Takashi Nihashi

Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography for Interim Response Assessment of Advanced-Stage Hodgkin's Lymphoma and Diffuse Large B-Cell Lymphoma: A Systematic Review

PURPOSE To systematically review the prognostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) for interim response assessment of patients with untreated advanced-stage Hodgkins lymphoma (HL) or diffuse large B-cell lymphoma (DLBCL). METHODS MEDLINE, EMBASE, SCOPUS, and Biologic Abstracts were searched for relevant studies. Two assessors independently reviewed studies for inclusion and extracted data. Relevant unpublished data were requested from the investigators if unavailable from publications. A meta-analysis of the prognostic accuracy was performed. RESULTS Thirteen studies involving 360 advanced-stage HL patients and 311 DLBCL patients met our inclusion criteria. Advanced-stage HL studies included few unfavorable-risk patients. DLBCL studies were heterogeneous. FDG-PET had an overall sensitivity of 0.81 (95% CI, 0.72 to 0.89) and a specificity of 0.97 (95% CI, 0.94 to 0.99) for advanced-stage HL, and a sensitivity of 0.78 (95% CI, 0.64 to 0.87) and a specificity of 0.87 (95% CI, 0.75 to 0.93) for DLBCL. Meta-regression and subgroup analyses did not identify factors that affect prognostic accuracy. CONCLUSION For low- to intermediate-risk advanced-stage HL, FDG-PET performed after a few cycles of standard chemotherapy seems to be a reliable prognostic test to identify poor responders, warranting prospective studies to assess PET-based treatment strategies. For DLBCL, no reliable conclusions can be drawn due to heterogeneity. Interim PET remains an unproven test for routine clinical practice. Its use should be reserved for research settings where treatment regimens and imaging conditions are standardized.

18F-FDG PET for Posttherapy Assessment of Hodgkin's Disease and Aggressive Non-Hodgkin's Lymphoma: A Systematic Review

Although studies have shown that 18F-FDG PET, when used to assess the response of malignant lymphoma after treatment, has a strong ability to predict relapse, its diagnostic accuracy in clinical practice remains unclear. The aim of this study was to systematically review the diagnostic accuracy of 18F-FDG PET in detecting residual disease at the completion of first-line therapy of Hodgkins disease (HD) and aggressive non-Hodgkins lymphoma (NHL). Methods: We searched relevant articles from 1966 to July 2006 using MEDLINE, EMBASE, SCOPUS, Biological Abstracts, bibliographies, review articles, and textbooks without language restriction. One assessor (for non–English-language studies) or 2 assessors (for English-language studies) independently reviewed each article to abstract relevant study characteristics and results. Relevant individual patient data or subgroup data were provided by the investigators if they were unavailable from the publications. We estimated summary receiver operating characteristic curves and confidence regions for summary sensitivity and specificity. Results: Nineteen studies consisting of 474 HD and 254 aggressive NHL patients were included. These studies had heterogeneity and suboptimal methodologic quality and reporting. Reported ranges for the sensitivity and specificity of 18F-FDG PET in predicting disease relapse were 0.50–1.00 and 0.67–1.00, respectively, for HD and 0.33–0.77 and 0.82–1.00, respectively, for NHL. These estimates were similar when conventional imaging tests showed a residual mass. For HD studies, the summary receiver operating characteristic curves were similar irrespective of whether a residual mass was detected by conventional tests. Factors explaining the variability of diagnostic estimates were not identified. Conclusion: Although currently available evidence is still limited, 18F-FDG PET seems to have good diagnostic accuracy for assessing residual HD at the completion of first-line treatment. Clinical data on this use of 18F-FDG PET for aggressive NHL are more limited. Prospective studies with a more rigorous research design, conduct, and reporting would more reliably reveal the clinical diagnostic accuracy of this imaging modality.

Expression and Distribution of Beta Amyloid Precursor Protein and Beta Amyloid Peptide in Reactive Astrocytes After Transient Middle Cerebral Artery Occlusion

Summary Background. In the brains of Alzheimers disease patients, beta amyloid protein is the major component of senile plaque. In ischemic stress, beta amyloid precursor protein (APP) and beta amyloid peptide are reported to be upregulated. Method. Using Male Wistar-ST rats, expression and distribution of APP and beta amyloid peptide were examined immunohistochemically after transient ischemia induced by a 2-h middle cerebral artery occlusion (MCAO). After reperfusion for 3, 7, 14, 30 and 60 days, brains were removed and immunostaining was performed. Findings. The reactive astrocytes with APP were observed in the periphery of infarct from 3 days to 60 days post-occlusion. The immunoreactivity of beta amyloid peptide was also localized in the reactive astrocytes in the peripheral zone of infarct at 7, 14, and 30 days post-occlusion. However, beta amyloid expression was not identified at 3 days or 60 days post MCAO. Transient ischemia temporarily induced beta amyloid peptide expression in reactive astrocytes, but this expression peaked at 30 days and disappeared at 60 days. Interpretation. These findings suggested that beta amyloid peptide was derived from the processing of APP produced in the same reactive astrocytes and the production of the peptide stopped within 60 days after the ischemic stress.

Diagnostic Accuracy of PET for Recurrent Glioma Diagnosis: A Meta-Analysis

These authors compared the diagnostic accuracy of PET with that of CT and MRI in the diagnosis of recurrent glioma in 26 previously published articles. PET studies with either FDG or carbon methionine were obtained once glioma recurrence was suspected on CT and/or MRI. Diagnostic accuracies were heterogeneous and studies did not compare PET with other imaging modalities. Despite these limitations, PET with both tracers appears to have a moderately good accuracy as an add-on test for diagnosing recurrent glioma. BACKGROUND AND PURPOSE: Studies have assessed PET by using various tracers to diagnose disease recurrence in patients with previously treated glioma; however, the accuracy of these methods, particularly compared with alternative imaging modalities, remains unclear. We conducted a meta-analysis to quantitatively synthesize the diagnostic accuracy of PET and compare it with alternative imaging modalities. MATERIALS AND METHODS: We searched PubMed and Scopus (until June 2011), bibliographies, and review articles. Two reviewers extracted study characteristics, validity items, and quantitative data on diagnostic accuracy. We performed meta-analysis when ≥5 studies were available. RESULTS: Twenty-six studies were eligible. Studies were heterogeneous in treatment strategies and diagnostic criteria of PET; recurrence was typically suspected by CT or MR imaging. The diagnostic accuracies of 18F-FDG (n = 16) and 11C-MET PET (n = 7) were heterogeneous across studies. 18F-FDG PET had a summary sensitivity of 0.77 (95% CI, 0.66–0.85) and specificity of 0.78 (95% CI, 0.54–0.91) for any glioma histology; 11C-methionine PET had a summary sensitivity of 0.70 (95% CI, 0.50–0.84) and specificity of 0.93 (95% CI, 0.44–1.0) for high-grade glioma. These estimates were stable in subgroup and sensitivity analyses. Data were limited on 18F-FET (n = 4), 18F-FLT (n = 2), and 18F-boronophenylalanine (n = 1). Few studies performed direct comparisons between different PET tracers or between PET and other imaging modalities. CONCLUSIONS: 18F-FDG and 11C-MET PET appear to have moderately good accuracy as add-on tests for diagnosing recurrent glioma suspected by CT or MR imaging. Studies comparing alternative tracers or PET versus other imaging modalities are scarce. Prospective studies performing head-to-head comparisons between alternative imaging modalities are needed.

Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Response Assessment Before High-Dose Chemotherapy for Lymphoma: A Systematic Review and Meta-Analysis

BACKGROUND We conducted a systematic review and meta-analysis to better define the prognostic ability of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) following salvage chemotherapy for relapsed or refractory Hodgkins lymphoma (HL) and aggressive non-Hodgkins lymphoma. METHODS We searched PubMed (from inception to January 31, 2010), bibliographies, and review articles without language restriction. Two assessors independently assessed study characteristics, quality, and results. We performed a meta-analysis to determine prognostic accuracy. RESULTS Twelve studies including 630 patients were eligible. The most commonly evaluated histologies were diffuse large B-cell lymphoma (n = 313) and HL (n = 187), which were typically treated with various salvage and high-dose chemotherapy regimens. Studies typically employed nonstandardized protocols and diagnostic criteria. The prognostic accuracy was heterogeneous across the included studies. (18)F-FDG PET had a summary sensitivity of 0.69 (95% confidence interval [CI], 0.56-0.81) and specificity of 0.81 (95% CI, 0.73-0.87). The summary estimates were stable in sensitivity analyses. In four studies that performed direct comparisons between PET and conventional restaging modalities, PET had a superior accuracy for predicting treatment outcomes. Subgroup and metaregression analyses did not identify any particular factor to explain the observed heterogeneity. CONCLUSION (18)F-FDG PET performed after salvage therapy appears to be an appropriate test to predict treatment failure in patients with refractory or relapsed lymphoma who receive high-dose chemotherapy. Some evidence suggests PET is superior to conventional restaging for this purpose. Given the methodological limitations in the primary studies, prospective studies with standardized methodologies are needed to confirm and refine these promising results.

Cerebral glucose metabolism change in patients with complex regional pain syndrome: a PET study

PurposeThe aim of this study was to examine abnormalities of the central nervous system in patients with chronic pain who were diagnosed with complex regional pain syndrome (CRPS).Materials and methodsBrain activity was assessed using 18F-fluorodeoxyglucose positron emission tomography. The data collected from 18 patients were compared with data obtained from 13 normal age-matched controls.ResultsOur results showed that glucose metabolism was bilaterally increased in the secondary somatosensory cortex, mid-anterior cingulated cortex (ACC) or posterior cingulated cortex (PCC) (or both), parietal cortex, posterior parietal cortex (PPC), and cerebellum as well as in the right posterior insula and right thalamus in our patients. In contrast, glucose metabolism was reduced contralaterally in the dorsal prefrontal cortex and primary motor cortex. Glucose metabolism was bilaterally elevated in the mid-ACC/PCC and the PPC, which correlated with pain duration.ConclusionThese data suggested that glucose metabolism in the brains of patients with CRPS changes dramatically at each location. In particular, glucose metabolism was increased in the areas concerned with somatosensory perception, possibly due to continuous painful stimulation.

Direct comparison study between FDG-PET and IMP-SPECT for diagnosing Alzheimer's disease using 3D-SSP analysis in the same patients

PurposeThe purpose of this study was to evaluate and compare the diagnostic ability of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) and N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography (IMP-SPECT) using three-dimensional stereotactic surface projections (3D-SSP) in patients with moderate Alzheimers disease (AD).Materials and methodsFDG-PET and IMP-SPECT were performed within 3 months in 14 patients with probable moderate AD. Z-score maps of FDG-PET and IMP-SPECT images of a patient were obtained by comparison with data obtained from control subjects. Four expert physicians evaluated and graded the glucose hypometabolism and regional cerebral blood flow (rCBF), focusing in particular on the posterior cingulate gyri/precunei and parietotemporal regions, and determined the reliability for AD. Receiver operating characteristic (ROC) curves were applied to the results for clarification. To evaluate the correlation between two modalities, the regions of interest (ROIs) were set in the posterior cingulate gyri/precunei and parietotemporal region on 3D-SSP images, and mean Z-values were calculated.ConclusionNo significant difference was observed in the area under the ROC curve (AUC) between FDG-PET and IMP-SPECT images (FDG-PET 0.95, IMP-SPECT 0.94). However, a significant difference (P < 0.05) was observed in the AUC for the posterior cingulate gyri/precuneus (FDG-PET 0.94, IMP-SPECT 0.81). The sensitivity and specificity of each modality were 86%, and 97% for FDG-PET and 70% and 100% for IMP-SPECT. We could find no significant difference between FDG-PET and IMP-SPECT in terms of diagnosing moderate AD using 3D-SSP. There was a high correlation between the two modalities in the parietotemporal region (Spearmans r = 0.82, P < 0.001). The correlation in the posterior cingulate gyri/precunei region was lower than that in the parietotemporal region (Spearmans r = 0.63, P < 0.016).

Increased signal intensity of the cochlea on pre- and post-contrast enhanced 3D-FLAIR in patients with vestibular schwannoma

IntroductionIn the vestibular schwannoma patients, the pathophysiologic mechanism of inner ear involvement is still unclear. We investigated the status of the cochleae in patients with vestibular schwannoma by evaluating the signal intensity of cochlear fluid on pre- and post-contrast enhanced thin section three-dimensional fluid-attenuated inversion recovery (3D-FLAIR).MethodsTwenty-eight patients were retrospectively analyzed. Post-contrast images were obtained in 18 patients, and 20 patients had the records of their pure-tone audiometry. Regions of interest of both cochleae (C) and of the medulla oblongata (M) were determined on 3D-FLAIR images by referring to 3D heavily T2-weighted images on a workstation. The signal intensity ratio between C and M on the 3D-FLAIR images (CM ratio) was then evaluated. In addition, correlation between the CM ratio and the hearing level was also evaluated.ResultsThe CM ratio of the affected side was significantly higher than that of the unaffected side (p < 0.001). In the affected side, post-contrast signal elevation was observed (p < 0.005). In 13 patients (26 cochleae) who underwent both gadolinium injection and the pure-tone audiometry, the post-contrast CM ratio correlated with hearing level (p < 0.05).ConclusionThe results of the present study suggest that alteration of cochlear fluid composition and increased permeability of the blood–labyrinthine barrier exist in the affected side in patients with vestibular schwannoma. Furthermore, although weak, positive correlation between post-contrast cochlear signal intensity on 3D-FLAIR and hearing level warrants further study to clarify the relationship between 3D-FLAIR findings and prognosis of hearing preservation surgery.

PET in the Clinical Management of Glioma: Evidence Map

OBJECTIVE Several studies have assessed PET to complement the anatomic information obtained from other imaging modalities in various clinical contexts for the management of glioma. We constructed an evidence map of clinical evidence on the use of PET in glioma and identified research gaps. MATERIALS AND METHODS We searched PubMed and Scopus (from inception through June 30, 2011) to identify studies assessing the use of PET for glioma regardless of setting of care or indication. We extracted test objectives, study characteristics, and phases of diagnostic evidence and then assessed research diversity and temporal trends in the literature. We excluded studies assessing only technical feasibility and optimization of PET. RESULTS A total of 129 studies were considered eligible; the number of articles published annually has greatly increased over time (p for trend < 0.001). Most studies (n = 118, 91%) assessed diagnostic or prognostic performance; fewer studies reported on the impact of PET on diagnostic thinking (n = 4, 3%), therapeutic decisions (n = 4, 3%), or patient-relevant clinical outcomes (n = 3; 2%). Fluorine-18 FDG (n = 73, 57%) or (11)C-methionine (n = 44, 34%) were the two most commonly evaluated PET tracers. Pretherapy assessment (n = 72, 56%) and monitoring of treatment response (n = 48, 37%) were the most common settings of test use assessed in the research studies. CONCLUSION More primary studies, particularly studies of newer tracers focusing on biopsy or treatment planning, are needed to better characterize the role of PET in specific contexts.

Limited efficacy of (18)F-FDG PET/CT for differentiation between metastasis-free pancreatic cancer and mass-forming pancreatitis.

Objective Differentiation between metastasis-free pancreatic cancer and mass-forming pancreatitis is important to avoid unnecessary operative procedures. This study was aimed at evaluating the efficacy of PET/CT with 18F-FDG (FDG PET/CT) for the differential diagnosis between them. Patients and Methods FDG-PET/CT was performed in 47 study patients with pancreatic masses and without any detectable metastases, 33 of which cases were finally diagnosed as pancreatic cancer and the other 14 as pancreatitis, and the corresponding imaging data were evaluated retrospectively. The maximal SUV (SUVmax) within the masses were determined at 1 hour and mostly at 2 hours after intravenous injection of FDG. Results SUVmax at 1 hour in pancreatic cancer was significantly higher than that in mass-forming pancreatitis, and the change in SUVmax from 1- to 2-hour time points was more consistent with pancreatic cancer than with mass-forming pancreatitis. However, there remained considerable overlapping between the SUVmax values of both diseases except either at the higher range for pancreatic cancer (> 7.7 at 1 hour or > 9.98 at 2 hours) or at the lower range for mass-forming pancreatitis (<3.37 at 1 hour or <3.53 at 2 hours). No obvious difference was found in the FDG uptake patterns of the mass areas between both diseases. Conclusions Differentiation between metastasis-free pancreatic cancer and mass-forming pancreatitis is difficult by FDG-PET/CT due to considerable overlapping between the SUVmax values of the two diseases, although the differential diagnosis may be possible either at the higher range of SUVmax (> 7.7 at 1 hour or > 9.98 at 2 hours) for pancreatic cancer or at the lower range of SUVmax (<3.37 at 1 hour or <3.53 at 2 hours) for mass-forming pancreatitis.