Daniel Silverman

CONTEXT: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined. OBJECTIVE: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia. DESIGN, SETTING, AND PATIENTS: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000. MAIN OUTCOME MEASURES: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses. RESULTS: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001). CONCLUSION: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur.

TO THE EDITOR: We read and re-read your outstanding supplement titled “A Tabulated Summary of the FDG PET Literature” ([1][1]). It helps take the world literature and put it in perspective. This has already helped us discuss the pros and cons of PET imaging in pancreatic carcinoma with a

The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments.

Bladder cancer has been associated with exposure to chlorination by-products in drinking water, and experimental evidence suggests that exposure also occurs through inhalation and dermal absorption. The authors examined whether bladder cancer risk was associated with exposure to trihalomethanes (THMs) through ingestion of water and through inhalation and dermal absorption during showering, bathing, and swimming in pools. Lifetime personal information on water consumption and water-related habits was collected for 1,219 cases and 1,271 controls in a 1998-2001 case-control study in Spain and was linked with THM levels in geographic study areas. Long-term THM exposure was associated with a twofold bladder cancer risk, with an odds ratio of 2.10 (95% confidence interval: 1.09, 4.02) for average household THM levels of >49 versus < or =8 micro g/liter. Compared with subjects not drinking chlorinated water, subjects with THM exposure of >35 micro g/day through ingestion had an odds ratio of 1.35 (95% confidence interval: 0.92, 1.99). The odds ratio for duration of shower or bath weighted by residential THM level was 1.83 (95% confidence interval: 1.17, 2.87) for the highest compared with the lowest quartile. Swimming in pools was associated with an odds ratio of 1.57 (95% confidence interval: 1.18, 2.09). Bladder cancer risk was associated with long-term exposure to THMs in chlorinated water at levels regularly occurring in industrialized countries.

OBJECTIVE: The aim of this study was to evaluate the usefulness of expandable RF needle electrodes in the treatment of hepatic cancer. SUBJECTS AND METHODS: Thirty-seven patients, 23 of whom had 26 hepatocellular carcinoma nodules and 14 of whom had 19 hepatic metastatic nodules, underwent treatment by RF interstitial thermal ablation with expandable needle electrodes. Forty-five tumor nodules were treated in 64 RF interstitial thermal ablation sessions with 83 needle electrode insertions. The mean diameter of the tumor nodules was 2.5 cm (range, 1.1-3.5 cm). Immediate posttreatment tumor necrosis was evaluated by dynamic CT in all cases. Two patients with hepatocellular carcinoma and three patients with metastases underwent surgical resection 20-60 days after RF treatment. The remaining 32 patients were followed up clinically. RESULTS: The mean number of RF interstitial thermal ablation sessions to complete tumor nodule treatment was 1.4. Mean number of needle electrode insertions was 1.8. No complications were observed. Posttreatment dynamic CT showed a completely nonenhancing area in the site of the treated tumor in 44 of 45 cases. The remaining patient with metastatic disease had persistent enhancing tissue. Histology showed complete necrosis in four treated tumor nodules and residual viable cancer in one. Twenty-one patients with hepatocellular carcinoma were followed up for 6-19 months (mean, 10 months). Of these patients, six showed recurrences and 15 remained apparently disease-free. Two patients died, one from advanced cancer and one from other causes. Eleven patients with hepatic metastases were followed up for 7-20 months (mean, 12 months). Of these patients, nine showed recurrent disease and only two remained apparently disease-free. Two patients died from disseminated disease. CONCLUSION: RF interstitial thermal ablation of hepatic tumor by expandable needle electrodes is a safe and effective technique. Local ablation of tumors not exceeding 3.5 cm in diameter is achieved in a short time without complications.