Louise Emmett

Prospective Comparison of 18F-Fluoromethylcholine Versus 68Ga-PSMA PET/CT in Prostate Cancer Patients Who Have Rising PSA After Curative Treatment and Are Being Considered for Targeted Therapy

In prostate cancer with biochemical failure after therapy, current imaging techniques have a low detection rate at the prostate-specific antigen (PSA) levels at which targeted salvage therapy is effective. 11C-choline and 18F-fluoromethylcholine, though widely used, have poor sensitivity at low PSA levels. 68Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[68Ga-N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid]) has shown promising results in retrospective trials. Our aim was to prospectively compare the detection rates of 68Ga-PSMA versus 18F-fluoromethylcholine PET/CT in men who were initially managed with radical prostatectomy, radiation treatment, or both and were being considered for targeted therapy. Methods: A sample of men with a rising PSA level after treatment, eligible for targeted treatment, was prospectively included. Patients on systemic treatment were excluded. 68Ga-PSMA, 18F-fluoromethylcholine PET/CT, and diagnostic CT were performed sequentially on all patients between January and April 2015, and the images were assessed by masked, experienced interpreters. The findings and their impact on management were documented, together with the results of histologic follow-up when feasible. Results: In total, 38 patients were enrolled. Of these, 34 (89%) had undergone radical prostatectomy and 4 (11%) had undergone radiation treatment. Twelve (32%) had undergone salvage radiation treatment after primary radical prostatectomy. The mean PSA level was 1.74 ± 2.54 ng/mL. The scan results were positive in 26 patients (68%) and negative with both tracers in 12 patients (32%). Of the 26 positive scans, 14 (54%) were positive with 68Ga-PSMA alone, 11 (42%) with both 18F-fluoromethylcholine and 68Ga-PSMA, and only 1 (4%) with 18F-fluoromethylcholine alone. When PSA was below 0.5 ng/mL, the detection rate was 50% for 68Ga-PSMA versus 12.5% for 18F-fluoromethylcholine. When PSA was 0.5–2.0 ng/mL, the detection rate was 69% for 68Ga-PSMA versus 31% for 18F-fluoromethylcholine, and when PSA was above 2.0, the detection rate was 86% for 68Ga-PSMA versus 57% for 18F-fluoromethylcholine. On lesion-based analysis, 68Ga-PSMA detected more lesions than 18F-fluoromethylcholine (59 vs. 29, P < 0.001). The tumor-to-background ratio in positive scans was higher for 68Ga-PSMA than for 18F-fluoromethylcholine (28.6 for 68Ga-PSMA vs. 9.4 for 18F-fluoromethylcholine, P < 0.001). There was a 63% (24/38 patients) management impact, with 54% (13/24 patients) being due to 68Ga-PSMA imaging alone. Histologic follow-up was available for 9 of 38 patients (24%), and 9 of 9 68Ga-PSMA–positive lesions were consistent with prostate cancer (68Ga-PSMA was true-positive). The lesion positive on 18F-fluoromethylcholine imaging and negative on 68Ga-PSMA imaging was shown at biopsy to be a false-positive 18F-fluoromethylcholine finding (68Ga-PSMA was true-negative). Conclusion: In patients with biochemical failure and a low PSA level, 68Ga-PSMA demonstrated a significantly higher detection rate than 18F-fluoromethylcholine and a high overall impact on management.

Reversible regional wall motion abnormalities on exercise technetium-99m–gated cardiac single photon emission computed tomography predict high-grade angiographic stenoses

OBJECTIVES We sought to determine the level of angiographic stenosis at which reversible regional wall motion abnormalities (RWMA) are present on exercise stress technetium-99m (Tc-99m)- gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and whether assessments of stress and rest RWMA add incremental diagnostic information. BACKGROUND Stress and rest gated SPECT MPI enables the detection of post-exercise stunning. Although some studies have correlated RWMA to the severity of MPI defects, only one previous study correlated RWMA on gated MPI to angiographic findings. However, this correlation excluded patients with rest perfusion defects and did not involve gating of rest images. METHODS One hundred patients undergoing angiography within six months of exercise stress Tc-99m (sestamibi)-gated SPECT MPI (in the absence of interim cardiac events or revascularization) were recruited. Images were acquired 15 to 30 min after stress and interpreted without knowledge of the Duke treadmill score, left ventricular ejection fraction and angiographic data. RESULTS The sensitivity of reversible RWMA for angiographic stenoses >70% was 53%, with a specificity of 100%. The presence of reversible RWMA was able to stratify patients with angiographic stenoses of 50% to 79% and 80% to 99% with a high positive predictive value. A good correlation was noted between the presence of reversible RWMA and the coronary artery jeopardy score (R = 0.49, p < 0.0001). Multivariate analysis showed that the post-stress RWMA, Duke treadmill and reversible RWMA scores were significant predictors of angiographic severity. CONCLUSIONS Post-stress and reversible RWMA, as shown by exercise stress Tc-99m-gated SPECT MPI, are significant predictors of angiographic disease and add incremental value to MPI for the assessment of angiographic severity.

68Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment

To examine the detection rates of 68Ga‐PSMA‐positron emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP), and also the impact on their management.

Prospective evaluation of 68Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer

To assess the accuracy of 68Gallium‐prostate‐specific membrane antigen (68Ga‐PSMA) positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging in intermediate‐ and high‐risk prostate cancer (PCa).

Paraspinal abscess complicating facet joint injection

A 58-year-old man had severe lower back pain after minor trauma. This was initially treated with simple analgesics but with little effect. He was referred for injection of betamethasone and lignocaine into the left iliolumbar angle, which was followed by immediate relief of pain. One week later, he was hospitalized for worsening back pain, fever, and night sweats. Results of plain radiographs of the lumbar spine were reported as normal. Scintigraphy was consistent with a paraspinal abscess, which was confirmed on CT, MRI, and blood cultures. Blood cultures obtained at the time of admission grew Staphylococcus aureus, which was sensitive to methicillin. The patient responded to intravenous antibiotics.

Platelet activation in acute pulmonary embolism

Summary.  Background: Platelet activation is implicated in thrombotic disorders, but has not been described in acute clinical pulmonary embolism (PE). Objectives: To investigate the natural history of platelet activation in PE and associated markers of inflammation, thrombosis and cardiac dysfunction. Methods: Thirty‐five consecutive patients (age 62 ±17 years) with acute PE were prospectively enrolled and followed for 6 months. Platelet activation was assessed by flow cytometry [measuring expression of platelet P‐selectin, conformational activation of glycoprotein IIb/IIIa complex (PAC‐1) and formation of platelet–leukocyte complexes] and by plasma soluble P‐selectin. Platelet activation, right ventricular (RV) function (assessed as RV ejection area by transthoracic echocardiography), D‐dimer and high‐sensitivity C‐reactive protein (hs‐CRP) were measured at presentation and repeated over 6 months follow‐up. Results: Soluble P‐selectin (56 ±19 ng mL−1, anovaP < 0.0001) and PAC‐1 (1.5 ± 1.8%, anovaP = 0.005) were mildly but significantly increased in patients with acute PE relative to healthy young men (soluble P‐selectin 33 ± 13 ng mL−1, P < 0.001; PAC‐1 binding 0.5 ± 0.6%, P < 0.01) and age‐matched controls (soluble P‐selectin 31 ± 9 ng mL−1, P < 0.001; PAC‐1 binding 0.4 ±0.4%, P < 0.05). Platelet P‐selectin expression and platelet–leukocyte complexes were not increased during acute PE. Echocardiographic RV ejection area correlated inversely with soluble P‐selectin (r = −0.47, P = 0.007) and positively with platelet P‐selectin (r = 0.49, P = 0.0007), suggesting P‐selectin is shed from activated platelets in proportion to the severity of RV dysfunction. Elevated soluble P‐selectin, D‐dimer and hs‐CRP demonstrated a time‐dependent return to normal during 6 months follow‐up. Conclusion: Platelet activation is evident after acute PE. Platelet activation correlates with the severity of RV dysfunction, and can persist for several months after acute PE.

Hypophosphataemic osteomalacia in patients on adefovir dipivoxil.

Fanconi syndrome results from generalised renal tubular toxicity and, owing to phosphate wasting can cause hypophosphataemic osteomalacia. Large clinical trials advocated the safety of adefovir dipivoxil at a daily dose of 10 mg, the standard dose given to patients with hepatitis B. We diagnosed Fanconi syndrome in conjunction with severe osteomalacia in 2 hepatitis B-positive patients on standard-dose adefovir therapy. The first patient was a 40-year-old male with a 5 month history of bone pain involving his knees, ankles, and ribs. He had been receiving adefovir dipivoxil for 27 months before the development of hypophosphataemia, urinary phosphate wasting, and aminoaciduria. These abnormalities resolved within weeks of discontinuation of adefovir dipivoxil and supplementation with elemental phosphate, calcium carbonate, and cholecalciferol. The second patient was a 53-year-old female with a 6 month history of lethargy, cachexia, and generalized bone pain. She had been receiving adefovir for 64 months before the development of these symptoms. She had hypophosphataemia, hypocalcaemia, metabolic acidosis, and severe vitamin D deficiency, but initially no urinary phosphate wasting. Four months of high-dose cholecalciferol supplementation unmasked her Fanconi syndrome including significant urinary phosphate wasting. The patient improved within weeks of discontinuation of adefovir and supplementation with elemental phosphate, calcium carbonate, and calcitriol. Despite large clinical trials advocating the safety of adefovir dipivoxil at 10-mg daily, long-term use of this agent may be nephrotoxic and in rare cases, cause Fanconi syndrome and severe hypophosphataemic osteomalacia. Clinicians prescribing this drug should be aware of this potential complication.

Hypophosphatemic Osteomalacia after Low-Dose Adefovir Dipivoxil Therapy for Hepatitis B

A 40-yr-old male presented with a 5-month history of bone pain involving both knees, ankles, and several ribs with no antecedent trauma. He had an antalgic gait, tenderness involving the bony margins of both knees, but no synovitis. He had a history of chronic hepatitis B infection, receiving lamivudine at a daily dose of 100 mg for 43 months and adefovir dipivoxil (adefovir) at a daily dose of 10 mg for the past 29 months. He had been receiving tramadol hydrochloride intermittently for pain relief. Investigations revealed a reduced serum phosphate level of 2.0 mg/dl (0.64 mmol/liter), normal serum corrected calcium of 8.8 mg/dl (2.20 mmol/liter), PTH of 39 pg/ml (4.1 pmol/liter), 25-hydroxyvitamin D3 level of 24.4 ng/ml (61 nmol/liter), and 1,25-hydroxyvitamin D level of 57 pmol/liter. Bone-specific alkaline phosphatase was elevated at 85.4 g/liter (normal, 3.7–20 g/liter). The urine deoxypyridinoline/creatinine ratio was elevated at 11 nmol/mmol (normal, 2.3–5.4 nmol/ mmol) with an estimated glomerular filtration rate of 60.1 ml/min. A 24-h urinalysis demonstrated hyperphosphaturia at 1.054 g/d (34 mmol/d) [normal, 0.465– 0.93 g/d (15–30 mmol/d)], hypercalciuria at 580 mg/d (14.5 mmol/d) [normal, 100 –300 mg/d (2.5–7.5 mmol/d)], glycosuria, and massive aminoaciduria. The 24-h creatinine excretion was normal at 1.41 g/d (12.5 mmol/d) [normal, 1.02–2.03 g/d (9 –18 mmol/d)]. Calculated maximal tubular phosphate reabsorption was reduced at 0.3% (normal, 0.8 –1.3%). Magnetic resonance imaging of both knees revealed microfractures across the femoral and tibial metaphyses (Fig. 1). A whole body bone scan showed intense uptake at the subchondral bone of both knees and several bilateral ribs (Fig. 2A). The diagnosis of hypophosphatemic osteomalacia in the context of Fanconi’s syndrome secondary to adefovir therapy was made. Fanconi’s syndrome is a recognized complication of high-dose adefovir therapy when used in the treatment of HIV (1). However, at the time of writing, there were only two other published reports of hypophosphatemic osteomalacia after low-dose adefovir therapy (2, 3). Fifteen weeks after cessation of adefovir and after regular phosphate supplementation, the patient reported significant improvement in his knee and other bony pain. ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright

The impact of 68Ga-PSMA PET/CT on management intent in prostate cancer: results of an Australian prospective multicenter study

68Ga-PSMA PET/CT scanning has been shown to be more sensitive than conventional imaging techniques in patients with prostate cancer. This prospective Australian multicenter study assessed whether 68Ga-PSMA PET/CT imaging affects management intent in patients with primary or recurrent prostate cancer. Methods: Before undertaking 68Ga-PSMA PET imaging, referring medical specialists completed a questionnaire detailing relevant demographic and clinical data as well as their proposed management plan. A separate follow-up questionnaire was completed after the 68Ga-PSMA PET/CT scan results were available to determine whether the management plan would change. Results: A total of 431 patients with prostate cancer from 4 Australian centers had pre– and post–68Ga-PSMA management plans completed. Scans were obtained for primary staging of intermediate- and high-risk disease in 25% of patients and for restaging/biochemical recurrence in 75% of patients. Overall, 68Ga-PSMA PET/CT scanning led to a change in planned management in 51% of patients. The impact was greater in the group of patients with biochemical failure after definitive surgery or radiation treatment (62% change in management intent) than in patients undergoing primary staging (21% change). Imaging with 68Ga-PSMA PET/CT revealed unsuspected disease in the prostate bed in 27% of patients, locoregional lymph nodes in 39%, and distant metastatic disease in 16%. Conclusion: 68Ga-PSMA PET/CT scans detect previously unsuspected disease and may influence planned clinical management in a high proportion of patients with prostate cancer. The impact was greater in patients with biochemical recurrence. These results demonstrate the potential clinical value of 68Ga-PSMA PET/CT in management of prostate cancer.

Rhabdomyolysis resulting from interaction of simvastatin and clarithromycin demonstrated by Tc-99m MDP scintigraphy

AbstractStatins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are well known to be able to cause a variety of muscle-related complications, the most serious of which is rhabdomyolysis. Rhabdomyolysis is a syndrome characterized by muscle pain with creatine kinase levels 10 times highe