PET/CT prior to salvage surgery in recurrent head and neck squamous cell carcinoma.

PURPOSE: The purpose of this study was to assess the use of 18F-FDG PET/CT scans for detecting distant metastases in patients with recurrent head and neck squamous cell carcinoma (HNSCC) and investigate the treatment and survival of patients with recurrence. METHODS: In this retrospective study, consecutive head and neck cancer patients referred for FDG PET/CT scan between 2012 and 2014 were included. Patient records were reviewed and only patients with recurrence of HNSCC were enrolled for further analysis. Information on distant metastases, surgery and survival was collected. A Kaplan-Meier analysis was used to report survival. RESULTS: Overall 275 PET/CT scans were performed due to suspected recurrence, and in 166 scans (144 patients), recurrence of HNSCC was confirmed, making them eligible for further analysis. Distant metastases were revealed in 29.8% of the scans (n = 51) and the proportion of revealed metastases remained constant at approximately 30% each year. Although the number of performed scans increased twofold each year, there was no statistically significant change in the proportion of scans with distant metastasis (p = 0.55). The distant metastases were most often seen in the lungs (n = 44) and bone (n = 15). A few patients had widespread dissemination to other areas. Salvage surgery was performed following 81 of the 166 PET/CT scans. Seven of the patients who underwent salvage surgery had M-site oligo-metastases. Patients who underwent salvage surgery had a median survival of 22 months whereas patients not treated with salvage surgery had a median survival of 6 months. After 5 years, 21% of the patients selected for salvage surgery were alive. CONCLUSIONS: Distant metastases occur frequently in patients with recurrent HNSCC disease and the proportion of revealed distant metastases remained the same (30%). Imaging with FDG PET/CT can be recommended in patients with recurrent HNSCC prior to putative salvage surgery.

The clinical utility of FDG PET/CT among solid organ transplant recipients suspected of malignancy or infection.

PURPOSE: Solid organ transplant (SOT) recipients are at high risk of developing infections and malignancies. 18F-FDG PET/CT may enable timely detection of these diseases and help to ensure early intervention. We aimed to describe the clinical utility of FDG PET/CT in consecutive, diagnostic unresolved SOT recipients transplanted from January 2004 to May 2015. METHODS: Recipients with a post-transplant FDG PET/CT performed as part of diagnostic work-up were included. Detailed chart reviews were done to extract relevant clinical information and determine the final diagnosis related to the FDG PET/CT. Based on á priori defined criteria and the final diagnosis, results from each scan were classified as true or false, and diagnostic values determined. RESULTS: Among the 1,814 recipients in the cohort, 145 had an FDG PET/CT performed; 122 under the indication of diagnostically unresolved symptoms with a suspicion of malignancy or infection. The remaining (N = 23) had an FDG PET/CT to follow-up on a known disease or to stage a known malignancy. The 122 recipients underwent a total of 133 FDG PET/CT scans performed for a suspected malignancy (66 %) or an infection (34 %). Sensitivity, specificity, and positive and negative predictive values of the FDG PET/CT in diagnosing these conditions were 97, 84, 87, and 96 %, respectively. CONCLUSION: FDG PET/CT is an accurate diagnostic tool for the work-up of diagnostic unresolved SOT recipients suspected of malignancy or infection. The high sensitivity and NPV underlines the potential usefulness of PET/CT for excluding malignancy or focal infections in this often complex clinical situation.

Ultrabroadband terahertz spectroscopy of a liquid crystal.

Liquid crystals (LCs) are becoming increasingly important for applications in the terahertz frequency range. A detailed understanding of the spectroscopic parameters of these materials over a broad frequency range is crucial in order to design customized LC mixtures for improved performance. We present the frequency dependent index of refraction and the absorption coefficients of the nematic liquid crystal 5CB over a frequency range from 0.3 THz to 15 THz using a dispersion-free THz time-domain spectrometer system based on two-color plasma generation and air biased coherent detection (ABCD). We show that the spectra are dominated by multiple strong spectral features mainly at frequencies above 4 THz, originating from intramolecular vibrational modes of the weakly LC molecules.

Combined dual energy and iterative metal artefact reduction for PET/CT in head and neck cancer.

Metal artefacts in PET/CT images hamper diagnostic accuracy in head and neck cancer (HNC). The aim of this study is to characterise the clinical effects of metal artefacts on PET/CT in HNC and to inform decision-making concerning implementation of MAR techniques. We study a combined dual energy CT and inpainting-based metal artefact reduction (DECT-I-MAR) technique for PET/CT in three settings: (A) A dental phantom with a removable amalgam-filled tooth to evaluate the PET error in comparison to a known reference. (B) PET-positive patients with metallic implants to demonstrate the relationship between CT metal artefacts and PET error. (C) Metabolic tumour volumes delineated in PET-positive patients with metal implants to evaluate the clinical impact. In (A) DECT-I-MAR reduced the PET error significantly. In (B) we demonstrate an increasing PET error with increasing CT artefact severity in patients. In (C) it is shown that the presence of artefacts in the same axial slices as the tumour significantly decreases biomarker stability and increase delineation variability. This work shows the practical feasibility of DECT-I-MAR-based PET/CT imaging, and indicates a positive clinical impact of using the technique routinely for HNC patients. The impact of CT artefacts on PET is considerable, especially in workflows where quantitative PET biomarkers and tumour volumes are used. In such cases, and for patients with tumours in proximity of metals, we recommend that a MAR technique for PET/CT is employed.

Reproducibility of (18)F-FDG PET uptake measurements in head and neck squamous cell carcinoma on both PET/CT and PET/MR.

OBJECTIVE: To investigate reproducibility of fluorine-18 fludeoxyglucose ((18)F-FDG) uptake on (18)F-FDG positron emission tomography (PET)/CT and (18)F-FDG PET/MR scans in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: 30 patients with HNSCC were included in this prospective study. The patients were scanned twice before radiotherapy treatment with both PET/CT and PET/MR. Patients were scanned on the same scanners, 3 days apart and according to the same protocol. Metabolic tumour activity was measured by the maximum and peak standardized uptake value (SUVmax and SUVpeak, respectively), and total lesion glycolysis from the metabolic tumour volume defined from ≥50% SUVmax. Bland-Altman analysis with limits of agreement, coefficient of variation (CV) from the two modalities were performed in order to test the reproducibility. Furthermore, CVs from SUVmax and SUVpeak were compared. The area under the curve from cumulative SUV-volume histograms were measured and tested for reproducibility of the distribution of (18)F-FDG uptake. RESULTS: 24 patients had two pre-treatment PET/CT scans and 21 patients had two pre-treatment PET/MR scans available for further analyses. Mean difference for SUVmax, peak and mean was approximately 4% for PET/CT and 3% for PET/MR, with 95% limits of agreement less than ±20%. CV was small (5-7%) for both modalities. There was no significant difference in CVs between PET/CT and PET/MR (p = 0.31). SUVmax was not more reproducible than SUVpeak (p = 0.09). CONCLUSION: (18)F-FDG uptake in PET/CT and PET/MR is highly reproducible and we found no difference in reproducibility between PET/CT and PET/MR. ADVANCES IN KNOWLEDGE: This is the first report to test reproducibility of PET/CT and PET/MR.

Concurrent production of reactive oxygen and nitrogen species by airway epithelial cells in vitro.

Intracellularly generated reactive species of both oxygen (ROS) and nitrogen (RNS) have been implicated in signaling responses in airway epithelial cells, but these radicals have not been measured directly in such cells. In this study, intracellular production of both ROS and RNS were measured in the same cell lysates of guinea pig tracheal epithelial (GPTE) cells maintained in primary culture. ROS and RNS were quantified under basal (constitutive) conditions and in response to different stimuli: LPS and TNFalpha [activators of inducible nitric oxide synthase (iNOS)]; several activators of calcium-dependent cNOS (ATP, bradykinin, ionophore A23187, and thapsigargin); and exogenous oxidant stress generated by addition of xanthine oxidase to purine (p + XO). Studies with LPS and TNFalpha also were performed using the murine macrophage cell line, RAW 264.7, as a positive control. Intracellular oxidant production was detected from oxidation of dihydrorhodamine to rhodamine. NOx was quantified by either chemiluminescent or fluorescent detection. NOS activity was measured as citrulline production from arginine. Basal production of oxidants by GPTE cells (0.08 + 0.00 nmol rhodamine) was less than 10% that of RAW.267 cells (0.91 + 0.03 nmol rhodamine). TNFalpha and LPS significantly increased intracellular oxidant production in GPTE cells, as did p + XO, but none of the cNOS activators affected production of oxidants in these cells. Concentrations of NO2 after 4 h in unstimulated RAW 264.7 and GPTE cells were similar and comprised 63% of total NOx in GPTE and 62% in RAW cells. TNFalpha and LPS both increased NO2 in GPTE cells, but none of the Ca++-mobilizing agents nor p + XO significantly affected intracellular RNS. The results suggest both ROS and RNS can be measured in the same lysates from airway epithelial cells, and that both ROS and RNS are produced in these cells in response to different stimuli.

The role of reactive oxygen and nitrogen species in the response of airway epithelium to particulates.

Epidemiologic and occupational studies indicate adverse health effects due to inhalation of particulate air pollutants, but precise biologic mechanisms responsible have yet to be fully established. The tracheobronchial epithelium forms the body's first physiologic barrier to such airborne pollutants, where ciliary movement functions to remove the offending substances caught in the overlying mucus layer. Resident and infiltrating phagocytic cells also function in this removal process. In this paper, we examine the role of reactive oxygen and nitrogen species (ROS/RNS) in the response of airway epithelium to particulates. Some particulates themselves can generate ROS, as can the epithelial cells, in response to appropriate stimulation. In addition, resident macrophages in the airways and the alveolar spaces can release ROS/RNS after phagocytosis of inhaled particles. These macrophages also release large amounts of tumor necrosis factor alpha (TNF-alpha), a cytokine that can generate responses within the airway epithelium dependent upon intracellular generation of ROS/RNS. As a result, signal transduction pathways are set in motion that may contribute to inflammation and other pathobiology in the airway. Such effects include increased expression of intercellular adhesion molecule 1, interleukin-6, cytosolic and inducible nitric oxide synthase, manganese superoxide dismutase, cytosolic phospholipase A2, and hypersecretion of mucus. Ultimately, ROS/RNS may play a role in the global response of the airway epithelium to particulate pollutants via activation of kinases and transcription factors common to many response genes. Thus, defense mechanisms involved in responding to offending particulates may result in a complex cascade of events that can contribute to airway pathology.

Tumor necrosis factor alpha (TNF alpha)-induced ICAM-1 surface expression in airway epithelial cells in vitro: possible signal transduction mechanisms.

Within the past several years research on the interaction of cytokines and adhesion molecules with airway epithelium in diseases has allowed us to develop a better understanding of the disease process. The cytokine, TNF alpha and the adhesion molecule ICAM-1 are important mediators in the pathogenesis of airway diseases such as asthma, chronic bronchitis, and adult respiratory distress syndrome. Effects of TNF alpha on ICAM-1 surface expression was investigated in both primary cultures of normal human bronchial epithelial (NHBE) cells and immortalized human bronchial epithelial cell line BEAS-2B. TNF alpha (0.015-150 ng/mL) significantly enhanced ICAM-1 surface expression (measured by flow cytometry) in a dose and time-dependent manner, with peak expression seen at 24 hours. This response was negated by heat inactivation of the TNF alpha prior to incubation. TNF alpha-induced ICAM-1 expression also was inhibited by pre- and coincubation of TNF alpha with 3 micrograms/mL soluble TNF-R1 or by the PKC inhibitor, Calphostin C (0.1 and 0.5 microM). The ROI scavengers, dimethylthiourea (4 mM), and dimethyl sulfoxide (0.001%), enhanced TNF alpha-induced ICAM-1 expression. Collectively, these results indicate that TNF alpha-induced ICAM-1 surface expression is a specific receptor-mediated response (TNF-R1), which is mediated by mechanisms dependent on PKC and intracellular reactive oxygen species.

Interactions between respiratory epithelial cells and cytokines: relationships to lung inflammation.

Epithelial cells lining respiratory airways can participate in inflammation in a number of ways. They can act as target cells, responding to exposure to a variety of inflammatory mediators and cytokines by altering one or several of their functions, such as mucin secretion, ion transport, or ciliary beating. Aberrations in any of these functions can affect local inflammatory responses and compromise pulmonary defense. For example, oxidant stress can increase secretion of mucin and depress ciliary beating efficiency, thereby affecting the ability of the mucociliary system to clear potentially pathogenic microbial agents. Recent studies have indicated that airway epithelial cells also can act as "effector" cells, synthesizing and releasing cytokines, lipid mediators, and reactive oxygen species in response to a number of pathologically relevant stimuli, thereby contributing to inflammation. Many of these epithelial-derived substances can act locally, affecting both neighboring cells and tissues, or, via autocrine or paracrine mechanisms, affect structure and function of the epithelial cells themselves. Studies in our laboratories utilized cell cultures of both human and guinea pig tracheobronchial and nasal epithelial cells, and isolated human nasal epithelial cells, to investigate activity of respiratory epithelial cells in vitro as sources of cytokines and inflammatory mediators. Primary cultures of guinea pig and human tracheobronchial and nasal epithelial cells synthesize and secrete low levels of IL-6 and IL-8 constitutively. Production and release of these cytokines increases substantially after exposure to specific inflammatory stimuli, such as TNF or IL-1, and after viral infection.

Far-infrared vibrational modes of DNA components studied by terahertz time-domain spectroscopy.

The far-infrared dielectric function of a wide range of organic molecules is dominated by vibrations involving a substantial fraction of the atoms forming the molecule and motion associated with intermolecular hydrogen bond vibrations. Due to their collective nature such modes are highly sensitive to the intra- and intermolecular structure and thus provide a unique fingerprint of the conformational state of the molecule and effects of its environment. We demonstrate the use of terahertz time-domain spectroscopy (THz-TDS) for recording the far-infrared (0.5-4.0 THz) dielectric function of the four nucleobases and corresponding nucleosides forming the building blocks of deoxyribose nucleic acid (DNA). We observe numerous distinct spectral features with large differences between the molecules in both frequency-dependent absorption coefficient and index of refraction. Assisted by results from density-functional calculations we interpret the origin of the observed resonances as vibrations of hydrogen bonds between the molecules.

Positron emission tomography of incidentally detected small pulmonary nodules.

The aim of this study was to assess the value of fluorodeoxyglucose positron emission tomography (FDG PET) imaging of small pulmonary nodules incidentally detected by spiral computed tomography (CT) in a high-risk population. Ten patients (five females, five males, aged 54-72 years) were recruited from an ongoing 4-year placebo controlled intervention study of the effect of inhaled steroids in 300 smokers with moderate to severe chronic obstructive pulmonary disease. The participants received yearly CT scans of the chest. Patients with a negative chest radiograph at the time of inclusion, but with pulmonary nodules indeterminate for malignancy detected by conventional spiral CT on a subsequent scan, were referred for FDG PET. Histological diagnoses were sought for all nodules with FDG uptake or where CT showed that they had grown. Ten patients had pulmonary nodules indeterminate for malignancy (approx. 3.3% of the entire study population). The prevalence of malignancy in this group was 50%. The accuracy of PET was high, in spite of the fact that seven patients had nodules smaller than 15 mm and two patients had bronchoalveolar cell carcinoma. This small prospective study indicates that subsequent assessment with FDG PET of small pulmonary nodules incidentally detected by CT has the potential to minimize the numbers of invasive procedures performed in individuals with a benign pulmonary lesion. FDG PET also increases the possibility of an early diagnosis as compared to the strategy of watchful waiting.

Efficacy and toxicity of doxorubicin/cyclophosphamide maintenance therapy in dogs with multicentric lymphosarcoma.

Doxorubicin/cyclophosphamide were evaluated as maintenance drugs for dogs with multicentric lymphosarcoma (n = 28). Median remission time of all dogs was 173 days. Remission duration was shorter, however, in dogs with stage IV/V disease, in dogs with pretreatment hypoalbuminemia, and in dogs that had received glucocorticoids before initiation of chemotherapy (P less than 0.04). Nineteen dogs were evaluable for toxicity. Dose-limiting gastrointestinal toxicosis was observed in three dogs, neutropenia was observed in three dogs, and cardiomyopathy was observed in three dogs. The doxorubicin/cyclophosphamide protocol described in this report is safe and effective in treating canine multicentric lymphosarcoma. Clinical stage, pretreatment steroid therapy, and hypoalbuminemia are prognostic factors for response to this protocol.

Functional imaging in lung cancer.

Lung cancer represents an increasingly frequent cancer diagnosis worldwide. An increasing awareness on smoking cessation as an important mean to reduce lung cancer incidence and mortality, an increasing number of therapy options and a steady focus on early diagnosis and adequate staging have resulted in a modestly improved survival. For early diagnosis and precise staging, imaging, especially positron emission tomography combined with CT (PET/CT), plays an important role. Other functional imaging modalities such as dynamic contrast-enhanced CT (DCE-CT) and diffusion-weighted MR imaging (DW-MRI) have demonstrated promising results within this field. The purpose of this review is to provide the reader with a brief and balanced introduction to these three functional imaging modalities and their current or potential application in the care of patients with lung cancer.

A prospective study of PET/CT in initial staging of small-cell lung cancer: comparison with CT, bone scintigraphy and bone marrow analysis.

BACKGROUND: Small-cell lung cancer (SCLC) accounts for 15%-20% of all lung cancer cases. Accurate and fast staging is mandatory when choosing treatment, but current staging procedures are time consuming and lack sensitivity. PATIENTS AND METHODS: A prospective study was designed to examine the role of combined positron emission tomography/computed tomography (PET/CT) compared with standard staging (CT, bone scintigraphy and immunocytochemical assessment of bone marrow biopsy) of patients with SCLC. Thirty-four consecutive patients were included. Twenty-nine patients received initial PET/CT. RESULTS: PET/CT caused change of stage in 5/29 (17%). Excluding patients with unconfirmed findings or pleural effusion, the sensitivity for accurate staging of patients with extensive disease was the following: for standard staging 79%, PET 93% and PET/CT 93%. Specificity was 100%, 83% and 100%, respectively. CONCLUSION: The results from this first study on PET/CT in SCLC indicates that PET/CT can simplify and perhaps even improve the accuracy of the current staging procedure in SCLC. A larger clinical trial, preferably with consequent histological confirmation in case of discordance, however, is warranted.

Positron emission tomography in the diagnosis and staging of lung cancer: a systematic, quantitative review.

Lung cancer is the cause of 32% of all male cancer deaths and 25% of all female cancer deaths. Because the prognosis depends on early diagnosis and staging, continuous evaluation of the diagnostic tools available is important. The aim of this study was to assess the diagnostic value of dedicated positron emission tomography (PET) and gamma-camera PET in the diagnostic investigation of non-small-cell lung cancer (NSCLC). A systematic literature search was carried out in the MEDLINE and EMBASE databases and the Cochrane Controlled Trials Register. We identified 55 original works on the diagnostic performance of PET with fluorodeoxyglucose in the investigation of NSCLC. For diagnosis of NSCLC, the mean sensitivities and specificities were, respectively, 0.96 (SE 0.01) and 0.78 (0.03) for dedicated PET, and 0.92 (0.04) and 0.86 (0.04) for gamma-camera PET. In the mediastinal staging of NSCLC, the results were 0.83 (0.02) and 0.96 (0.01) for dedicated PET and 0.81 (0.04) and 0.95 (0.02) for ganuna-camera PET. We conclude that dedicated PET could be a valuable tool in the diagnosis and staging of NSCLC. However, studies of populations with a lower prevalence of NSCLC are recommended.

[The variable course of pulmonary histiocytosis X]. / Variabler Verlauf der pulmonalen Histiozytosis X.

The authors report on the course seen in 7 cases of pulmonary histiocytosis X. In Group I (3 patients) immunosuppressive therapy was initiated on account of severe general symptoms and reduced pulmonary function. Remission was induced in 2 cases, whereas relapses occurred intermittently in one patient. In Group II without general symptoms and largely normal pulmonary function the course was only monitored. Progression did not occur with any of the patients. Pulmonary histiocytosis X should be treated with corticosteroid monotherapy in case of progressive deterioration of pulmonary function and/or if there are severe general symptoms. Chance findings in patients who are otherwise free from complaints should merely result in a closely meshed control checkup before taking any action.