Clinical practice guidelines for the utilization of positron emission tomography/computed tomography imaging in selected oncologic applications: suggestions from a provider group.

PURPOSE: Positron emission tomography, combined with computed tomography (PET/CT) has provided clinicians with useful information regarding the diagnosis, initial staging, restaging, and therapy monitoring of malignancies since the beginning of the current century. Our intent here is to identify the critical steps in clinical workups and follow-up, in the true outpatient clinical setting of a freestanding imaging center, for utilization of PET/CT in four different cancer types. METHODS: The four most common reasons for referrals to our facility were identified by reviewing two years of referral data. They were lung cancer (including solitary pulmonary nodule), lymphomas, breast cancer, and colorectal cancer. A review of published literature from 1996 and later was accepted as evidence of appropriateness for utilizing PET/CT in various clinical scenarios. In addition, a medical advisory board consisting of 15 referring physicians representing various specialties was established to provide practical advice regarding the appropriate use of PET/CT in clinical situations. National Comprehensive Cancer Network (NCCN) guidelines were also referenced to establish a baseline for clinical workups at various stages of disease. RESULTS: Several inconsistencies were identified among the three primary sources of information leading to the establishment of a standardized algorithm for each cancer type. NCCN data did not always agree with published literature, which was also often different from actual clinical practices of referring physicians. The most common inconsistencies included differing opinions from the referrers vs what was published in the NCCN guidelines, especially with regard to the utilization of PET/CT for applications not yet covered by insurance companies. After a reconciliation of the medical advisory board's clinical practices and several published articles, a consensus was established by the medical advisory board for the use of PET/CT imaging for the four cancer types, enabling us to identify the appropriate timing of PET/CT utilization in patient work-ups. CONCLUSIONS: A PET/CT-centric clinical practice decision tree algorithm can be established by assessing a variety of sources of information. Although published literature and NCCN guidelines offer validated guidance to appropriateness, and third party insurance payors have established their own appropriateness standards, our experience showed that inclusion of practical experience from referring physicians who frequently utilize PET/CT imaging provided additional, useful input.

Effect of the Colorless non-ripening mutation on cell wall biochemistry and gene expression during tomato fruit development and ripening.

The Colorless non-ripening (Cnr) mutation in tomato (Solanum lycopersicum) results in mature fruits with colorless pericarp tissue showing an excessive loss of cell adhesion (A.J. Thompson, M. Tor, C.S. Barry, J. Vrebalov, C. Orfila, M.C. Jarvis, J.J. Giovannoni, D. Grierson, G.B. Seymour [1999] Plant Physiol 120: 383-390). This pleiotropic mutation is an important tool for investigating the biochemical and molecular basis of cell separation during ripening. This study reports on the changes in enzyme activity associated with cell wall disassembly in Cnr and the effect of the mutation on the program of ripening-related gene expression. Real-time PCR and biochemical analysis demonstrated that the expression and activity of a range of cell wall-degrading enzymes was altered in Cnr during both development and ripening. These enzymes included polygalacturonase, pectinesterase (PE), galactanase, and xyloglucan endotransglycosylase. In the case of PE, the protein product of the ripening-related isoform PE2 was not detected in the mutant. In contrast with wild type, Cnr fruits were rich in basic chitinase and peroxidase activity. A microarray and differential screen were used to profile the pattern of gene expression in wild-type and Cnr fruits. They revealed a picture of the gene expression in the mutant that was largely consistent with the real-time PCR and biochemical experiments. Additionally, these experiments demonstrated that the Cnr mutation had a profound effect on many aspects of ripening-related gene expression. This included a severe reduction in the expression of ripening-related genes in mature fruits and indications of premature expression of some of these genes in immature fruits. The program of gene expression in Cnr resembles to some degree that found in dehiscence or abscission zones. We speculate that there is a link between events controlling cell separation in tomato, a fleshy fruit, and those involved in the formation of dehiscence zones in dry fruits.