Why Do Canadians Travel Abroad for Cosmetic Surgery? A Qualitative Analysis on Motivations for Cosmetic Surgery Tourism.

Background: Canadians are increasingly engaging in medial tourism. The purpose of this study was to review Canadians' experiences with travelling abroad for cosmetic surgery, including primary motivations for seeking care outside of Canada. Methods: A qualitative analysis was conducted using semistructured interviews following a pre-determined topic guide. People who had undergone cosmetic surgery outside of Canada were interviewed. The interviews were transcribed and coded to determine motivational themes. Patients were recruited until thematic saturation was achieved. Results: Thematic saturation was achieved after recruitment of 11 patients. The most common motivational themes identified in this study for seeking cosmetic surgery outside of Canada included cost, post-operative care provided, marketing/customer service, and word-of-mouth. Member checking and theory triangulation were validation techniques used to verify identified themes. Mexico was the most common location for cosmetic tourism. The most common procedures were breast augmentation, mastopexy, and abdominoplasty. Participants gathered pre- and post-operative information primarily through pamphlets and contact with surgeons' offices. Follow-up was only available for half of the participants in this study, and only 5 of the participants felt that they had received informed consent. Conclusions: The majority of participants engaged in cosmetic tourism due to cost reasons and the level of post-operative care provided.

Historique: Les Canadiens font de plus en plus de tourisme médical. La présente étude vise à analyser les expériences des Canadiens qui se rendent à l'étranger pour recevoir des soins de chirurgie esthétique, y compris leur motivation primaire à faire ce choix. Méthodologie: Les chercheurs ont effectué une analyse qualitative au moyen d'entrevues semi-structurées selon un guide de sujets préétablis auprès de personnes ayant subi des chirurgies esthétiques hors du Canada. Les entrevues ont été transcrites et codées pour en tirer les thèmes. Des patients ont été recrutés jusqu'à ce que tous les thèmes aient été abordés. Résultats: Onze patients ont été recrutés pour parvenir au point de saturation des thèmes. Les principales motivations pour obtenir une chirurgie esthétique hors du Canada incluaient les coûts, les soins postopératoires reçus, les services de marketing et à la clientèle et le bouche-à-oreille. Les chercheurs ont utilisé la vérification des membres et la triangulation des théories pour vérifier les thèmes établis. Le tourisme esthétique avait surtout lieu au Mexique. Les interventions les plus courantes étaient l'augmentation mammaire, la mastopexie et l'abdominoplastie. Les participants accumulaient l'information préopératoire et postopératoire d'abord à l'aide de dépliants et de contacts au bureau des chirurgiens. Seulement la moitié des participants à l'étude ont eu accès au suivi, et seulement cinq ont eu l'impression d'avoir donné leur consentement éclairé. Conclusions: La majorité des participants faisaient du tourisme esthétique pour une question d'argent et pour le taux de soins postopératoires fournis.

BAX 335 hemophilia B gene therapy clinical trial results: potential impact of CpG sequences on gene expression.

Gene therapy has the potential to maintain therapeutic blood clotting factor IX (FIX) levels in patients with hemophilia B by delivering a functional human F9 gene into liver cells. This phase 1/2, open-label dose-escalation study investigated BAX 335 (AskBio009, AAV8.sc-TTR-FIXR338Lopt), an adeno-associated virus serotype 8 (AAV8)-based FIX Padua gene therapy, in patients with hemophilia B. This report focuses on 12-month interim analyses of safety, pharmacokinetic variables, effects on FIX activity, and immune responses for dosed participants. Eight adult male participants (aged 20-69 years; range FIX activity, 0.5% to 2.0%) received 1 of 3 BAX 335 IV doses: 2.0 × 1011; 1.0 × 1012; or 3.0 × 1012 vector genomes/kg. Three (37.5%) participants had 4 serious adverse events, all considered unrelated to BAX 335. No serious adverse event led to death. No clinical thrombosis, inhibitors, or other FIX Padua-directed immunity was reported. FIX expression was measurable in 7 of 8 participants; peak FIX activity displayed dose dependence (32.0% to 58.5% in cohort 3). One participant achieved sustained therapeutic FIX activity of ∼20%, without bleeding or replacement therapy, for 4 years; in others, FIX activity was not sustained beyond 5 to 11 weeks. In contrast to some previous studies, corticosteroid treatment did not stabilize FIX activity loss. We hypothesize that the loss of transgene expression could have been caused by stimulation of innate immune responses, including CpG oligodeoxynucleotides introduced into the BAX 335 coding sequence by codon optimization. This trial was registered at www.clinicaltrials.gov as #NCT01687608.

Worldwide Esophageal Cancer Collaboration: pathologic staging data.

We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning.

Worldwide Esophageal Cancer Collaboration: clinical staging data.

To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection.

Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging data.

To address uncertainty of whether pathologic stage groupings after neoadjuvant therapy (ypTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for pathologically staged cancers after neoadjuvant therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 7,773 pathologically staged neoadjuvant patients, 2,045 had squamous cell carcinoma, 5,686 adenocarcinoma, 31 adenosquamous carcinoma, and 11 undifferentiated carcinoma. Patients were older (61 years) men (83%) with normal (40%) or overweight (35%) body mass index, 0-1 Eastern Cooperative Oncology Group performance status (96%), and a history of smoking (69%). Cancers were ypT0 (20%), ypT1 (13%), ypT2 (18%), ypT3 (44%), ypN0 (55%), ypM0 (94%), and G2-G3 (72%); most involved the distal esophagus (80%). Non-risk-adjusted survival for yp categories was unequally depressed, more for earlier categories than later, compared with equivalent categories from prior WECC data for esophagectomy-alone patients. Thus, survival of patients with ypT0-2N0M0 cancers was intermediate and similar regardless of ypT; survival for ypN+ cancers was poor. Because prognoses for ypTNM and pTNM categories are dissimilar, prognostication should be based on separate ypTNM categories and groupings. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics and should direct 9th edition data collection.

Employing a gain-of-function factor IX variant R338L to advance the efficacy and safety of hemophilia B human gene therapy: preclinical evaluation supporting an ongoing adeno-associated virus clinical trial.

Vector capsid dose-dependent inflammation of transduced liver has limited the ability of adeno-associated virus (AAV) factor IX (FIX) gene therapy vectors to reliably convert severe to mild hemophilia B in human clinical trials. These trials also identified the need to understand AAV neutralizing antibodies and empty AAV capsids regarding their impact on clinical success. To address these safety concerns, we have used a scalable manufacturing process to produce GMP-grade AAV8 expressing the FIXR338L gain-of-function variant with minimal (<10%) empty capsid and have performed comprehensive dose-response, biodistribution, and safety evaluations in clinically relevant hemophilia models. The scAAV8.FIXR338L vector produced greater than 6-fold increased FIX specific activity compared with wild-type FIX and demonstrated linear dose responses from doses that produced 2-500% FIX activity, associated with dose-dependent hemostasis in a tail transection bleeding challenge. More importantly, using a bleeding model that closely mimics the clinical morbidity of hemophilic arthropathy, mice that received the scAAV8.FIXR338L vector developed minimal histopathological findings of synovitis after hemarthrosis, when compared with mice that received identical doses of wild-type FIX vector. Hemostatically normal mice (n=20) and hemophilic mice (n=88) developed no FIX antibodies after peripheral intravenous vector delivery. No CD8(+) T cell liver infiltrates were observed, despite the marked tropism of scAAV8.FIXR338L for the liver in a comprehensive biodistribution evaluation (n=60 animals). With respect to the role of empty capsids, we demonstrated that in vivo FIXR338L expression was not influenced by the presence of empty AAV particles, either in the presence or absence of various titers of AAV8-neutralizing antibodies. Necropsy of FIX(-/-) mice 8-10 months after vector delivery revealed no microvascular or macrovascular thrombosis in mice expressing FIXR338L (plasma FIX activity, 100-500%). These preclinical studies demonstrate a safety:efficacy profile supporting an ongoing phase 1/2 human clinical trial of the scAAV8.FIXR338L vector (designated BAX335).

Long-term follow-up after gene therapy for canavan disease.

Canavan disease is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to loss of enzyme activity and increased concentrations of the substrate N-acetyl-aspartate (NAA) in the brain. Accumulation of NAA results in spongiform degeneration of white matter and severe impairment of psychomotor development. The goal of this prospective cohort study was to assess long-term safety and preliminary efficacy measures after gene therapy with an adeno-associated viral vector carrying the ASPA gene (AAV2-ASPA). Using noninvasive magnetic resonance imaging and standardized clinical rating scales, we observed Canavan disease in 28 patients, with a subset of 13 patients being treated with AAV2-ASPA. Each patient received 9 × 10(11) vector genomes via intraparenchymal delivery at six brain infusion sites. Safety data collected over a minimum 5-year follow-up period showed a lack of long-term adverse events related to the AAV2 vector. Posttreatment effects were analyzed using a generalized linear mixed model, which showed changes in predefined surrogate markers of disease progression and clinical assessment subscores. AAV2-ASPA gene therapy resulted in a decrease in elevated NAA in the brain and slowed progression of brain atrophy, with some improvement in seizure frequency and with stabilization of overall clinical status.

Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector.

Efficient and widespread gene transfer is required for successful treatment of Duchenne muscular dystrophy (DMD). Here, we performed the first clinical trial using a chimeric adeno-associated virus (AAV) capsid variant (designated AAV2.5) derived from a rational design strategy. AAV2.5 was generated from the AAV2 capsid with five mutations from AAV1. The novel chimeric vector combines the improved muscle transduction capacity of AAV1 with reduced antigenic crossreactivity against both parental serotypes, while keeping the AAV2 receptor binding. In a randomized double-blind placebo-controlled phase I clinical study in DMD boys, AAV2.5 vector was injected into the bicep muscle in one arm, with saline control in the contralateral arm. A subset of patients received AAV empty capsid instead of saline in an effort to distinguish an immune response to vector versus minidystrophin transgene. Recombinant AAV genomes were detected in all patients with up to 2.56 vector copies per diploid genome. There was no cellular immune response to AAV2.5 capsid. This trial established that rationally designed AAV2.5 vector was safe and well tolerated, lays the foundation of customizing AAV vectors that best suit the clinical objective (e.g., limb infusion gene delivery) and should usher in the next generation of viral delivery systems for human gene transfer.

Assessment of hippocampal adeno-associated viral vector gene delivery via frameless stereotaxis in a nonhuman primate.

BACKGROUND/AIMS: Expression of the neuropeptide galanin in hippocampal neurons reduces seizures in the kainic acid rodent model of epilepsy. In order to translate these findings into a human clinical trial, the safety and feasibility of hippocampal adeno-associated viral (AAV) vector expression must be demonstrated in a nonhuman primate model. METHODS: The Stealth Frameless Stereotactic System and Navigus Biopsy Appliance (Medtronic) were used to inject self-complementary AAV2 carrying the gene for green fluorescent protein (GFP) into monkey hippocampi. Using a single occipital trajectory per side (n = 8 trajectories), multiple injections spaced by 5 mm were delivered to each hippocampus. RESULTS: GFP was expressed in both neuronal and glial cells. Injections led to nonhomogeneous gene expression, suggesting closer spacing of injections may lead to more gene expression. Increasing injection volumes entailed a general increase in volume of expression, but there was no overlap of expression within the 5-mm injection interval. Efforts to avoid the occipital horn failed to prevent leaking of vector into the ventricle, and resulted in deviation of the trajectory at proximal points from the hippocampus. CONCLUSION: Using the occipital approach, adequate cannulation of the monkey hippocampus will require transventricular trajectories.

Adeno-associated virus for the treatment of muscle diseases: toward clinical trials.

Muscle diseases include muscular dystrophies, cardiomyopathies, neuromuscular and metabolic disorders. The loss of normal muscle structure and function is associated with significant morbidity and mortality. Patients with Duchenne muscular dystrophy usually lose ambulation in their teenage years, and frequently experience severe respiratory problems and heart failure in later stages of life. These unmet medical needs have encouraged the development of genetic strategies targeting the underlying muscle disease processes. Adeno-associated virus (AAV) vectors have been identified as promising gene delivery candidates because of their ability to transduce muscle tissue efficiently while transporting a genetic payload. There is currently significant momentum in the research of AAV-mediated delivery of muscle genes. Various AAV-based therapeutic strategies are undergoing preclinical and clinical testing, including the use of miniaturized and codon-optimized transgenes, exon skipping expression cassettes, novel tissue-specific promoters, AAV capsid mutants and chimeras, and localized intravascular administration procedures. These advancements in gene delivery have led to the generation of AAV vectors with targeted transgene expression, tissue-selective tropism and minimal off-target effects. This review describes advances in AAV gene therapy that are specific to the treatment of muscle diseases, and discusses the implications of their clinical application.

Worldwide esophageal cancer collaboration.

The aim of this study is to report assemblage of a large multi-institutional international database of esophageal cancer patients, patient and tumor characteristics, and survival of patients undergoing esophagectomy alone and its correlates. Forty-eight institutions were approached and agreed to participate in a worldwide esophageal cancer collaboration (WECC), and 13 (Asia, 2; Europe, 2; North America, 9) submitted data as of July 1, 2007. These were used to construct a de-identified database of 7884 esophageal cancer patients who underwent esophagectomy. Four thousand six hundred and twenty-seven esophagectomy patients had no induction or adjuvant therapy. Mean age was 62 +/- 11 years, 77% were men, and 33% were Asian. Mean tumor length was 3.3 +/- 2.5 cm, and esophageal location was upper in 4.1%, middle in 27%, and lower in 69%. Histopathologic cell type was adenocarcinoma in 60% and squamous cell in 40%. Histologic grade was G1 in 32%, G2 in 33%, G3 in 35%, and G4 in 0.18%. pT classification was pTis in 7.3%, pT1 in 23%, pT2 in 16%, pT3 in 51%, and pT4 in 3.3%. pN classification was pN0 in 56% and pN1 in 44%. The number of lymph nodes positive for cancer was 1 in 12%, 2 in 8%, 3 in 5%, and >3 in 18%. Resection was R0 in 87%, R1 in 11%, and R2 in 3%. Overall survival was 78, 42, and 31% at 1, 5, and 10 years, respectively. Unlike single-institution studies, in this worldwide collaboration, survival progressively decreases and is distinctively stratified by all variables except region of the world. A worldwide esophageal cancer database has been assembled that overcomes problems of rarity of this cancer. It reveals that survival progressively (monotonically) decreased and was distinctively stratified by all variables except region of the world. Thus, it forms the basis for data-driven esophageal cancer staging. More centers are needed and encouraged to join WECC.

p38 kinase inhibitors for the treatment of arthritis and osteoporosis: thienyl, furyl, and pyrrolyl ureas.

Inhibitors of the MAP kinase p38 are potentially useful for the treatment for osteoporosis, arthritis, and other inflammatory diseases. A series of thienyl, furyl, and pyrrolyl ureas has been identified as potent p38 inhibitors, displaying in vitro activity in the nanomolar range.

Disrupting the establishment of polarizing activity by teratogen exposure.

Between days 9.5 and 10, the forelimb buds of developing murine embryos progress from stage 1 which are just beginning to express shh and whose posterior mesoderm has only weak polarizing activity to stage 2 limbs with a distinguishable shh expression domain and full polarizing activity. We find that exposure on day 9.5 to teratogens that induce the loss of posterior skeletal elements disrupts the polarizing activity of the stage 2 postaxial mesoderm and polarizing activity is not subsequently restored. The ontogeny of expression of the mesodermal markers shh, ptc, bmp2, and hoxd-12 and 13, as well as the ectodermal markers wnt7a, fgf4, fgf8, cx43, and p21 occurred normally in day 9.5 teratogen-exposed limb buds. At stage 3, the treated limb apical ectodermal ridge usually possessed no detectable abnormalities, but with continued outgrowth postaxial deficiencies became evident. Recombining control, stage matched limb bud ectoderm with treated mesoderm prior to ZPA grafting restored the duplicating activity of treated ZPA tissue. We conclude that in addition to shh an early ectoderm-dependent signal is required for the establishment of the mouse ZPA and that this factor is dependent on the posterior ectoderm.

Differential sensitivity of the SWV and C57BL/6 mouse strains to the teratogenic action of single administrations of cadmium given throughout the period of anterior neuropore closure.

When administered to mice during gestation, the heavy metal, cadmium, is known to induce malformations of the neural tube, craniofacial region, limbs, trunk, viscera, and axial skeleton that vary in scope and severity among inbred strains of mice. Two strains, C57BL/6 and SWV, were previously shown to differ in their susceptibility to exencephaly induced by many teratogenic treatments, including sodium 2-ethylhexanoate, hyperthermia, valproic acid, and carbon dioxide, with the SWV strain being consistently more sensitive than the C57BL/6 strain. These findings support the observation of Finnell et al. ([1988] Teratology 38:313-320) of shared hierarchies of relative susceptibility to exencephaly induced by biochemically distinct teratogens, and suggest that the SWV strain would also be more sensitive to exencephaly induced by cadmium. In the present study, pregnant mice from the two strains were exposed to single i.p. injections of cadmium chloride at 4 mg/kg-BW on day 6.5, 7.0, 7.5, 8.0, 8.5, or 9.0 of gestation. Fetuses were removed by cesarean section on day 18 of gestation and scored for malformations. The C57BL/6 strain was observed to be more sensitive than the SWV strain to the induction of exencephaly by cadmium on days 6.5, 7.0, and 8.0, with mean litter percentages of 3.6%, 88.3%, and 62.2%, respectively, compared to 0.0%, 4.1%, and 27.7% for the SWV strain. This finding provides evidence in contrast to the hypothesis of shared hierarchies of sensitivity to teratogen-induced exencephaly. Data on a number of other cadmium-induced malformations are also presented.

Percutaneous transthoracic needle aspiration biopsy: a comprehensive review of its current role in the diagnosis and treatment of lung tumors.

OBJECTIVE: The purpose of this study is to examine the accuracy and complications of transthoracic needle aspiration biopsy (TTNA) to determine its optimal role in the evaluation of patients with lung tumors. MATERIALS AND METHODS: The charts of 130 consecutive patients who had undergone CT-guided TTNA were reviewed retrospectively. Thirty-two (25%) of these patients had subsequent surgery and 5 had subsequent transbronchial biopsy (TBB). Using the final surgical and TBB diagnosis as a reference, the accuracy, sensitivity, specificity, and prevalence of malignancy were calculated. Each case was also examined to determine the presence or absence of complications. RESULTS: Of the 130 biopsy results, 95 (73%) were malignant, 33 (25%) were nonspecific, and only 2 (2%) had a specific benign diagnosis. Thirty-two patients subsequently underwent surgical resection. The overall prevalence of malignancy after surgical diagnosis was 91%. The overall diagnostic accuracy of TTNA was 76%. The sensitivity of TTNA for the detection of malignancy was 74% and its specificity was 100%. When comparing TTNA results of small (<3 cm) and large (> or = 3 cm) tumors, the occurrence of nonspecific results was 36% and 16%, respectively. Fifty-six (43%) patients had a pneumothorax subsequent to TTNA. Twenty-four (43%) of these patients required a chest tube and remained hospitalized for a mean of 6 days. CONCLUSION: Patients who are surgical candidates and have a high clinical suspicion for malignancy should undergo surgical biopsy and resection of their lung tumors if indicated. Information gained from TTNAs performed on this patient population will rarely result in a change in their clinical management.

The loss of ventral ectoderm identity correlates with the inability to form an AER in the legless hindlimb bud.

We have characterized the early stages of murine hindlimb morphogenesis in the legless (lgl)mutant and non-mutant littermates. Initially the entire ventral ectoderm expresses many genetic markers characteristic of the AER (en-1, fgf-8, msx-2, dlx-2, cd44, and cx-43). Subsequently, the expression domain of most of these genes is restricted to the thickened ectoderm of the disto-ventral limb margin prior to forming an AER. In lgl, the expression of these genes is initiated but not maintained and the disto-ventral marginal ectoderm does not thicken. In contrast, Wnt7a expression is initiated and maintained in the dorsal ectoderm. The limb mesenchyme of lgl and non-mutant embryos initially expresses lmx-1b and fgf-10 uniformly. As the ventro-distal marginal ectoderm thickens, lmx-1b is progressively dorsally restricted in non-mutants but continues to be expressed ventrally in lgl hindlimb buds. These data suggest that establishment of a dorso-ventral ectodermal interface is not sufficient for AER formation and that restriction of lmx-1b to the dorsal mesenchyme is coordinately linked to AER formation.

Cost-effectiveness of FDG-PET for staging non-small cell lung cancer: a decision analysis.

BACKGROUND: Preliminary studies have shown that thoracic positron emission tomography (PET) is more accurate than thoracic computed tomography (CT) for the staging of non-small cell lung carcinoma. In the present study the cost-effectiveness, as measured by national Medicare reimbursed costs, and patient life expectancy are used to compare several thoracic PET-based strategies with a conventional thoracic CT-based strategy for preoperative staging. METHODS: Five decision strategies for selection of potential surgical candidates were compared; thoracic CT alone or four different strategies that use thoracic CT plus thoracic PET. The various paths of each strategy are dependent on numerous variables that were determined from a review of the medical literature. Life expectancy was calculated using the declining exponential approximation of life expectancy and reduced on the basis of procedural morbidity and mortality. Costs were based on national Medicare reimbursed costs. For all possible outcomes of each strategy, the expected cost and projected life expectancy were determined. The effects of changing one or more variables on the expected cost and life expectancy were studied using sensitivity analysis. RESULTS: A strategy that uses PET only after a negative CT study is shown to be a cost-effective alternative to the CT-alone strategy ($25,286 per life-year saved). CONCLUSIONS: These results show through rigorous decision tree analysis the potential cost-effectiveness of using thoracic PET in the management of non-small cell lung carcinoma. Greater use of thoracic PET for nonsmall cell lung carcinoma staging is warranted, and further clinical trials should help to validate the analytic results predicted from this study.

Likelihood of malignancy in a solitary pulmonary nodule: comparison of Bayesian analysis and results of FDG-PET scan.

OBJECTIVE: To compare the probability of cancer in a solitary pulmonary nodule using standard criteria with Bayesian analysis and result of 2-[F-18] fluoro-2-deoxy-D-glucose-positron emission tomographic (FDG-PET) scan. SETTING: A university hospital and a teaching Veteran Affairs Medical Center. METHODS: Retrospective analysis of 52 patients who had undergone both CT scan of the chest and a FDG-PET scan for evaluation of a solitary pulmonary nodule. FDG-PET scan was classified as abnormal or normal. Utilizing Bayesian analysis, the probability of cancer using "standard criteria" available in the literature, based on patient's age, history of previous malignancy, smoking history, size and edge of nodule, and presence or absence of calcification were calculated and compared to the probability of cancer based on an abnormal or normal FDG-PET scan. Histologic study of the nodules was the gold standard. RESULTS: The likelihood ratios for malignancy in a solitary pulmonary nodule with an abnormal FDG-PET scan was 7.11 (95% confidence interval [CI], 6.36 to 7.96), suggesting a high probability for malignancy, and 0.06 (95% CI, 0.05 to 0.07) when the PET scan was normal, suggesting a high probability for benign nodule. FDG-PET scan as a single test alone was more accurate than the standard criteria and standard criteria plus PET scan in correctly classifying nodules as malignant or benign. CONCLUSION: FDG-PET scan as a single test was a better predictor of malignancy in solitary pulmonary nodules than the standard criteria using Bayesian analysis. FDG-PET scan can be a useful adjunct test in the evaluation of solitary pulmonary nodules.