Search

Purpose: To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect residual malignancy., Methods: F-FDG PET/CT was performed before and after CCRT in 136 patients with cervical cancer. The maximum and mean standardized uptake values (SUVmax and SUVmean) were recorded from PET/CT scans performed pre- and post-treatment. SUVs were correlated with treatment response after CCRT. Final treatment response was determined by MRI and further follow-up PET/CT. One hundred four of 136 patients underwent pelvic MRI, and 32 of 136 patients underwent further follow-up PET/CT. Patients were classified into two categories: patients with residual tumor or patients without residual tumor (complete responder). Pre- and post-treatment serum squamous cell carcinoma antigen (SCC) levels were also recorded for comparison. The optimal cutoff value of SUVmax for predicting residual cervical tumor was determined using receiver-operating characteristic (ROC) analysis., Results: Of 136 patients, 124 showed complete response on further follow-up studies and 12 were confirmed to have residual tumor. The post-treatment SUVmax and pre-/post-treatment SUVmean of complete responders were significantly lower than those of patients with residual tumor: 2.5 ± 0.8 and 7.2 ± 4.2/1.9 ± 0.7 for complete responders and 5.7 ± 2.6 and 12.8 ± 6.9/3.7 ± 0.7 for patients with residual tumor (p < 0.05). The pre-treatment SUVmax and pre-/post-treatment serum SCC levels of the complete responders tended to be lower than those of patients with residual tumor, but this did not have statistical significance. Using ROC analysis, an optimal cutoff SUVmax of 4.0 on the post-treatment PET/CT yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 92 %, 94 %, 61 %, and 99 %, respectively (p < 0.001)., Conclusions: Persistent cervical FDG uptake in(18)F-FDG PET/CT after CCRT for cervical cancer may be caused by residual tumor or post-therapy inflammation. A higher cutoff SUVmax than conventional criteria for cervical cancer in post-CCRT PET/CT might help to detect residual tumor.

Objective: The purpose of this study was to evaluate the diagnostic performance of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a single imaging agent in neuroblastoma in comparison with other imaging modalities., Methods: A total of 30 patients with pathologically proven neuroblastoma who underwent FDG PET for staging were enrolled. Diagnostic performance of FDG PET and abdomen CT was compared in detecting soft tissue lesions. FDG PET and bone scintigraphy (BS) were compared in bone metastases. Maximal standardized uptake value (SUVmax) of primary or recurrent lesions was calculated for quantitative analysis., Results: Tumor FDG uptake was detected in 29 of 30 patients with primary neuroblastoma. On initial FDG PET, SUVmax of primary lesions were lower in early stage (I-II) than in late stage (III-IV) (3.03 vs. 5.45, respectively, p = 0.019). FDG PET was superior to CT scan in detecting distant lymph nodes (23 vs. 18 from 23 lymph nodes). FDG PET showed higher accuracy to identify bone metastases than BS both on patient-based analyses (100 vs. 94.4 % in sensitivity, 100 vs. 77.8 % in specificity), and on lesion-based analyses (FDG PET: 203 lesions, BS: 86 lesions). Sensitivity and specificity of FDG PET to detect recurrence were 87.5 % and 93.8, respectively., Conclusion: FDG PET was superior to CT in detecting distant LN metastasis and to BS in detecting skeletal metastasis in neuroblastoma. BS might be eliminated in the evaluation of neuroblastoma when FDG PET is performed.

Enteroviruses are found in most environments and cause several diseases in humans. Loop-mediated isothermal amplification (LAMP) was adapted and evaluated for the rapid detection of enteroviruses. Based on the highly conserved 5' untranslated region (5'-UTR) of the human enteroviruses (HEVs), particularly human enterovirus A (HEV-A) and HEV-B, a set of universal primers was designed. The LAMP amplification was carried out under isothermal conditions at 61 °C, depending on the template concentration results were obtained within 45-90 min. The detection limits were found to be 10(1) copies of cloned enterovirus 71 fragments, more sensitive than conventional PCR. Nine water samples collected from drinking water sources during three seasons and 19 stool specimens collected from HFMD patients were analyzed. By using the LAMP assay, the majority of samples was tested positive, 9/9 (100 %) and 18/19 (94.7 %), respectively. LAMP is a practical method for the rapid detection of enteroviruses in environmental and clinical samples.

Objectives: To retrospectively evaluate concordance rates and predictive values in concordant cases among multiparametric MR techniques and FDG-PET to grade cerebral gliomas., Methods: Multiparametric MR imaging and FDG-PET were performed in 60 consecutive patients with cerebral gliomas (12 low-grade and 48 high-grade gliomas). As the dichotomic variables, conventional MRI, minimum apparent diffusion coefficient in diffusion-weighted imaging, maximum relative cerebral blood volume ratio in perfusion-weighted imaging, choline/creatine ratio and (lipid and lactate)/creatine ratio in MR spectroscopy, and maximum standardised uptake value ratio in FDG-PET in low- and high-grade gliomas were compared. Their concordance rates and positive/negative predictive values (PPV/NPV) in concordant cases were obtained for the various combinations of multiparametric MR techniques and FDG-PET., Results: There were significant differences between low- and high-grade gliomas in all techniques. Combinations of two, three, four, and five out of the five techniques showed concordance rates of 77.0 ± 4.8%, 65.5 ± 4.0%, 58.3 ± 2.6% and 53.3%, PPV in high-grade concordant cases of 97.3 ± 1.7%, 99.1 ± 1.4%, 100.0 ± 0% and 100.0% and NPV in low-grade concordant cases of 70.2 ± 7.5%, 78.0 ± 6.0%, 80.3 ± 3.4% and 80.0%, respectively., Conclusion: Multiparametric MR techniques and FDG-PET have a concordant tendency in a two-tiered classification for the grading of cerebral glioma. If at least two examinations concordantly indicated high-grade gliomas, the PPV was about 95%., Key Points: • Modern imaging techniques can help predict the aggressiveness of cerebral gliomas. • Multiparametric MRI and FDG-PET have a concordant tendency to grade cerebral gliomas. • Their high-grade concordant cases revealed at least 95 % positive predictive values. • Their low-grade concordant cases revealed about 70–80% negative predictive values.

Purpose: To assess the risk of malignancy of thyroid incidentalomas found on 18F-FDG PET/CT by US features and cytologic results, and to evaluate the clinical usage of a combination of US features and cytology for post-FNA management of thyroid incidentalomas on 18F-FDG PET/CT., Materials and Methods: From September 2006 to December 2008, 132 patients with 134 thyroid incidentalomas detected on 18F-FDG PET/CT who had undergone US and US-FNA were included in this study. We evaluated the malignancy rate of thyroid incidentalomas in different subgroups subdivided by US features and US-FNA cytology results. Several variables were compared between the benign and malignant group., Results: The risk of malignancy was 58.2 % (78/132) in thyroid incidentalomas on 18F-FDG PET/CT. Age, gender, and tumor size were not significantly different between the malignant and benign group.  Malignancy rate of thyroid incidentalomas was significantly higher in the suspicious malignant (88.9 %) than in the probably benign group (11.3 %) on US (p < 0.001). Malignancy rates were high in thyroid nodules with "malignancy", "suspicious for malignancy", or "follicular neoplasm" on cytologic results, regardless of US features. However, malignancy rates of thyroid incidentalomas with "unsatisfactory" or "benign" results on cytology were higher in the suspicious malignant (75 %, 12.5 %, respectively) than in the probably benign (0 %) group on US. , Conclusions: This study demonstrated that the risk of malignancy was high in thyroid incidentalomas on 18F-FDG PET/CT even without suspicious US features. However, there was no malignancy in nodules with no suspicious US features and benign cytology. Based on these results, we concluded that US may not replace FNA in the diagnosis of PET incidentalomas, and that a follow-up may be considered of thyroid incidentalomas with benign cytology and no suspicious US features., (© Georg Thieme Verlag KG Stuttgart · New York.)

The dislocation evolution in substrate/film systems with Ag and Cu was investigated by the molecular dynamics simulation of nanoindentation. Film thickness in the range from 2 to 5 nm with the crystalline direction (001), which is the same as that of the substrate, was modelled in the present study. It was observed that the slip of the misfit dislocations in the interface is determined by indentation force and lattice constants of the substrate and the film. It was also shown that the crystal direction and the initial indentation position relative to misfit dislocation have a major role in the form of dislocation structures. The hardness of the bulk Cu is observed to be higher than that of the bulk Ag, as expected, however, it was also observed that soft film coating on the hard substrate cannot increase the hardness of the overall substrate/film system. On the contrary, the hard film, which is thicker than 4 nm, coating on the soft substrate increases the hardness of the overall substrate/film system.

Purpose: We evaluated the potential prognostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with stage IIIC/IV endometrial cancer., Methods: Patients with stage IIIC/IV endometrial cancer who had undergone FDG PET/CT workup for staging were enrolled. Maximum standardized uptake values (SUVmax) measured from regions of interest (ROIs) of the primary tumor (SUVt) and lymph nodes (SUVn) were correlated with overall survival (OS). The SUVn was defined as the highest SUVmax of the metastatic lymph nodes. Survival probability was assessed using the Kaplan-Meier method., Results: A total of 42 patients with a median age of 55.5 years (range 32-76 years) were included. Twenty-nine percent (n = 12) of patients were premenopausal and 71 % (n = 30) were postmenopausal. The average SUVt was 12.9 (range 1.8-36.5), and the average SUVn was 7.3 (range 2.0-22.5). Median follow-up time was 25.9 months (range 1-84 months). Using a SUVt of 9.5 as a cutoff value, two groups with different rates were determined (P = 0.026). In addition, patients with a low SUVn had significantly better OS than those with a high SUVn (P = 0.003). Patients in the International Federation of Obstetrics and Gynecology (FIGO) stage IV group with SUVt ≥ 9.5 or SUVn ≥ 7.3 showed a significantly longer OS than the other groups., Conclusions: FDG uptake of primary endometrial cancer and lymph nodes might be a prognostic factor in advanced endometrial cancer. More aggressive therapy could be considered in patients with stage IV endometrial cancer and high SUVt and/or high SUVn.

Objectives: This study aims to evaluate whether (18)F-FDG excretion patterns reflect renal function in malignant obstructive uropathy and to evaluate if these patterns predict internal ureteral stent success., Methods: One hundred twelve patients who underwent PET/CT for abdominal tumors and displayed hydronephrosis on CT and 59 patients who underwent PET/CT for cancer screening were included in a retrospective study. Hydronephrosis was graded by initial CT and correlated with visual analysis of (18)F-FDG renal parenchymal uptake and excretion patterns. Stent insertion was performed for 84 patients after PET. Follow-up CT was reviewed for hydronephrosis improvement., Results: There were 4 PET patterns in obstructive hydronephrosis which correlated linearly with hydronephrosis severity and serum creatinine levels. Patients with no parenchymal retention and renal excretion (PET pattern 1) showed 97% (28/29) hydronephrosis improvement after stent insertion, and patients with no parenchymal retention and no renal excretion showed 0% (0/9) hydronephrosis improvement after stent insertion. Multivariate analysis showed creatinine levels and PET pattern predicted stent success, but CT hydronephrosis did not., Conclusions: There are 4 PET patterns of obstructive hydronephrosis which correlated with hydronephrosis grade and creatinine levels. Some of these PET patterns can be useful in the prediction of hydronephrosis improvement after stent insertion. Recognition of these patterns in obstructive hydronephrosis may be helpful in improving patient prognosis and quality of life.

Objectives: Glucose metabolism, perfusion, and water diffusion may have a relationship or affect each other in the same tumor. The understanding of their relationship could expand the knowledge of tumor characteristics and contribute to the field of oncologic imaging. The purpose of this study was to evaluate the relationships between metabolism, vasculature and cellularity of advanced hepatocellular carcinoma (HCC), using multimodality imaging such as ¹⁸F-FDG positron emission tomography (PET), dynamic contrast enhanced (DCE)-MRI, and diffusion weighted imaging(DWI)., Materials and Methods: Twenty-one patients with advanced HCC underwent ¹⁸F-FDG PET, DCE-MRI, and DWI before treatment. Maximum standard uptake values (SUV(max)) from ¹⁸F-FDG-PET, variables of the volume transfer constant (K(trans)) from DCE-MRI and apparent diffusion coefficient (ADC) from DWI were obtained for the tumor and their relationships were examined by Spearman's correlation analysis. The influence of portal vein thrombosis on SUV(max) and variables of K(trans) and ADC was evaluated by Mann-Whitney test., Results: SUV(max) showed significant negative correlation with K(trans)(max) (ρ = -0.622, p = 0.002). However, variables of ADC showed no relationship with variables of K(trans) or SUV(max) (p>0.05). Whether portal vein thrombosis was present or not did not influence the SUV max and variables of ADC and K(trans) (p>0.05)., Conclusion: In this study, SUV was shown to be correlated with K(trans) in advanced HCCs; the higher the glucose metabolism a tumor had, the lower the perfusion it had, which might help in guiding target therapy.

Since microRNAs (miRNA, miR) are known to be critical in various cellular processes and diseases, non-invasive molecular imaging system for miRNA is very important for imaging cellular therapy and disease diagnosis. In this study, we developed a radionuclide imaging system for miR-9 using sodium iodide symporter (NIS). During neuronal differentiation of P 19 cells induced by the treatment of retinoic acid (RA), in vitro and in vivo imaging demonstrated that the expression and activity of NIS from the miR-9 NIS reporter gene was clearly repressed by the increased expression and functional activity of miR-9 that bound with the target sequences in the NIS reporter gene and resulted in destabilized the transcriptional activity of NIS gene, compared with the undifferentiated P19 cells. The decreased activity of NIS from the differentiated P19 cells resulted in low uptake of radionuclide and decreased radioisotope signals. The NIS reporter gene-based miRNA imaging system showed a great specificity of imaging miRNA biogenesis during cellular developments. The miRNA NIS reporter gene will provide high sensitive imaging for visualizing miRNA-regulating cellular developments and diseases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The major role of herpes simplex virus (HSV) type 1 infection in Behçet's disease (BD) immunopathogenesis has been demonstrated and inoculating the earlobes of ICR mice with HSV produced a BD-like mouse model. (18)Ffluorodeoxyglucose positron emission tomography (FDG PET) is widely used for diagnosing numerous human diseases other than malignancies. The aim of our study was to evaluate the inflammatory activities of BD-like symptoms in a HSV type 1-induced BD-like mouse model by small-animal FDG PET., Methods: Five HSV-infected ICR mice with BD-like lesions, two asymptomatic HSV-infected mice, and two untreated mice were scanned with microPET, and autopsy specimens were histopathologically assessed to evaluate for infiltration by mixed inflammatory cells., Results: The histopathological evaluation of the inflammatory process in knee and elbow joints significantly correlated with the quantitative assessment of FDG accumulation in the same joints in BD-like ICR mice, HSV-infected asymptomatic mice, and untreated control mice. Small-animal FDG PET clearly detected asymptomatic joint inflammatory processes in both BD-like mice and HSV-infected asymptomatic mice. In addition, genital ulcers and skin ulcers with associated perilesional lymphadenopathies in BD-like models were detected by microPET. However, biodistributed PET-positive images from the stasis of secreted FDG into the bowel lumen could not be distinguished from the inflammatory bowel lesions of BD when compared to FDG uptake in control mice., Conclusions: Our data indicate that FDG PET can non-invasively and quantitatively detect the inflammatory process in an HSV-induced BD-like mouse model.

Background: A correct estimate of the tracheal tube insertion depth can prevent complications, including endobronchial intubation and vocal cord trauma. We evaluated a new topographical method for endotracheal tube positioning relative to the carina, using a well-known prior topographical method for comparison., Methods: One hundred adult (male 50, female 50) patients were studied. The comparison topographic length (in cm) was measured by adding the distance between the right mouth corner and the right mandibular angle to the distance between the right mandibular angle and the center of the sternal manubrium. The new endotracheal tube insertion depth (in cm) was determined by adding the distance between the right mouth corner and the vocal cords, measured with the endotracheal tube itself, to the distance between the thyroid prominence and the manubriosternal joint, and then subtracting 4 cm. After intubation, the endotracheal tube was positioned properly at the right mouth corner and the endotracheal tube tip was evaluated using a fiberoptic bronchoscope at the carina., Results: The distances from the tip of the endotracheal tube to the carina were not significantly different between the methods in the same gender. However, our method allowed endotracheal tube tip placement between 3 cm and 5 cm, above the carina more frequently than the prior method in males., Conclusions: The new topographical method can be used as a guide to positioning the endotracheal tubes.

Purpose: Mutations in the epidermal growth factor receptor (EGFR) gene have been identified as potential targets for the treatment and prognostic factors for non-small cell lung cancer (NSCLC). We assessed the correlation between fluorodeoxyglucose (FDG) uptake and EGFR mutations, as well as their prognostic implications., Methods: A total of 163 patients with pathologically confirmed NSCLC were enrolled (99 males and 64 females; median age, 60 years). All patients underwent FDG positron emission tomography before treatment, and genetic studies of EGFR mutations were performed. The maximum standardized uptake value (SUVmax) of the primary lung cancer was measured and normalized with regard to liver uptake. The SUVmax between the wild-type and EGFR mutant groups was compared. Survival was evaluated according to SUVmax and EGFR mutation status., Results: EGFR mutations were found in 57 patients (60.8 %). The SUVmax tended to be higher in wild-type than mutant tumors, but was not significantly different (11.1 ± 5.7 vs. 9.8 ± 4.4, P = 0.103). The SUVmax was significantly lower in patients with an exon 19 mutation than in those with either an exon 21 mutation or wild type (P = 0.003 and 0.009, respectively). The EGFR mutation showed prolonged overall survival (OS) compared to wild-type tumors (P = 0.004). There was no significant difference in survival according to SUVmax. Both OS and progression-free survival of patients with a mutation in exon 19 were significant longer than in patients with wild-type tumors., Conclusion: In patients with NSCLC, a mutation in exon 19 was associated with a lower SUVmax and is a reliable predictor for good survival.

Dual optical microRNA (miRNA) imaging systems, bioluminescent reporter gene (a signal-off mechanism)- or fluorescent molecular beacon (MB) (a signal-on mechanism)-based miRNA imaging system, have individually allowed us to sense miRNA biogenesis in a noninvasive and iterative manner. Both of these imaging systems have shortcomings with respect to image quality. Therefore, we designed a dual optical imaging systems by simultaneous imaging of a miRNA-1 reporter gene (CMV/Gluc/3xPT&#95;miR-1) and miRNA-1 MB in a single cell to overcome these limitations and used it to visualize miRNA-1, a highly expressed miRNA in cardiac and skeletal muscle. During myogenic differentiation of C2C12 cells, the bioluminescence intensity from CMV/Gluc/3xPT&#95;miR-1 revealed a miRNA-1-dependent gradual decrease and the fluorescence intensity from miR-1 MB demonstrated a miRNA-1-dependent gradual increase both in vitro and in vivo. The dual miRNA-1 imaging systems, which provides the complementary imaging information about miRNA biogenesis, could be useful to sense miRNA expression during various biologic processes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To investigate the therapic choice of intertrochanteric fractures of femur in aged patient., Methods: From June 2006 to June 2010,58 patients with intertrochanteric fracture were treated with surgical methods. There were 25 males and 33 females, aged from 65 to 93 years old (averaged 79 years old). According to the Evans type, type I was in 30 cases, type II was in 28 cases. Of them, 25 patients were treated with hip replacement (group A) and 33 patients were treated with internal fixation (group B). The operative time, blood loss volume, the time of get out of bed, drainage volume, complications and function of joint motion were compared between two groups. According to Harris scoring to evaluate function of joint motion at the 3rd, 6th, 12th months after operation., Results: All patients were followed up more than 12 months (averaged 16.4 months). One patient in group A died of pneumonia one month later after operation and other patients live safely through peri-operation. The group B was better than that of group A at operative time, blood loss volume, drainage volume. In group A, 1 case died and 1 case got DVT, 2 cases got urinary tract infection and 1 case got pneumonia. While in group B, 1 case got bedsore, 1 case got coxa vara and 2 cases got urinary tract infection. The incidence rate of complication in group B was lower than that of group A (P < 0.05). According to Harris scoring system, at the 3rd, 6th,12th months after operation, Harris scoring in group A was respectively (78.43 +/- 5.32), (81.67 +/- 4.87), (87.66 +/- 4.01) scores and in group B was respectively (75.45 +/- 3.22), (76.33 +/- 4.12), (88.65 +/- 3.77) scores. There was statistical significance in Harris scoring at the 3rd, 6th months after operation between two groups (P < 0.05) and there was no statistical significance at the 12th months after operation (P > 0.05). At three months after operation, in group A,14 cases obtained excellent results, 5 good, 5 fair and 1 poor; and in group B, 8 cases obtained excellent results, 13 good, 9 fair and 3 poor. Six months later, in group A,18 excellent, 5 good, 2 fair and 0 poor, and in group B,10 excellent, 15 good, 6 fair and 2 poor. Twelve months later,in group A,18 excellent, 5 good, 1 fair and 1 poor; and in group B, 21 excellent, 9 good, 3 fair and 0 poor. Three and six months later after operation, the clinical effect in group A was better than that of group B (P < 0.05); but twelve months later, there was no significant differences between two groups (P > 0.05)., Conclusion: The internal fixation is especially the preferred method for the aged patient with intertrochanteric fractures. Hip replacement refer to pathologicalfracture caused by cancer, unheeded fracture abnormity, osteoprosis too serious to be treated by internal fixation or patients with ipsilateral symptomatic degenerative joint or revisions caused by failed internal fixation and severely intertrochanteric comminuted fractures and merged severely osteoporosis.

Objective: The purposes of this study were to assess the diagnostic accuracy of 18F-FDG PET (FDG PET) for the detection of metastatic supraclavicular lymph nodes (LNs) and to propose an optimal diagnostic strategy with additional sonography, contrast-enhanced CT (CECT), or both., Materials and Methods: One hundred supraclavicular LNs initially detected using FDG PET were examined using sonography. Regardless of the imaging findings, all 100 supraclavicular LNs underwent sonography-guided fine-needle aspiration biopsy. The maximum standardized uptake values (SUVsmax) of the supraclavicular LNs were measured, and a receiver operating characteristic (ROC) analysis was performed to determine the cutoff SUVmax. Then we evaluated the diagnostic performance of FDG PET and figured out the optimal combination of FDG PET and sonography or CECT to improve the diagnostic accuracy of the imaging studies and minimize procedures., Results: In total, 86 of 100 PET-detected supraclavicular LNs were malignant. With application of the cutoff value obtained by ROC analysis (SUVmax=3.0), the diagnostic accuracy of FDG PET was 75.0% with a sensitivity of 74.4% and specificity of 78.6%. For supraclavicular LNs with an SUVmax of more than 3.0, FDG PET showed a positive predictive value of 95.5%; for supraclavicular LNs with an SUVmax of 3.0 or less, sonography excluded all false-negative FDG PET cases and showed a high negative predictive value of 100%. When sonography was selectively applied to cases with an SUVmax of 3.0 or less, the overall diagnostic accuracy increased to 92%., Conclusion: Our study revealed a high incidence rate of metastasis in PET-detected supraclavicular LNs in cancer patients. We believe that our proposed diagnostic workflow could decrease unnecessary diagnostic procedures in the evaluation of PET-positive supraclavicular LNs in cancer patients with reliability.

Background: Metabolic activity assessed by (18)F-fluorodeoxyglocuse-positron emission tomography ((18)F-FDG-PET) reflects biological aggressiveness and prognoses in various tumors. The authors present a correlation between tumor metabolic activity and clinical outcomes in patients with hepatocellular carcinoma (HCC)., Methods: Over a 3-year period (2005-2008), 135 locally advanced HCC patients were treated with localized concurrent chemoradiotherapy (CCRT; external beam radiotherapy at 45 grays for 5 weeks plus concurrent hepatic arterial infusion of 5-fluorouracil during the first and fifth week) followed by repetitive hepatic arterial infusional chemotherapy with 5-fluorouracil and cisplatin. Among them, the authors studied 107 who received (18)F-FDG-PET before CCRT. Maximal standardized uptake values (SUVs) of tumors were calculated., Results: The median maximal tumor SUV was 6.1 (range, 2.4-∼19.2). Patients with low maximal tumor SUVs (<6.1) had a higher disease control rate than those with high maximal tumor SUVs (≥6.1) (86.8% vs 68.5%, respectively, P = .023). Both median progression-free survival (PFS; 8.4 vs 5.2 months; P = .003) and overall survival (OS; 17.9 vs 11.3 months; P = .013) were significantly longer in the low maximal tumor SUV group than in the high maximal tumor SUV group, respectively. In multivariate analysis, low maximal tumor SUV and objective responses to CCRT remained significant for PFS and OS. The high maximal tumor SUV group was more likely to have extrahepatic metastasis within 6 months than the low maximal tumor SUV group (58.1% vs 26.8%, respectively; P < .001). Similar results were obtained for the maximal tumor SUV/normal liver maximal SUV ratio (<2 vs ≥2) concerning progression, death, and extrahepatic metastasis., Conclusions: Metabolic activity may be useful not only in predicting prognosis and treatment responses, but also in establishing optimal treatment plans in locally advanced HCC., (Copyright © 2011 American Cancer Society.)

Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by renal phosphate excretion, hypophosphatemia, and osteomalacia. This syndrome is often caused by tumors of mesenchymal origin. Patients with oncogenic osteomalacia have abnormal bone mineralization, resulting in a high frequency of fractures. Tumor resection is the treatment of choice, as it will often correct the metabolic imbalance. Although oncogenic osteomalacia is a potentially curable disease, diagnosis is difficult and often delayed because of the small size and sporadic location of the tumor. Bone scintigraphy and radiography best characterize osteomalacia; magnetic resonance imaging findings are nonspecific. Here, we report a case of oncogenic osteomalacia secondary to a phosphaturic mesenchymal tumor that was successfully detected by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). This case illustrates the advantages of (18)F-FDG PET/CT in detecting the occult mesenchymal tumor that causes oncogenic osteomalacia.

Purpose: Bone metastasis from hepatocellular carcinoma (HCC) can present with soft tissue formation, resulting in oncologic emergency. Contrast-enhanced FDG PET/CT and bone scintigraphy were compared to evaluate characteristics of bone metastases with or without soft tissue formation from HCC., Methods: Of 4,151 patients with HCC, 263 patients had bone metastases. Eighty-five patients with bone metastasis from HCC underwent contrast-enhanced FDG PET/CT. Fifty-four of the enrolled subjects had recent (99m)Tc-HDP bone scintigraphy available for comparison. Metastatic bone lesions were identified with visual inspection on FDG PET/CT, and maximum standardized uptake value (SUVmax) was used for the quantitative analysis. Confirmation of bone metastasis was based on histopathology, combined imaging modalities, or serial follow-up studies., Results: Forty-seven patients (55%) presented with soft tissue formation, while the remaining 38 patients presented without soft tissue formation. Frequent sites of bone metastases from HCC were the spine (39%), pelvis (19%), and rib cage (14%). The soft-tissue-formation group had more frequent bone pain (77 vs. 37%, p < 0.0001), higher SUVmax (6.02 vs. 3.52, p < 0.007), and higher incidence of photon defect in bone scintigraphy (75 vs. 0%) compared to the non-soft-tissue-formation group. FDG PET/CT had higher detection rate for bone metastasis than bone scintigraphy both in lesion-based analysis (98 vs. 53%, p = 0.0015) and in patient-based analysis (100 vs. 80%, p < 0 .001)., Conclusions: Bone metastasis from HCC showed a high incidence of soft tissue formation requiring emergency treatment. Although the characteristic findings for soft tissue formation such as photon defect in bone scintigraphy are helpful in detection, overall detectability of bone metastasis is higher in FDG PET/CT. Contrast-enhanced PET/CT will be useful in finding and delineating soft-tissue-forming bone metastasis from HCC.

Background: Carcinoma of unknown primary tumors (CUP) is present in 0.5%-9% of all patients with malignant neoplasms; only 20%-27% of primary sites are identified before the patients die. Currently, 18F-fluorodeoxy-glucose positron-emission tomography (18F-FDG PET) or PET combined with computed tomography (PET/CT) is widely used for the diagnosis of CUP. However, the diagnostic yield of the primary site varies. The aim of this study was to determine whether PET or PET/CT has additional advantages over the conventional diagnostic workup in detecting the primary origin of CUP., Findings: Twenty patients with unknown primary tumors that underwent PET or PET/CT were included in this study. For all patients, the conventional diagnostic workup was unsuccessful in detecting the primary sites. Among 20 patients, 11 had PET scans. The remaining nine patients had PET/CT. In all 20 patients, neither the PET nor PET/CT identified the primary site of the tumor, including six cases with cervical lymph node metastases. The PET and PET/CT revealed sites of FDG uptake other than those associated with known metastases in seven patients, but these findings did not influence patient management or therapy. Two patients had unnecessary invasive diagnostic procedures due to false positive results on the PET or PET/CT., Conclusions: Although it is inconclusive because of small sample size of the study, the additional value of PET or PET/CT for the detection of primary sites in patients with CUP might be less than expected; especially in patients that have already had extensive conventional diagnostic workups. Further study is needed to confirm this finding.

MicroRNAs (miRNAs, miR) are associated with multiple cellular processes and diseases. Here, we designed fluorescent DNA probes composed of stem loop-structured DNA complementary to miRNAs and fluorophore-quencher pairs [molecular beacon (MB)] to simultaneously monitor the biogenesis of miR-206 and miR-26a, which are highly expressed during myogenic differentiation. C2C12 cells were transfected with an MB targeting miR-26a and containing a 6-FAM-BHQ1 pair (miRNA-26a MB) or an MB targeting miR-206 with a Texas Red-BHQ2 pair (miRNA-206 MB). In vitro and in vivo fluorescence analysis revealed that, only in differentiated single C2C12 cell, significantly increased fluorescence signals of miRNA-26a MB, miRNA-206 MB or simultaneous incubation of both beacons were detected due to the hybridization of miR-206 or miR-26a with their respective beacons, resulting in activation of fluorescence. Our MB-based miRNA imaging system may serve as a new imaging probe for monitoring multiple miRNAs during various cellular or disease processes associated with miRNAs., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Purpose: To review the 2-deoxy-2-fluoro-[F-18]-D: -glucose (FDG) positron emission tomography (PET) findings of focal eosinophilic liver disease (FELD) and to correlate them with radiologic and pathologic findings., Materials and Methods: Fourteen patients, who were clinically or pathologically diagnosed as FELD and underwent CT and/or MR and PET, were enrolled. Two radiologists analyzed CT and MRI regarding size, shape, margin, attenuation, signal intensity (SI), and enhancement patterns of the lesion, both qualitatively and quantitatively. One pathologist determined whether the lesion is eosinophilic abscess (EA) or infiltration. One nuclear medicine physician reviewed the PET images and calculated the peak standardized uptake value (SUV) of the lesion. PET findings were then correlated with CT or MRI, and pathologic findings., Results: Eighty-five lesions were detected on CT (n = 85) and MRI (n = 10). Only four of the lesions showed FDG uptake and their mean SUV was 4.0. The size of the lesions with FDG uptake (26.5 mm) was significantly larger than those without uptake (11.8 mm). Mean attenuation and SI differences between the lesion and adjacent liver on CT and T2-weighted MRI tended to be larger in the uptake group (64.3 and 124.5) than the group without uptake (28.5 and 43.5). Among the four histologically confirmed lesions, two EAs and one of the two EIs showed FDG uptake., Conclusion: Most FELD do not show FDG uptake on PET. However, larger nodules with greater attenuation or SI differences from the background liver on CT or T2-weighted MRI or those with EA on pathology tend to show FDG uptake on PET.

Purpose: We evaluated the short-term and mid-term differences in perfusion and function after off-pump and on-pump coronary artery bypass grafting (CABG) using gated myocardial single photon emission computed tomography., Materials and Methods: A total of 70 patients with coronary artery disease who underwent CABG were included based on the propensity score matching results from 165 patients. Thirty-five patients underwent off-pump and 35 patients on-pump CABG. Rest (201)Tl/dipyridamole stress (99 m)Tc-methoxyisobutylisonitrile gated single photon emission computed tomographies were performed preoperatively and postoperatively at short-term (103 ± 23 days after surgery) and mid-term follow-up (502 ± 111 days after surgery). Changes in left ventricular ejection fraction, end systolic volume, stress and rest segmental perfusion, and segmental wall thickening were compared between the two groups. The segments with preoperative rest (201)Tl uptake under 60% of maximum uptake were included in the segmental analysis., Results: Left ventricular ejection fraction (P = 0.001) and end systolic volume (P = 0.008) showed significant improvement in both groups. There were no significant short-term and mid-term differences between the two groups in terms of left ventricular ejection fraction (P = 0.309) and end systolic volume (P = 0.938). Likewise, segmental rest (P = 0.178) and stress perfusion (P = 0.071), and systolic wall thickening (P = 0.241) showed significant improvement in both groups with similar time courses., Conclusion: Off-pump CABG resulted in significant improvements in left ventricular ejection fraction, end systolic volume, and regional myocardial perfusion and function that are comparable to on-pump CABG at short-term and mid-term. Gated myocardial SPECT successfully revealed that off-pump CABG is as good as on-pump CABG from the viewpoint of myocardial perfusion and function.

Thousands of proteins are simultaneously involved in the maintenance of a single cancer cell. Fluorescent resonance energy transfer (FRET) is one of the most general techniques for imaging biologically interacting molecules in a cell. Here, we applied FRET to image the co-localization of two proteins that do not interact biologically (nucleolin and integrin α(v) β(3),) both of which are highly expressed in the plasma membrane of cancer cells. AS1411 aptamer, which targets nucleolin, was labeled by Cy3 (Cy3-AS1411) and arginine-glycine-aspartic acid (RGD) peptide, which targets integrin α(v) β(3) , was conjugated with quantum dot (525 nm, Qd) Qd arginine-glycine-aspartic acid (Qd-RGD). FRET activities between Cy3-AS1411 and Qd-RGD were measured in HeLa cells, a human cervical cancer cell line. FRET phenomena between Qd and Cy3 showed good compatibility according to proximity. The fluorescence signature using Qd-RGD and Cy3-AS1411 showed that nucleolin and integrin α(v) β(3) proteins were highly expressed in HeLa cells. Co-incubation of Qd-RGD and Cy3-AS1411 in a single HeLa cell demonstrated that the fluorescence overlay by FRET was quantitatively and geographically quite different from that of individual confocal images. These results suggest that Qd-based FRET analysis can provide information on geographical co-localization of proteins in naïve cells, which is very important for determining the molecular and cellular functions of genes involved in cancers and other clinical diseases., (Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

As lymph node metastasis is the most important factor determining the surgical outcome of lung cancer, we evaluated the accuracy and clinical usefulness of functional imaging with integrated positron-emission tomography and computed tomography in nodal staging of non-small-cell lung cancer. Between October 2003 and August 2004, 43 newly diagnosed patients underwent curative surgical resection or mediastinoscopic nodal biopsy after chest computed tomography as well as whole-body functional imaging for clinical staging. Based on histopathologic findings in the lymph nodes, we compared the diagnostic usefulness of computed tomography and functional imaging. Twenty-two patients were N0 stage, 6 were N1, 11 were N2, and 4 were N3. Although functional imaging seemed to be superior for evaluation of N2 nodes, there were no significant differences in the sensitivity, specificity, positive-predictive value, negative-predictive value, or accuracy. The situation was similar for N1 nodes, and there were no significant differences except for the false-negative rate. High false-positive and negative-rates for N2 lymph nodes suggest that functional imaging should not replace mediastinoscopy.

Purpose: The aim of the study was to assess the accuracy of (18)F-fluorodeoxyglucose (FDG) PET/CT in mediastinal lymph node staging of patients with non-small-cell lung cancer (NSCLC) in a region with a high prevalence of granulomatous disease., Methods: Between March 2004 and February 2006, all patients with NSCLC underwent FDG PET/CT and contrast-enhanced thoracic CT, and subsequent surgical resection. PET/CT and contrast-enhanced CT images of 182 patients (126 men and 56 women; mean age 60.7 years) with NSCLC were acquired. Mediastinal node staging was determined using the American Joint Committee on Cancer (AJCC) staging system. Surgical and histological findings served as the reference standard., Results: A total of 182 patients with 778 mediastinal node stations were evaluated. Sensitivity and specificity of contrast-enhanced CT were 36% and 80% on a per-patient basis and 23% and 92% on a per-node station basis. Sensitivity and specificity of PET/CT were 81% and 73% on a per-patient basis and 75% and 85% on a per-node station basis. After lymph nodes with calcification and bilateral hilar distribution were considered benign, sensitivity and specificity of PET/CT were 75% and 89% on a per-patient basis and 66% and 96% on a per-node station basis., Conclusion: This prospective study suggests that FDG PET/CT can more accurately stage mediastinal lymph nodes than CT. Considering lymph node calcification and distribution pattern could improve specificity at the cost of a decrease in sensitivity.

Unlabelled: The (18)F-FDG uptake pattern on PET could be an indicator of the prognosis and aggressiveness of various tumors, including hepatocellular carcinoma (HCC). Hexokinase, especially hexokinase type II (HKII), plays a critical role in (18)F-FDG uptake in rapidly growing tumors. We established a stable cell line overexpressing HKII by the transfection of full DNA of HKII to HCC cells (SNU449) that express low levels of HKII and investigated how (18)F-FDG uptake mechanisms, especially overexpression of HKII, are linked to tumor proliferation mechanisms., Methods: The HKII gene was stably transfected to SNU449 cells with an expression vector. HKII expression in the cells was verified by reverse-transcriptase polymerase chain reaction, Western blot analysis, adenosine triphosphate (ATP) and lactate production, (18)F-FDG uptake measurement, and confocal microscopy. Cellular proliferation activity and response to the anticancer drug cisplatin were evaluated by cell counting using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. For the evaluation of molecular pathways involved in tumor proliferation, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was investigated., Results: The stable cell line produced HKII effectively, but expression of other enzymes or transporters for glycolysis, such as glucose-6-phosphatase (G6Pase), HKI and III, and glucose transporter type 1 and 2 (Glut-1 and Glut-2), did not show any changes. (18)F-FDG uptake was significantly increased after transfection. ATP and lactate production was also increased after transfection. Overexpressed HKII was associated with mitochondria on confocal microscopy. Cells with overexpression of HKII, compared with the nontransfected cell line, showed 1.5- to 2-fold higher cell survival and resistance to the anticancer agent cisplatin (2- to 8-fold). In the molecular study, the activated form of Akt was increased after transfection, and PI3K inhibitor dissociated the mitochondrial HKII to the cytoplasm. In addition, the adenosine monophosphate-activated protein kinase (AMPK) pathway is also involved in Akt signaling., Conclusion: HKII plays an important role in (18)F-FDG uptake and tumor proliferation by both the PI3K-dependent and the PI3K-independent Akt signal pathways; therefore, the (18)F-FDG uptake pattern on a PET scan can be a surrogate marker of prognosis in HCC.

Objective: We sought to determine whether positron emission tomography-computed tomography (PET-CT) is more accurate than CT for detecting metastatic cervical lymph nodes in recurrent papillary thyroid carcinoma (PTC) and to determine the relationship between the CT features and PET-CT findings of metastatic nodes., Methods: Eleven consecutive patients with recurrent PTC underwent contrast-enhanced CT (CECT) and PET-CT before surgery. We retrospectively evaluated CECT and PET-CT images to determine the presence of metastatic nodes by level-by-level analysis. The CT findings of the PET-CT results that were positive and negative for metastatic nodes were compared., Results: Metastatic nodes were found at 28 (78%) of 36 neck levels surgically explored. The sensitivity, specificity, and accuracy of CECT for the detection of metastatic nodes were 75.0%, 87.5%, and 77.8%, respectively, and those of PET-CT were 35.7%, 87.5%, and 48.6%, respectively, by level-by-level analysis. No significant difference in the CT features was found between the PET-CT findings positive and negative for metastatic nodes (P > 0.05)., Conclusions: Computed tomography is more sensitive and accurate than PET-CT for detecting metastatic lymph nodes in recurrent PTC. No significant relationship was found between the CT features and the PET-CT findings of the metastatic nodes.

Background: (18)F-FDG PET/CT has been used to differentiate malignant solid lung nodules from benign nodules. We assess the feasibility of integrated (18)F-FDG PET/CT for the differentiation of malignancy from inflammation manifested as ground-glass nodules (GGNs) on chest CT., Methods: A total of 68 GGNs in 45 patients (M:F=24:21; mean age, 61) fulfilled the following criteria: (a) nodules composed of >/=50% ground-glass opacity, (b) patients who underwent integrated PET/CT within 1 week following dedicated chest CT, (c) definitive diagnosis determined by pathological specimen or at least 9 months of follow-up, and (d) lesions >/=10mm in diameter. 36 malignant GGNs were pathologically proved as adenocarcinoma (n=20), bronchioloalveolar carcinoma (n=11), low-grade lymphoma (n=3), metastatic mucinous adenocarcinoma (n=1) and unknown low-grade malignancy (n=1). 32 inflammatory GGNs were confirmed as pneumonic infiltration as they had disappeared on follow-up CT and were associated with compatible clinical features (n=26) or as chronic inflammation with fibrosis by VATS biopsy (n=6). Using CT density histogram analysis, 14 were classified as pure GGNs and 54 as part-solid nodules. Integrated PET/CT was evaluated by measuring the maximum standardized uptake value (SUV) at the region of interest located at each lesion. The Mann-Whitney U test was performed to compare the SUV of malignancy and inflammation. The optimal cut-off value of SUV to differentiate malignancy from inflammation was determined using a receiver operating characteristic-based positive test. Sensitivity, specificity, accuracy, and positive predictive values (PPV) and negative predictive values (NPV) were calculated at the level of the optimal cut-off value. SUV showing 100% PPV for inflammatory GGNs was evaluated., Results: In part-solid nodules, the maximum SUV was significantly higher in inflammation (2.00+/-1.18; range, 0.48-5.60) than in malignancy (1.26+/-0.71; range, 0.32-2.6) (P=0.018). On the other hand, in pure GGNs, the maximum SUV of malignancy (0.64+/-0.19; range, 0.43-0.96) and inflammation (0.74+/-0.28; range, 0.32-1.00) showed no difference (P=0.37). Using the optimal cut-off value of SUV as 1.2 (P=0.01) sensitivity, specificity, accuracy, PPV and NPV in part-solid nodules were 62.1%, 80.0%, 70.4%, 78.3% and 64.5%, respectively. Six part-solid nodules, which showed a maximum SUV of higher than 2.6, were all inflammations., Conclusion: The part-solid nodules with positive FDG-PET could be inflammatory nodules rather than malignant nodules. This is a quite paradoxical result when considering the basic knowledge that malignant pulmonary nodules have higher glucose metabolism.

Myocardial SPECT using (99m)Tc-sestamibi, (99m)Tc-tetrofosmin, (201)Thallium is widely used in nuclear cardiology. Left ventricular systolic wall thickening (SWT) by SPECT and regional maximal elastance (rE(max)) using arterial tonometry were compared. rE(max) was calculated from time-pressure and time-volume curves. In normal heart, improvement of SWT was 4.1+/-11%, while 6.0+/-16% in dilated heart. Improvement of rE(max) was 0.67+/-1.0mmHg/mL in normal heart and 0.32+/-0.7mmHg/mL in dilated heart (p<0.05). rE(max) can be an alternative variable as an index of regional contractility.

Background: To investigate the utility of CT volumetry for primary gastric lesions in the prediction of pathologic response to neoadjuvant chemotherapy in patients with resectable advanced gastric cancer (AGC)., Materials and Methods: Thirty-three consecutive patients with resectable AGC stage >or=T2 and N1), who had been treated with neoadjuvant chemotherapy and radical gastric resection, were prospectively enrolled in this study. There were 30 men and 3 women with a mean age of 53.8 years. Contrast-enhanced CT was obtained after gastric distention with air before and after chemotherapy using a MDCT scanner. Pre- and post-chemotherapy thickness or short diameter and volume of the primary gastric tumor and largest lymph node (LN), were measured using a dedicated 3D software by two radiologists in consensus. PET/CT was also performed and the peak standardized uptake value (SUV) of primary gastric tumor and largest LN before and after chemotherapy was measured. The percentage diameter, volume, and SUV reduction rates for both the primary gastric tumor and the LN, were calculated and correlated with the histopathologic grades of regression using the Spearman correlation test. Differentiation between pathologic responders and nonresponders was assessed using receiver operating characteristic (ROC) analysis., Results: Among the three CT parameters which showed significant correlation with the histopathologic grades of regression, the correlation factor was highest in the percentage volume reduction rate of primary gastric tumor (rho = 0.484, P = 0.004) followed by percentage volume reduction of the index node (rho = 0.397, P = 0.022), and percentage diameter reduction of the index node (rho = 0.359, P = 0.04). However, the percentage thickness decrease rate (P = 0.208) and the percentage SUV reduction rate (P = 0.619) of primary gastric tumor were not significantly correlated with the histopathologic grades of regression. When the optimal cutoff value of the percentage volume reduction rate of primary gastric tumor was determined to be 35.6%, a sensitivity of 100% (16/16) and a specificity of 58.8% (10/17) were achieved., Conclusion: CT volumetry for primary gastric tumor may be the most accurate tool in the prediction of pathologic response following neoadjuvant chemotherapy in patients with resectable AGC.

It has been reported that 4-1BB triggering in vivo selectively suppressed the recall response of staphylococcal enterotoxin A (SEA)-specific CD4(+) T cells, in which CD8(+) T-derived TGF-beta was involved. Here, we have examined an alternative mechanism for the 4-1BB-mediated CD4(+) T suppression, as the neutralization of TGF-beta is only effective in rescuing the SEA-specific recall response at high cellular concentrations. We show that this selective suppression of CD4(+) T cells by 4-1BB triggering in vivo is mediated mainly by induction of indoleamine 2,3-dioxygenase (IDO) in an IFN-gamma-dependent manner. SEA-specific CD4(+) T responses were suppressed partly by TGF-beta-expressing CD8(+) T cells, particularly CD11c(+)CD8(+) T cells, but strongly inhibited by dendritic cells (DCs) expressing IDO. IFN-gamma that increased IDO in DCs was produced primarily from CD11c(+)CD8(+) T cells, which were expanded selectively by 4-1BB stimulation. CD4(+), CD8(+), and plasmacytoid DCs exerted a similar suppressive activity toward the SEA-specific CD4(+) T cells. Neutralization of IFN-gamma or IDO activity in vivo largely reversed the 4-1BB-mediated CD4(+) T suppression. Collectively, these data indicate that 4-1BB-dependent suppression of SEA-specific CD4(+) T responses was mediated mainly by IFN-gamma-dependent IDO induction and partially by TGF-beta.

Semiconductor quantum dots (QDs), which have broad absorption with narrow emission spectra, are useful for multiplex imaging. Here, fluorescence derby imaging using dual color QDs conjugated by the AS1411 aptamer (targeting nucleolin) and the arginine-glycine-aspartic acid (targeting the integrin alpha(v)beta(3)) in cancer cells is reported. Simultaneous fluorescence imaging of cellular distribution of nucleolin and integrin alpha(v)beta(3) using QDs enables easy monitoring of separate targets in the cancer cells and the normal healthy cells. These results suggest the feasibility of a concurrent visualization of QD-based multiple cancer biomarkers using small molecules such as aptamer or peptide ligands.

Background: Tourniquet deflation during lower extremity surgery affects the hemodynamics and metabolism of the patient, which can affect brain activity. This study examined the changes in brain activity during tourniquet deflation by measuring the bispectral index (BIS)., Methods: The BIS was measured during surgery in forty patients who had received knee arthroscopic surgery under general anaesthesia. The BIS was measured 5 minutes before deflation (DB5) and 5 minutes after deflation (DA5)., Results: The BIS at DB5 and DA5 was 50.2 +/- 9.9 and 44.4 +/- 10.4, respectively. The BIS of DA5 was significantly lower than that of DB5 (P < 0.05)., Conclusions: Tourniquet deflation during lower extremity surgery decreases the BIS associated with hemodynamic and metabolic changes. However, its clinical significance in neurologically critical patients, such as geriatric or neurologically disabled patients, remains to be clarified.

Background: The use of CO2 for pneumoperitoneum during laparoscopic surgery provokes a decrement in the gastric pH. Since the incidence rate of PONV increases after laparoscopic surgery, the possibility of lung aspiration of gastric juice with a low pH during a postanesthetic emergence may increase and this could be fatal for the patient. We conducted this study to determine the effects of esomeprazole premedication on inhibiting the decrement of the gastric pH during laparoscopic surgery., Methods: 40 adult patients with no underlying diseases were chosen and 20 patients each were grouped as C (the control group) and E (the esomeprazole group). In both group, 0.2 mg glycopyrrolate was given intramuscularly 30 minutes prior to the surgery. In group E, esomeprazole was given orally 2 hours prior to the surgery. The pH, PaCO2, and PETCO2 were measured via pH probe, an ABGA and an capnogram at preinsufflation and 15, 30 and 60 minutes after the CO2 insufflation and right before CO2 exhaustion (predeflation)., Results: Comparing the measurements of the gastric pH between group E and group C, all the results showed a significant increase in group E (P < 0.05). The difference of the PaCO2 and PETCO2 in the two groups was not significance., Conclusions: In contrast to the decrease in the gastric pH as the PaCO2 and PETCO2 increased in group C, the gastric pH in group E remained high until the end of the surgery despite the increase in the PaCO2 and PETCO2. Esomeprazole premedication seem to have an effect for inhibiting the gastric pH decrement regardless of the increase in the PaCO2 and PETCO2 during laparoscopic surgery.

Background: In the course of surveillance of gastric cancer recurrence after curative resection, contrast CT scan is used in general. However, new findings from CT scan are not always confirmatory for the recurrence. In this case, we usually use short-term follow up strategy or therapeutic intervention with clinical decision. Recently, the use of fusion Positron Emission Tomography/Computed Tomography (PET/CT) is increasing. The purpose of this study is to evaluate the efficacy and usefulness of PET/CT for detecting recurrence of gastric cancer after curative resection., Methods: Fifty two patients who received curative resection of gastric cancer and had undergone PET/CT and contrast CT for surveillance of recurrence until Dec 2006 in Seoul National University Hospital were analyzed retrospectively. Recurrence of gastric cancer was validated by histologic confirmation (n = 17) or serial contrast CT follow up with at least 5 month interval (n = 35). McNemar's test and Fisher's exact test were used to evaluate sensitivity and specificity of PET/CT and contrast CT., Results: Of 52 patients, 38 patients were confirmed as recurrence. The sensitivity was 68.4% (26/38) for PET/CT and 89.4% (34/38) for contrast CT (p = 0.057). The specificity was 71.4% (10/14) and 64.2% (9/14), respectively (p = 1.0). In terms of the recurred sites, the sensitivity and specificity of PET/CT were similar to those of contrast CT in all sites except peritoneum. Contrast CT was more sensitive than PET/CT (p = 0.039) for detecting peritoneal seeding. Additional PET/CT on contrast CT showed no further increase of positive predictive value regardless of sites. Among 13 patients whose image findings between two methods were discordant and tissue confirmation was difficult, the treatment decision was made in 7 patients based on PET/CT, showing the final diagnostic accuracy of 42.8% (3/7)., Conclusion: PET/CT was as sensitive and specific as contrast CT in detection of recurred gastric cancer except peritoneal seeding. However, additional PET/CT on contrast CT did not increase diagnostic accuracy in detection of recurred gastric cancer. Further studies are warranted to validate the role of PET/CT in detection of gastric cancer recurrence.

Chemotherapy can precondition for immunotherapy by creating an environment for homeostatic lymphoproliferation and eliminating some of the suppressive immune networks. We found that combination therapy with anti-4-1BB and cyclophosphamide (CTX) produced synergistic anticancer effects in the poorly immunogenic B16 melanoma model in mice. The antitumor effect of the combination therapy depended mainly on CD8(+) T cells, the 4-1BB-dependent expansion and differentiation of which into IFN-gamma-producing CD11c(+)CD8(+) T cells was enhanced by CTX. Anti-4-1BB induced a rapid repopulation of T and B cells from CTX-mediated lymphopenia. Anti-4-1BB protected naïve T cells from CTX and promoted proliferation of memory/effector and memory T cells. The combination treatment produced approximately 60- and 2.2-fold more CTLs per tumor-associated antigen compared with CTX or anti-4-1BB alone, respectively. This indicates that anti-4-1BB promoted a preferential expansion of tumor-specific CD8(+) T cells among the repopulated lymphocytes following CTX-mediated lymphopenia. CTX treatment enhanced 4-1BB expression on CD4 and CD8 T cells, and CTX alone or in combination with anti-4-1BB effectively suppressed peripheral regulatory T cells. Our results indicate that anti-4-1BB and CTX can be practical partners in cancer therapy because CTX creates an environment in which anti-4-1BB actively promotes the differentiation and expansion of tumor-specific CTLs.

Objective: The maximal safe dose (MSD) on the basis of bone marrow irradiation levels allows the delivery of a large amount of I-131 to thyroid cancer tissue. The efficacy of MSD therapy in differentiated metastatic thyroid cancers that persisted after conventional fixed dose therapy is investigated., Methods: Forty-seven differentiated thyroid carcinoma patients with non-responsive residual disease despite repetitive fixed dose I-131 therapy were enrolled in this study. Their postoperative pathologies were 43 papillary carcinomas and 4 follicular carcinomas. The MSD was calculated with the Memorial Sloan-Kettering Cancer Center protocol using serial blood samples. The MSDs were administered at intervals of 6 months. Treatment responses were evaluated using I-131 whole-body scans and serum thyroglobulin measurements., Results: The mean calculated MSD was 12.5 +/- 2.1 GBq (339.6 +/- 57.5 mCi). Of the 46 patients, 7 (14.9%) showed complete remission, 15 (31.9%) partial remission, 19 (40.4%) stable disease, and 6 (12.8%) disease progression. Of the patients who showed complete or partial remission, 15 (65%) showed response after the first MSD session and 6 (26%) showed response after the second session. Twenty-nine patients (62%) experienced transient cytopenia after therapy, but three did not recover to the baseline level., Conclusions: The maximal safe dose provides an effective means of treatment in patients who failed to respond adequately to conventional fixed dose therapy. I-131 MSD therapy can be considered in patients who fail fixed dose therapy.

Herpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers CD4(+) T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in CD4(+) T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed CD4(+) T cells expressing CCR2 and CCR5. Expression of MCP-1 in the corneal stroma was confirmed in vivo. Finally, when HSV-1-primed CD4(+) T cells were adoptively transferred into wild type and MCP-1-deficient mice that had been sublethally irradiated to minimize chemokine production from immune cells, infiltration of CD4(+) T cells was markedly reduced in the MCP-1-deficient mice, suggesting that it is the MCP-1 from HSV-1-infected keratocytes that attracts CD4(+) T cells into the cornea.

Purpose: The purpose of this study was to evaluate the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) for the identification of suspected recurrent endometrial cancer after treatment., Methods: Thirty-one women (median age, 53 years) with endometrial cancer treated by primary staging laparotomy who had [(18)F]fluorodeoxyglucose (FDG) PET/CT performed for suspected recurrence were retrospectively reviewed. The findings of the PET/CT scans were compared, with the histological examination after a surgical biopsy in 20 cases and with clinical follow-up in 11 cases to determine the diagnostic accuracy of PET/CT., Results: Twelve (38.7%) of the 31 patients had a documented recurrence by surgical biopsy or clinical follow-up, and 19 (61.3%) had no evidence of recurrence. Of the 12 patients with recurrent disease, nine (75.0%) women were confirmed to have a recurrence by surgical biopsy. A close correlation was found between the PET/CT and histological or clinical analyses (kappa = 0.933, p < 0.001). The overall sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and accuracy of PET/CT were 100, 94.7, 92.3, 100, and 96.8%, respectively. The PET/CT results modified the diagnostic or treatment plan in seven (22.6%) patients, resulting in five (16.1%) patients undergoing previously unplanned therapeutic procedures and eliminating previously planned diagnostic procedures in two (6.5%) patients. Patients with negative PET/CT scans showed significantly better progression-free survival than those with positive scans (p = 0.015)., Conclusion: Integrated PET/CT appears to be highly sensitive, specific, and accurate as a post-therapy surveillance modality for endometrial cancer in well-selected patients. The PET/CT might be used to improve patient surveillance and prognosis.

F-18-FDG PET and PET/CT are useful for staging, predicting the prognosis, and evaluating recurrence and treatment response in hepatocellular carcinomas (HCCs) and cholangiocarcinomas. Increased F-18-FDG uptake within tumors could be a surrogate marker of aggressive behavior and poor clinical outcome, despite high false-negative rates in detecting primary intrahepatic low-grade HCCs and periductal-infiltrating cholangiocarcinomas. Dualtracer PET or PET/CT using carbon-11-acetate and F-18-FDG will increase diagnostic performance in HCC., (Copyright © 2008 Elsevier Inc. All rights reserved.)

This study was undertaken to investigate age-dependent and postmenopausal changes in the serum levels of anti-Mullerian hormone (AMH), inhibin B, insulin-like growth factor (IGF)-I, IGF-binding protein-3 (IGFBP-3), and follicle-stimulating hormone (FSH), and to determine which of these markers best reflects the aging process in women. A total of 144 women aged 20-59 yr were enrolled in this cross-sectional study. Blood samples were obtained on cycle day 3 of regularly menstruating women (n=111), or at random in postmenopausal women (n=33). Data were analyzed with respect to premenopausal women age groups and compared in pre- and postmenopausal women. Area under the receiver operating characteristic curve (ROCAUC) analyses were performed to assess the ability of each marker to discriminate between the pre- and postmenopausal status. Serum levels of AMH, IGF-I, and IGFBP-3 decreased and serum levels of FSH increased significantly with age in premenopausal women. Serum luteinizing hormone (LH) was higher and inhibin B was lower in women in their 20-30's than in 40's. Serum levels of AMH and IGF-I showed a consistent decrease with all age groups. ROCAUC analysis showed that the diagnostic accuracy of AMH for menopausal status was similar to those of FSH, LH, and inhibin B, and was better than that of IGF-I. In conclusion, the serum AMH level appears to be the best marker of the aging process in premenopausal women.

Objective: The Taq1A polymorphism in the dopamine D2 receptor (DRD2) gene has been reported to be associated with the pharmacodynamics of antipsychotic drugs. We investigated the metabolic response of glucose in the brain to aripiprazole in relation to the DRD2 Taq1A polymorphism., Methods: Twenty healthy male volunteers were recruited and were divided into two groups of 10 participants, according to their DRD2 genotypes (A1A1, n=10; A2A2, n=10). The volunteers received single oral doses of aripiprazole (10 mg) and a placebo, following a single-blind, placebo-controlled, randomized, two-way crossover study design. Brain glucose metabolism was assessed using positron emission tomography, scanned with 18F-fluorodeoxyglucose 12 h after the administration of the drug or placebo., Results: In voxel-based analysis using SPM2, volunteers with the A2A2 genotype showed decreased metabolism in the right middle frontal gyrus, the left middle and inferior frontal gyrus, the right and left inferior temporal gyrus, and the right cingulate gyrus, and increased metabolism in the pons. In contrast, volunteers with the A1A1 genotype exhibited increased metabolism in the right caudate head, and no brain region showed decreased metabolism. In a region-of-interest analysis, significant interactions between drug and genotype were observed in the right medial orbitofrontal gyrus and the left caudate nucleus., Conclusions: This suggests that DRD2 Taq1A polymorphism status may be associated with the clinical response to aripiprazole.

The asymmetric unit of the crystal structure of the title complex, [Ni(C(18)H(12)N(2)O(3))(C(5)H(5)N)(3)]·3C(5)H(5)N, contains two independent Ni(II) complex mol-ecules and six uncoordinated pyridine mol-ecules. Each Ni(II) atom is coordinated by two O and four N atoms, from three pyridine and a chelating 3-hydr-oxy-N'-(2-oxidobenzyl-idene)-2-naphthohydrazide dianionic ligand, with a distorted octa-hedral geometry. Intra-molecular O-H⋯N hydrogen bonding exists in both complex mol-ecules but no inter-molecular hydrogen bonding is observed in the crystal structure.

Anti-4-1BB-mediated anticancer effects were potentiated by depletion of CD4+ cells in B16F10 melanoma-bearing C57BL/6 mice. Anti-4-1BB induced the expansion and differentiation of polyclonal tumor-specific CD8+ T cells into IFN-gamma-producing CD11c+CD8+ T cells. The CD4+ cell depletion was responsible for facilitating immune cell infiltration into tumor tissues and removing some regulatory barriers such as T regulatory and indoleamine-2,3-dioxygenase (IDO)+ dendritic cells. Both monoclonal antibodies (mAb) contributed to the efficient induction of MHC class I molecules on the tumor cells in vivo. The effectors that mediated the anti-4-1BB effect were NKG2D+KLRG1+CD11c+CD8+ T cells that accumulated preferentially in the tumor tissues. Blocking NKG2D reduced the therapeutic effect by 20% to 26%, which may indicate that NKG2D contributes partially to tumor killing by the differentiated CD8+ T cells. Our results indicate that the combination of the two mAbs, agonistic anti-4-1BB and depleting anti-CD4, results in enhanced production of efficient tumor-killing CTLs, facilitation of their infiltration, and production of a susceptible tumor microenvironment.

Objective: We wanted to investigate the feasibility of using FDG-PET for evaluating the antitumor effect of intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model., Materials and Methods: VX2 carcinoma was grown in the livers of ten rabbits. Two weeks later, liver CT was performed to confirm appropriate tumor growth for the experiment. After tumor volume-matched grouping of the rabbits, transcatheter intraarterial administration of 3-BrPA was performed (1 mM and 5 mM in five animals each, respectively). FDG-PET scan was performed the day before, immediately after and a week after 3-BrPA administration. FDG uptake was semiquantified by measuring the standardized uptake value (SUV). A week after treatment, the experimental animals were sacrificed and the necrosis rates of the tumors were calculated based on the histopathology., Results: The SUV of the VX2 tumors before treatment (3.87+/-1.51 [mean+/-SD]) was significantly higher than that of nontumorous liver parenchyma (1.72+/-0.34) (p < 0.0001, Mann-Whitney U test). The SUV was significantly decreased immediately after 3-BrPA administration (2.05+/-1.21) (p = 0.002, Wilcoxon signed rank test). On the one-week follow up PET scan, the FDG uptake remained significantly lower (SUV 1.41+/-0.73) than that before treatment (p = 0.002), although three out of ten animals showed a slightly increasing tendency for the FDG uptake. The tumor necrosis rate ranged from 50.00% to 99.90% (85.48%+/-15.87). There was no significant correlation between the SUV or the SUV decrease rate and the tumor necrosis rate in that range., Conclusion: Even though FDG-PET cannot exactly reflect the tumor necrosis rate, FDG-PET is a useful modality for the early assessment of the antitumor effect of intraarterial administration of 3-BrPA in VX2 liver tumor.