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We assessed the role of [18F]FDG-PET/CT in identifying and managing cancer of unknown primary site (CUP syndrome). We reviewed [18F]FDG-PET/CT scans of individuals with CUP syndrome recorded in clinical referral letters from 2012 to 2019. We evaluated the identification of primary tumor (PT) by [18F]FDG-PET/CT, according to histological subtype, and the impact on clinical management. The median age was 65 years, 36/64 males (56%). PTs were detected in 28/64 (44%) patients. Detection was significantly lower in patients with squamous cell carcinoma (SCC) than with other histologies combined, p = 0.034. Mean age, mean SUVmax (10.6 ± 6.0) and organ involvement were similar between patients with and without discovered PTs; and between patients with SCC and with other histologies combined. However, those with SCC were less likely than the others to present with multi-lesion involvement, p < 0.001. [18F]FDG-PET/CT interpretations apparently affected treatment of 8/28 (29%) patients with PT detected, and in none of the 35 whose PT was not discovered, p < 0.001. [18F]FDG-PET/CT appeared helpful in detecting PT in almost half the patients with CUP syndrome; the lowest rate was for patients with SCC pathology. PET/CT showed limited overall value in guiding clinical management, however benefited those with discovered PT.

While penile metastases are rare, PET/CT has facilitated their detection. We aimed to describe penile secondary lesions (PSL) identified by PET/CT. We reviewed 18F-FDG and Ga68-PSMA PET/CT records performed in a single center during May 2012-March 2020, for PSL. Of 16,774 18F-FDG and 1,963 Ga68-PSMA-PET scans, PSL were found in 24(0.13%) men with a mean age of 74. PSMA detected PSL in 12 with prostate cancer; FDG identified PSL in 4 with lymphoma, 3 with colorectal cancer, 2 with lung cancer, and one each with bladder cancer, pelvic sarcoma, and leukemia. Mean SUVmax of PSL was 7.9 ± 4.2 with focal uptake in 13(54%). Mean lesion size was 16.5 ± 6.8 mm; 8 at the penile root, 4 along the shaft, and 1 at the glans. CT detected loss of the penile texture in 15(63%). PSL were observed only during relapse or follow-up of disseminated disease. Among those with prostate cancer, PSA varied widely. Fifteen (62.5%) died, at a mean 13.3 ± 15.9 months following PSL demonstration, nine had non-prostate malignancies. PET/CT identified and characterized PSL in a fraction of cancer patients, most commonly those with prostate cancer. PSL universally surfaced in advanced disease, and signaled high mortality, especially in non-prostate cancers.

Objectives To evaluate if radiomics with machine learning can differentiate between F-18-fluorodeoxyglucose (FDG)-avid breast cancer metastatic lymphadenopathy and FDG-avid COVID-19 mRNA vaccine–related axillary lymphadenopathy. Materials and methods We retrospectively analyzed FDG-positive, pathology-proven, metastatic axillary lymph nodes in 53 breast cancer patients who had PET/CT for follow-up or staging, and FDG-positive axillary lymph nodes in 46 patients who were vaccinated with the COVID-19 mRNA vaccine. Radiomics features (110 features classified into 7 groups) were extracted from all segmented lymph nodes. Analysis was performed on PET, CT, and combined PET/CT inputs. Lymph nodes were randomly assigned to a training ( n = 132) and validation cohort ( n = 33) by 5-fold cross-validation. K-nearest neighbors (KNN) and random forest (RF) machine learning models were used. Performance was evaluated using an area under the receiver-operator characteristic curve (AUC-ROC) score. Results Axillary lymph nodes from breast cancer patients ( n = 85) and COVID-19-vaccinated individuals ( n = 80) were analyzed. Analysis of first-order features showed statistically significant differences ( p < 0.05) in all combined PET/CT features, most PET features, and half of the CT features. The KNN model showed the best performance score for combined PET/CT and PET input with 0.98 (± 0.03) and 0.88 (± 0.07) validation AUC, and 96% (± 4%) and 85% (± 9%) validation accuracy, respectively. The RF model showed the best result for CT input with 0.96 (± 0.04) validation AUC and 90% (± 6%) validation accuracy. Conclusion Radiomics features can differentiate between FDG-avid breast cancer metastatic and FDG-avid COVID-19 vaccine–related axillary lymphadenopathy. Such a model may have a role in differentiating benign nodes from malignant ones. Key Points • Patients who were vaccinated with the COVID-19 mRNA vaccine have shown FDG-avid reactive axillary lymph nodes in PET-CT scans. • We evaluated if radiomics and machine learning can distinguish between FDG-avid metastatic axillary lymphadenopathy in breast cancer patients and FDG-avid reactive axillary lymph nodes. • Combined PET and CT radiomics data showed good test AUC (0.98) for distinguishing between metastatic axillary lymphadenopathy and post-COVID-19 vaccine–associated axillary lymphadenopathy. Therefore, the use of radiomics may have a role in differentiating between benign from malignant FDG-avid nodes.

Objective To investigate the patterns of breast cancer-related and lactation-related 18 F-FDG uptake in breasts of lactating patients with pregnancy-associated breast cancer (PABC) and without breast cancer. Methods 18 F-FDG-PET/CT datasets of 16 lactating patients with PABC and 16 non-breast cancer lactating patients (controls) were retrospectively evaluated. Uptake was assessed in the tumor and non-affected lactating tissue of the PABC group, and in healthy lactating breasts of the control group, using maximum and mean standardized uptake values (SUVmax and SUVmean, respectively), and breast-SUVmax/liver-SUVmean ratio. Statistical tests were used to evaluate differences and correlations between the groups. Results Physiological uptake in non-breast cancer lactating patients’ breasts was characteristically high regardless of active malignancy status other than breast cancer (SUVmax = 5.0 ± 1.7, n  = 32 breasts). Uptake correlated highly between the two breasts ( r  = 0.61, p  = 0.01), but was not correlated with age or lactation duration ( p  = 0.24 and p  = 0.61, respectively). Among PABC patients, the tumors demonstrated high 18 F-FDG uptake (SUVmax = 7.8 ± 7.2, n  = 16), which was 326–643% higher than the mostly low physiological FDG uptake observed in the non-affected lactating parenchyma of these patients (SUVmax = 2.1 ± 1.1). Overall, 18 F-FDG uptake in lactating breasts of PABC patients was significantly decreased by 59% ( p  < 0.0001) compared with that of lactating controls without breast cancer. Conclusion 18 F-FDG uptake in lactating tissue of PABC patients is markedly lower compared with the characteristically high physiological uptake among lactating patients without breast cancer. Consequently, breast tumors visualized by 18 F-FDG uptake in PET/CT were comfortably depicted on top of the background 18 F-FDG uptake in lactating tissue of PABC patients. Key Points • FDG uptake in the breast is characteristically high among lactating patients regardless of the presence of an active malignancy other than breast cancer. • FDG uptake in non-affected lactating breast tissue is significantly lower among PABC patients compared with that in lactating women who do not have breast cancer. • In pregnancy-associated breast cancer patients, 18 F-FDG uptake is markedly increased in the breast tumor compared with uptake in the non-affected lactating tissue, enabling its prompt visualization on PET/CT.

Detection of anti-nuclear autoantibodies (ANA) is based on a two-step algorithm including indirect immunofluorescence (IIF) on HEp2 cells and subsequent reflex/confirmatory testing for specific autoantibodies. Simultaneous cell- and microbead-based autoantibody detection by IIF may be utilized for the evaluation of systemic autoimmune rheumatic diseases (SARDs). In the present study, we assessed the performance of CytoBead ANA 2 in the detection of ANA and ANA-specific autoantibodies, compared to ANA IIF and BioPlex™ 2200. We also tested the ability of CytoBead ANA DFS-70 to identify dense-fine speckled (DFS) pattern associated with anti-DFS70 antibodies in non-SARDs patients. Hundred-twelve routine sera samples were assessed by manual CytoBead ANA 2 for the presence of ANA and specific autoantibodies. In parallel, these samples were analyzed by HEp2 ANA IIF test and a subsequent multiplexed assay BioPlex™ 2200 ANA. Twenty-nine ANA-positive samples obtained from non-SARDs patients and exhibiting DFS pattern by ANA IIF were further tested by CytoBead ANA DFS-70. A substantial agreement was observed between classical ANA IIF and manual CytoBead ANA 2 for the detection of ANA (k = 0.74). Discordant results were mainly associated with the presence of anti-SSA/Ro antibodies detected by CytoBead ANA 2 in ANA IIF negative patients. A good to almost perfect agreement was found between CytoBead ANA 2 and BioPlex™ 2200 for detection of specific antibodies with kappa values ranging from 0.70 to 0.90. Twenty samples (68.9%) obtained from 29 ANA IIF positive without SARDs patients exhibited DFS pattern in CytoBead ANA DFS-70, which confirmed the presence of anti-DFS70 antibodies. The diagnostic performance of manual CytoBead ANA 2 for ANA screening and detection of ANA specific antibodies is comparable to the diagnostic performance of ANA IIF followed by BioPlex™ 2200. This novel one-step assay enables simultaneous ANA screening and confirmation and represents a promising alternative approach to the time-consuming and costly two-tier ANA analysis.

Background 68Ga-PSMA PET/CT has an important role in assessment of prostate cancer patients with biochemical recurrence and is evolving in staging high- and intermediate risk disease. The aim of present study was to describe the metastatic patterns and frequency of involved sites of prostate cancer and to assess the incidence of benign Ga68-PSMA avid PET/CT findings in a large patient population. Methods 68Ga-PSMA PET/CT studies performed in two tertiary medical centers over a period of 24 months were retrospectively reviewed. The incidence and location of pathological 68Ga-PSMA avid foci, suspicious to represent malignancy, as well as those of unexpected benign foci of increased 68Ga-PSMA activity were documented and analyzed. Results There were 445 68Ga-PSMA studies in 438 men (mean age 72.4, range 51–92 years) with prostate cancer referred for biochemical failure ( n  = 270, 61%), staging high-risk disease ( n  = 112, 25%), response assessment ( n  = 30, 7%), follow-up ( n  = 22, 5%) and suspected bone metastases (n = 11, 2%). 68Ga-PSMA avid disease sites were observed in 319 studies (72%), in 181 studies (67%) for biochemical recurrence, 94 studies for staging (84%) ( p  < 0.05), in 22 studies for response assessment (73%), 10 follow up studies (45%) and in five patients with suspected bone metastases (45%). 68Ga-PSMA avid lesions were most commonly detected in the prostate ( n  = 193, 43%), loco-regional spread ( n  = 51, 11%), abdomino-pelvic nodes ( n  = 129, 29%) and distant metastases ( n  = 158, 36%), including bone metastases ( n  = 11, 25%), distant lymphadenopathy ( n  = 29, 7%) and other organs ( n  = 18, 4%). Distant 68Ga-PSMA-avid metastases were commonly seen in patients with biochemical recurrence (14/21 lesions), but were not seen in patient referred for staging ( p  < 0.013). There were 96 non-malignant 68Ga-PSMA avid foci in 81 studies, most common in reactive lymph nodes ( n  = 36, 38%), nonmalignant bone lesions ( n  = 21, 22%), thyroid nodules ( n  = 9, 9%), ganglions (n = 9, 9%) and lung findings ( n  = 8, 8%). Conclusion The distribution of 68Ga-PSMA avid metastatic lesions is similar to data previously reported mainly from autopsy with comparable detection rates, indicating 68Ga-PSMA PET/CT is an accurate detection tool in patients with metastatic prostate cancer. If confirmed by further prospective studies 68Ga-PSMA PET/CT should be included in the guidelines to evaluate disease extent in these patients.

Background Advances in imaging, biomaterials and precision radiotherapy provide new opportunities to salvage locally recurrent prostate cancer (PC). This study evaluates the efficacy and safety of re-irradiation using stereotactic body radiation therapy (SBRT). We hypothesized that patients with castrate-resistant PC (CRPC) would benefit less from local salvage. Methods A prospective clinical database was reviewed to extract 30 consecutive patients treated with prostate re-irradiation. Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography was performed following prostate-specific antigen failure in all patients and biopsy was obtained in 18 patients (60%). Re-irradiation was either focal (n = 13) or whole-gland (n = 17). Endo-rectal balloons were used in twenty-two patients and hydrogel spacers in eight patients. The median prescription dose was 5 fractions of 6.5 (range: 6–8) Gray (Gy). Results Median follow-up was 28 months . Failure occurred in 10 (out of 11) CRPC patients versus 6 (out of 19) castrate-sensitive patients (91% vs. 32%, p  = 0.008) after a median of 13 and 23 months, respectively. Metastases occurred in 64% (n = 7) of CRPC patients versus 16% (n = 3) of castrate-sensitive patients ( p  = 0.007). Two patients experienced local in-field recurrence, thus local control was 93%. The 2 and 3-year recurrence-free survival were 84% and 79% for castrate-sensitive patients versus 18% and 9% for CRPC patients ( p  < 0.001), and 3-year metastasis-free survival was 90% versus 27% ( p  < 0.01) for castrate-sensitive and CRPC patients, respectively. Acute grade II and III genitourinary (GU) toxicity occurred in 27% and 3%, and late GU toxicity in 30% and 3%, respectively. No ≥ grade II acute gastrointestinal (GI) toxicity occurred, and only one patient (3%) developed late grade II toxicity. Conclusions Early delivery of salvage SBRT for local recurrence is associated with excellent 3-year disease control and acceptable toxicity in the castrate-sensitive phenotype. PSMA imaging for detection of local recurrence and the use of precision radiotherapy with rectal protective devices should be further investigated as a novel salvage strategy for radio-recurrent PC.

Fever of unknown origin (FUO) poses a diagnostic challenge, and 18-fluorodexoyglucose positron emission tomography with computed tomography (18FDG-PET/CT) may identify the source. We aimed to evaluate the diagnostic yield of 18FDG-PET/CT in the work-up of FUO. The records of patients admitted to Sheba Medical Center between January 2013 and January 2018 who underwent 18FDG-PET/CT for the evaluation of FUO were reviewed. Following examination of available medical test results, 18FDG-PET/CT findings were assessed to determine whether lesions identified proved diagnostic. Of 225 patients who underwent 18FDG-PET/CT for FUO work-up, 128 (57%) met inclusion criteria. Eighty (62.5%) were males; mean age was 59 ± 20.3 (range: 18–93). A final diagnosis was made in 95 (74%) patients. Of the 128 18FDG-PET/CT tests conducted for the workup of FUO, 61 (48%) were true positive, 26 (20%) false positive, 26 (20%) true negative, and 15 (12%) false negative. In a multivariate analysis, weight loss and anemia were independently associated with having a contributary results of 18FDG-PET/CT. The test yielded a sensitivity of 70%, specificity of 37%, positive predictive value of 70%, and negative predictive value of 37%. 18FDG-PET/CT is a valuable tool in the diagnostic workup of FUO. It proved effective in diagnosing almost half the patients, especially in those with anemia and weight loss.

Streptococcus is well associated with a myriad of inflammatory diseases. Among others, this bacterium is linked to the triggering of psoriasis and to post-streptococcal reactive arthritis (PSRA), an arthritis which is typically confined to peripheral joints. Three patients who developed acute psoriatic spondyloarthritis (SpA) following a recent streptococcal infection are described in this article. We searched the existing literature for cases of axial involvement in PSRA and reviewed the association between streptococcal infection and psoriasis or psoriatic arthritis )PsA). In all patients, psoriatic SpA occurred within 7–10 days of a confirmed streptococcal infection. The main presenting syndrome was inflammatory back pain with evidence of acute axial spondyloarthritis on magnetic resonance imaging. One patient had guttate psoriasis, the second patient developed pustular psoriasis, and the third patient had exacerbation of pustular palmoplantar psoriasis. Two patients required treatment with tumor necrosis factor alpha (TNF-α) blockers. Axial involvement in PSRA is very rare. A potential association of streptococcal infection and development of PsA has been explored in several articles. However, to the best of our knowledge, acute psoriatic SpA as a manifestation of PSRA has yet to be described. Acute psoriatic SpA should be considered in the differential diagnosis of new-onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection.Key Points• Our case series describes three cases of acute psoriatic spondyloarthritis that occurred within 7–-10 days of a confirmed streptococcal infection and progressed to full blown chronic disease.• Acute psoriatic spondyloarthritis as a manifestation of post streptococcal reactive arthritis should be considered in the differential diagnosis of new onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection.

Since psoriasis (PsO) is a chronic inflammatory disease, patients may experience a drug failure also with very effective drugs (i.e., secukinumab) and, consequently, dermatologists have two therapeutic options: switching or perform a combination therapy (rescue therapy) to save the drug that had decreased its efficacy. At the moment no studies focused on combination/rescue therapy of secukinumab, so we performed a 52-weeks multicenter retrospective observational study that involved 40 subjects with plaque psoriasis that experienced a secondary failure and were treated with combination therapy (ciclosporin (n = 11), MTX (n = 15), NB-UVB (n = 7) and apremilast (n = 7)). After 16 weeks of rescue/combination therapy, PASI and a DLQI varied respectively from 8 [7.0–9.0] and 13 [12.0–15.0], to 3 [2.8–4.0] and 3 [2.0–3.3]), suggesting a significant improvement of daily functionality and quality of life. Results were maintained at 52 weeks. No side effects were experienced during the study. Secukinumab remains a safety and effective drug for PsO patients also in the IL-23 and JAK inhibitors era. The rescue therapy is a valid therapeutic option in case of secukinumab secondary failure.