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 mm²/s showed the highest sensitivity. These results confirm the usefulness of ADC in differentiating metastatic from non-metastatic LNs in LACC. [ABSTRACT FROM AUTHOR]

The utilization of 2-[fluorine 18] fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in combination with computed tomography (CT) in the assessment of gynecologic malignancies has been rapidly growing in recent years; however, its role in clinical practice has yet to be established. A number of pitfalls are commonly encountered, including normal physiologic activity in bowel loops and blood vessels, or focal retained activity in ureters and urinary bladder. Increased uptake has also been reported in many benign pelvic processes and in premenopausal patients; endometrial activity changes cyclically, whereas increased ovarian uptake may be functional. FDG PET-CT has an emerging role in staging nodal disease and in the evaluation of local recurrence or peritoneal spread of gynecologic malignancies and is also useful in monitoring response to therapy and in long-term follow-up. FDG PET-CT is most suitable in patients with high tumor markers and negative or uncertain conventional imaging data. Patient preparation, proper scanning protocol, combined assessment of PET and CT data, and the evaluation of conventional imaging findings are essential to define disease and to avoid diagnostic pitfalls. [ABSTRACT FROM AUTHOR]

Early diagnosis of peritoneal spread in malignant disease is essential to prevent unnecessary laparotomies and to select the patients in whom complete cytoreduction is feasible. Although anatomic imaging is the mainstay for evaluating peritoneal seeding, small neoplastic implants can be difficult to detect with CT and MR imaging. FDG PET-CT has the potential to improve detection of peritoneal metastases as lesion conspicuity is high at PET due to low background activity and fused PET-CT offers the combined benefits of anatomic and functional imaging. Correlation of uptake modalities with the pathogenesis of intraperitoneal spread of malignancies, provides a rational system of analysis and is essential to define disease. Distinct patterns appear to predict the presence of either nodular or diffuse peritoneal pathology. Main pitfalls are related to normal physiologic activity in bowel loops and blood vessels or focal retained activity in ureters and urinary bladder. PET-CT is most suitable in patients with high tumor markers and negative or uncertain conventional imaging data and in selecting patients for complete cytoreduction. FDG PET-CT adds to conventional imaging in the detection and staging of peritoneal carcinomatosis and is a useful diagnostic tool in monitoring response to therapy and in long term follow-up. [ABSTRACT FROM AUTHOR]

To evaluate the risk of performing inappropriate131I ablative therapies for thyroid carcinoma in patients lacking thyroid remnants or metastases, using a strategy of treatment without a preliminary iodine-131 diagnostic whole-body scan (DxWBS).Retrospective evaluation of post-therapy whole-body scans to assess the prevalence of thyroid remnants or metastases after total thyroidectomy. Comparison of131I uptake test and thyroglobulin (Tg) off levothyroxine (L-T4) performed before therapy with post-therapy scans, in order to evaluate the ability to predict inappropriate treatments.A group of 875 consecutive patients with previous total or near-total thyroidectomy for differentiated thyroid carcinoma underwent131I ablative therapy without a preliminary131I-DxWBS. All patients were clinically free of distant metastases and macroscopic residual tumour.Whole-body scans were performed 2–5 days after the treatment as gold standard for thyroid remnants and metastases; 24-h131I quantitative neck uptake test and Tg off L-T4 were performed before131I therapy.The majority of patients (94%) were found to have thyroid remnants or metastases at post-therapy scans, in most cases (91·2%) with detectable Tg off L-T4 and positive 24-h neck uptake. 14 patients (1·6%) with tiny lymph-node metastases positive at post-therapy scans showed undetectable Tg off L-T4. In 30 patients (3·6%) faint positive post-therapy images for thyroid remnants have been classified as false-positive results on the basis of both negative 24-h neck uptake and undetectable Tg off L-T4.This study confirms that most patients have residual thyroid tissue after total thyroidectomy and that it seems reasonable to omit routine diagnostic whole-body scans before131I treatment with clinical, managerial and economic advantages. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this review is to give an overview of the current status of molecular image–guided surgery in gynaecological malignancies, from both clinical and technological points of view.A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image–guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices.The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging.After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach.Methods: The aim of this review is to give an overview of the current status of molecular image–guided surgery in gynaecological malignancies, from both clinical and technological points of view.A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image–guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices.The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging.After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach.Results: The aim of this review is to give an overview of the current status of molecular image–guided surgery in gynaecological malignancies, from both clinical and technological points of view.A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image–guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices.The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging.After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach.Conclusion: The aim of this review is to give an overview of the current status of molecular image–guided surgery in gynaecological malignancies, from both clinical and technological points of view.A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image–guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices.The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging.After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach. [ABSTRACT FROM AUTHOR]

Early response evaluation with [18F]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. [ABSTRACT FROM AUTHOR]

Study Design. Retrospective study. Objective. To evaluate, in a pediatric population, 18F-Fluorodeoxy- glucose (18F-FDG) metabolic activity of normal spinal cord and to assess the correlation with demographic, clinical, and environmental variables. Summary of Background Data. 18F-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 18F-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 18F-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. [ABSTRACT FROM AUTHOR]

ABSTRACT 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. Muscle Nerve 50: 1016-1022, 2014 [ABSTRACT FROM AUTHOR]

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 18F- 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 18F- DOPA PET- CT. [ABSTRACT FROM AUTHOR]

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 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 F-FDG PET/CT, and surgery. Results: Of the 26 ocular lesions, 23 showed 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 F-FDG in evaluating prognosis. [ABSTRACT FROM AUTHOR]

The assessment of hepatobiliary and pancreatic tumors is commonly achieved by ultrasound, computed tomography (CT), and magnetic resonance. The 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) detects increased glucose metabolism associated with neoplastic lesions, provides high accuracy in most cancer imaging applications and is now widely used in clinical practice. However, PET is not always useful and accurate knowledge of appropriate indications is essential for a proper clinical management. (18)F-FDG is transported into cells and phosphorylated by the enzyme hexokinase to (18)F-FDG-6-phosphate, which cannot proceed down the glycolytic pathway and therefore is accumulated in the malignant tissue. PET allows accurate quantification of FDG uptake in tissue, and previous studies have demonstrated that standardized uptake values provide highly reproducible parameters of tumor glucose use (Weber et al., J Nucl Med 40:1771-1777, 1999). The recent development and diffusion of hybrid PET-CT scanners allows functional and anatomic data to be obtained in a single examination, improving lesion localization and resulting in significant diagnostic improvement (Wahl, J Nucl Med 45:82S-95S, 2004). Moreover, CT can be performed diagnostically with the use of intravenous and oral contrast and simultaneous PET-contrast-enhanced CT scanning appears to be an efficient method in cancer evaluation. However, in most centers, a low-dose CT is routinely performed without contrast media infusion.Proper patient preparation, scanning protocol, combined assessment of PET and CT data, and the evaluation of conventional imaging findings are essential to define disease and to avoid diagnostic pitfalls. The role of PET and PET-CT in malignancies of the liver, biliary tract, and pancreas is here reviewed; normal patterns, representative cases, and common pitfalls are also presented. [ABSTRACT FROM AUTHOR]

Introduction: We performed a meta-analysis on published data on the diagnostic performance of fluorine-18 dihydroxyphenylalanine (F-DOPA) positron emission tomography (PET) in diagnosing and localizing focal congenital hyperinsulinism (CHI). Materials and methods: A comprehensive computer literature search of studies published up to 31 January 2012 regarding F-DOPA PET or PET/CT in patients with CHI was performed. Pooled sensitivity and specificity, area under the ROC curve and diagnostic odds ratio (DOR) of F-DOPA PET or PET/CT in diagnosing focal CHI were calculated. The localization accuracy of focal CHI was also estimated. Seven studies comprising 195 CHI patients were included. Results: The pooled sensitivity and specificity of F-DOPA PET or PET/CT in differentiating between focal and diffuse CHI were 89% (95% confidence interval [CI]:81-95%) and 98% (95% CI:89-100%), respectively. The DOR was 74.5 (95% CI:18-307). The area under the ROC curve was 0.95. The pooled accuracy of these functional imaging methods in localizing focal CHI was 80% (95% CI:71-88%). Discussion: In CHI patients, F-DOPA PET or PET/CT demonstrated high sensitivity and specificity in differentiating between focal and diffuse CHI. F-DOPA PET or PET/CT are accurate methods of localizing focal CHI. Nevertheless, possible sources of false-negative results for focal CHI should be kept in mind. [ABSTRACT FROM AUTHOR]

A case study is presented of a 48-year-old man who developed a nodal recurrence of cancer in a spared parotid gland following induction chemotherapy and intensity-modulated radiation therapy (IMRT) for nasopharyngeal cancer. Topics include studies of recurrence risks of head and neck cancers treated with parotid-sparing IMRT, sparing of submandibular glands, and salivary flow preservation.

Purpose: The aim of this study was to systematically review and conduct a meta-analysis of published data about the diagnostic performance of F-dihydroxyphenylalanine (DOPA) positron emission tomography (PET) in patients with paraganglioma (PG). Methods: A comprehensive computer literature search of studies published through 30 June 2011 regarding F-DOPA PET or PET/computed tomography (PET/CT) in patients with PG was performed in PubMed/MEDLINE, Embase and Scopus databases. Pooled sensitivity and specificity of F-DOPA PET or PET/CT in patients with PG on a per patient- and on a per lesion-based analysis were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of F-DOPA PET or PET/CT in patients with PG. Furthermore, a sub-analysis taking into account the different genetic mutations in PG patients was also performed. Results: Eleven studies comprising 275 patients with suspected PG were included in this meta-analysis. The pooled sensitivity of F-DOPA PET and PET/CT in detecting PG was 91% [95% confidence interval (CI) 87-94%] on a per patient-based analysis and 79% (95% CI 76-81%) on a per lesion-based analysis. The pooled specificity of F-DOPA PET and PET/CT in detecting PG was 95% (95% CI 86-99%) on a per patient-based analysis and 95% (95% CI 84-99%) on a per lesion-based analysis. The area under the ROC curve was 0.95 on a per patient- and 0.94 on a per lesion-based analysis. Heterogeneity between the studies about sensitivity of F-DOPA PET or PET/CT was found. A significant increase in sensitivity of F-DOPA PET or PET/CT was observed when a sub-analysis excluding patients with succinate dehydrogenase subunit B (SDHB) gene mutations was performed. Conclusion: In patients with suspected PG F-DOPA PET or PET/CT demonstrated high sensitivity and specificity. F-DOPA PET or PET/CT are accurate methods in this setting. Nevertheless, possible sources of false-negative results should be kept in mind. Furthermore, SDHB gene mutations could influence F-DOPA PET or PET/CT diagnostic performance. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To systematically review the role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in evaluating treatment response to imatinib or other drugs in gastrointestinal stromal tumors (GIST). Methods: A comprehensive literature search of published studies through February 2011 in PubMed/MEDLINE and EMBASE databases was performed. Results: We identified 19 studies including 628 patients with GIST. Main findings of included studies are presented. Conclusions: 18F-FDG PET has a significant value in assessing treatment response to imatinib or other drugs in GIST patients. 18F-FDG PET allows an early assessment of treatment response and is a strong predictor of clinical outcome. [Copyright &y& Elsevier]

Purpose: To retrospectively evaluate and compare F-FDG, F-DOPA and Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels. Methods: Included in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis. Results: At least one focus of abnormal uptake was observed on PET/CT in 13 patients with F-DOPA (72.2% sensitivity), in 6 patients with Ga-somatostatin analogues (33.3%) and in 3 patients with F-FDG (16.7%) ( p < 0.01). There was a statistically significant difference in sensitivity between F-DOPA and F-FDG PET/CT ( p < 0.01) and between F-DOPA and Ga-somatostatin analogue PET/CT ( p = 0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. F-DOPA PET/CT detected 85% of lesions (61 of 72), Ga-somatostatin analogue PET/CT 20% (14 of 72) and F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers ( p < 0.01). In particular, post-hoc tests showed a significant difference in the number of lymph node, liver and bone lesions detected by F-DOPA PET/CT and F-FDG PET/CT ( p < 0.01 for all the analyses) and by F-DOPA PET/CT and Ga-somatostatin analogue PET/CT ( p < 0.01 for all the analyses). The PET/CT results led to a change in management of eight patients (44%). Conclusion: F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than F-FDG and Ga-somatostatin analogue PET/CT. F-FDG may complement F-DOPA in patients with an aggressive tumour. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively evaluate and compare F-FDG, F-DOPA and Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels. Methods: Included in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis. Results: At least one focus of abnormal uptake was observed on PET/CT in 13 patients with F-DOPA (72.2% sensitivity), in 6 patients with Ga-somatostatin analogues (33.3%) and in 3 patients with F-FDG (16.7%) ( p < 0.01). There was a statistically significant difference in sensitivity between F-DOPA and F-FDG PET/CT ( p < 0.01) and between F-DOPA and Ga-somatostatin analogue PET/CT ( p = 0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. F-DOPA PET/CT detected 85% of lesions (61 of 72), Ga-somatostatin analogue PET/CT 20% (14 of 72) and F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers ( p < 0.01). In particular, post-hoc tests showed a significant difference in the number of lymph node, liver and bone lesions detected by F-DOPA PET/CT and F-FDG PET/CT ( p < 0.01 for all the analyses) and by F-DOPA PET/CT and Ga-somatostatin analogue PET/CT ( p < 0.01 for all the analyses). The PET/CT results led to a change in management of eight patients (44%). Conclusion: F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than F-FDG and Ga-somatostatin analogue PET/CT. F-FDG may complement F-DOPA in patients with an aggressive tumour. [ABSTRACT FROM AUTHOR]

Primary pancreatic lymphoma (PPL) is an extremely rare disease which occurs in pancreas, accounts for less than 1% of extra-nodal malignant lymphomas and 0,5% of cases of pancreatic masses. We report the case of PPL in a 15 year-old boy suffering from Maturity Onset Diabetes of the Young type 3 (MODY3) diagnosed at the age of 1 year. [ABSTRACT FROM AUTHOR]

BACKGROUND: The goal of this study was to prospectively analyze the diagnostic performances of magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT) in predicting pathologically assessed residual disease in a large, single-institution series of locally advanced cervical cancer (LACC) patients triaged to neoadjuvant treatments followed by radical surgery. METHODS: Between April 2007 and March 2010, 96 patients with histologically documented cervical cancer (any histology) and FIGO stage IB2-IVA were enrolled. MRI and PET/CT were recommended to be performed within 4-6 weeks from the end of treatment, and histology was the reference standard. Sensitivity, specificity, and accuracy were compared using the McNemar test. RESULTS: For residual disease in the cervix, sensitivity was higher for MRI than for PET/CT (86.1% vs 63.1%; P = .002), while specificity was significantly higher for PET/CT compared with MRI ( P = .002). There was no difference in accuracy values between the 2 imaging modalities. For MRI analysis of lymph node groups, sensitivity, specificity, and accuracy were 35.7%, 95.9%, and 88.0%, respectively. Conversely, sensitivity, specificity, and accuracy for PET/CT were 28.6%, 97.8%, and 88.7%, respectively. Absence of follicular structures replaced by prevalent sclerosis and/or sinus histiocytosis was the most frequently documented morphological pattern in false-positive cases. CONCLUSION: Neither MRI nor PET/CT accurately detected residual disease in LACC patients triaged to radical surgery after neoadjuvant treatment, disallowing the option of avoiding or modulating completion surgery. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: 18F-fluoro-deoxy-glucose (18F-FDG) positron emission tomography integrated/combined with computed tomography (PET-CT) provides the best diagnostic results in the metabolic characterization of undetermined solid pulmonary nodules. The diagnostic performance of 18F-FDG is similar for nodules measuring at least 1 cm and for larger masses, but few data exist for nodules smaller than 1 cm. Case presentation: We report five cases of oncologic patients showing focal lung 18F-FDG uptake on PET-CT in nodules smaller than 1 cm. We also discuss the most common causes of 18F-FDG false-positive and false-negative results in the pulmonary parenchyma. In patient 1, contrast-enhanced CT performed 10 days before PET-CT did not show any abnormality in the site of uptake; in patient 2, high-resolution CT performed 1 month after PET showed a bronchiole filled with dense material interpreted as a mucoid impaction; in patient 3, contrast-enhanced CT performed 15 days before PET-CT did not identify any nodules; in patients 4 and 5, contrast-enhanced CT revealed a nodule smaller than 1 cm which could not be characterized. The 18F-FDG uptake at follow-up confirmed the malignant nature of pulmonary nodules smaller than 1 cm which were undetectable, misinterpreted, not recognized or undetermined at contrast-enhanced CT. Conclusion: In all five oncologic patients, 18F-FDG was able to metabolically characterize as malignant those nodules smaller than 1 cm, underlining that: 18F-FDG uptake is not only a function of tumor size but it is strongly related to the tumor biology; functional alterations may precede morphologic abnormalities. In the oncologic population, especially in higher-risk patients, PET can be performed even when the nodules are smaller than 1 cm, because it might give an earlier characterization and, sometimes, could guide in the identification of alterations missed on CT. [ABSTRACT FROM AUTHOR]

Objective: The ATP-sensitive K(+) channel (K(ATP)) controls insulin secretion from the islet. Gain- or loss-of-function mutations in channel subunits underlie human neonatal diabetes and congenital hyperinsulinism (HI), respectively. In this study, we sought to identify the mechanistic basis of K(ATP)-induced HI in two probands and to characterize the clinical course.Research Design and Methods: We analyzed HI in two probands and characterized the course of clinical treatment in each, as well as properties of mutant K(ATP) channels expressed in COSm6 cells using Rb efflux and patch-clamp methods.Results: We identified mutation V290M in the pore-forming Kir6.2 subunit in each proband. In vitro expression in COSm6 cells supports the mutation resulting in an inactivating phenotype, which leads to significantly reduced activity in intact cells when expressed homomerically, and to a lesser extent when expressed heteromerically with wild-type subunits. In one heterozygous proband, a fluoro-DOPA scan revealed a causal focal lesion, indicating uniparental disomy with loss of heterozygosity. In a second family, the proband, homozygous for the mutation, was diagnosed with severe diazoxide-unresponsive hypersinsulinism at 2 weeks of age. The patient continues to be treated successfully with octreotide and amlodipine. The parents and a male sibling are heterozygous carriers without overt clinical HI. Interestingly, both the mother and the sibling exhibit evidence of abnormally enhanced glucose tolerance.Conclusions: V290M results in inactivating K(ATP) channels that underlie HI. Homozygous individuals may be managed medically, without pancreatectomy. Heterozygous carriers also show evidence of enhanced glucose sensitivity, consistent with incomplete loss of K(ATP) channel activity. [ABSTRACT FROM AUTHOR]

OBJECTIVE--The ATP-sensitive K+ channel (KATP) controls insulin secretion from the islet. Gain- or loss-of-function mutations in channel subunits underlie human neonatal diabetes and congenital hyperinsulinism (HI), respectively. In this study, we sought to identify the mechanistic basis of KATP-induced HI in two probands and to characterize the clinical course. RESEARCH DESIGN AND METHODS--We analyzed HI in two probands and characterized the course of clinical treatment in each, as well as properties of mutant KATP channels expressed in COSm6 cells using Rb efflux and patch-clamp methods. RESULTS--We identified mutation V290M in the pore-forming Kir6.2 subunit in each proband. In vitro expression in COSm6 cells supports the mutation resulting in an inactivating phenotype, which leads to significantly reduced activity in intact cells when expressed homomerically, and to a lesser extent when expressed heteromerically with wild-type subunits. In one heterozygous proband, a fluoro-DOPA scan revealed a causal focal lesion, indicating uniparental disomy with loss of heterozygosity. In a second family, the proband, homozygous for the mutation, was diagnosed with severe diazoxide-unresponsive hypersinsulinism at 2 weeks of age. The patient continues to be treated successfully with octreotide and amlodipine. The parents and a male sibling are heterozygous carriers without overt clinical HI. Interestingly, both the mother and the sibling exhibit evidence of abnormally enhanced glucose tolerance. CONCLUSIONS--V290M results in inactivating KATP channels that underlie HI. Homozygous individuals may be managed medically, without pancreatectomy. Heterozygous carriers also show evidence of enhanced glucose sensitivity, consistent with incomplete loss of K[sub ATP] channel activity. Diabetes 60:209-217, 2011 [ABSTRACT FROM AUTHOR]

The most common causes of hyperaldosteronism (HA) are bilateral idiopathic hyperaldosteronism (IHA), aldosterone-producing adenoma (APA), and unilateral primary adrenal hyperplasia (PAH). We evaluated if non-invasive preoperative imaging studies are able to reliably differentiate these causes of hyperaldosteronism. The medical records of 50 consecutive patients with HA were reviewed. Follow up was obtained by outpatient consultation or phone contact. Thirty-five patients (70%) underwent successful adrenalectomy for APA, basing on the computed tomography (CT) scan results only. All these patients were biochemically cured. The remaining 15 patients underwent dexamethasone suppression adrenal cortical scintiscan (ACS) because of equivocal or inconclusive CT scan. In 11 of these patients, ACS showed a bilateral uptake, suggesting IHA. They were followed-up. In the remaining four patients, ACS showed a unilateral uptake. These patients underwent adrenalectomy. Final histology showed APA in three patients and PAH in one. They were biochemically cured. Sensitivity of combined non-invasive imaging procedures (CT and ACS) in detecting histologically proven and biochemically cured APA and PAH was 100%. Non-invasive adrenal imaging studies are accurate in distinguishing between IHA and APA/PAH. Invasive diagnostic tests (adrenal venous sampling) should be indicated only when they do not conclusively localize hypersecretion. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing response to 5-azacytidine in a patient with relapsed Hodgkin Lymphoma and a therapy-related myelodysplastic syndrome.

Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor. Currently, 18F-fluoro-deoxy-glucose (18F-FDG) PET/CT is the functional imaging modality of choice. Few data are available on the use of 68Ga-somatostatin analogs. The aim of our study was to evaluate and compare the diagnostic performance of 18F-FDG and 68Ga-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 18F-FDG and 68Ga-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, 18F-FDG and 68Ga-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, 18F-FDG detected 67/75 lesions (89%) and 68Ga-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 18F-FDG and 68Ga-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 18F-FDG PET/CT should be replaced by 68Ga-somatostatin receptor imaging, which should be performed in addition, according to clinical indication, to the perspective of “personalized medicine.” [ABSTRACT FROM AUTHOR]