Diagnostic value of [18F]FDG-PET/CT for treatment monitoring in large vessel vasculitis: a systematic review and meta-analysis.

PURPOSE: Monitoring disease activity in patients with large vessel vasculitis (LVV) can be challenging. [18F]FDG-PET/CT is increasingly used to evaluate treatment response in LVV. In this systematic review and meta-analysis, we aimed to summarize the current evidence on the value of [18F]FDG-PET/CT for treatment monitoring in LVV. METHODS: PubMed/MEDLINE and the Cochrane library database were searched from inception through October 21, 2020. Studies containing patients with LVV (i.e. giant cell arteritis, Takayasu arteritis and isolated aortitis) that received treatment and underwent [18F]FDG-PET/CT were included. Screening, full-text review and data extraction were performed by 2 investigators. The risk of bias was examined with the QUADAS-2 tool. Meta-analysis of proportions and diagnostic test accuracy was performed by a random-effects model and bivariate model, respectively. RESULTS: Twenty-one studies were included in the systematic review, of which 8 studies were eligible for meta-analysis. Arterial [18F]FDG uptake decreased upon clinical remission in longitudinal studies. High heterogeneity (I2 statistic 94%) precluded meta-analysis of the proportion of patients in which the scan normalized during clinical remission. Meta-analysis of cross-sectional studies indicated that [18F]FDG-PET/CT may detect relapsing/refractory disease with a sensitivity of 77% (95%CI 57-90%) and specificity of 71% (95%CI 47-87%). Substantial heterogeneity was observed among the cross-sectional studies. Both variation in clinical aspects and imaging procedures contributed to the heterogeneity. CONCLUSION: Treatment of LVV leads to reduction of arterial [18F]FDG uptake during clinical remission. [18F]FDG-PET/CT has moderate diagnostic accuracy for detecting active LVV. [18F]FDG-PET/CT may aid treatment monitoring in LVV, but its findings should be interpreted in the context of the clinical suspicion of disease activity. This study underlines the relevance of published procedural recommendations for the use of [18F]FDG-PET/CT in LVV.

Diagnostic value of [18F]FDG-PET/CT in polymyalgia rheumatica: a systematic review and meta-analysis.

PURPOSE: Polymyalgia rheumatica (PMR) can be difficult to diagnose. Whole-body [18F]FDG-PET/CT allows for a comprehensive evaluation of all relevant articular and extra-articular structures affected by PMR. We aimed to summarize current evidence on the diagnostic value of [18F]FDG-PET/CT for a diagnosis of PMR. METHODS: PubMed/MEDLINE and the Cochrane Library database were searched from inception through May 31, 2020. Studies containing patients with PMR who underwent [18F]FDG-PET/CT were included. Screening and full-text review were performed by 3 investigators and data extraction by 2 investigators. Risk of bias was examined with the QUADAS-2 tool. Diagnostic test meta-analysis was performed with a bivariate model. RESULTS: Twenty studies were included in the systematic review, of which 9 studies (n = 636 patients) were eligible for meta-analysis. [18F]FDG positivity at the following sites was associated with a diagnosis of PMR: interspinous bursae (positive likelihood ratio (LR+) 4.00; 95% CI 1.84-8.71), hips (LR+ 2.91; 95% CI 2.09-4.05), ischial tuberosities (LR+ 2.86; 95% CI 1.91-4.28), shoulders (LR+ 2.57; 95% CI 1.24-5.32) and sternoclavicular joints (LR+ 2.31; 95% CI 1.33-4.02). Negative likelihood ratios (LR-) for these sites, as well as the greater trochanters, were all less than 0.50. Composite [18F]FDG-PET/CT scores, as reported in 3 studies, provided a pooled LR+ of 3.91 (95% CI 2.42-6.32) and LR- of 0.19 (95% CI 0.10-0.36). Moderate to high heterogeneity was observed across the studies, mainly due to differences in patient selection, scanning procedures and/or interpretation criteria. CONCLUSION: Significant [18F]FDG uptake at a combination of anatomic sites is informative for a diagnosis of PMR. [18F]FDG-PET/CT might be an important diagnostic tool in patients with suspected PMR. This study also highlights the need for adherence to published procedural recommendations and standardized interpretation criteria for the use of [18F]FDG-PET/CT in PMR.

90Y TOF-PET based EUD reunifies patient survival prediction in resin and glass microspheres radioembolization of HCC tumours.

Clinical studies reported a twofold ratio between the efficacies per Gy of resin versus glass spheres. Our aim is to investigate whether this difference could result from the different degrees of heterogeneity in sphere distribution between the two medical devices. The 90Y TOF-PET based equivalent uniform doses (EUD) was used for this purpose. 58 consecutive HCC radioembolizations were retrospectively analyzed. Absorbed doses D and Jones-Hoban EUD in lesions were computed. Radioembolization efficacy was assessed using Kaplan-Meier survival curves. In order to match together the glass and resin spheres survival curves using a 40 Gy-threshold, an efficacy factor of 0.73 and 0.36 has to be applied on their absorbed dose, respectively. Using EUD, a nice matching between glass and resin survival curves was obtained with a better separation of the responding and not responding survival curves. The results clearly support the fact that the activity heterogeneity observed in 90Y TOF-PET post radioembolization does not only result from statistical noise, but also reflects the actual heterogeneity of the spheres distribution. Use of EUD reunifies the efficacy of the two medical devices.

Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy: an EANM procedural guideline.

INTRODUCTION: Radiolabelled autologous white blood cells (WBC) scintigraphy is being standardized all over the world to ensure high quality, specificity and reproducibility. Similarly, in many European countries radiolabelled anti-granulocyte antibodies (anti-G-mAb) are used instead of WBC with high diagnostic accuracy. The EANM Inflammation & Infection Committee is deeply involved in this process of standardization as a primary goal of the group. AIM: The main aim of this guideline is to support and promote good clinical practice despite the complex environment of a national health care system with its ethical, economic and legal aspects that must also be taken into consideration. METHOD: After the standardization of the WBC labelling procedure (already published), a group of experts from the EANM Infection & Inflammation Committee developed and validated these guidelines based on published evidences. RESULTS: Here we describe image acquisition protocols, image display procedures and image analyses as well as image interpretation criteria for the use of radiolabelled WBC and monoclonal antigranulocyte antibodies. Clinical application for WBC and anti-G-mAb scintigraphy is also described. CONCLUSIONS: These guidelines should be applied by all nuclear medicine centers in favor of a highly reproducible standardized practice.

Common diagnostic flowcharts in vascular and endovascular surgery.

Vascular and endovascular procedures are typically very "clean" procedures, with a very low infection rate. However, these complications, although rare, are unfortunately associated with a high rate of morbidity and mortality. The first rule to effectively treat the infection is always prevention, but when the infection has been established the only solution is given by an early diagnosis and proper medical care and often surgical treatment. The hardest thing is to obtain is an early and correct diagnosis, especially for low-grade infections. The purpose of our work was to strengthen the conviction that only an integrated work as a team will enable effective and quick management of this serious complication.

Unusual cause of severe anaemia in a patient with metastatic haemangiopericytoma.

Haemangiopericytoma is a rare tumor of vascular origin. We report the case of patient with severe refractory anaemia due to peripheral destruction of red blood cells by spleen metastases. Anaemia was successfully treated by splenectomy. Afterwards, our patient developed liver and lung metastases and was treated, in a clinical trial, with gefitinib that stabilised the disease during nine years. These interesting features are discussed.

Sonic aerosol therapy to target maxillary sinuses.

AIM: Intranasal aerosol administration of drugs is widely used by ENT specialists. Although clinical evidence is still lacking, intranasal nebulization appears to be an interesting therapeutic option for local drug delivery, targeting anatomic sites beyond the nasal valve. The sonic nebulizer NL11SN associates a 100Hertz (Hz) sound to the aerosolization to improve deposition in the nasal/paranasal sinuses. The aim of the present study was: to evaluate in vivo the influence of associating a 100Hz sound on sinus ventilation and nasal and pulmonary aerosol deposition in normal volunteers, and; to quantify in vitro aerosol deposition in the maxillary sinuses in a plastinated head model. MATERIAL AND METHODS: Scintigraphic analysis of (81m)Kr gas ventilation and of sonic aerosol ((99m)Tc-DTPA) deposition using the NL11SN was performed in vivo in seven healthy volunteers. In parallel, NL11SN gentamicin nebulization was performed, with or without associated 100Hz sound, in a plastinated human head model; the gross amount of gentamicin delivered to the paranasal sinuses was determined by fluorescence polarization immunoassay. RESULTS: Associating the 100Hz sound to (81m)Kr gas ensured paranasal sinus ventilation in healthy volunteers. (99m)Tc-DTPA particles nebulized with the NL11SN were deposited predominantly in the nasal cavities (2/3, vs 1/3 in the lungs). In vitro, the use of NL11SN in sonic mode increased gentamicin deposition threefold in the plastinated model sinuses (P<0.002); the resulting antibiotic deposit would be sufficient to induce a local therapeutic effect. CONCLUSION: The NL11SN nebulizer ensured preferential nasal cavity aerosol deposition and successfully targeted the maxillary sinuses.

Nonspecific human immunoglobulin G for imaging infection and inflammation: what did we learn?

Radiolabeled human non specific immunoglobulin G (IgG or HIG) was proposed in the early nineties as a potential tracer for imaging infection and sterile inflammation. Formulations with ¹¹¹In and (99m)Tc as the label were developed and extensive preclinical work was undertaken to assess its potential as a diagnostic agent. ¹¹¹In-HIG was used in a number of clinical studies and proved efficient in detecting orthopedic infections, especially in patients with prostheses, fever of unknown origin, opportunistic infections in immunocompromised patients, including patients infected with the human immunodeficiency virus and neutropenic patients. In the latter patients, there was no need for blood manipulation to harvest white cells for leukocyte labeling which was a considerable advantage. (99m)Tc-HIG was also successfully used for imaging sterile arthritis, especially rheumatoid arthritis. Two decades later, radiolabeled HIG is almost completely abandoned as a general purpose tracer for imaging infection and inflammation and this article aims to find out why this has happened.

Diagnostic pitfalls in digestive neuroendocrine tumours.

Gastro-entero-pancreatic neuroendocrine tumours (GEP NET) represent a rare and highly heterogeneous entity that often is revealed by vague and non-specific symptoms, leading to a delayed diagnosis. Here we will review some of the most regularly observed false positive and false negative cases and provide clues to recognize and manage them properly. Particularly, the value of chromogranin-A as a serum tumour marker and Somatostatin receptor scintigraphy as an imaging test, are reviewed. Indeed, chromogranin-A and other hormones, such as gastrin, as well as urinary 5-hydroxy-indolic acetic acid (5-HIAA) are often tested to diagnose NET without appraising the clinical situation, leading to extensive work-up on false bases. On the other hand, some tests are performed in situations where they do not add additional information (e.g. 5-HIAA in pancreatic or rectal NET) because invariably negative. Somatostatin receptor scintigraphy is an expensive examination, still not reimbursed in Belgium, for which indications must be carefully assessed, knowing its specificity and sensitivity.

Calculation of the renal perfusion and glomerular filtration rate from the renal impulse response obtained with MRI.

The aim of this study was to assess the importance of deconvolution for the calculation of renal perfusion and glomerular filtration rate (GFR) on the basis of concentration-time curves as measured with perfusion MRI. Six rabbits were scanned dynamically after injection of a gadolinium chelate. Concentration-time curves were generated by manually drawing regions of interest in the aorta and the renal cortex. To remove the dependency on the arterial input function, a regularized structured total least-squares deconvolution algorithm was used to calculate the renal impulse response. This curve was fitted by the sum of two gamma variate functions, corresponding to the passage of the contrast agent in the glomeruli and the proximal convoluted tubules. Tracer kinetics models were applied to these two functions to obtain the renal perfusion and GFR. For comparison, these two parameters were also calculated on the basis of the renal concentration-time curve before deconvolution. The renal perfusion values correlated well (r = 0.9, P = 0.014) with the values calculated by a validated upslope method. The GFR values correlated well (r = 0.9, P = 0.014) with the values obtained from the clearance of (51)Cr-EDTA. A comparison of the values obtained with and without deconvolution demonstrated the necessity of deconvolution.

Parapharyngeal metastases from thyroid cancer.

AIM: To emphasise the pattern of lymphatic dissemination in the parapharyngeal space from thyroid cancer. PATIENTS AND METHOD: Among 696 patients treated for thyroid cancer between 1986 and 2001, parapharyngeal metastasis was diagnosed in three patients, previously treated for papillary thyroid carcinoma. RESULTS: All three patients have been treated by surgical resection through lateral cervical approach. Two of them were controlled regionally whereas the remaining one had a submucosal pharyngeal metastasis locally resected 27 months after parapharyngeal resection. CONCLUSIONS: Parapharyngeal metastasis is rare, but should be a recognized pattern of lymphatic dissemination from thyroid carcinoma to avoid unnecessary radioiodine and because surgical resection is efficacious with acceptable morbidity.

[Pharyngoesophagolaryngeal metastases of medullary thyroid carcinoma. A case report]. / Métastases pharyngo-oeso-laryngées d'un carcinome médullaire de la thyroïde. A propso d'un cas.

We report the case of a patient with medullary thyroid carcinoma (MTC) who presented multiple pharyngoesophagolaryngeal metastases detected by flexible laryngoscopy. Pathology confirmed the diagnosis after resection with CO2 laser under direct laryngoscopy. Because of worsening dyspnea, complete circular pharyngolaryngectomy was performed with reconstruction of the pharyngeal region with a major pectoralis musculocutaneous flap. The postoperative period was satisfactory. At 17 months, calcitonin level was elevated; subcutaneous cervical metastases of the MTC developed and were resected. At 27 months, oral nutrition and phonation remained satisfactory. We discuss the diagnostic and therapeutic strategies used for this very unusual form of locoregional spread of medullary carcinoma of the thyroid gland.

Scintigraphy using a technetium 99m-labelled anti-E-selectin Fab fragment in rheumatoid arthritis.

OBJECTIVE: We previously described a novel radiolabelled monoclonal antibody (1.2B6), which reacts with porcine E-selectin, for targeting activated endothelium as a means of imaging inflammatory disorders, and presented initial clinical work based on (111)In-labelled antibody. The aim of the present study was to evaluate a Fab fragment of 1.2B6 labelled with (99m)Tc in patients with rheumatoid arthritis (RA) by comparison with (i) (111)In-labelled 1.2B6 F(ab')(2) and (ii) conventional bone scanning. METHODS: (99m)Tc-1.2B6-Fab ( approximately 440 MBq) and (111)In-1.2B6-F(ab')(2) ( approximately 27 MBq) were compared in 10 patients using a double-isotope protocol. Images were obtained 4 and 20-24 h after injection. Two normal volunteers were also imaged. In a separate group of 16 patients, (99m)Tc-1.2B6-Fab and (99m)Tc-oxidronate ((99m)Tc-HDP) ( approximately 740 MBq) were compared on the basis of visual and semi-quantitative analysis of joint uptake (joint/soft tissue ratios) 4 h after injection. The respective biodistributions and blood clearances of the two 1.2B6 fragments were also compared. RESULTS: Image contrast was slightly better with (99m)Tc-Fab at 4 h but equal for the two tracers at 24 h. Diagnostic accuracy, taking joint tenderness or swelling as the clinical endpoint, was 76% for both fragments at 24 h. Plasma clearance of (99m)Tc-Fab was faster than that of (111)In-F(ab')(2) (t(1/2) 142 vs 421 min; P<0.0001). (99m)Tc-Fab appeared somewhat unstable in vivo, as shown by activity in the thyroid gland and bowel. The diagnostic accuracy of (99m)Tc-Fab was 88%, higher than that of (99m)Tc-HDP (57%) as a result of the low specificity of the latter in RA. Receiver operating characteristic (ROC) curve analysis using joint/soft tissue ratios as a variable cut-off showed that (99m)Tc-Fab discriminates better than (99m)Tc-HDP between actively inflamed and silent joints (Z=4.72; P<0.0001). No uptake of (99m)Tc-Fab was observed by inactive or normal joints, whereas (99m)Tc-HDP was taken up by all joints to a variable degree, making the decision as to whether a particular joint is actively involved or chronically damaged very difficult. CONCLUSION: (99m)Tc-anti-E-selectin-Fab scintigraphy can be used successfully to image synovitis with better specificity than (99m)Tc-HDP bone scanning. The advantages over (111)In-1.2B6-F(ab')(2) are easier availability of the radionuclide, improved physical properties and optimal imaging 4 h after injection.

Video-assisted neck exploration for primary and secondary hyperparathyroidism: initial experience.

BACKGROUND: Minimally invasive surgery (MIS) for primary hyperparathyroidism includes unilateral neck exploration, access via a totally endoscopic approach, and access via a video-assisted procedure. We report herein our initial experience with the video-assisted neck exploration procedure for primary (PHPT) and secondary hyperparathyroidism (SHPT). METHODS: Between June 1999 and May 2000, 35 patients were selected for PHPT (n = 25) and SHPT (n = 10). In all cases, video-assisted neck exploration was performed under general anesthesia, leading to selective adenoma removal in PHPT or subtotal parathyroid resection in SHPT. Patient selection was based on the preoperative localization studies (ultrasonography and sestamibi scintigraphy). RESULTS: Five of the 25 patients operated on for PHPT (20%) and three of the 10 patients who underwent surgery for SHPT (30 %) were converted to a conventional surgical technique. The mean operative times in PHPT and SHPT were 48.9 +/- 18.7 min and 136.8 +/- 18.7 min, respectively. The recurrent laryngeal nerve was identified in 45% of the patients. The median size and weight of the resected parathyroid glands were 1.8 cm (range, 0.9-2.5) and 1 g (range, 0.5-7), respectively. The length of skin incision was 24 +/- 1.2 mm. All but one patient are currently cured, with a median follow-up of 6 months (range, 2-13). Postoperative complications included hematoma and transient hoarseness in one patient each (2.85%). The median pain intensity, based on the visual analogue scale (VAS) method, as measured at postoperative day 1 was 0.5 (range, 0-3.6). In the PHPT group, the postoperative hospital stay was

Tc-99m HDP bone scan showing bone changes in a case of tuberous sclerosis or Bourneville's disease.

Whole-body Tc-99m HDP scintigraphy was performed in a 25-year-old woman with known tuberous sclerosis. The scintigraphic pattern showed multiple foci of abnormal activity over the hands, phalanges, feet, tibias, fibulas, ulnas, and radii, where radiographs showed periosteal apposition, irregular cortical thickening, and cystlike lesions on the phalanges. The spine, pelvis, and ribs showed heterogeneous tracer uptake where radiographs showed patchy areas of increased bone density. This radiographic pattern is characteristic of osseous tuberous sclerosis. Although previous reports suggested the opposite conclusion, this observation indicates that an abnormal result of bone scintiscan can be observed in osseous tuberous sclerosis.

A survey of guidelines in 27 EANM associated societies by the EANM Task Group on Quality Assurance and Standardisation. European Association of Nuclear Medicine.

The main aim of the EANM Task Group on Quality Assurance and Standardisation is to develop harmonised clinical procedures that are accepted within Europe. In order to achieve an evidence-based analysis of guidelines in the 27 EANM member societies, a survey was conducted. A questionnaire in mid 1999 investigated three major questions: (1) current status of national guidelines in EANM member societies, (2) specification of the cover and level of these national guidelines, and (3) future desires for national, EANM and SNM guidelines. The complete response rate was 96% (26/27). Guidelines are required by 19 of 27 member societies and have been initiated by 16 member societies. Guidelines are provided by 13 member societies, generally in the national language. In ten societies, specialists other than nuclear medicine physicians, mostly physicists and radiopharmacists, take the lead on some guidelines. Moreover, in some national societies there is active collaboration with other medical societies when writing guidelines, particularly cardiology societies. Currently, only 18% of the necessary procedure guidelines are covered. Compared with a survey conducted in 1993 by the EANM Committee on Quality Assurance and Standardisation, slow progress has been made in this regard, but compared with a survey conducted by the same committee in 1996 in 23 EANM member societies, the number of member societies providing guidelines has approximately doubled. Moreover, 26 of 27 member societies share a commitment for future development of guidelines and 21 of 27 prefer EANM guidelines to national guidelines. The results of this questionnaire justify the need for close co-operation between EANM, EANM member societies, the EANM Task Group on "Quality Assurance and Standardisation" and the Guideline Committee of the SNM. The clinical priorities are considered to be cardiac, renal and brain procedures.

OctreoTher: ongoing early clinical development of a somatostatin-receptor-targeted radionuclide antineoplastic therapy.

OctreoTher ((90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide, a.k.a. (90)Y-SMT 487) consists of a somatostatin peptide analogue (Tyr(3)-octreotide), coupled with a complexing moiety (DOTA), and labeled with a tightly bound beta-emitter (yttrium-90). By targeting somatostatin receptor-positive tumors (as imaged by OctreaScan it may deliver a tumoricidal dose of radiation. Phase I clinical trials, conducted in patients with neuroendocrine tumors, established the safety and tolerability of the dose selected for further study and demonstrated the capacity of OctreoTher to deliver radiation doses to tumors that resulted in significant neuroendocrine tumor shrinkage. Novartis-sponsored phase II studies will soon begin to test the efficacy of OctreoTher in breast and small cell lung cancer. A fixed-dose regimen of 120 mCi/cycle x 3 cycles administered with concomitant amino acid infusion has been chosen for the study. Phase I data and published literature support that this fixed dose regimen will be safely tolerated.