PURPOSE Neoadjuvant chemotherapy (NAC) has potential advantages over standard postoperative chemotherapy for locally advanced colon cancer but requires formal evaluation. METHODS Patients with radiologically staged T3-4, N0-2, M0 colon cancer were randomly allocated (2:1) to 6 weeks oxaliplatin-fluoropyrimidine preoperatively plus 18 postoperatively (NAC group) or 24 weeks postoperatively (control group). Patients with RAS-wildtype tumors could also be randomly assigned 1:1 to receive panitumumab or not during NAC. The primary end point was residual disease or recurrence within 2 years. Secondary outcomes included surgical morbidity, histopathologic stage, regression grade, completeness of resection, and cause-specific mortality. Log-rank analyses were by intention-to-treat. RESULTS Of 699 patients allocated to NAC, 674 (96%) started and 606 (87%) completed NAC. In total, 686 of 699 (98.1%) NAC patients and 351 of 354 (99.2%) control patients underwent surgery. Thirty patients (4.3%) allocated to NAC developed obstructive symptoms requiring expedited surgery, but there were fewer serious postoperative complications with NAC than with control. NAC produced marked T and N downstaging and histologic tumor regression (all P < .001). Resection was more often histopathologically complete: 94% (648/686) versus 89% (311/351), P < .001. Fewer NAC than control patients had residual or recurrent disease within 2 years: 16.9% (118/699) versus 21.5% (76/354), rate ratio = 0.72 (95% CI, 0.54 to 0.98), P = .037. Tumor regression correlated strongly with freedom from recurrence. Panitumumab did not enhance the benefit from NAC. Little benefit from NAC was seen in mismatch repair–deficient tumors. CONCLUSION Six weeks of preoperative oxaliplatin-fluoropyrimidine chemotherapy for operable colon cancer can be delivered safely, without increasing perioperative morbidity. This chemotherapy regimen, when given preoperatively, produces marked histopathologic down-staging, fewer incomplete resections, and better 2-year disease control. Histologic regression after NAC is a strong predictor of lower postoperative recurrence risk so has potential use as a guide for postoperative therapy. Six weeks of NAC should be considered as a treatment option for locally advanced colon cancer.

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Abnormalities in the oxidative metabolism of glucose in human cerebral gliomas have been studied in seven patients using positron emission tomography. Measurements of regional cerebral blood flow and oxygen consumption were obtained using the oxygen-15 steady-state inhalation technique. Values of regional cerebral glucose consumption were obtained using fluorine 18-labeled 2-fluoro-2-deoxy-D-glucose and a simplification of the method of Sokoloff. Functional values were obtained for regions of tumor and brain tissue in the middle cerebral artery territory of the contralateral cortex. Values of regional glucose consumption were calculated for both regions using a value of the lumped constant quoted for normal brain tissue (0.42). Tumor regional cerebral blood flow was comparable to that in the contralateral cortex, whereas regional cerebral oxygen consumption was depressed. This depression resulted in low tumor values of the fractional oxygen extraction ratio (0.21 +/- 0.07), indicating that oxygen supply exceeded the metabolic demand. In contrast, tumor regional cerebral glucose consumption was not depressed and regional glucose extraction ratios were similar for tumor and brain tissue. The metabolic uncoupling between regional oxygen consumption and regional glucose consumption (CMRO2/CMRGlu = 0.24 +/- 0.07 ml of oxygen per milligram of glucose) is indicative of increased aerobic glycolysis.

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Summary: A number of different analytical methods were applied to dynamic scans obtained with [18F12-fluoro-2-deoxy-o-glucose and positron emission tomog raphy, In particular, methods applying three, four, stan dard, or no rate constants were compared in four studies on three normal subjects. In addition, regional cerebral blood flow, oxygen utilisation, and blood volume were measured using the oxygen-I5 steady-state inhalation technique. There was a large difference between values of glucose utilisation obtained with the various analytical methods, in particular between methods using three or four rate constants. This difference was not due to con tamination of the tracer with [18F12-fluoro-2-deoxy-o mannose. For dynamic techniques, the separate mea-The measurement of regional cerebral glucose utilisation (rCMRglu) with [18F]2-fluoro-2-deoxY-D glucose (FDG) and positron emission tomography (PET) has been a widely used technique to study regional metabolism in the human brain (see, for example, Phelps et aI. , 1982;. The method was adapted (Phelps et aI. , 1979b; Reivich et al. , 1979;Huang et al. , 1980) from the original tracer model developed for [14C]2-deoxY-D-glucose and quantitative autora diography (Sokoloff et al. , 1977).Although FDG has provided valuable clinical in formation, interpretation of results has been re stricted by the existence of several uncertainties in the implementation of the model. Of these limita tions, the value and regional constancy of the so- 161surement of regional cerebral blood volume was essen tial. Static techniques (single scans with standard or no rate constants) were best related to dynamic techniques utilising four rate constants. From the results, it fol lowed, however, that these static techniques can only be applied clinically if relatively large disturbances of glu cose metabolism and no changes in rate constants are an ticipated. The lumped constant was assessed from the combined measurement of oxygen and glucose utilisation and was higher than previously reported. called lumped constant in pathology has attracted a great deal of attention (see, for example, Sokoloff et al., 1977;Hawkins et al. , 1981;Gjedde, 1982;Gjedde et al., 1985; Ingvar and Siesj6, 1985). In ad dition, there have been discussions about the va lidity of using standard rate constants in a single scan obtained at least 40 min after injection. This has resulted in several alternative operational equa tions (Sokoloff et al., 1977;Phelps et al., 1979b;Brooks, 1982;Rhodes et al., 1983; Hutchins et aI. , 1984; Wienhard et aI., 1985) in an effort to reduce the sensitivity to the actual values of the rate con stants. However, other workers (Hawkins et al. , 1981; Heiss et aI. , 1984; Hutchins et al. , 1984;Wienhard et al., 1985) have indicated that this ap proach is less accurate (especially in pathology) than measuring the whole tissue time-activity curve by multiple FDG scans starting at time of in jection. The number of rate constants has also been a topic of discussion. In particular, there is di...

Ten patients with rapidly progressive glomerulonephritis and acute renal failure were treated with extracorporeal immunoadsorption, prednisolone, and cyclophosphamide. Three patients had systemic lupus erythematosus, five had microscopic polyarteritis and two had Wegener's granulomatosis. All ten patients were dialysis-dependent prior to immunoadsorption. Nine of ten patients rapidly regained renal function and seven continue to have independent renal function between 9 and 30 months after immunoadsorption. Three patients at presentation were not dialysis dependent. Despite treatment with methylprednisolone, cyclophosphamide, and oral prednisolone, renal function continued to deteriorate and they required dialysis. Immunoadsorption was then started without alteration in baseline immunosuppression. Within a mean of 4.6 days, range 3-7 days, renal function improved and the patients no longer required dialysis. Antineutrophil cytoplasmic antibodies and double-stranded DNA antibodies were rapidly removed by immunoadsorption. Only one patient with systemic lupus erythematosus and two with microscopic polyarteritis had significant resynthesis of antibody at 1 month post-immunoadsorption. Renal biopsy before and after immunoadsorption and immunosuppressive therapy showed resolution of glomerular crescents and no evidence of active disease. Immunoadsorption coupled with prednisolone and cyclophosphamide may be of value in the treatment of rapidly progressive glomerulonephritis.

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