18F-FET and 18F-choline PET-CT in patients with MRI-suspected low-grade gliomas: a pilot study.

AIM: To investigate the diagnostic accuracy of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) and fluoromethyl-(18F)-dimethyl-2-hydroxyethyl-ammonium chloride (18F-FCH) computed tomography (CT) in patients with primary low-grade gliomas (LGG). METHODS: The study enrolled patients with magnetic resonance imaging (MRI)-suspected LGG. Patients underwent both 18F-FET and 18F-FCH positron emission tomography (PET)-CT. Brain PET-CT was performed according to standard protocol - 20 minutes after intravenous injection of 185 MBq of 18F-FET and 185 MBq of 18F-FCH PET. Surgery and pathohistological diagnosis were performed in the next two weeks. RESULTS: We observed significantly better concordance between tumor histology and 18F-FET PET (weighted Kappa 0.74) compared with both 18F-FCH (weighted Kappa 0.15) and MRI (weighted Kappa 0.00). Tumor histology was significantly associated with 18F-FET (odds ratio 12.87; 95% confidence interval [CI], 0.49-333.70; P=0.013, logistic regression analysis). Receiver operating characteristic curve analysis comparing 18F-FCH (area under the curve [AUC] 0.625, 95% CI 0.298-0.884) and 18F-FET (AUC 0.833, 95% CI 0.499-0.982) showed better diagnostic properties of 18F-FET (AUC difference 0.208, 95% CI -0.145 to 0.562, P=0.248). CONCLUSION: Performing PET-CT in patients with newly diagnosed LGG should be preceded by a selection of an appropriate radiopharmaceutical. 18F-FET seems to be more accurate than 18F-FCH in the LGG diagnosis.

Kinase Inhibitors in the Treatment of Thyroid Cancer: Institutional Experience.

Although most patients with thyroid cancer have a favorable clinical course, some patients develop a more aggressive type of cancer and exhibit more rapid disease progression with worse prognosis. Those patients usually exhibit mutations of proteins such as tyrosine kinase enzymes that play a significant role in regulation of tumor proliferation and spreading. Development of targeted therapies is based on the inhibition of mutated kinases which are involved in the MAPK signaling pathway. The aim of this study was to present the initial results of clinical experience with kinase inhibitors in patients with metastatic differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC), and medullary thyroid cancer (MTC) who exhibited rapid disease progression. A total of 17 adult patients (11 women, mean age 53.3 years) managed for progressive, metastatic disease were included in the study. Twelve patients with DTC and PDTC were previously tested for BRAF mutations, of whom nine that had tumor tissue negative for the BRAF V600E mutation received sorafenib, while three patients with tumors harboring the BRAF V600E mutation were treated with vemurafenib. Patients with MTC were treated with sunitinib, vandetanib, and sorafenib. Two patients with tumors harboring the BRAF mutation treated with vemurafenib showed restoration of radioiodine uptake. Most of patients showed significant improvement in disease status but of limited duration until disease progression. Although there was an improvement in progression-free survival, future research has to achieve a greater and longer-lasting response, probably by utilizing combined targeted therapy.

GIANT CELL AORTITIS DIAGNOSED WITH PET/CT - PARANEOPLASTIC SYNDROME?

Vasculitides are heterogenic group of autoimmune connective tissue diseases which often present difficulties in early diagnosing. Giant cell arteritis is vasculitis of large and medium arteries. It predominantly presents with symptoms of affection of the external carotid artery branches. Furthermore, the only symptoms can be constitutional. In clinical practice, vasculitides are sometimes considered as paraneoplastic, but no definite association with malignancies has been established and the mechanisms are still debated. The gold standard for diagnosing giant cell arteritis is a positive temporal artery biopsy, but the results can often be false negative. Additionally, more than half of the patients have aorta and its main branches affected. Considering aforementioned, imaging studies are essential in confirming large-vessel vasculitis, amongst which is highly sensitive PET/CT. We present the case of a 70-year-old female patient with constitutional symptoms and elevated sedimentation rate. After extensive diagnostic tests, she was admitted to our Rheumatology unit. Aortitis of the abdominal aorta has been confirmed by PET/CT and after the introduction of glucocorticoids the disease soon went into clinical and laboratory remission. Shortly after aortitis has been diagnosed, lung carcinoma was revealed of which the patient died. At the time of the comprehensive diagnostics, there was no reasonable doubt for underlying malignoma. To the best of our knowledge, there are no recent publications concerning giant cell arteritis and neoplastic processes in the context of up-to-date non-invasive diagnostic methods (i.e. PET/CT). In the light of previous research results, we underline that the sensitivity of PET/CT is not satisfactory when estimating cancer dissemination in non-enlarged lymph nodes and that its value can at times be overestimated.

The most common factors influencing on quality of life of thyroid cancer patients after thyroid hormone withdrawal.

BACKGROUND: The aim of study was to evaluate which factors impact mostly on life-quality of patients with differentiated thyroid carcinoma after thyroid hormone withdrawal. SUBJECTS AND METHODS: 150 patients were enrolled in the study by using Quality of life- Thyroid version questionnaire in which they expressed their physical, psychological, social and spiritual well-being. The answers have been interpreted on a scale from 0 to 10. All patients underwent four weeks levothyroxine withdrawal in preparation for I-131 procedures and thyroglobulin testing. RESULTS: Individual statements on the physical subscale showed that patients had most difficulties with fatigue, intolerance to cold and heat, sleep changes and weight gain, but with higher average values than expected. Fatigue was one of the most common physical difficulties. Female patients had significantly more difficulties than male respondents. Five most expressed psychological difficulties have been stress caused by initial diagnosis, followed by stress caused by surgical treatment, fear of metastases, stress caused by initial radioiodine ablation treatment and fear of cancer recurrence. Generally, results revealed troubles mostly in physical symptoms relating to thyroid hormone withdrawal, as well as psychological distress caused by initial diagnosis. Respondents with higher educational level achieved a significantly higher score than less educated patients (p=0.026, Mann-Whitney U test). Illness was very distressing for their families (median value 1, range: 0 to 10) and they reported insufficient support from others (1, range: 0 to 10), but they did not feel isolated. Family and work consequences were less apparent. CONCLUSION: The results of QOL-Thyroid questionnaire help to identify high-risk areas in patients' lives that are negatively affected by hormone withdrawal. Regarding the wide definition of quality of life, a positive impact on patients' recovery could be achieved by directing attention to most expressed difficulties noted in this questionnaire.

Clinical utility of [68Ga]Ga-PSMA-11 PET/CT in initial staging of patients with prostate cancer and importance of intraprostatic SUVmax values.

BACKGROUND: As in disease recurrence, providing clinicians with the exact extent of the disease at the time of initial diagnosis is key in the management and individual treatment of prostate cancer (PC) patients. Intending to examine the usefulness of gallium- 68 PSMA-11 positron emission tomography/computed tomography ([68Ga]Ga-PSMA-11 PET/CT) and to determine if there is a correlation between prostate-specific antigen (PSA) serum values, WHO/ISUP (World Health Organization/International Society of Urological Pathology's) grade group of the tumor and SUVmax (maximized standardized uptake value) values we retrospectively analyzed PET/CT studies performed for initial staging of the disease. PATIENTS AND METHODS: We retrospectively evaluated 34 studies of patients who underwent [68Ga]Ga-PSMA-11 PET/CT as part of the initial staging of prostate cancer. All patients had prostate cancer confirmed by histological assessment after biopsy and had Gleason score and PSA serum values obtained. The mean PSA value was 33.8 ± 40.9 nmol/L (range 2.2-232). RESULTS: Nineteen patients had extended disease (55.9%). The mean SUVmax in prostate lesions was 19.5 ± 12.6. The mean value of SUVmax of PET studies in the high-risk group was significantly higher than those of low risk (23.5 ± 13.2 and 10.6 ± 5.4, p < 0.05). A positive correlation was observed between the ISUP group and SUVmax value of prostate lesions (Pearson's r = 0.557, p < 0.01). A positive correlation was also found in the comparison between PSA values and SUVmax (Pearson's r = 0.34, p < 0.05). CONCLUSIONS: In our study, [68Ga]Ga-PSMA-11 PET/CT scans detected the extended disease in more than half of the patients. Locating disease beyond the prostate gland allowed better informed clinical decisions and modified treatment. A positive correlation was found between intraprostatic SUVmax values and the ISUP group of prostate cancer. High-risk patients had SUVmax values that were significantly higher than those of low-risk patients. The correlation between the Gleason score and SUVmax value can be explained by the increased intensity of PSMA expression as the tumor grade increases.

[Lymphoma diagnosis and treatment - second Croatian consensus]. / Dijagnostika i lijecenje limfoma - drugi hrvatski konsenzus.

New, extended and modernized recommendations for diagnostics and treatment of lymphomas were accepted at a meeting held in March 2012 with the participation of major Croatian experts. They encompass morphological, radiological and nuclear diagnostics, systemic treatment, radiotherapy and follow-up of most tumors of lymphoid tissues occurring in adults. The recommendations were agreed upon by consensus. Reporters presented data and suggested recommendations which had been first discussed in working groups and then agreed upon on the plenary session.

Detection of brown tumors by [18F]F-choline PET/CT performed in a patient with secondary hyperparathyroidism.

Brown tumours are rare bone lesions occurring in patients with severe hyperparathyroidism (HPT) because of increased osteoclastic activity due to high levels of parathyroid hormone (PTH). We report the case of 30-year-old woman with secondary hyperparathyroidism due to severe chronic kidney diseases who underwent [18F]F-choline PET/CT scan for localization of the hyperfunctioning parathyroid gland before surgical treatment. [18F]F-choline PET/CT scan showed increased choline uptake in the lower left parathyroid gland and in multiple bone lytic lesions. Multiple focal choline uptake in bone corresponded to brown tumours - fibrous osteitis cystica.

Reliability of sentinel node assay in vulvar cancer: the first Croatian validation trial.

OBJECTIVE: To evaluate the reliability of sentinel node assay in early stage vulvar cancer patients by using preoperative lymphoscintigraphy. METHODS: Technetium-99m colloid albumin was injected intradermally around the tumor for lymphoscintigraphic mapping and intraoperative hand-held gamma probe detection of sentinel nodes. For all patients, sentinel node biopsy was followed by inguinofemoral lymphadenectomy, regardless of the sentinel lymph node status. RESULTS: From December 2008 until May 2011, 25 consecutive patients with T1 or T2 stage of vulvar squamous cell cancer were enrolled. The median age of patients was 69 years (range, 48-79). The detection of sentinel lymph node was successful in all 25 patients. A total of 36 sentinel lymph nodes were harvested and metastatic carcinoma was identified in 12 sentinel nodes from 8 patients. There was 1 patient with metastatic non-sentinel lymph node despite the negative sentinel node. Two patients with negative sentinel nodes proven by routine histopathological examination were positive by immunohistochemical staining. The sensitivity, specificity and negative predictive value of sentinel node assay with immunohistochemistry included were 89%, 100%, and 94%, respectively. CONCLUSIONS: Lymphoscintigraphy and sentinel lymph node biopsy under gamma-detecting probe guidance proved to be an easy and reliable method for the detection of sentinel node in early vulvar cancer. Immunohistochemical analysis improves the sensitivity for the detection of regional micrometastases. The sentinel node assay is highly accurate in predicting the status of the remaining inguinofemoral lymph nodes. Our results indicate that patients best suited to SLN assay have had a simple punch biopsy to confirm the diagnosis rather than a previous tumor excision. This technique represents a true advance in the selection of patients for less radical surgery.

Incidental detection of breast cancer by 18F-fluorocholine PET/CT performed for primary hyperparathyroidism.

We present a case report of incidental detection of breast cancer in a female patient referred for 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) due to primary hyperparathyroidism. This imaging method was recently shown as more sensitive for the detection of metabolically hyperactive parathyroid glands than neck ultrasound and (2-metoksyizobutyloizonitryl labeled with technetium-99m) [99mTc]MIBI. Increased accumulation of FCH was found in the hyperactive parathyroid gland and unexpectedly in the right breast lesion. The surgery confirmed parathyroid adenoma. One month later right upper medial quadrantectomy confirmed breast carcinoma - a combination of invasive ductal carcinoma and intracystic papillary breast carcinoma. To the best of our knowledge, this is the first reporting of simultaneous detection of parathyroid adenoma and breast cancer by using 18F-fluorocholine PET/CT.

Role of Matrix Metalloproteinases and Their Inhibitors in Locally Invasive Papillary Thyroid Cancer.

Locally invasive papillary thyroid carcinoma (PTC) protrudes beyond the thyroid capsule and invades local structures. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in local invasion and metastasis in PTC. The aim of our study was to determine expression levels of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 in tissue specimens of invasive and non-invasive PTC. Our hypothesis was that expression levels of these biomarkers correlate with the development of locally invasive PTC. In our single-center study we retrospectively investigated MMP and TIMP expression levels in 50 samples of thyroid tissue diagnosed as locally invasive papillary carcinoma (study group) and 30 samples of thyroid tissue diagnosed as non-invasive, non-metastatic papillary carcinoma (control group). Tissue specimens were immunohistochemically stained with primary monoclonal antibodies against MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2. When correlating expression levels of MMPs and TIMPs in thyroid tissue, statistically significant differences were found for MMP-1 and TIMP-1 expression (p < 0.001; Mann−Whitney U test) with the highest levels of expression in the invasive PTC group. Although expression of MMP-9 and TIMP-2 was higher in invasive PTC, the differences were not statistically significant. Elevated expression of MMP-1 and TIMP-1 in tumor tissue can predict invasiveness for PTC.

Efficacy of long-term ultrasonography in follow-up of patients with papillary thyroid carcinoma: a case of neck metastasis developed 19 years following primary treatment.

The cases of relapse in papillary thyroid cancer patients who were initially considered low-risk and for many years were without signs of the disease are extremely rare, but exist. This is supported by the clinical case of a patient who underwent a total thyroidectomy due to papillary thyroid cancer and 19 years later metastasis with extracapsular spreading in a presumed thyroid place was revealed. Due to such cases, the importance of long-term ultrasound monitoring is emphasized.

Intraoperative Detection of Hyperplastic Parathyroid Gland With Positron Emitter 18F-Fluorocholine and Handheld Probe.

We present the first intraoperative detection of a hyperplastic parathyroid gland with a positron emitter F-fluorocholine and handheld probe, with the estimation of the absorbed dose to the surgeon and surgical staff. Intraoperative positron emitter detection enabled the resection of a small parathyroid gland, resulting in normal postoperative values of PTH and serum calcium in a 69-year-old woman. Calculated whole-body dose to the surgical staff and surgeons' fingers is well below the annual limits for exposed workers and the general public. Intraoperative F-FCH detection with handheld probe is a safe and feasible method for localizing small parathyroid glands.

Can inflammatory markers and clinical indices serve as useful referral criteria for leukocyte scan with inflammatory bowel disease?

BACKGROUND: In the follow-up of patients with inflammatory bowel disease (IBD), Tc-99m-HMPAO labelled leukocytes scintigraphy (leukocyte scan; LS) has long been established as a valuable diagnostic tool. The aim of this study was to estimate the relationship between scintigraphic results, inflammatory markers (IM) (including white blood cells (WBCs) and C-reactive protein (CRP)), clinical parameters and clinical indices of the disease activity (CI), in order to determine clinical settings in which LS is indicated. MATERIALS AND METHODS: A total of 147 patients who underwent LS, (79 males, 68 females, median age 36), were examined from April 2010 until December 2017 at the University Hospital Centre Zagreb, Croatia. Among these, 126 (86%) had Crohn's disease (CD) and 21 (14%) had ulcerative colitis (UC). Either increased IM (either WBCs ≥10x109/L and/or CRP ≥7.4 mg/L) and/or CI, Crohn's disease activity index (CDAI) score ≥220 points, Harvey-Bradshaw index (HBI) score ≥8 points, and severe colitis defined according to Truelove and Witts' criteria (TWC) for UC, respectively, were considered consistent with active disease. RESULTS: Eighty-two patients (56%) had negative scans, while in 65 (44%) the scans were positive. Positive correlations were found between LS and all of the 3 parameters, WBCs, CRP and CI. When combined, the 3 parameters demonstrated even stronger positive correlation with the LS results with the correlation coefficient 0.76 (p<0.0001, 95% CI [0.68-0.82]). Using endoscopy and histological study findings of the obtained specimens as a composite reference standard, the overall sensitivity, specificity, positive predictive value and negative predictive value of IM and CI for LS were determined, being 91%, 85%, 83%, and 92%, respectively. IM and CI were both negative in 76 (52%) out of the total subjects. Of these, 70 had negative LS as well. CONCLUSION: In the presence of normal IM with CI pointing to no active or mildly active disease, LS is not necessarily indicated.

[Sentinel lymphadenectomy in squamous cell carcinoma of the pharynx and larynx]. / Sentinelna limfadenektomija kod planocelularnih karcinoma larinksa i hipofarinksa.

The study included 20 patients with carcinoma of the pharynx and larynx. The incidence of metastases was compared between sentinel lymph nodes and the rest of lymph nodes in resected material. Patient inclusion criteria were primary tumor verified as squamous cell carcinoma by preoperative histopathology and negative clinical neck finding (cN0). Human serum albumin radiocolloid labeled with radioactive technetium-99m 0.5 mCi (18 MBq) was used. In two patients (with tumors of the hypopharynx and glottis), lymph nodes were not preoperatively visualized by scintigraphy. A total of 32 lymph nodes (range 0-4), were visualized. All nodes were found in regions II-IV, mostly in region II. In three patients, sentinel lymph nodes were detected bilaterally. Twenty six selective neck resections were performed (bilateral in six patients). A total of 319 (mean 12) lymph nodes were isolated in resected material, 7 of them were positive, all ipsilateral. A positive definitive histopathology finding was recorded in five patients. Three patients had one positive lymph node each (pN1), all sentinel lymph nodes. In one patient, positive sentinel lymph node histopathology was associated with tumor lesions detected in other lymph nodes (pN2b). One patient had false negative result. Study results confirmed the lymphatic drainage of the upper aerodigestive tract and metastasizing area from tumors of this localization are constant and predictable.

F-18 FDG PET/CT in pulmonary artery sarcoma: clinical vignette.

Pulmonary artery sarcomas (PAS's) are extremely rare malignant tumors that arise from the endothelial lining of the pulmonary arteries. On CT scans PAS's appear as intraluminal filling defects in the pulmonary arteries, mimicking pulmonary embolism (PE). Due to the similarities in radiographic features as well as in clinical presentation, PAS's are usually misdiagnosed as pulmonary embolism. Since PASs are F-18 FDG avid, F-18 FDG PET/CT scan is a useful imaging tool for differentiating between these two conditions, as shown in this case report. We report a case of a 60-year-old woman presented with a 6-month history of chest pain, dyspnea on exertion, non-productive cough and weight loss. The initial CT pulmonary artery angiography showed extensive intraluminal mass in the pulmonary trunk and left pulmonary artery, diagnosed as massive pulmonary embolism. Since there was no clinical improvement after anticoagulant therapy, CT pulmonary angiography was repeated, and with no change observed in the intraluminal filling defect in pulmonary trunk, the possibility of tumor was raised. For further evaluation of a possible malignancy, F-18 FDG PET/CT was performed. It showed increased FDG uptake, suspicious for an aggressive tumor, in the intraluminal lesion of the pulmonary trunk and along the wall of the left pulmonary artery. There was no extrathoracic abnormality seen on PET/CT scan. Histopathological finding after complete pulmonary artery resection showed high grade undifferentiated pleomorphic sarcoma. F-18 FDG PET/CT is a useful tool for differentiating between pulmonary embolism and malignant intraluminal mass, and at the same time it enables the proper staging of the malignancy. < p > < /p >.

The Significance of Thallium-201-Chloride SPECT Myocardial Perfusion Imaging in the Management of Patients With Stable Chronic Coronary Artery Disease.

BACKGROUND: Patients with stable coronary artery disease (CAD) can be evaluated for myocardial viability by examining reverse redistribution of Thallium-201 (201TI) through cardiac scintigraphy. There is limited knowledge about association of a reverse redistribution with favorable cardiac outcomes. In this study, we hypothesized that higher left ventricular ejection fraction (LVEF), lower myocardial necrosis, fewer ischemic events, and less angina will be associated with reverse redistribution of 201TI imaging. METHODS: Adult patients with stable CAD included in this study underwent exercise-redistribution Thallium single-photon emission computed tomography (SPECT) and were followed for one year. LVEF and regional wall motion abnormalities were evaluated with echocardiography, exercise duration by bicycle testing, and myocardial ischemia and viability by Thallium SPECT. RESULTS: We studied 159 patients (87 men, 72 women, median age 60 years, range: 38-84) with well-developed collaterals. Those with reverse redistribution on SPECT (n = 61, 38.3%) had significantly better exercise tolerance (⩾85%; P < .001). Subjects with reverse redistribution had better LVEF (P < .001), wall motion parameters (P < .001), a lower degree of myocardial necrosis (P < .05), less angina during follow-up (P = .02), and fewer ischemic events whether treated with OMT or PCI (P < .001). CONCLUSIONS: Reverse redistribution of 201Tl on scintigraphic images is a predictor of myocardial viability. Evidence from our study suggests that optimally treated chronic CAD patients with reverse redistribution may have lower likelihood of future adverse cardiovascular events and better prognosis.

The value of 18F-DOPA PET/CT in patients with medullary thyroid carcinoma and increased calcitonin values.

AIM: The aim of this prospective observational study was to examine the benefit of a fluorine-18-L-dihydroxyphenylalanine (F-DOPA) PET/computed tomography (CT) scan in patients with medullary thyroid carcinoma (MTC) in terms of increased calcitonin levels. PATIENTS AND METHODS: Twenty-eight MTC patients after initial total thyreoidectomy with increasing follow-up calcitonin levels suggestive for active disease after negative conventional imaging findings (neck ultrasound or thorax, abdomen, pelvis multislice computed tomography as standard imaging) were scanned using F-DOPA PET/CT from November 2012 to April 2016. The mean calcitonin level was 108.5 (range: 6.7-290) pmol/l and the mean carcinoembryonic antigen level was 15.7 (range: 1.1-221.9) µg/l. The mean follow-up period was 19.7 months. RESULTS: F-DOPA PET/CT was positive in 16 out of 28 (57%) patients, mostly because of metabolically active neck and mediastinal lymph nodes metastases. Previously unknown bone metastases were found in six patients. A positive scan was reported in four patients (25% of positive scans) with a very low calcitonin value of less than 49.9 pmol/l. PET/CT findings led to a change of management and therapy in 16 out of 28 patients, with surgical procedure performed in eight patients, radiotherapy in five patients, and chemotherapy in two patients. CONCLUSION: F-DOPA PET/CT is a clinically useful modality in MTC whenever the calcitonin level is increased. There is a clear trend toward more positive scans with the higher calcitonin values, but patients with moderately elevated calcitonin values should also be taken into consideration for molecular imaging with F-DOPA PET/CT as the tumor burden in these patients is probably low, enabling further therapy to be individualized and consequently more efficient.

[90Y-ibritumomab tiuxetan in patients with follicular lymphoma relapsing or refractory to rituximab]. / 90Y-ibritumomab tiuksetan u bolesnika s refraktornim folikularnim limfomom ili u relapsu nakon rituksimaba.

Radioimmunotherapy is a new antineoplastic treatment modality combining the effects of irradiation and monoclonal antibodies. 90Y-ibritumomab tiuxetan is a monoclonal antibody directed against the CD20 antigen to which a radioactive isotope of yttrium is attached, used for treating follicular lymphomas (FL). Using this compound we treated 8 patients with FL relapsing or refractory to combinations of rituximab and chemotherapy. Severe neutropenia developed in 5, and severe thrombocytopenia and anemia in 3 patients. Serious infections developed in 2 patients, one died. Six patients responded to treatment, 4 are still in remission after a median follow-up of 15 months, 2 died of lymphoma. Best response was achieved in low-risk patients with a low tumor burden. 90Y-ibritumomab tiuxetan is an effective treatment for FL with significant hematological toxicity and a high price.