A B S T R A C T PurposeSquamous cell carcinoma of the head and neck (SCCHN) is characterized by upregulation of the epidermal growth factor receptor (EGFR). We developed a novel strategy to target EGFR by using a therapeutic gene that consisted of an EGFR antisense (AS) gene sequence under U6 promoter control. A phase I clinical trial was conducted to evaluate the safety and biologic effects of EGFR AS. Patients and MethodsPatients with advanced SCCHN who were refractory to standard therapies and who had at least one assessable and accessible lesion were enrolled. The EGFR AS dose was escalated in successive cohorts (six dose levels; 60 to 1,920 g/injection). Patients received four weekly intratumoral EGFR AS injections. Tumor biopsies were performed before and after completion of therapy. Treatment response was assessed by tumor volume measurements (positron emission tomography/computed tomography), and levels of target proteins were assessed by immunohistochemistry. ResultsSeventeen assessable patients were treated. No grades 3 to 4 or dose-limiting toxicities were noted, and a maximum-tolerated dose was not reached. Five patients (29%) achieved a clinical response, which included two complete responses (CRs) and three partial responses (PRs); two additional patients had stable disease (SD) as the best response. Patients with disease control (CR ϩ PR ϩ SD) had tumors with higher EGFR and lower STAT3 expression at baseline compared with patients who had progressive disease (P ϭ .0312 and P ϭ .095, respectively). ConclusionIntratumoral EGFR AS was safe and resulted in antitumor activity in patients with advanced SCCHN. Baseline levels of high EGFR and low STAT3 may be associated with antitumor effects.

Biomarkers providing in vivo quantification of the basic elements of cystic fibrosis (CF) lung disease are needed. A study was performed to determine whether the absorption of a small radiolabelled hydrophilic molecule (Indium-111 (In-)DTPA) would be increased in CF airways. DTPA clearance has been used previously to assess epithelial permeability and may also be useful for quantifying liquid absorption.The absorptive clearance rate of DTPA was quantified in 10 CF and 11 control subjects using a novel aerosol technique. Subjects inhaled an aerosol containing nonabsorbable technetium-99m sulfur colloid (Tc-SC) particles and In-DTPA. Tc-SC clearance from the lung is exclusively mucociliary, while In-DTPA is cleared by both absorption and mucociliary clearance. The difference between the In-DTPA and Tc-SC clearance rates estimates In-DTPA absorption.Tc-SC (mucociliary) clearance was similar in central and peripheral zones in CF and non-CF lungs. Total In-DTPA clearance was increased in both zones in CF lungs. The absorptive component of In-DTPA clearance was increased in the airway-dominated central lung zones in CF (42%?h -1 versus 32%?h -1 , p50.03).The absorption of In-DTPA is increased in the CF airway. Further study is needed to understand the relative roles of fluid absorption, inflammation and other mechanisms potentially affecting epithelial permeability and DTPA absorption.

Objective: To report a case of intestinal malrotation predisposing to cecal volvulus following nonabdominal surgery in an adult. Presentation and Intervention: A 23-year-old male with known anorectal malformation developed a postoperative intestinal obstruction following percutaneous nephrolithotomy for left renal calculus. Computed tomography of the abdomen revealed a grossly dilated cecum (9 cm) with ileocecal junction on the left side and small bowel loops on the right side of the abdomen. The patient underwent emergency exploratory laparotomy and retroperitonealization cecopexy. Bowel functions were normal at the follow-ups. Conclusion: This case highlights the importance of suspecting cecal volvulus even following nonabdominal surgery in the presence of predisposing factors.

Airway surface liquid hyper-absorption and mucus accumulation are key elements of cystic fibrosis (CF) lung disease that can be assessed in vivo using functional imaging methods. In this study we evaluated experimental factors affecting measurements of mucociliary clearance (MCC) and small-molecule absorption (ABS) and patient factors associated with abnormal absorption and mucus clearance. Our imaging technique utilizes two radiopharmaceutical probes delivered by inhalation. Measurement repeatability was assessed in 10 adult CF subjects. Experimental factors were assessed in 29 adult and pediatric CF subjects (51 scans). Patient factors were assessed in a sub-group with optimal aerosol deposition (37 scans, 24 subjects). Pediatric subjects (n=9) performed initial and 2 year follow-up scans. Control subjects from a previously reported study are included for comparison. High rates of central aerosol deposition influenced measurements of ABS and to a lesser extent MCC. Depressed MCC in CF was only detectable in subjects with previous Pseudomonas aeruginosa (PA) infection. CF subjects without PA had similar MCC to control subjects. CF subjects had consistently higher ABS rates. We conclude that the primary experimental factor affecting MCC/ABS measurements is central deposition percentage. Depressed MCC in CF is associated with PA infection. ABS is consistently increased in CF.

Hybrid imaging with F-18 fludeoxyglucose positron emission tomography/magnetic resonance imaging (FDG PET/MRI) has increasing clinical applications supplementing conventional ultrasound, CT, and MRI imaging as well as hybrid PET/CT imaging in assessing cervical, endometrial, and ovarian cancer. This article summarizes the existing literature and discusses the emerging role of hybrid PET/MRI in gynecologic malignancies. Thus, far, the published literature on the applications of FDG PET/MRI shows that it can have a significant impact on patient management by improving the staging of the cancers compared with PET/CT, influencing clinical decision and treatment strategy. For disease restaging, current literature indicates that PET/MRI performs equivalently to PET/CT. There appears to be a mild-moderate inverse correlation between standard-uptake-value (SUV) and apparent-diffusion-coefficient (ADC) values, which could be used to predict tumor grading and risk stratification. It remains to be seen as to whether multi-parametric PET/MRI imaging could prove valuable for prognostication and outcome. PET/MRI provides the opportunity for reduced radiation exposure, which is particularly relevant for a young female in need of multiple scans for treatment monitoring and follow-up. Fast acquisition protocols and optimized methods for attenuation correction are still evolving. Major limitations of PET/MRI remains such as suboptimal detection of small pulmonary nodules and lack of utility for radiation treatment planning, which pose an impediment in making PET/MRI a viable one-stop-shop imaging option to compete with PET/CT.

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Objective: To assess the clinical utility of SPECT/ CT in subjects with endocrine and neuroendocrine tumors compared to SPECT alone.Material and Methods: 48 subjects (31 women;17 men; mean age 54±11) with clinical suspicion or diagnosis of endocrine and neuroendocrine tumor had 50 SPECT/CT scans (32 Tc-99m MIBI, 5 post treatment I-131, 8 In-111 Pentetreotide, and 5 I-123 MIBG). SPECT alone findings were compared to SPECT/CT and to pathology or radiological follow up.Results: From the 32 Tc-99m MIBI scans, SPECT accurately localized the lesion in 22 positive subjects while SPECT/CT did in 31 subjects. Parathyroid lesions not seen on SPECT alone were smaller than 10 mm. In five post treatment I-131 scans, SPECT alone neither characterized, nor localized any lesions accurately. SPECT/CT revealed 3 benign etiologies, a metastatic lymph node, and one equivocal lesion. In 8 In-111 Pentetreotide scans, SPECT alone could not localize primary or metastatic lesions in 6 subjects all of which were localized with SPECT/CT. In five I-123 MIBG scans, SPECT alone could not detect a 1.1 cm adrenal lesion or correctly characterize normal physiologic adrenal uptake in consecutive scans of the same patient with prior history of adrenelectomy, all of which were correctly localized and characterized with SPECT/CT.Conclusion: SPECT/CT is superior to SPECT alone in the assessment of endocrine and neuroendocrine tumors. It is better in lesion localization and lesion characterization leading to a decrease in the number of equivocal findings. SPECT/CT should be included in the clinical work up of all patients with diagnosis or suspicion of endocrine and neuroendocrine tumors.Conflict of interest:None declared.

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