Outcome after Discontinuing Long-Term Benzimidazole Treatment in 11 Patients with Non-resectable Alveolar Echinococcosis with Negative FDG-PET/CT and Anti-EmII/3-10 Serology.

BACKGROUND/AIMS: Benzimidazoles are efficacious for treating non-resectable alveolar echinococcosis (AE), but their long-term parasitocidal (curative) effect is disputed. In this study, we prospectively analyzed the potential parasitocidal effect of benzimidazoles and whether normalization of FDG-PET/CT scans and anti-Emll/3-10-antibody levels could act as reliable "in vivo" parameters of AE-inactivation permitting to abrogate chemotherapy with a low risk for AE-recurrence. METHOD: This prospective study included 34 patients with non-resectable AE subdivided into group A (n = 11), followed-up after diagnosis and begin of chemotherapy at months 6, 12 and 24, and group B (n = 23) with a medium duration of chemotherapy of 10 (range 2-25) years. All patients were assessed by FDG-PET/CT examinations and anti-EmII/3-10 serology. Chemotherapy was abrogated in patients with normalization of FDG-PET/CT and serum anti-EmII/3-10 levels. These patients were closely followed-up for AE recurrence. Endpoint (parasitocidal efficacy) was defined by the absence of AE-recurrence >24 months after stopping treatment. RESULTS: Normalization of FDG-PET/CT scan and anti-EmII/3-10 levels occurred in 11 of 34 patients (32%). After abrogation of chemotherapy in these 11 patients, there was no evidence of AE-recurrence within a median of 70.5 (range 16-82) months. However, the patients' immunocompetence appears pivotal for the described long-term parasitocidal effect of benzimidazoles. CONCLUSIONS: The combination of negative FDG-PET/CT-scans and anti-EmII/3-10 antibody levels seem to be reliable parameters for assessing in vivo AE-larval inactivity after long-term benzimidazole chemotherapy. TRIAL REGISTRATION: clinicaltrials.gov: NCT00658294.

High bone turnover assessed by 18F-fluoride PET/CT in the spine and sacroiliac joints of patients with ankylosing spondylitis: comparison with inflammatory lesions detected by whole body MRI.

BACKGROUND: This study compares the frequency and distribution of increased activity on 18 F-fluoride PET/CT with the presence of bone marrow edema on whole-body MR imaging in the spine and sacroiliac joints (SIJ) of patients with active ankylosing spondylitis (AS). METHODS: Ten patients (6 men and 4 women), between 30 and 58 years old (median 44) with active AS, were prospectively examined with both whole-body MRI and 18 F-fluoride PET/CT. Patients fulfilled modified NY criteria and had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of at least 4. Increased radiotracer uptake in PET/CT and bone marrow edema in whole-body MRI of spine and SIJ was evaluated independently by two blinded observers for each modality. Kappa statistics were used to compare interobserver agreement as well as scores of consensus reading of the two imaging modalities. RESULTS: Analysis of interobserver agreement for PET/CT yielded a kappa value of 0.68 for spinal lesions and of 0.88 for SIJ lesions. The corresponding kappa values for the MRI modality were 0.64 and 0.93, respectively. More spinal lesions were detected by MRI in comparison to PET/CT (68 vs. 38), whereas a similar number of SIJ quadrants scored positive in both modalities (19 vs. 17). Analysis of agreement of lesion detection between both imaging modalities yielded a kappa value of only 0.25 for spinal lesions and of 0.64 for SIJ lesions. CONCLUSION: Increased 18 F-fluoride uptake in PET/CT is only modestly associated with bone marrow edema on MRI in the spine and SIJ of patients with AS, suggesting different aspects of bone involvement in AS.

18F-fluoride PET/CT for detection of sacroiliitis in ankylosing spondylitis.

PURPOSE: The aim of this study was to evaluate the performance of (18)F-fluoride-PET/CT (PET/CT) for the diagnosis of sacroiliac joint (SIJ) arthritis in patients with active ankylosing spondylitis (AS). METHODS: Included in the study were 15 patients with AS according to the modified New York criteria (AS group) and with active disease and 13 patients with mechanical low back pain (MLBP; control group) who were investigated with whole-body (18)F-fluoride PET/CT. The ratio of the uptake in the SIJ and that in the sacrum (SIJ/S) was calculated for every joint. RESULTS: The mean SIJ/S ratio of 30 quantified joints in the AS group was 1.66 (range 1.10-3.07) with PET/CT, and the mean SIJ/S ratio of 26 quantified joints in the MLBP group was 1.12 (range 0.71-1.52). The area under the receiver operating characteristic curve for SIJ arthritis was 0.84. With plain radiography as a the gold standard and taking an SIJ/S ratio of >1.3 as the threshold, the sensitivity, specificity and accuracy on a per patient basis were 80%, 77% and 79%, respectively. On a per SIJ basis, the greatest sensitivity (94%) was found in grade 3 sacroiliitis (n = 16). CONCLUSION: Our results suggest that quantitative (18)F-fluoride PET/CT may play a role in the diagnosis of sacroiliitis in active AS and is an alternative to conventional bone scintigraphy in times of molybdenum shortage.

Expanding role of 18F-fluoro-D-deoxyglucose PET and PET/CT in spinal infections.

(18)F-fluoro-D -deoxyglucose positron emission tomography ([(18)F]-FDG PET) is successfully employed as a molecular imaging technique in oncology, and has become a promising imaging modality in the field of infection. The non-invasive diagnosis of spinal infections (SI) has been a challenge for physicians for many years. Morphological imaging modalities such as conventional radiography, computed tomography (CT), and magnetic resonance imaging (MRI) are techniques frequently used in patients with SI. However, these methods are sometimes non-specific, and difficulties in differentiating infectious from degenerative end-plate abnormalities or postoperative changes can occur. Moreover, in contrast to CT and MRI, FDG uptake in PET is not hampered by metallic implant-associated artifacts. Conventional radionuclide imaging tests, such as bone scintigraphy, labeled leukocyte, and gallium scanning, suffer from relatively poor spatial resolution and lack sensitivity, specificity, or both. Initial data show that [(18)F]-FDG PET is an emerging imaging technique for diagnosing SI. [(18)F]-FDG PET appears to be especially helpful in those cases in which MRI cannot be performed or is non-diagnostic, and as an adjunct in patients in whom the diagnosis is inconclusive. The article reviews the currently available literature on [(18)F]-FDG PET and PET/CT in the diagnosis of SI.

Osteomyelitis and arthritis.

Infections of bone and the joints can represent major diagnostic and therapeutic challenges to all clinicians. Together with osteomyelitis and septic arthritis, soft-tissue infections like cellulites/fasciitis and abscess formation can occur, which have to be treated appropriately. Bone scintigraphy is a sensitive method that can be used to search for bone and joint infections. Labeled leukocytes often are used as the gold standard to identify infectious foci in the musculoskeletal system, but major drawbacks of this method are the imaging of chronic infections and imaging of the axial skeleton. Like (111)In-labeled leukocyte imaging, (99m)Tc-labeled antigranulocyte antibody scintigraphy has a role in the imaging of osteomyelitis of the peripheral skeleton. Magnetic resonance imaging is widely used to evaluate musculoskeletal infections and is excellent in identifying abscess formation, but the extent and spread of infection is sometimes difficult to delineate because hyperemia and infection are not congruent.

Diagnostic value of 18F-FDG PET/CT in trauma patients with suspected chronic osteomyelitis.

PURPOSE: To retrospectively evaluate the diagnostic value of (18)F-FDG PET/CT in trauma patients with suspected chronic osteomyelitis. METHODS: Thirty-three partial body (18)F-FDG PET/CT scans were performed in 33 patients with trauma suspected of having chronic osteomyelitis. In 10 and 23 patients, infection was suspected in the axial and appendicular skeleton, respectively. In 18 patients, PET/CT was performed in the presence of metallic implants. Histopathology or bacteriological culture was used as the standard of reference. For statistical analysis, sensitivity, specificity and accuracy were calculated in relation to findings of the reference standard. RESULTS: Of 33 PET/CT scans, 17 were true positive, 13 true negative, two false positive and one false negative. Eighteen patients had chronic osteomyelitis and 15 had no osseous infection according to the reference standard. Sensitivity, specificity and accuracy for (18)F-FDG PET/CT was 94%, 87% and 91% for the whole group, 88%, 100% and 90% for the axial skeleton and 100%, 85% and 91% for the appendicular skeleton, respectively. CONCLUSION: (18)F-FDG PET/CT is a highly sensitive and specific method for the evaluation of chronic infection in the axial and appendicular skeleton in patients with trauma. PET/CT allows precise anatomical localisation and characterisation of the infectious focus and demonstrates the extent of chronic osteomyelitis with a high degree of accuracy.

PET/CT in musculoskeletal infection.

Early diagnosis of musculoskeletal infections is the key to successful therapy and prevention of complications. Fluorine-18 (F-18) fluorodeoxyglucose-positron emission tomography (FDG-PET) is a promising modality for imaging musculoskeletal infection and might play an important role in the evaluation of chronic osteomyelitis and spinal infection. FDG-PET has shown promising results for diagnosing both acute and chronic infection of the axial and appendicular skeletons. PET imaging will have increased importance in patients with metallic implants because FDG uptake, in contrast to magnetic resonance imaging (MRI) and computed tomography (CT), is not hampered by metallic artifacts. In patients with suspected prosthetic joint infection, results of PET are controversial, and combined indium-111-labeled leukocyte and technetium-99m-sulfur colloid marrow scintigraphy still remains the gold standard. PET/CT with the combination of PET and a low-dose or full-dose diagnostic CT provides exact anatomical correlation of bone and joint lesions and increases the accuracy of the test compared with PET alone. The question of in which situations PET/CT becomes the preferred imaging method in suspected musculoskeletal infection depends on several factors, including cost and availability. This article reviews the currently available literature and addresses the use of FDG-PET/CT in the diagnosis of musculoskeletal infections.

The value of FDG-PET in patients with painful total knee arthroplasty.

PURPOSE: The purpose of this study was to evaluate 18F-fluorodeoxyglucose (FDG) uptake in patients with painful total knee arthroplasty and to relate FDG uptake to the location of soft tissue pain. METHODS: Twenty-eight patients with painful total knee arthroplasty had a clinical examination, standard radiographs, CT measurement of rotation of the femoral component and FDG-PET (18 PET/CT, 10 PET). The diagnosis of infection was based on microbiological examinations of surgical specimens (n=12) or clinical follow-up for at least 6 months (n=16), 99mTc-labelled monoclonal antibody scintigraphy and joint aspiration. RESULTS: Twenty-seven of 28 patients presented with diffuse synovial FDG uptake. Additional focal extrasynovial FDG uptake was observed in 19 knees. Twenty-four of the 28 patients had a diagnosis of internal femoral malrotation. The remaining four patients showed no rotation (0 degrees) and 3 degrees, 4 degrees and 7 degrees of external rotation, respectively. Three patients presented with the additional diagnosis of an infected total knee replacement. Pain was described as diffuse (n=10) or focal (n=18). In two knees a relationship between pain location and FDG uptake was observed. Of ten patients with a severe internal femoral component rotation (>6 degrees), seven had focal uptake, four in the femoral periosteum and three in the tibial periosteum. The difference between knees with severe malrotation and the remaining knees was not significant (p=1.000, Fisher's Exact Test). CONCLUSION: Diffuse synovial and focal extrasynovial FDG-PET uptake is commonly found in patients with malrotation of the femoral component and is not related to pain location. The information provided by FDG-PET does not contribute to the diagnosis and management of individual patients with persistent pain after total knee replacement.

Successful low toxicity hematopoietic stem cell transplantation for high-risk adult chronic granulomatous disease patients.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation for chronic granulomatous disease (CGD) is associated with a significant risk of transplant-related mortality. Adult age, overt infection, and residual inflammatory disease at transplant are major risk factors. METHODS: Here we report the favorable outcome after bone marrow transplantation in three high-risk adult CGD patients (ages 18, 35, and 39) with severe disease-related complications (overt pneumonia, liver abscess, steroid-dependent granulomatous colitis, diabetes, restrictive lung disease, renal insufficiency, epilepsia). Bone marrow donors were human leukocyte antigen-matched related or unrelated. The conditioning regimen consisted of 2 x 4 mg/kg oral busulphan (d -3, -2), fludarabine 6 x 30 mg/qm (d -7 to -2), rabbit anti-T-cell-globulin (Fresenius) 4 x 10 mg/kg (d -4 to -1). Graft versus host disease prophylaxis consisted of cyclosporine A and mycophenolate-mofetil. RESULTS: Mean neutrophil and platelet engraftment was observed at day +18.5 and +22.5, respectively. All infectious and inflammatory lesions resolved and restrictive lung disease improved. No signs of grade II-IV acute or chronic graft versus host disease were observed. With a follow-up of 12 to 27 months, all patients are alive and well with full donor chimerism, normalized superoxide production, and documented T- and B-cell function. CONCLUSION: This modified reduced intensity conditioning protocol is a promising treatment modality for high-risk adult CGD patients.

Significance of incidental 18F-FDG accumulations in the gastrointestinal tract in PET/CT: correlation with endoscopic and histopathologic results.

UNLABELLED: This study was undertaken to identify the clinical value of incidentally detected lesions (IDLs) in the gastrointestinal tract (GIT) with (18)F-FDG PET/CT. METHODS: The reported database of 3,281 patients who underwent partial-body (18)F-FDG PET/CT scans from April 2001 to September 2003 was reviewed. Patients with incidental (18)F-FDG accumulations in the GIT that were associated with concomitant abnormal soft-tissue density or wall thickening on the native CT were evaluated. Incidental PET/CT findings were correlated with endoscopic and histopathologic results. RESULTS: According to our selection criteria, 98 (3%) of the 3,281 patients had an IDL of the GIT on (18)F-FDG PET/CT. Correlative endoscopic findings were available in 69 (70%) of 98 patients. Of these, 13 patients (19%) were harboring newly occurring cancers of the GIT in addition to preexisting aerodigestive tract tumors (n = 12) and malignant melanoma (n = 1). Twenty-nine (42%) patients were identified with precancerous lesions, such as advanced colonic adenomas (n = 27), Barrett's esophagus (n = 1), and intestinal metaplasia of the gastric mucosa (n = 1). Inflammatory and other benign GIT lesions were detected in 12 (17%) and 6 (8%) patients, respectively. In 9 (13%) patients, PET/CT was false-positive, showing normal findings in subsequent endoscopic examinations. In 20 (28%) of 69 patients, PET/CT findings had a relevant impact on the clinical management. Twenty-nine (30%) of the 98 patients were not subject to a further endoscopic examination because of the extent and nature of the primary tumor (n = 17), loss to follow-up (n = 7), death shortly after PET (n = 3), and patient unwillingness (n = 2). CONCLUSION: Although IDLs of the GIT on (18)F-FDG PET/CT scans are found only in about 3% of cases, they are associated with a substantial risk of an underlying cancerous or precancerous lesion. Early identification of these occult lesions may have a major impact on the patients' management and outcome.

Non-Hodgkin lymphoma and Hodgkin disease: coregistered FDG PET and CT at staging and restaging--do we need contrast-enhanced CT?

PURPOSE: To retrospectively compare diagnostic value of coregistered fluorine 18 fluorodeoxyglucose positron emission tomographic (PET) and computed tomographic (CT) scans obtained with low-dose nonenhanced CT (PET/CT) with those routinely obtained with contrast material-enhanced CT for staging and restaging of disease in patients with Hodgkin disease or high-grade non-Hodgkin lymphoma. MATERIALS AND METHODS: Sixty patients (mean age, 39.6 years +/- 17.1 [standard deviation]) with Hodgkin disease (n = 42) or high-grade non-Hodgkin lymphoma (n = 18) were included in this retrospective study. All patients underwent PET/CT and contrast-enhanced CT within a maximum of 24 days (mean, 9.1 days +/- 7.0) of each other for staging (n = 19) or first follow-up examination (n = 41). Findings were extracted from original written reports (PET/CT, contrast-enhanced CT) and compared with findings of reference standard, which included biopsy or follow-up with clinical, laboratory, or other imaging findings. For statistical analysis, sensitivity and specificity were calculated with findings of the reference standard. Agreement of both methods was determined with Cohen kappa and McNemar tests on a per-patient basis. RESULTS: For evaluation of lymph node involvement, sensitivity of PET/CT and contrast-enhanced CT was 94% and 88%, and specificity was 100% and 86%, respectively. For evaluation of organ involvement, sensitivity of PET/CT and contrast-enhanced CT was 88% and 50%, and specificity was 100% and 90%, respectively. Agreement of both methods was excellent (kappa = 0.84) for assignment of lymph node involvement but only fair (kappa = 0.50) for extranodal disease. A difference with P <.05 (McNemar test) was considered significant in regard to exclusion of disease with PET/CT, compared with contrast-enhanced CT. CONCLUSION: PET/CT performed with nonenhanced CT is more sensitive and specific than is contrast-enhanced CT for evaluation of lymph node and organ involvement, especially regarding exclusion of disease, in patients with Hodgkin disease and high-grade non-Hodgkin lymphoma.

FDG PET for differentiation of infection and aseptic loosening in total hip replacements: comparison with conventional radiography and three-phase bone scintigraphy.

PURPOSE: To compare the diagnostic efficacy of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) with that of conventional radiography and three-phase bone scintigraphy in patients suspected of having infection in their total hip replacements. MATERIALS AND METHODS: Thirty-five patients with painful total hip replacements and possible septic prosthetic loosening were examined with FDG PET, conventional radiography, and three-phase bone scintigraphy. PET, radiographic, and scintigraphic images were each evaluated by two independent observers in a blinded fashion. For 32 of 35 patients, serial conventional radiographs were available. Results of microbiologic examinations of surgical specimens represented the standard of reference in 26 patients, and results of joint aspiration plus clinical follow-up of at least 6 months represented the standard of reference in the remaining nine patients. Sensitivity, specificity, accuracy, and interobserver variability (kappa) values were calculated. The imaging modalities were compared in terms of diagnostic confidence by using the sign test. RESULTS: Nine patients had septic and 21 patients had aseptic loosening. In five patients, neither loosening nor infection was confirmed. For diagnosing infection with FDG PET, conventional radiography, and bone scintigraphy, respectively, sensitivity values for reader 1 and reader 2 were 33% and 22%, 89% and 78%, and 56% and 44%, while specificity values were 81% and 85%, 50% and 65%, and 88% and 92% and accuracy values were 69% for both readers, 60% and 69%, and 80% for both readers. PET was significantly more specific (P =.035) but less sensitive (P =.016) than conventional radiography for the diagnosis of infection. CONCLUSION: In a study population of patients suspected of having infected total hip replacements, FDG PET performed similarly to three-phase bone scintigraphy. FDG PET was more specific but less sensitive than conventional radiography for the diagnosis of infection.

Whole-body (18)F-FDG PET improves the management of patients with small cell lung cancer.

UNLABELLED: The aim of this study was to evaluate the impact of whole-body (18)F-FDG PET on staging and managing patients with small cell lung cancer (SCLC). METHODS: The treatment records of 42 consecutive patients (27 men, 15 women; mean age, 62 y; age range, 45-83 y) with SCLC were reviewed. Whole-body (18)F-FDG PET was performed for initial staging in 24 patients and for restaging after chemotherapy or radiation treatment in 20 patients. Two patients of the initial staging group were restaged with PET after therapy. PET findings were correlated with clinical and radiologic findings (CT of the chest and abdomen, bone scan, and CT or MRI of the brain). The impact of PET on staging and management decisions was determined. RESULTS: For 12 of 42 patients (29%), PET results changed the patient's management. In 8 patients (19%), PET resulted in a change of radiation therapy because of the detection of previously unknown tumor foci. Adjuvant radiation therapy was cancelled in 3 patients. A change of radiation field and volume was necessary in 5 patients. In 1 patient, PET results excluded extensive disease, which permitted surgical resection of the tumor. Chemotherapy was discontinued in 2 patients and restarted in 1 patient on the basis of the PET findings. In 5 patients (12%), PET excluded malignancy as the suspicious lesions found with conventional cross-sectional imaging did not take up (18)F-FDG. CONCLUSION: The results of this study show that (18)F-FDG PET has a major impact on the management of patients with SCLC, influencing both the stage and the management in 29% of patients. PET is a highly valuable tool for accurate target definition of radiation treatment by reducing the probability of overlooking involved areas.

Detection of metallic implant-associated infections with FDG PET in patients with trauma: correlation with microbiologic results.

PURPOSE: To prospectively evaluate the value of positron emission tomography (PET) with fluorine 18 fluorodeoxyglucose (FDG) in the detection of metallic implant-associated infections in patients with trauma. MATERIALS AND METHODS: Twenty-nine partial-body FDG PET scans in 22 patients suspected of having metallic implant-associated infections were obtained prior to surgery. In two of the 22 patients, data were acquired with a combined PET-CT in-line system. Soft-tissue and bone infections were evaluated. PET scans were analyzed by two experienced nuclear medicine physicians first separately and then in consensus. Disease status was defined on the basis of the results of microbiologic evaluation of surgical specimens together with intraoperative findings. Sensitivities, specificities, accuracies, interobserver variability (determination of kappa values), and receiver operating characteristic curves were obtained. RESULTS: Of 29 PET scans, 14 were true-positive, 14 were true-negative, and one was false-positive. Sensitivity, specificity, and accuracy were 100%, 93.3%, and 97%, respectively, for all PET data; 100%, 100%, and 100%, respectively, for the central skeleton; and 100%, 87.5%, and 95%, respectively, for the peripheral skeleton. The degree of overall interobserver concordance was high (kappa = 0.96). CONCLUSION: FDG PET appears to be a sensitive and specific method for the detection of infectious foci due to metallic implants in patients with trauma.

FDG positron emission tomography for differentiation of degenerative and infectious endplate abnormalities in the lumbar spine detected on MR imaging.

OBJECTIVE: The objective of our study was to evaluate the usefulness of FDG positron emission tomography (PET) for the differentiation of degenerative and infectious endplate abnormalities in the lumbar spine that were detected on MR imaging. SUBJECTS AND METHODS: FDG PET was performed prospectively in 30 consecutive patients with substantial endplate abnormalities (craniocaudal diameter of bone marrow abnormalities, > or = 25% of vertebral height) found during MR imaging of the lumbar spine. Both the MR and PET images were evaluated by two experienced musculoskeletal radiologists and two experienced nuclear physicians. The diagnosis of either degeneration with different types of endplate abnormalities or disk-space infection was determined. Clinical follow-up and, in selected cases, bone biopsies with cultures were used as the standard of reference. RESULTS: On the MR images, 25 of the 38 degenerated levels were classified as Modic type I, 13 levels as type II, and none as type III. Five disk-space infections were diagnosed in four patients. MR imaging findings were false-positive at one disk level with type I abnormalities and false-negative at two levels with infection. PET did not show FDG uptake in the intervertebral spaces of any patient with degenerative disease. FDG PET findings were true-positive in all five levels with disk-space infection. The sensitivity and specificity for MR imaging in detecting disk-space infection were 50% and 96%, and were 100% and 100% for FDG PET, respectively (not significant, McNemar test, p = 0.5). CONCLUSION: Our findings suggest that FDG PET may prove useful for differentiation of degenerative and infectious endplate abnormalities detected on MR imaging. Even in active (Modic type I) degenerative endplate abnormalities in our series, PET did not show increased FDG uptake.