A prospective study of the feasibility of FDG-PET/CT imaging to quantify radiation-induced lung inflammation in locally advanced non-small cell lung cancer patients receiving proton or photon radiotherapy.

PURPOSE: This prospective study assessed the feasibility of 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) to quantify radiation-induced lung inflammation in patients with locally advanced non-small cell lung cancer (NSCLC) who received radiotherapy (RT), and compared the differences in inflammation in the ipsilateral and contralateral lungs following proton and photon RT. METHODS: Thirty-nine consecutive patients with NSCLC underwent FDG-PET/CT imaging before and after RT on a prospective study. A novel quantitative approach utilized regions of interest placed around the anatomical boundaries of the lung parenchyma and provided lung mean standardized uptake value (SUVmean), global lung glycolysis (GLG), global lung parenchymal glycolysis (GLPG) and total lung volume (LV). To quantify primary tumor metabolic response to RT, an adaptive contrast-oriented thresholding algorithm was applied to measure metabolically active tumor volume (MTV), tumor uncorrected SUVmean, tumor partial volume corrected SUVmean (tumor-PVC-SUVmean), and total lesion glycolysis (TLG). Parameters of FDG-PET/CT scans before and after RT were compared using two-tailed paired t-tests. RESULTS: All tumor parameters after either proton or photon RT decreased significantly (p < 0.001). Among the 21 patients treated exclusively with proton RT, no significant increase in PVC-SUVmean or PVC-GLPG was observed in ipsilateral lungs after the PVC parameters of primary tumor were subtracted (p = 0.114 and p = 0.453, respectively). Also, there were no significant increases in SUVmean or GLG of contralateral lungs of patients who received proton RT (p = 0.841, p = 0.241, respectively). In contrast, among the nine patients who received photon RT, there was a statistically significant increase in PVC-GLPG of ipsilateral lung (p < 0.001) and in GLG of contralateral (p = 0.036) lung. In the subset of nine patients who received a combined proton and photon RT, there was a statistically significant increase in PVC-GLPG of ipsilateral lung (p < 0.001). CONCLUSION: Our data suggest less induction of inflammatory response in both the ipsilateral and contralateral lungs of patients treated with proton compared to photon or combined proton-photon RT.

Fooled by the fragments: vitamin B12 deficiency masquerading as thrombotic thrombocytopenic purpura.

Background: Thrombotic thrombocytopenic purpura (TTP) is a hematological emergency requiring prompt plasmapheresis. Conversely, vitamin B12 deficiency is a relatively benign diagnosis that can mimic microangiopathic hemolytic anemia, characterized by the presence of anemia, thrombocytopenia, indirect hyperbilirubinemia, markers of hemolysis, and schistocytes. This case series highlights the association of vitamin B12 deficiency and its TTP-like presentations. Cases: The first case describes a 72-year-old man with shortness of breath and weakness. Diagnostics were notable for pancytopenia, schistocytes, and a low reticulocyte index. Intriguingly, total bilirubin was only mildly elevated however LDH and Haptoglobin were elevated and low, respectively. Additional diagnostic workup demonstrated an undetectable B12, elevated methylmalonic acid and elevated homocysteine. Initiation of B12 supplementation resolved his pancytopenia. The second case describes a 57-year-old man with chest tightness, dyspnea on exertion, and night sweats. Diagnostic evaluation demonstrated pancytopenia, schistocytes, a low reticulocyte index, and a remarkably low B12. He had associated high methylmalonic acid and homocysteine levels, confirming the diagnosis. B12 supplementation resolved his pancytopenia. Conclusion: The polysymptomatic presentation of vitamin B12 deficiency-induced pseudothrombotic microangiopathy highlights the vitamin's role in essential physiological cellular functions. Rapid recognition of the underlying etiology of microangiopathic hemolytic anemia is necessary as treatment approaches diverge greatly.

Implementation of FDG-PET/CT imaging methodology for quantification of inflammatory response in patients with locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG 0235 trial.

We measured changes in 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) images in the lung parenchyma to quantify the degree of lung inflammation in patients with locally advanced non-small cell lung cancer (NSCLC) who received radiotherapy (RT). The goal of this study was to demonstrate successful implementation of this imaging methodology on NSCLC patients and to report quantitative statistics between pre-RT and post-RT. Seventy-one patients with NSCLC underwent FDG-PET/CT imaging before and after RT in a prospective study (ACRIN 6668/RTOG 0235). Comparisons between pre-RT and post-RT PET/CT were conducted for partial volume corrected (PVC)-mean standardized uptake value (SUVmean), PVC-global lung parenchymal glycolysis (GLPG), and lung volume for both ipsilateral and contralateral lungs using the nonparametric Wilcoxon signed-rank test. Regression modeling was conducted to associate clinical characteristics with post-RT PET/CT parameters. There was a significant increase in average SUVmean and GLPG of the ipsilateral lung (relative change 40% and 20%) between pre-RT and post-RT PET/CT scans (P<0.0001 and P=0.004). Absolute increases in PVC-SUVmean and PVC-GLPG were more pronounced (ΔPVC-SUVmean 0.32 versus ΔSUVmean 0.28; ΔPVC-GLPG 463.34 cc versus ΔGLPG 352.90 cc) and highly significant (P<0.0001). In contrast, the contralateral lung demonstrated no significant difference between pre-RT to post-RT in either GLPG (P=0.12) or SUVmean (P=0.18). The only clinical feature significantly associated with post-RT PET/CT parameters was clinical staging. Our study demonstrated inflammatory response in the ipsilateral lung of NSCLC patients treated with photon RT, suggesting that PET/CT parameters may serve as biomarkers for radiation pneumonitis (RP).

Evolving Role of Novel Quantitative PET Techniques to Detect Radiation-Induced Complications.

Radiation-induced normal tissue toxicities vary in terms of pathophysiologic determinants and timing of disease development, and they are influenced by the dose and radiation volume the critical organs receive, and the radiosensitivity of normal tissues and their baseline rate of cell turnover. Radiation-induced lung injury is dose limiting for the treatment of lung and thoracic cancers and can lead to fibrosis and potentially fatal pneumonitis. This article focuses on pulmonary and cardiovascular complications of radiation therapy and discusses how PET-based novel quantitative techniques can be used to detect these events earlier than current imaging modalities or clinical presentation allow.

In Vivo Molecular Imaging of Musculoskeletal Inflammation and Infection.

In vivo molecular imaging detects biologic processes at molecular level and provides diagnostic information at an earlier time point during disease onset or repair. It offers definite advantage over anatomic imaging in terms of improved sensitivity and ability to quantify. Radionuclide molecular imaging has been widely used in clinical practice. This article discusses the role of radionuclide imaging in various infective and inflammatory diseases affecting musculoskeletal system with a focus on PET. It appears that, as more data become available, combined PET/MR imaging could emerge as a front runner in the imaging of musculoskeletal infection and inflammation.

Dynamics of fluorine-18-fluorodeoxyglucose uptake in the liver and its correlation with hepatic fat content and BMI.

PURPOSE: The aim of this study was to explore the rate of elimination of fluorine-18-fluorodeoxyglucose (F-FDG) from the liver and assess the impact of hepatic fat and obesity on F-FDG clearance in early and delayed PET scans. We hypothesized that an increase in liver fat may cause a decline in hepatic F-FDG elimination with potential consequences as measured by dual time-point F-FDG PET/CT imaging. PATIENTS AND METHODS: A total of 32 patients from the Cardiovascular Molecular Calcification Assessed by F-NaF PET/CT (CAMONA) clinical trial (17 males, 15 females; mean age: 47.2 years, range: 23-69 years, mean BMI: 27.2 kg/m) were enrolled and underwent F-FDG PET/CT 90 and 180 min after tracer injection. Global mean standardized uptake value (SUVmean) (i.e. the average of SUVmean in segmented liver slices) and average maximum standardized uptake value (SUVmax) (i.e. the average of the SUVmax values recorded in same slices) were calculated for semiquantification of liver F-FDG uptake at both time-points. Percentage difference in global SUVmean and average SUVmax were also calculated to yield respective retention indices (RImean and RImax). Changes in global SUVmean, average SUVmax, RImean, and RImax from 90 to 180 min were correlated with BMI and liver fat content as measured by CT Hounsfield units. RESULTS: There was a 12.2±3.5 percent reduction in global liver SUVmean and a 4.1±5.8 percent reduction in average SUVmax at 180 min scan as compared with the 90 min time-point. RImean and RImax were inversely correlated with liver fat content and positively correlated with BMI. CONCLUSION: We observed a time-dependent decrease in global hepatic SUVmean and average SUVmax, which was affected by the amount of liver fat. Patients with higher BMI and hepatic fat content tended to retain F-FDG.

Gastroesophageal Reflux Disease in Iran: SEPAHAN Systematic Review No. 2.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most prevalent disorders affecting gastrointestinal tract with a wide range of frequency around the world. In this study, we aimed to review all of the published studies about GERD's prevalence in Iran systematically. METHODS: We searched bibliographic databases including PubMed and Google Scholar and local databases (Scientific Information Database and Iran Medex) to achieve all relevant articles to our subject and included them based on predefined inclusion criteria. RESULTS: Twenty-two articles were included in the study to estimate the prevalence of GERD in Iran. Based on these articles, the prevalence of GERD in Iran was within the range of 1.9 to 52%. CONCLUSIONS: Due to the differences between studies, such as characteristics of the sampled population and the diagnostic criteria, the reported prevalence of GERD was remarkably different in the reviewed studies. Nonetheless, because of the high prevalence of GERD in Iran, conducting large-scale epidemiological studies should be considered to determine factors associated with the prevalence of GERD to prevent and control it.

Dyspepsia in Iran: SEPAHAN Systematic Review No. 3.

BACKGROUND: Dyspepsia is an upper gastrointestinal tract syndrome presenting epigastric pain and discomfort, fullness sensation, early satiety, nausea, vomiting, and belching. The prevalence of dyspepsia has been reported to be high all over the world. In this study, we reviewed studies reporting the prevalence of dyspepsia in Iran and discussed the probable risk factors of dyspepsia to shed light on future research on this topic. METHODS: The four electronic databases of PubMed, Google Scholar, IranMedex, and Scientific Information Database were searched. The keywords for the electronic search were "dyspepsia" and "Iran". A manual search of the reference lists of the selected articles was also carried out. Two reviewers reviewed and identified articles independently and selected relevant studies based on our inclusion and exclusion criteria. RESULTS: Nine articles reporting the prevalence of dyspepsia in Iran were included. The reported prevalence ranged from 2.2% to 29.9%. The majority of studies have reported the prevalence of dyspepsia to be higher in women. CONCLUSION: Dyspepsia seems to be highly prevalent in Iran. Considering the wide range of data reported in different studies, conducting further population-based studies is necessary to investigate the epidemiology and risk factors of dyspepsia among Iranians.

Irritable Bowel Syndrome in Iran: SEPAHAN Systematic Review No. 1.

OBJECTIVES: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. Due to its high prevalence and absence of curative therapy, IBS has the potential to create tremendous burden on the health care system. Herein, we systematically reviewed the published literature to investigate the epidemiology of IBS in Iran. METHODS: Studies that were reviewed in this article were primarily identified through four online bibliographic databases including PubMed, Google Scholar, Iran Medex, and Scientific Information Database. Manual search of reference lists was carried out to identify any additional studies such as relevant abstracts and also recent review articles which may have been missed. Potentially related studies were retrieved and the selection criteria were applied. Eligible articles were reviewed. RESULTS: From 4176 studies identified, 18 eligible studies were included. It was reported that in Iran, the prevalence of IBS was in the range of 1.1% to 25% and was more common in women. In addition, the difference in frequency of different age groups was minimal. There was a minimal difference in IBS prevalence within different age groups. CONCLUSIONS: In Iran, the incidence of IBS was in the wide range. Since there are not enough population-based studies, researchers should focus on developing well-designed population-based studies to determine the epidemiology of IBS in Iran. Moreover, cohort studies should be conducted in order to investigate the natural history of IBS. Investigating the etiology of IBS and attempt to organize health promotion programs are highly suggested.

Edentulism and Tooth Loss in Iran: SEPAHAN Systematic Review No. 6.

OBJECTIVES: Tooth loss appears to have an important role in the loss of mastication and esthetics. The aim of this systematic review was to investigate the prevalence of tooth loss and edentulism in the Iranian population. METHODS: Studies reviewed in this article were primarily identified via search of the online bibliographic databases including PubMed and Iranian Biomedical Journals, by using "tooth loss", "edentulism", "epidemiology", and "Iran" as keywords. Studies potentially related to this topic were retrieved and the selection criteria applied. From the chosen studies the eligible articles were reviewed. RESULTS: Of the studies identified after conducting the search, 10 eligible studies were extracted. The prevalence of tooth loss ranges between 0.3% in 3 to 5-year-old children to 70.7% in adults over 65. There is a lack of well-designed epidemiological studies on edentulism and tooth loss in Iran. The prevalence of tooth loss is high and it increases by aging. CONCLUSIONS: It seems that the prevalence of tooth loss is high among adults in Iran. It is highly suggested that population-based studies should be established to investigate the epidemiology and risk factors of tooth loss in Iran. The results of such studies will be useful in the adoption of appropriate preventive strategies.