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Purpose: Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation. Methods: This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records. Results: Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1–45.9) versus 30.9 months (19.6–46.8); p = 0.243); stage B: 18.4 months (11.2–19.4) versus 22.8 months (10.9–34.2); p = 0.815; and stage C: 8.8 months (7.1–10.8) versus 10.8 months (7.7–12.6); p = 0.976. Conclusions: Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.

The whole-body 131-I scan remains an important component of the treatment of postthyroidectomy patients with well-differentiated thyroid cancer. Because normal thyroid tissue remnants and residual or metastatic foci of well-differentiated thyroid cancer have the unique ability to concentrate, organify, and store 131-I, the whole-body scan provides a functional map of tissues that can be definitively treated with therapeutic doses of 131-I. Despite the high sensitivity and specificity of radioiodine imaging, the whole-body scan may also depict concentrations of 131-I from a wide variety of other “nonthyroid” etiologies. In this chapter, we update our article from the Seminars of Nuclear Medicine (modified with permission. Shapiro B, Rufini V, Jarwan A, et al. Seminars in Nuclear Medicine 30:115–132, 2000.) in 2000 that described the pathophysiological classification of artifacts, anatomical and physiological variants, and nonthyroidal diseases responsible for false-positive whole-body scans in postthyroidectomy patients with thyroid cancer. These confounding imaging findings include ectopic foci of normal thyroid tissue, nonthyroidal physiologic uptake (e.g., choroid plexus, salivary glands, gastric mucosa, urinary tract), contamination by physiological secretions, ectopic gastric mucosa and other anatomic gastrointestinal abnormalities, urinary tract abnormalities, mammary abnormalities, serous cavities and cysts, inflammation and infection, nonthyroidal neoplasms, and other unexplained causes.

A multicenter analysis was conducted to evaluate the main prognostic factors driving survival after radioembolization using yttrium-90-labeled resin microspheres in patients with hepatocellular carcinoma at eight European centers. In total, 325 patients received a median activity of 1.6 GBq between September 2003 and December 2009, predominantly as whole-liver (45.2%) or right-lobe (38.5%) infusions. Typically, patients were Child-Pugh class A (82.5%), had underlying cirrhosis (78.5%), and had good Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0-1; 87.7%), but many had multinodular disease (75.9%) invading both lobes (53.1%) and/or portal vein occlusion (13.5% branch; 9.8% main). Over half had advanced Barcelona Clinic Liver Cancer (BCLC) staging (BCLC C, 56.3%) and one-quarter had intermediate staging (BCLC B, 26.8%). The median overall survival was 12.8 months (95% confidence interval, 10.9-15.7), which varied significantly by disease stage (BCLC A, 24.4 months [95% CI, 18.6-38.1 months]; BCLC B, 16.9 months [95% CI, 12.8-22.8 months]; BCLC C, 10.0 months [95% CI, 7.7-10.9 months]). Consistent with this finding, survival varied significantly by ECOG status, hepatic function (Child-Pugh class, ascites, and baseline total bilirubin), tumor burden (number of nodules, alpha-fetoprotein), and presence of extrahepatic disease. When considered within the framework of BCLC staging, variables reflecting tumor burden and liver function provided additional prognostic information. The most significant independent prognostic factors for survival upon multivariate analysis were ECOG status, tumor burden (nodules >5), international normalized ratio >1.2, and extrahepatic disease. Common adverse events were: fatigue, nausea/vomiting, and abdominal pain. Grade 3 or higher increases in bilirubin were reported in 5.8% of patients. All-cause mortality was 0.6% and 6.8% at 30 and 90 days, respectively. Conclusion: This analysis provides robust evidence of the survival achieved with radioembolization, including those with advanced disease and few treatment options. © 2011 American Association for the Study of Liver Diseases.

Background:This multi-centre phase II clinical trial is the first prospective evaluation of radioembolisation of patients with colorectal liver metastases (mCRC) who failed previous oxaliplatin-and irinotecan-based systemic chemotherapy regimens.Methods:Eligible patients had adequate hepatic, haemopoietic and renal function, and an absence of major hepatic vascular anomalies and hepato-pulmonary shunting. Gastroduodenal and right gastric arteries were embolised before hepatic arterial administration of yttrium-90 resin microspheres (median activity, 1.7 GBq; range, 0.9-2.2).Results:Of 50 eligible patients, 38 (76%) had received ≥4 lines of chemotherapy. Most presented with synchronous disease (72%)

99mTechnetium-labeled methylene diphosphonate bone scan (BS) is the most commonly used imaging test to screen for skeletal metastases in patients with breast cancer. Since its introduction into cli

The aim of this study was to evaluate the usefulness of technetium-99m sestamibi scintimammography (SSM) and combined use of SSM and X-ray mammography (MG) in premenopausal patients with small (≤2 cm) suspicious breast lesions. Eighty-seven premenopausal women (median age 47 years, range 32–52) with breast lesions ranging from 4 to 20 mm in greatest diameter (median 12 mm) and detected by MG, underwent SSM prior to open breast biopsy. A planar camera and single-photon emission tomography (SPET) technique were used in 23 (26.4%) and 64 (73.6%) patients, respectively. At histological examination, 72 (82.8%) breast cancers (pT1a=3, pT1b=27, pT1c=42) and 15 (17.2%) benign masses were found. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MG and SSM were 80.6% vs 80.6%, 60.0% vs 93.3% (P

We determined the prevalence of celiac disease in subjects with autoimmune thyroiditis compared with sick and healthy subjects. The screening was performed with IgA-class endomysium antibody, by indirect immunofluorescence using human umbilical cord as the antigenic substrate. Six of the 172 patients with autoimmune thyroiditis were found to be anti-endomysium positive (3.4%) and five of these underwent intestinal biopsy, which showed total villous atrophy. By contrast, 3 (0.75%) of 396 patients with nongastroenterologic malignancies and 10 (0.25%) of 4000 blood donors were found to have celiac disease. The prevalence of autoimmune diseases was significantly higher in patients with both celiac disease and autoimmune thyroiditis than in patients with autoimmune thyroiditis alone (P = 0.01). This study confirms that celiac disease is increased among patients with autoimmune thyroiditis. We suggest that these patients may benefit from screening for celiac disease so as to eliminate symptoms and limit the risk of developing other autoimmune disorders.

Background & Aims The European Network on Radioembolization with Yttrium-90 resin microspheres study group (ENRY) conducted a retrospective study to evaluate the outcomes among elderly (≥70 years) and younger patients (

Uptake of I-131 in the pericardial area is described in an asymptomatic patient who underwent total body scan for recurrent papillary thyroid cancer. Ultrasonography demonstrated a small pericardial effusion that persisted after I-thyroxine therapy was reinstituted. Two I-131 therapeutic doses were given, and follow-up total body scans were performed during the next 6 years. Although tracer accumulation in the neck was eliminated and the serum thyroglobulin level was not elevated, I-131 uptake persisted in pericardial effusion. Despite diligent study, no neoplastic, infectious, or autoimmune etiology could be demonstrated, and we thus classified it as idiopathic pericardial effusion. This phenomenon should be considered when interpreting I-131 scans that show I-131 uptake in the region of the heart.

Mutations in the progranulin gene (GRN) were recently identified as an important cause of familial frontotemporal dementia (FTD). More than 60 pathogenic mutations have been reported up to now and prominent phenotypic variability within and among affected kindreds has been described. We have studied an Italian family with clinical evidence of dementia, and here we report detailed clinical records, imaging, sequential neurological examinations, cognitive assessments, and genetic analysis of three affected members of the same generation. Genetic analysis revealed the presence of the null mutation IVS6 + 5_8delGTGA in GRN, leading to haploinsufficiency, as documented by mRNA analysis. The mutation is associated with wide variation of the clinical phenotype, ranging from FTD to Alzheimer's disease and to a rapidly-progressive dementia. In summary, the patients of this kindred showed highly variable clinical features that do not have a close correspondence with the pattern of the cerebral atrophy. Our data extend the phenotypic spectrum and the complexity of neurodegenerative diseases linked to GRN mutations.

A 60-year-old woman with Cushing's syndrome in whom high-dose dexamethasone failed to suppress glucocorticoids was studied by ultrasound and CT. Neither of these morphological studies was interpreted as revealing any adrenal abnormality. Functional imaging with NP-59 (131-I-beta-iodomethylnorcholesterol) revealed unequivocal, intense, unilateral uptake in the left adrenal gland and subsequent surgery removed a 2.5 cm adrenocortical adenoma from this site. Following surgery the patient was temporarily adrenocortically insufficient but later returned to normal. It is unusual for adrenocortical adenomas causing Cushing's syndrome not to be correctly located by CT. NP-59 scintigraphy in addition to being highly accurate in the location of adrenocortical adenomas also has the advantage of correctly depicting bilateral cortical nodular hyperplasia in which CT will frequently reveal only the largest nodule, which may be incorrectly designated a unilateral adenoma. Furthermore, scintigraphy provides evidence of suppression of the contralateral, normal adrenal cortical tissue in Cushing's syndrome caused by an adrenal adenoma and predicts the vulnerability of such patients to postoperative adrenocortical insufficiency.

A patient presented with recurrent pheochromocytoma 10 years following the apparently successful surgical cure of a right adrenal pheochromocytoma. Conventional medical imaging techniques, (chest radiograph, abdominal ultrasound, and abdominal CT) suggested local recurrence for which surgery was planned. I-131 MIBG scintigraphy revealed disseminated metastatic disease that rendered attempts at surgical cure futile. The patient was treated with three therapeutic doses of I-131 MIBG with good symptomatic palliation and improvement of some biochemical parameters.

Background and Objectives Bone lesions in multiple myeloma (MM) have been traditionally detected by whole body X-ray (WBXR) survey although magnetic resonance imaging (MRI) has become the gold standard for detecting MM involvement of the spine and pelvis. The aim of this study was to compare a new technique, positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) integrated with computed tomography (18F-FDG PET-CT), with MRI and WBXR for baseline assessment of bone disease in MM. Design and Methods We prospectively compared 18F-FDG PET-CT, MRI of the spine-pelvis and WBXR for baseline assessment of bone disease in a series of 46 patients with newly diagnosed MM. In 23 patients who received up front autologous transplantation, we also compared post-treatment PET-CT scans with MR images of the spine and pelvis. Results Overall, PET-CT was superior to planar radiographs in 46% of patients, including 19% with negative WBXR. In 30% of patients, PET-CT scans of the spine and pelvis failed to show abnormal findings in areas in which MRI revealed an abnormal pattern of bone marrow involvement, more frequently of diffuse type. In contrast, in 35% of patients PET-CT enabled the detection of myelomatous lesions in areas which were out of the field of view of MRI. By combining MRI of the spine-pelvis and 18F-FDG PET-CT, the ability to detect sites of active MM, both medullary and extramedullary, was as high as 92%. Following transplantation, 15 patients had negative PET-CT scans (including 13 with a very good partial response or at least near complete response), but only 8 had normal MRI. Interpretation and Conclusions MRI of the spine and pelvis still remains the gold standard imaging technique for the detection of bone marrow involvement in MM. 18F-FDG PET-CT provides additional and valuable information for the assessment of myeloma bone disease in areas not covered by MRI.

Aims: To evaluate the usefulness of 99m-Tc-sestamibi scintimammography (SSM) in the detection of T1-2, N0-1, M0 breast cancer (BC) and axillary node (AN) metastases. Patients and methods: A series of 239 women (median age 55 years) who had already been selected for breast biopsy underwent both mammography (MG) and SSM before surgery. The final diagnosis confirmed in 207 (86.6%) patients, and benign breast lesions in 32 (13.4%). Results: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MG and SSM in BC detection were 88.9% vs 87.9%, 62.5% vs 93.8% (P

The whole body 131-I scan remains an important component in the postoperative treatment of patients with well-differentiated thyroid cancer. Because normal thyroid tissue remnants and residual or metastatic foci of well-differentiated thyroid cancer have the unique ability to concentrate, organify, and store 131-I, the whole body scan provides a depiction of those tissues that can be ablated with therapeutic doses of 131-I. Over time, it has become obvious that the whole body scan may also reveal foci of 131-i uptake owing to a wide variety of other causes. We provide a detailed pathophysiological classification of the artifacts, anatomic and physiological variants, and nonthyroidal diseases that may give rise to false-positive whole body scans in postoperative patients with thyroid cancer. These include ectopic foci of normal thyroid tissue; nonthyroidal physiological sites (eg, choroid plexus, salivary glands, gastric mucosa, urinary tract); contamination by physiological sections; ectopic gastric mucosa; other gastrointestinal abnormalities; urinary tract abnormalities; mammary abnormalities; serous cavities and cysts; inflammation and infection; nonthyroidal neoplasms; and currently unexplained causes. This article also provides a detailed review of the widely scattered English language literature in which these phenomena were originally described.

Varicocele, a varicosity of the gonadal venous plexus, is a well-recognized disorder occurring in up to 10% of men. In women, an analogous varicosity of the salpingo-ovarian plexus is rare. This may be explained, in part, by the lack of obvious findings on clinical examination in women compared with men and the need, until recently, to use invasive venographic methods to confirm the diagnosis. Two cases of "female varicocele" diagnosed by means of echo Doppler and Tc-99m red blood cell scintigraphy and their cure by percutaneous phlebographic occlusion of the ovarian venous varicosity are described.

When mild asymptomatic hypercalcemia occurs in a patient with hyperthyroidism, it may or may not be due to concurrent hyperparathyroidism and at times only the control of the hyperthyroidism will resolve the problem. Moreover, the presence of hyperfunctioning thyroid nodules will interfere with Tl-201/Tc-99m pertechnetate parathyroid scintigraphy. Initial treatment of hyperthyroidism with I-131 in this situation controls hyperthyroidism and permits successful localization of parathyroid adenomas, which may then be excised--a result that was achieved in three cases.

Technetium-99m methoxyisobutylisonitrile (MIBI), like thallium-201, has recently been introduced as a myocardial perfusion agent and is now also showing very promising results in parathyroid scintigrapy. The results of 201Tl/99mTc-pertechnetate and 99mTc-MIBI/99mTc-pertechnetate subtraction scintigraphy, ultrasonography and computed tomography are presented in a series of 43 patients operated on for hyperparathyroidism. All four imaging modalities were confirmed to be reliable, scintigraphy being the most accurate. Sensitivities ranged from 81% to 95%, that of 99mTc-MIBI being the highest. Moreover this tracer, which has more favourable physical and also biochemical properties, yielded images of superior quality. This allowed localization of the lesion by visual inspection only in as many as 86% of the patients with positive 99mTc-MIBI/99mTc-pertechnetate subtraction scintigraphy. We believe that the higher sensitivity, superior image quality and lower cost of 99mTc-MIBI imaging will make 99mTc-MIBI the new radiopharmaceutical of choice for parathyroid scintigraphy (when one takes into account the stability of labelling with large activities it is possible to perform three or four cardiac studies together with one parathyroid scintigraphic examination using one lyophililzed vial).

Positron emission tomography (PET) integrated with computed tomography (PET/CT) has been reported to be useful for screening myelomatous lesions at diagnosis in patients with multiple myeloma (MM) and for monitoring response to autologous stem cell transplantation (auto-SCT). The aim of the study was to evaluate the prognostic significance of PET/CT in MM patients who received allogeneic stem cell transplantation (allo-SCT). Patients who underwent upfront auto-SCT followed by allo-SCT, either as consolidation or salvage treatment, were studied with PET/CT before and/or within 6 months after allo-SCT. The number, the maximum standard uptake value (SUV), and the location (medullary or extramedullary) of focal lesions (FLs) were recorded and investigated as predictors of progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analyses. Fifty-four patients had a PET/CT scan before allo-SCT. Of these, 22 patients (41%) had a negative PET/CT scan, 11 patients (20%) showed 1 to 3 FLs, and 21 patients (39%) had either a diffuse bone marrow involvement or more than 3 FLs. SUV was >4.2 in 21 patients (39%) and extramedullary disease (EMD) was present in 6 patients (11%). Multivariate analysis of prognostic factors before allo-SCT showed that persistence of EMD at transplantation was an independent predictor of poor PFS, whereas OS was negatively influenced by unrelated donor and SUV > 4.2. Fifty-nine patients had a PET/CT scan within 6 months after allo-SCT. Multivariate analysis of post-treatment variables showed that persistence of EMD and failure to obtain complete response or very good partial response after allo-SCT were strongly associated with shorter PFS and OS. Of the 46 patients with evaluable PET/CT scans both before and 6 months after allo-SCT, the 23 patients who maintained or reached a PET complete remission showed a significantly prolonged PFS and OS compared with the 23 patients with persistence of any PET positivity (2-year PFS: 51% versus 25%, P = .03; 2-year OS: 81% versus 47%, P = .001). This study indicates that PET/CT imaging before and after allo-SCT is significantly associated with the outcome, suggesting the utility of this technique for MM staging before allo-SCT and for response monitoring after the transplantation.

Direct in vivo assessment of parathyroid hormone-calcium relation curve in renal patients. Secondary hyperparathyroidism (SHP) is a well documented finding even in the early stages of chronic renal failure (CRF). A sigmoidal relationship, fitting a four parameter model, links PTH secretion rate and calcium concentration changes. To our knowledge, PTH secretory parameters have only been studied in uremic patients who are in dialysis treatment. As a result of these studies, a possible role for derangement in setpoint values (that is, the serum calcium concentration corresponding to the mid-range value on the sigmoidal curve) has been suggested in the pathogenesis of SHP in CRF. Our study was undertaken to gain insight into the calcium-PTH relationship curve in the first course of CRF and to assess whether a change in any of the secretory parameters is related to the beginning of SHP. We studied 27 male renal patients with a variable degree of renal function (creatinine clearance 12 to 164 ml/min) and 9 control subjects. In all patients and controls the following parameters were evaluated: (1) basal 1,25(OH)2 vitamin D, 25(OH)vitamin D, calcitonin (CT), intact PTH; (2) GFR by Cr51EDTA clearance; (3) the sigmoidal PTH-ionized calcium relation curve, by means of a hypocalcemie stimulating test (Na2-EDTA 37 mg/kg body weight/2hr) and a hypercalcemie test (Ca gluconate giving 8 mg/kg of body weight/2hr of Ca element), performed on two consecutive days. The main results were: (1) the progressive reduction of GFR was accompanied by an increase in the maximum secretory capacity of PTH, without any change in setpoint values; (2) in addition to the already known factors, CT seems to be, in some as yet undefined way, related to PTH hypersecretion in the course of CRF.

Scintigraphy with I-131 metaiodobenzylguanidine (MIBG) was effective in depicting a pancreatic insulinoma in a patient suffering from intermittent hypoglycemia. This observation widens the range of neuroendocrine tumors that take up to I-131 MIBG and supports the concept that many tumors of the amine precursor uptake and decarboxylation system may be imaged in this way.

The i.p. delivery of murine monoclonal antibody was compared with i.v. delivery in normal mice and rats, in normal nude mice and in those with i.p. human ovarian carcinoma xenografts. In normal rats, all classes of antibodies and antibody fragments evaluated were cleared from the peritoneal cavity at comparable rates. The regional delivery (Rd1) advantage to the peritoneal cavity following i.p. delivery was thus most dependent on the rate of clearance of the antibody or fragment from the blood stream. Determining the exact i.p. delivery advantage was problematic due to the difficulty in reliably obtaining peritoneal fluid later than 9-10 h after i.p. injection in normal animals. During the first 9 h following i.p. injection, the Rd(0-9/0-9) was, for a murine IgG2ak Fab greater than F(ab')2 greater than IgG (at 13.6 greater than 10 greater than 7.9). Two murine IgMs evaluated differed in Rd(0-9) at 27.1 and 9.2 respectively. When blood levels were extrapolated to infinity, these Rd (0-9/affinity) values were considerably lower with the Fab having the highest Rd at 4.67. The i.p. Rd advantage was almost solely due to the i.p. antibody levels seen in the first 24 h after injection, as after that time, blood levels become comparable to those seen following i.v. injection. Normal tissues obtained at sacrifice 5-7 days after i.p. injection. Normal tissues obtained at sacrifice 5-7 days after i.p. or i.v. injection in rats showed comparable levels of radioantibody activity, whether the injection was i.p. or i.v. (except for higher diaphragmatic levels following i.p. delivery). In nude mice with i.p. human-derived ovarian tumors, intact IgG clearance from the peritoneal cavity to the blood was considerably slower than in normal animals, and early i.p. tumor uptake of specific antibody was significantly higher than that following i.v. antibody delivery. With higher early tumor uptake and lower systemic exposure, early tumor/nontumor ratios were significantly greater than those for i.v. delivery, though not beyond 48 h after i.p. injection. This study demonstrates the pharmacokinetic rationale for i.p. monoclonal antibody delivery, especially for agents cleared rapidly from the blood, such as antibody fragments. In addition, definite i.p. delivery benefit for antibody specific to i.p. tumors in the i.p. ovarian cancer system was shown soon after injection. These data regarding i.p. antibody delivery should be useful in rationally planning diagnostic and therapeutic studies involving the i.p. delivery of unmodified and immunoconjugated monoclonal antibodies.

We evaluated the feasibility of systemic vascular perfusion with saline (mimicking plasmapheresis) as a method to enhance tumor-specific monoclonal antibody (MoAb) tumor/background ratios. Initially, groups of rats were injected intravenously (i.v.) with i3’I-5G6.4 MoAb (mutine IgGZaK reactive with ovarian carcinoma). These animal’s radioactivity levels were determined by dose calibrator and they were imaged before and after perfusion which was conducted at 4 or 24 h post-antibody injection. Animals were sacrificed after perfusion, as were controls, and normal organ radioactivity levels determined. In addition, nude mice bearing HTB77 ovarian cancers subcutaneously were injected i.v. with 13’1-5G6.4 MoAb and were imaged before and after systemic perfusion with saline 24 h post-5G6.4 injection. Perfusion in rats dropped whole-body 566.4 levels significantly at both perfusion times (P < 0.0005). The drop in whole-body radioactivity with perfusion was significantly greater for the animals perfused at 4 h post i.v. 566.4 antibody injection (48.3 + 5.1%) than for those perfused at 24 h post i.v. antibody injection (32.9 f. 2.9%) (P < 0.025). In the nude mice with ovarian cancer xenografts, y camera images of tumors were visually and quantitatively (by computer image analysis) enhanced by perfusion, with a 2.33-fold greater decline in whole body uptake than in the tumor (P < 0.05). These studies show that (1) much background antibody radioactivity can be removed using whole-body perfusion with saline, (2) that the decline in whole body activity is larger with 4 than 24 h perfusion and (3) tumor imaging can be enhanced by this approach. This and similar approaches that increase relative tumor antibody uptake such as plasmapheresis may be useful in imaging and therapy with radiolabeled antibodies.