Noninvasive Assessment of Acute Graft-Versus-Host Disease of the Gastrointestinal Tract After Allogeneic Hemopoietic Stem Cell Transplantation Using 18F-FDG PET.

Acute graft-versus-host disease of the gastrointestinal tract (acute GIT-GVHD) often complicates allogeneic hemopoietic stem cell transplantation (AHSCT). 18F-FDG PET/CT is known to detect active inflammation and may be a useful noninvasive test for acute GIT-GVHD. The objective of this study was to evaluate the diagnostic utility of 18F-FDG PET/CT to noninvasively assess patients with clinically suspected acute GIT-GVHD. Fifty-one AHSCT patients with clinically suspected acute GIT-GVHD prospectively underwent 18F-FDG PET/CT scanning followed by upper and lower GIT endoscopy within 7 d. Endoscopic biopsies of 4 upper GIT and 4 colonic segments were obtained for histology to compare with corresponding quantitative segmental 18F-FDG PET/CT SUVmax Receiver-operating-characteristic curve (ROC) analysis was performed to determine predictive capacity of 18F-FDG PET/CT SUVmax for acute GIT-GVHD. A separate qualitative visual 18F-FDG PET/CT analysis was also performed for comparison. Results: Twenty-three of 51 (45.1%) patients had biopsy-confirmed acute GIT-GVHD, with 19 of 23 (82.6%) having upper GIT and 22 of 22 (100%) colonic involvement. One of 23 patients did not undergo a colonoscopy. GVHD involved the entire colon contiguously in 21 of 22 patients. For quantitative analysis, histology from 4 upper GIT and 4 colonic segments were compared with 18F-FDG PET/CT SUVmax Colonic segments positive for GVHD had a higher SUVmax (4.1 [95% CI, 3.6-4.5]) than did normal colonic segments (2.3 [1.9-2.7], P = 0.006). No difference was demonstrated in upper GIT segments. Quantitative 18F-FDG PET/CT yielded a 69% sensitivity, 57% specificity, 73% negative predictive value, and 59% positive predictive value for the detection of GVHD compared with 70%, 76%, 76%, and 68%, respectively, for qualitative analysis. Conclusion: 18F-FDG PET is a useful noninvasive diagnostic test for acute GIT-GVHD, which when present always involves the colon and usually in its entirety, suggesting colonic biopsy obtained by sigmoidoscopy is adequate for histologic confirmation when acute GIT-GVHD is suspected. Of note, 18F-FDG PET cannot distinguish acute GIT-GVHD from non-GVHD inflammatory changes in the colon.

18 F-FDG PET/CT features of immune-related adverse events and pitfalls following immunotherapy.

18 F-FDG PET/CT scanning is routinely performed to stage and evaluate the treatment response in many malignancies. Immunotherapy is a rapidly growing treatment option for many cancers, and both clinicians and imaging specialists need to be familiar with 18 F-FDG PET/CT imaging characteristics unique to patients on this type of treatment. In particular, many immune-related adverse events (irAEs) can be detected on 18 F-FDG PET/CT and early accurate identification is critical to reduce treatment related morbidity and incorrect interpretation of malignant disease status. This pictorial essay reviews frequently encountered irAEs in clinical practice and their appearances on 18 F-FDG PET/CT along with a brief discussion on pseudoprogression and hyperprogression.

Clinical utility of stimulated cholescintigraphy using a standardized Ensure-Plus fatty meal protocol in patients with suspected functional gallbladder disorder: a retrospective study of seven-years clinical experience.

BACKGROUND: The clinical utility of fatty meal stimulated cholescintigraphy particularly using a standardized formulation in patients with suspected functional gallbladder disorder has not been extensively studied. We present our seven-year clinical experience using an Ensure plus protocol. METHODS: A retrospective study was performed on patients undergoing stimulated cholescintigraphy using Ensure Plus for evaluation of suspected functional gallbladder disorder. A gallbladder ejection fraction (GBEF) of <33% was considered abnormal. RESULTS: Of the 173 patients evaluated, 57 (33%) had an abnormal GBEF, 112 (65%) had a normal GBEF and 4 (2%) had no gallbladder visualization. Of the 57 patients with an abnormal GBEF, symptom improvement occurred in 30/31 (97%) who underwent cholecystectomy and in 17/26 (65%) who were managed conservatively (p = 0.003). Of the 112 patients with a normal GBEF, symptom improvement occurred in 8/10 (80%) who underwent cholecystectomy and 74/102 (73%) who were managed conservatively (p = 1.000). In the subgroup of 102 patients with a normal GBEF managed conservatively, those without symptomatic improvement had lower GBEFs compared to those with symptomatic improvement (median GBEF 46% versus 57%, p = 0.019). CONCLUSION: Our retrospective results support a clinical role for stimulated cholescintigraphy using Ensure Plus in the evaluation of patients with suspected functional gallbladder disorder. While an abnormal GBEF predicts good surgical outcome, our results suggest that using an absolute GBEF cut off value of <33% may not apply to all patients and hence GBEF results should only be used as an adjunct in the surgical decision-making process.

Excellent suppression of physiological myocardial FDG activity in patients with cardiac sarcoidosis.

INTRODUCTION: Suppression of physiological myocardial FDG activity is vital in patients undergoing PET/CT for assessment of known or suspected cardiac sarcoidosis. This study aims to evaluate the efficacy of physiological myocardial FDG suppression following a protocol change to a 24-h high fat very low carbohydrate (HFVLC) diet and prolonged fast. METHODS: A retrospective review of patients undergoing FDG PET/CT for the evaluation of cardiac sarcoidosis was performed. Prior to June-2018, patients were prepared with a single very high-fat low carbohydrate meal followed by a 12-18 h fast (group 1). After June-2018, a protocol change was initiated with patients prepared with a HFVLC diet for 24-h followed by a 12-18 h fast (group 2). Focal myocardial activity was classified as positive, absent activity as negative and diffuse/focal on diffuse activity as indeterminate. RESULTS: A total of 94 FDG PET/CT scans were included with 46 scans in group 1 and 48 scans in group 2. Studies were classified as positive, negative or indeterminate in 25 (54%), 7 (15%) and 14 (30%) scans in group 1 and in 13 (27%), 33 (69%) and 2 (4%) scans in group 2, respectively. In scans classified as negative, myocardial FDG activity was less than mediastinal blood pool activity in 5/7 (71%) scans in group 1 and 33/33 (100%) scans in group 2. CONCLUSION: Excellent myocardial FDG suppression can be achieved using a 24-h HFVLC diet and prolonged fast, resulting in a very low indeterminate scan rate in patients with known or suspected cardiac sarcoidosis.

Changes in biodistribution on 68Ga-DOTA-Octreotate PET/CT after long acting somatostatin analogue therapy in neuroendocrine tumour patients may result in pseudoprogression.

BACKGROUND: To evaluate the effects of long-acting somatostatin analogue (SSA) therapy on 68Ga-DOTA-octreotate (GaTate) uptake at physiological and metastatic sites in neuroendocrine tumour (NET) patients. METHODS: Twenty-one patients who underwent GaTate PET/CT before and after commencement of SSA therapy were reviewed. Maximum standardized uptake values (SUVmax) were measured in normal organs. Changes in uptake of 49 metastatic lesions in 12 patients with stable disease were also compared. Serum chromogranin-A (CgA) levels were available for correlation between scans in 17/21 patients. RESULTS: Mean thyroid, spleen and liver SUVmax decreased significantly following SSA therapy from a baseline of 5.9 to 3.5, 30.3 to 23.1 and 10.3 to 8.0, respectively (p = < 0.0001 for all). Pituitary SUVmax increased from 10.2 to 11.0 (p = 0.004) whereas adrenal and salivary gland SUVmax did not change. Tumour SUVmax increased in 7 of 12 patients with stable disease; CgA was stable or decreasing in 5 of these patients. 30/49 (61%) metastatic lesions had an increase in SUVmax and lesion-to-liver uptake ratio increased in 40/49 (82%) following SSA therapy. CONCLUSION: Long-acting SSA therapy decreases GaTate uptake in the thyroid, spleen and liver but in most cases increases intensity of uptake within metastases. This has significant implications for interpretation of GaTate PET/CT following commencement of therapy as increased intensity alone may not represent true progression. Our findings also suggest pre-dosing with SSA prior to PRRT may enable higher doses to be delivered to tumour whilst decreasing dose to normal tissues.

Correction to: Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans.

The baseline insulin data given in Table 1 for the placebo group were incorrectly reported as 51 ± 10 pmol/l instead of 48 ± 10 pmol/l. This mistake also impacts on data reported in Table 4.

Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans.

AIMS/HYPOTHESIS: Increasing brown adipose tissue (BAT) activity is a possible therapeutic strategy to increase energy expenditure and glucose and lipid clearance to ameliorate obesity and associated comorbidities. The thiazolidinedione (TZD) class of glucose-lowering drugs increase BAT browning in preclinical experimental models but whether these actions extend to humans in vivo is unknown. The aim of this study was to determine the effect of pioglitazone treatment on adipocyte browning and adaptive thermogenesis in humans. METHODS: We first examined whether pioglitazone treatment of cultured human primary subacromioclavicular-derived adipocytes induced browning. Then, in a blinded, placebo-controlled, parallel trial, conducted within the Baker Institute clinical research laboratories, 14 lean male participants who were free of cardiometabolic disease were randomised to receive either placebo (lactose; n = 7, age 22 ± 1 years) or pioglitazone (45 mg/day, n = 7, age 21 ± 1 years) for 28 days. Participants were allocated to treatments by Alfred Hospital staff independent from the study via electronic generation of a random number sequence. Researchers conducting trials and analysing data were blind to treatment allocation. The change in cold-stimulated BAT activity, assessed before and after the intervention by [18F]fluorodeoxyglucose uptake via positron emission tomography/computed tomography in upper thoracic and cervical adipose tissue, was the primary outcome measure. Energy expenditure, cardiovascular responses, core temperature, blood metabolites and hormones were measured in response to acute cold exposure along with body composition before and after the intervention. RESULTS: Pioglitazone significantly increased in vitro browning and adipogenesis of adipocytes. In the clinical trial, cold-induced BAT maximum standardised uptake value was significantly reduced after pioglitazone compared with placebo (-57 ± 6% vs -12 ± 18%, respectively; p < 0.05). BAT total glucose uptake followed a similar but non-significant trend (-50 ± 10% vs -6 ± 24%, respectively; p = 0.097). Pioglitazone increased total and lean body mass compared with placebo (p < 0.05). No other changes between groups were detected. CONCLUSIONS/INTERPRETATION: The disparity in the actions of pioglitazone on BAT between preclinical experimental models and our in vivo human trial highlight the imperative to conduct human proof-of-concept studies as early as possible in BAT research programmes aimed at therapeutic development. Our clinical trial findings suggest that reduced BAT activity may contribute to weight gain associated with pioglitazone and other TZDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02236962 FUNDING: This work was supported by the Diabetes Australia Research Program and OIS scheme from the Victorian State Government.

Correlation of clinical outcomes with bremsstrahlung and Y-90 PET/CT imaging findings following Y-90 radiosynoviorthesis: a prospective study.

BACKGROUND: It is unclear how to predict which patients will respond to Y-90 radiosynoviorthesis. The aim of this study is to correlate clinical outcomes following Y-90 radiosynoviorthesis with bremsstrahlung and Y-90 PET/CT imaging findings. METHODS: Fifty-one joints underwent bremsstrahlung planar and Y-90 PET/CT imaging following Y-90 radiosynoviorthesis. The Y-90 distribution pattern on bremsstrahlung planar imaging was classified as diffuse or non-diffuse and compared with the intra or extra-articular location of activity on Y-90 PET/CT. Treatment response was assessed by patients and clinicians at 6 months. In patients who underwent bremsstrahlung SPECT, side-by-side comparison with PET was performed with image quality/resolution scored using a five-point-scale. FINDINGS: Bremsstrahlung planar images were classified as diffuse in 33/51 (65 %) and non-diffuse in 18/51 (35 %) scans. There was no association between treatment response and the bremsstrahlung planar imaging pattern. PET/CT confirmed an intra-articular location in all 33/33 (100 %) diffuse scans and an extra-articular location in 3/18 (17 %) non-diffuse scans. Of the three joints with extra-articular activity, none had any treatment response. Excluding these three joints, there remained no association between the bremsstrahlung planar imaging pattern and treatment response. Of the 42 joints imaged with SPECT, PET image quality/resolution was classified as superior in 40 (95 %). In one patient with extra-articular activity on PET/CT, SPECT/CT was unable to definitively localise the activity to the intra or extra-articular space. CONCLUSIONS: The distribution pattern on bremsstrahlung planar imaging did not correlate with clinical outcome following Y-90 radiosynoviorthesis in our study population. However, in patients with non-diffuse planar imaging patterns, Y-90 PET/CT should be considered to exclude extra-articular activity with PET providing superior image quality compared to SPECT.

Chronic ephedrine administration decreases brown adipose tissue activity in a randomised controlled human trial: implications for obesity.

AIMS/HYPOTHESIS: Brown adipose tissue (BAT) activation increases energy expenditure and may have therapeutic potential to combat obesity. The primary activating and adaptive signal for BAT is via ß-adrenergic signalling. We previously demonstrated that human BAT is acutely responsive to oral administration of the sympathomimetic, ephedrine. Here we aimed to determine whether adaptive thermogenesis can be induced via chronic treatment with ephedrine. METHODS: Twenty-three healthy young men, recruited from the general public in Melbourne, Australia, who were non-smokers, physically inactive and non-medicated with no prior history of cardiovascular disease or diabetes were recruited for this study. They were assigned to receive either 1.5 mg kg(-1) day(-1) ephedrine ('active' group; n = 12, age 23 ± 1 years, BMI 24 ± 1 kg/m(2)) or placebo (n = 11; 22 ± 2 years, 23 ± 2 kg/m(2)) for 28 days in a randomised (computer-generated random order sequence), placebo-controlled, parallel-group trial. Participants and all investigators were blinded to treatments. Body composition was measured before and after the intervention by dual energy X-ray absorptiometry. BAT activity, measured via (18)F-fluorodeoxyglucose positron emission tomography-computed tomography, in response to a single dose of 2.5 mg/kg ephedrine, was the primary outcome measure to be determined before and after the 28 day treatment period. RESULTS: Twenty-eight individuals were randomised and consented to the study. Twenty-three completed the trial and only these participants were included in the final analyses. After 28 days of treatment, the active group lost a significant amount of total body fat (placebo 1.1 ± 0.3 kg, ephedrine -0.9 ± 0.5 kg; p < 0.01) and visceral fat (placebo 6.4 ± 19.1 g, ephedrine -134 ± 43 g; p < 0.01), with no change in lean mass or bone mineral content compared with the placebo group. In response to acute ephedrine, BAT activity (change in mean standardised uptake value: placebo -3 ± 7%, ephedrine -22 ± 6%) and the increase in systolic blood pressure were significantly reduced (p < 0.05) in the active group compared with placebo. CONCLUSIONS/INTERPRETATION: Chronic ephedrine treatment reduced body fat content, but this was not associated with an increase in BAT activity. Rather, chronic ephedrine suppressed BAT glucose disposal, suggesting that chronic ephedrine treatment decreased, rather than increased, BAT activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT02236962 FUNDING: This study was funded by the National Health and Medical Research Council of Australia Program Grant (1036352) and the OIS scheme from the Victorian State Government.

Heterogeneous bone marrow uptake on interim 18F-fluorodeoxyglucose positron emission tomography for lymphoma mimicking disease progression: a case report.

INTRODUCTION: The use of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scanning for baseline staging and assessment of treatment response for higher grade lymphomas is considered to be the standard of care. Evaluation of lymphomatous bone marrow infiltration on 18F-FDG PET can usually distinguish between normal regenerating marrow following chemotherapy by a characteristic pattern of uptake. CASE PRESENTATION: Here we report the case of a 51-year-old Caucasian woman with mixed low- and high-grade lymphoma with biopsy confirmed marrow infiltration. An interim post-three cycle chemotherapy 18F-FDG PET scan revealed apparent progression of marrow disease. Subsequent investigations were performed including bone marrow biopsies, repeat 18F-FDG PET scanning and a white cell scan. These revealed the interim 18F-FDG PET scan appearance was due to a highly unusual pattern of scattered islands of regenerating normal marrow, rather than progressive lymphoma. CONCLUSIONS: Our case report highlights that apparent severe bone marrow abnormalities on 18F-FDG PET scans in lymphoma patients treated with chemotherapy are not always due to disease. Clinicians should retain a high index of suspicion for benign causes when 18F-FDG PET scan results appear incongruent with clinical response.

The prevalence of thyroglossal tract thyroid tissue on SPECT/CT following (131) I ablation therapy after total thyroidectomy for thyroid cancer.

OBJECTIVE: To determine the prevalence of thyroglossal tract thyroid tissue on SPECT/CT and to assess the contribution of this tissue to total neck radioactive iodine (RAI) activity in patients given (131) I ablation therapy after total thyroidectomy for thyroid cancer. PATIENTS AND METHODS: Eighty-three consecutive patients with thyroid cancer treated with total thyroidectomy underwent whole-body planar and SPECT/CT imaging of the neck following initial RAI ablation. On SPECT/CT, thyroglossal tract thyroid tissue was defined as RAI in the anterior neck, superior to the thyroid bed in close proximity to the midline without evidence of localization to lymph nodes. Quantification was performed using region of interest analysis on planar imaging following localization on SPECT/CT. SPECT/CT, and planar images were classified by two reviewers as positive, negative or equivocal with interobserver agreement quantified using a Kappa score. Disagreement was resolved using a third reviewer. RESULTS: Thyroglossal tract thyroid tissue was present in 39/83 (47%; 95%CI: 36-58%) patients on SPECT/CT. In these 39 patients, this tissue contributed to a significant amount of total neck activity (median = 50%; IQR 19-74%). Interobserver agreement for the presence of thyroglossal tract thyroid tissue was substantial on SPECT/CT (Kappa = 0.73) and fair on planar imaging (Kappa = 0.31). CONCLUSION: Thyroglossal tract thyroid tissue was present in one half of our study population and contributed to a significant amount of total neck RAI activity. Given the high prevalence of this tissue, our results suggest that total neck RAI activity on planar imaging may not be suitable to assess the completeness of thyroid bed surgery.

Efficacy of yttrium-90 synovectomy across a spectrum of arthropathies in an era of improved disease modifying drugs and treatment protocols.

AIM: To evaluate clinical response rates, duration of response and complication rates of yttrium radiosynovectomy (RSV) in an era of improved disease modifying antirheumatic drugs (DMARDS) and increased access to replacement therapy for clotting factor deficiencies introduced in the mid 2000s. METHODS: A retrospective review of 167 consecutive joints treated with RSV between 2000 and 2010 was conducted. Clinical response and complication rates in 167 joints (119 patients: 45 female,74 male, mean age 52 years) with rheumatoid, psoriatic, hemophilic, large joint mono-arthropathy and miscellaneous arthropathies refractory to conventional therapy were reviewed. Clinical response was determined at 3 months with responding patients reviewed again at 36 months to assess whether response was sustained. Comparison of response rates pre- and post-introduction of improved DMARDS in the mid 2000s was also performed. RESULTS: Satisfactory clinical response was highest for large joint mono-arthropathy (85%) and lower for other arthropathies (47-64%). A strong relationship was demonstrated between degree and duration of response with 90% of complete responders compared to 41% of incomplete responders having a sustained response at 36 months (P ≤ 0.0001). Major complication rates were low (1%). No difference was demonstrated in response rates pre- and post-introduction of improved DMARDS in the mid 2000s. CONCLUSION: In an era of improved DMARDS, yttrium synovectomy remains a safe and effective procedure across a broad spectrum of arthropathies and should continue to be considered in cases refractory to conventional therapies. Complete responders can be expected to have symptom relief for at least 36 months and complication rates are low.

Comparison of positron emission tomography/CT and bremsstrahlung imaging following Y-90 radiation synovectomy.

INTRODUCTION: The aim of this study is to compare the results of positron emission tomography (PET)/CT with bremsstrahlung imaging following Y-90 radiation synovectomy. METHODS: All patients referred to our institution for Y-90 radiation synovectomy between July 2011 and February 2012 underwent both PET/CT and bremsstrahlung planar (± single photon emission computed tomography (SPECT) or SPECT/CT) imaging at 4 or 24 h following administration of Y-90 silicate colloid. PET image acquisition was performed for between 15 and 20 min. In patients who underwent SPECT, side-by-side comparison with PET was performed and image quality/resolution scored using a five-point scale. The distribution pattern of Y-90 on PET and bremsstrahlung imaging was compared with the intra- or extra-articular location of Y-90 activity on fused PET/CT. RESULTS: Thirteen joints (11 knees and two ankles) were imaged with both PET/CT and planar bremsstrahlung imaging with 12 joints also imaged with bremsstrahlung SPECT. Of the 12 joints imaged with SPECT, PET image quality/resolution was superior in 11 and inferior in one. PET demonstrated a concordant distribution pattern compared with bremsstrahlung imaging in all scans, with the pattern classified as diffuse in 12 and predominantly focal in one. In all 12 diffuse scans, PET/CT confirmed the Y-90 activity to be located intra-articularly. In the one predominantly focal scan, the fused PET/CT images localised the Y-90 activity to mostly lie in the extra-articular space of the knee. CONCLUSION: PET/CT can provide superior image quality compared with bremsstrahlung imaging and may enable reliable detection of extra-articular Y-90 activity when there are focal patterns on planar bremsstrahlung imaging.

Optimal reproducibility of gated sestamibi and thallium myocardial perfusion study left ventricular ejection fractions obtained on a solid-state CZT cardiac camera requires operator input.

AIM: To evaluate the reproducibility of serial re-acquisitions of gated Tl-201 and Tc-99m sestamibi left ventricular ejection fraction (LVEF) measurements obtained on a new generation solid-state cardiac camera system during myocardial perfusion imaging and the importance of manual operator optimization of left ventricular wall tracking. METHODS: Resting blinded automated (auto) and manual operator optimized (opt) LVEF measurements were measured using ECT toolbox (ECT) and Cedars-Sinai QGS software in two separate cohorts of 55 Tc-99m sestamibi (MIBI) and 50 thallium (Tl-201) myocardial perfusion studies (MPS) acquired in both supine and prone positions on a cadmium zinc telluride (CZT) solid-state camera system. Resting supine and prone automated LVEF measurements were similarly obtained in a further separate cohort of 52 gated cardiac blood pool scans (GCBPS) for validation of methodology and comparison. Appropriate use of Bland-Altman, chi-squared and Levene's equality of variance tests was used to analyse the resultant data comparisons. RESULTS: For all radiotracer and software combinations, manual checking and optimization of valve planes (+/- centre radius with ECT software) resulted in significant improvement in MPS LVEF reproducibility that approached that of planar GCBPS. No difference was demonstrated between optimized MIBI/Tl-201 QGS and planar GCBPS LVEF reproducibility (P = .17 and P = .48, respectively). ECT required significantly more manual optimization compared to QGS software in both supine and prone positions independent of radiotracer used (P < .02). CONCLUSIONS: Reproducibility of gated sestamibi and Tl-201 LVEF measurements obtained during myocardial perfusion imaging with ECT toolbox or QGS software packages using a new generation solid-state cardiac camera with improved image quality approaches that of planar GCBPS however requires visual quality control and operator optimization of left ventricular wall tracking for best results. Using this superior cardiac technology, Tl-201 reproducibility also appears at least equivalent to sestamibi for measuring LVEF.

Incidence and implications of negative serum thyroglobulin but positive I-131 whole-body scans in patients with well-differentiated thyroid cancer prepared with rhTSH or thyroid hormone withdrawal.

AIMS: To evaluate the incidence and clinical implications of a positive whole-body I-131 scan but negative stimulated serum Tg/TgAb level following an ablative or diagnostic I-131 dose in patients with well-differentiated thyroid cancer and whether there is a difference in incidence if prepared with thyroid hormone withdrawal compared with rhTSH stimulation. METHODS: I-131 scan findings, serum Tg/TgAb levels, TNM stage and method of thyroid tissue stimulation in 193 consecutive patients (138F, 55M) with well-differentiated thyroid cancer undergoing postoperative ablative I-131 therapy and 121 consecutive (94F, 27M) patients undergoing diagnostic I-131 surveillance scans were retrospectively reviewed. Comparisons of proportions were performed using Chi-square tests. Clinical, biochemical and I-131 scan follow-up data were obtained for each patient cohort. RESULTS: 39/193 (20·2%) postablative I-131 and 10/121 (8·3%) diagnostic I-131 patients had negative stimulated serum Tg/TgAb levels but positive I-131 scans for residual thyroid tissue. Nine (4·7%) of the postablative patients had I-131 uptake in the lateral neck suspicious for loco-regional metastatic disease. In the postablative I-131 group, 38/169 (22·5%) prepared with rhTSH compared to 1/24 (4·2%) prepared with thyroid hormone withdrawal were Tg/TgAb negative but I-131 scan positive (P = 0·04). Follow-up of 21/39 postablative I-131 patients with negative Tg/TgAb but positive I-131 scans confirmed a significant proportion of patients (4/21) (19·1%), remained Tg/TgAb negative/I-131 scan positive, some of whom had higher-risk disease at original diagnosis (2/4) (50%). CONCLUSIONS: Our study confirms that in the setting of I-131 ablation therapy or diagnostic I-131 scanning, a significant proportion of patients (20·2% and 8·3%, respectively) have residual benign or malignant thyroid tissue on whole-body scanning despite a negative stimulated serum Tg level. Whether such patients who would otherwise be missed as having residual thyroid tissue on serum Tg testing alone have a worse clinical outcome remains uncertain. Our findings do however suggest performing both stimulated serum Tg/TgAb levels and I-131 scans for the follow-up of patients with higher-risk thyroid cancer may be important. There may also be a slightly higher incidence of this phenomenon in patients prepared with rhTSH rather than by thyroxine withdrawal.

18F-fluorodeoxyglucose positron emission tomography-positive sarcoidosis after chemoradiotherapy for Hodgkin's disease: a case report.

INTRODUCTION: The occurrence of granulomatous disease in the setting of Hodgkin's disease is rare; however, when it occurs it can pose significant clinical and diagnostic challenges for physicians treating these patients. CASE PRESENTATION: We report the case of a 33-year-old Caucasian woman of Mediterranean descent with newly diagnosed 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) scan-positive, early-stage Hodgkin's disease involving the cervical nodes who, despite having an excellent clinical response to chemotherapy, had a persistent 18F-FDG PET scan-positive study, which was suggestive of residual or progressive disease. A subsequent biopsy of her post-chemotherapy PET-positive nodes demonstrated sarcoidosis with no evidence of Hodgkin's disease. CONCLUSION: This case highlights the fact that abnormalities observed on posttherapy PET/CT scans in patients with Hodgkin's disease are not always due to residual or progressive disease. An association between Hodgkin's disease and/or its treatment with an increased incidence of granulomatous disease appears to exist. Certain patterns of 18F-FDG uptake observed on PET/CT scans may suggest other pathologies, such as granulomatous inflammation, and because of the significant differences in prognosis and management, clinicians should maintain a low threshold of confidence for basing their diagnosis on histopathological evaluations when PET/CT results appear to be incongruent with the patient's clinical response.

Metastatic colorectal cancer to a primary thyroid cancer.

BACKGROUND: Metastatic malignancy to the thyroid gland is generally uncommon due to an unfavourable local thyroid micro-environment which impairs the ability of metastatic cells to settle and thrive. Metastases to the thyroid gland have however been reported to occur occasionally particularly if there has been disruption to normal thyroid tissue architecture. CASE PRESENTATION: We report a patient with a history of surgically resected rectal adenocarcinoma who presents with a rising serum CEA level and an 18F-FDG PET scan positive thyroid nodule which was subsequently confirmed at surgery to be a focus of metastatic rectal adenocarcinoma within a primary poorly differentiated papillary thyroid carcinoma.Subsequent treatment involved right hemi-thyroidectomy, pulmonary wedge resection of oligometastatic metastatic colorectal cancer and chemotherapy. CONCLUSION: Metastatic rectal carcinoma to the thyroid gland and in particular to a primary thyroid malignancy is rare and unusual. Prognosis is likely to be more dependent on underlying metastatic disease rather than the primary thyroid malignancy hence primary treatments should be tailored towards treating and controlling metastatic disease and less emphasis placed on the primary thyroid malignancy.

Incidence of radiation thyroiditis and thyroid remnant ablation success rates following 1110 MBq (30 mCi) and 3700 MBq (100 mCi) post-surgical 131I ablation therapy for differentiated thyroid carcinoma.

OBJECTIVE: To evaluate the relationships between thyroid remnant (131)I uptake, radiation thyroiditis and remnant ablation success rate between lower (1110 MBq) and higher (3700 MBq) initial ablative (131)I dose for post-surgical ablation therapy for differentiated thyroid cancer. DESIGN: Patients having post-surgical administration of 1110 MBq (68 patients) or 3700 MBq (115 patients) (131)I were retrospectively reviewed. Thyroid remnant (131)I uptake on a 48 h post-administration scan was correlated with neck symptoms experienced. Patients were classified as having insignificant, mild or severe thyroiditis based on symptoms. Absent thyroid bed (131)I uptake on a follow-up 74 MBq (131)I study was considered successful ablation. RESULTS: 183 patients were included. Median (131)I remnant uptake was 37 MBq. 21% (39/183) of patients developed thyroiditis. Incidence and severity of thyroiditis increased with increasing remnant (131)I activity (P 73 MBq. For patients treated with 1110 MBq and 3700 MBq, incidence of thyroiditis was 12% and 27% (P = 0.02) and remnant ablation success rate was 76% and 84% (P = NS), respectively. Occurrence of thyroiditis did not correlate with successful ablation. CONCLUSIONS: Incidence and severity of radiation thyroiditis following (131)I remnant ablation therapy is directly related to thyroid remnant (131)I uptake. As 1110 MBq (131)I is associated with a significantly lower frequency of thyroiditis but similar remnant ablation rate to 3700 MBq, it warrants consideration for thyroid remnant ablation particularly in patients with low risk disease.

Lack of correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in non-small cell lung cancer assessed by 18F-Fluoromisonidazole and 18F-FDG PET.

UNLABELLED: PET offers a noninvasive means to assess neoplasms, in view of its sensitivity and accuracy in staging tumors and potentially in monitoring treatment response. The aim of this study was to evaluate newly diagnosed non-small cell lung cancer (NSCLC) for the presence of hypoxia, as indicated by the uptake of (18)F-Fluoromisonidazole ((18)F-FMISO), and to examine the relationship of hypoxia to the uptake of (18)F-FDG, microvessel density, and other molecular markers of hypoxia. METHODS: Twenty-one patients with suspected or biopsy-proven NSCLC were enrolled prospectively in this study. All patients had PET studies with (18)F-FMISO and (18)F-FDG. Seventeen patients subsequently underwent surgery, with analysis performed for tumor markers of angiogenesis and hypoxia. RESULTS: In the 17 patients with resectable NSCLC (13 men, 4 women; age range, 51-77 y), the mean (18)F-FMISO uptake in tumor was significantly lower than that of (18)F-FDG uptake (P < 0.0001) and showed no correlation with (18)F-FDG uptake (r = 0.26). The mean (95% confidence interval [CI]) (18)F-FMISO SUV(max) (maximum standardized uptake value) was 1.20 [0.95-1.45] compared with the mean [95% CI] (18)F-FDG SUV(max) of 5.99 [4.62-7.35]. The correlation between (18)F-FMISO uptake, (18)F-FDG uptake, and tumor markers of hypoxia and angiogenesis was poor. A weakly positive correlation between (18)F-FMISO and (18)F-FDG uptake and Ki67 was found. CONCLUSION: The hypoxic cell fraction of primary NSCLC is consistently low, and there is no significant correlation in NSCLC between hypoxia and glucose metabolism in NSCLC assessed by (18)F-FDG. These findings have direct implications in understanding the role of angiogenesis and hypoxia in NSCLC biology.