Single Patient Classifier Assay, Microsatellite Instability, and Epstein-Barr Virus Status Predict Clinical Outcomes in Stage II/III Gastric Cancer: Results from CLASSIC Trial

PURPOSE: Clinical implications of single patient classifier (SPC) and microsatellite instability (MSI) in stage II/III gastric cancer have been reported. We investigated SPC and the status of MSI and Epstein-Barr virus (EBV) as combinatory biomarkers to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer. MATERIALS AND METHODS: Tumor specimens and clinical information were collected from patients enrolled in CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. The results of nine-gene based SPC assay were classified as prognostication (SPC-prognosis) and prediction of chemotherapy benefit (SPC-prediction). Five quasimonomorphic mononucleotide markers were used to assess tumor MSI status. EBV-encoded small RNA in situ hybridization was performed to define EBV status. RESULTS: There were positive associations among SPC, MSI, and EBV statuses among 586 patients. In multivariate analysis of disease-free survival, SPC-prognosis [hazard ratio (HR): 1.879 (1.101–3.205), 2.399 (1.415–4.067), p=0.003] and MSI status (HR: 0.363, 95% confidence interval: 0.161–0.820, p=0.015) were independent prognostic factors along with age, Lauren classification, TNM stage, and chemotherapy. Patient survival of SPC-prognosis was well stratified regardless of EBV status and in microsatellite stable (MSS) group, but not in MSI-high group. Significant survival benefit from adjuvant chemotherapy was observed by SPC-Prediction in MSS and EBV-negative gastric cancer. CONCLUSION: SPC, MSI, and EBV statuses could be used in combination to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.

Modification of the TNM Staging System for Stage II/III Gastric Cancer Based on a Prognostic Single Patient Classifier Algorithm

PURPOSE: The modification of the cancer classification system aimed to improve the classical anatomy-based tumor, node, metastasis (TNM) staging by considering tumor biology, which is associated with patient prognosis, because such information provides additional precision and flexibility. MATERIALS AND METHODS: We previously developed an mRNA expression-based single patient classifier (SPC) algorithm that could predict the prognosis of patients with stage II/III gastric cancer. We also validated its utilization in clinical settings. The prognostic single patient classifier (pSPC) differentiates based on 3 prognostic groups (low-, intermediate-, and high-risk), and these groups were considered as independent prognostic factors along with TNM stages. We evaluated whether the modified TNM staging system based on the pSPC has a better prognostic performance than the TNM 8th edition staging system. The data of 652 patients who underwent gastrectomy with curative intent for gastric cancer between 2000 and 2004 were evaluated. Furthermore, 2 other cohorts (n=307 and 625) from a previous study were assessed. Thus, 1,584 patients were included in the analysis. To modify the TNM staging system, one-grade down-staging was applied to low-risk patients according to the pSPC in the TNM 8th edition staging system; for intermediate- and high-risk groups, the modified TNM and TNM 8th edition staging systems were identical. RESULTS: Among the 1,584 patients, 187 (11.8%), 664 (41.9%), and 733 (46.3%) were classified into the low-, intermediate-, and high-risk groups, respectively, according to the pSPC. pSPC prognoses and survival curves of the overall population were well stratified, and the TNM stage-adjusted hazard ratios of the intermediate- and high-risk groups were 1.96 (95% confidence interval [CI], 1.41–2.72; P < 0.001) and 2.54 (95% CI, 1.84–3.50; P < 0.001), respectively. Using Harrell's C-index, the prognostic performance of the modified TNM system was evaluated, and the results showed that its prognostic performance was better than that of the TNM 8th edition staging system in terms of overall survival (0.635 vs. 0.620, P < 0.001). CONCLUSIONS: The pSPC-modified TNM staging is an alternative staging system for stage II/III gastric cancer.

Ankle MRI for Anterolateral Soft Tissue Impingement: Increased Accuracy with the Use of Contrast-Enhanced Fat-Suppressed 3D-FSPGR MRI

OBJECTIVE: To validate the use of contrast-enhanced (CE) fat-suppressed three-dimensional (3D) fast gradient-recalled acquisition in the steady state with radiofrequency spoiling (FSPGR) magnetic resonance imaging (MRI) for the diagnosis of anterolateral soft tissue impingement of the ankle, as compared to the use of routine ankle MRI. MATERIALS AND METHODS: Contrast-enhanced fat-suppressed 3D-FSPGR MRI and routine MRI scans were retrospectively reviewed for 45 patients with arthroscopically proven anterolateral impingement. In addition, scans were reviewed in 45 control subjects with diagnoses other than impingement. Two radiologists independently reviewed the two sets of images in random order. Using areas (Az) under the receiver operating characteristic curve (ROC), we compared the depiction of anterolateral soft tissue impingement in the two sets of images. RESULTS: The overall accuracy for lesion characterization was significantly higher (p < 0.05) using the CE fat-suppressed 3D-FSPGR MR images (Az = 0.892 and 0.881 for reader 1 and 2, respectively) than using the routine MR images (Az = 0.763 and 0.745). The use of CE fat-suppressed 3D-FSPGR MRI enhanced impingement depiction in most cases. However, in cases with a thickened non-enhancing scar or joint effusion, the routine images better depicted a soft tissue mass that intruded into anterolateral gutter than the CE images. CONCLUSION: The use of CE fat-suppressed 3D-FSPGR MRI of the ankle allows a more accurate assessment of anterolateral soft tissue impingement of the ankle, as compared to the use of routine MRI.

Morton Neuroma: Evaluated with Ultrasonography and MR Imaging

OBJECTIVE: The purpose of this study was to compare the diagnostic accuracy of both ultrasonography (US) and magnetic resonance imaging (MRI) for the assessment of Morton neuroma. MATERIALS AND METHODS: Our study group was comprised of 20 neuromas from 17 patients, and the neuromas were confirmed on surgery following evaluation with US, MRI, or both US and MRI. The diagnostic criterion for Morton neuroma, as examined by US, was the presence of a round or ovoid, well-defined, hypoechoic mass. The diagnostic criterion, based on MR imaging, was a well defined mass with intermediate to low signal intensity on both the T1- and T2-weighted images. The retrospective comparison between the sonographic and MR images was done by two experienced radiologists working in consensus with the surgical and pathologic correlations. RESULTS: The detection rate of Morton neuroma was 79% for 14 neuromas from 11 patients who had undergone US followed by an operation. The detection rate was 76% for 17 neuromas from 15 patients who had undergone MRI and a subsequent operation. The mean size of the examined neuromas was 4.9 mm on the US images and it was 5.1 mm on the MRI studies. Ten neuromas (71%) were 5 mm or less as measured by US, and three neuromas were not detected, whereas on the MRI analysis, 10 neuromas (59%) were 5 mm or less and four neuromas were not visualized. Among the patients examined during postoperative follow-up, symptoms were completely relieved in 85% and the symptoms were partially relieved in 15%. CONCLUSION: US and MR imaging are comparable modalities with high detection rate for the evaluation of Morton neuroma.

Low-grade Osteosarcoma of the Spine: A Case Report

Low-grade osteosarcoma is not typically found in the long bone and pelvis. Most primary osteosarcomas that arise in the spine are high-grade malignancies. A low-grade osteosarcoma arising in the spine has not been previously described. We report here the clinical, radiological, and histological findings of a case of low-grade osteosarcoma that arose in the spine.

The Role of Popliteal Lymph Nodes in Differentiating Rheumatoid Arthritis from Osteoarthritis by Using CE 3D-FSPGR MR Imaging: Relationship of the Inflamed Synovial Volume

OBJECTIVE: We wanted to assess the role of the popliteal lymph nodes for differentiating rheumatoid arthritis (RA) from osteoarthritis (OA), and we also wanted to investigate the relationship between the popliteal lymph nodes and the inflamed synovial volume (ISV) by using contrast enhanced (CE), fat suppressed, three dimensional-fast spoiled gradient echo (3D-FSPGR) MR imaging. MATERIALS AND METHODS: Contrast enhanced 3D-FSGPR MR imaging of 94 knees (21 with RA and 73 with OA) was analyzed. A lymph node was defined as being 'observed' if it could be seen in at least two planes of the three orthogonal reformatted planes. The number of observed lymph nodes, the mean of the smallest dimension of each lymph node and the existence of central fatty change were recorded. The OA group was graded according to the ISV calculated by a segmentation method: grade I was 40 cm3. Statistical analysis of the number and the mean size of the popliteal lymph nodes among the four groups (the RA group and the grade I-III OA groups) was performed. RESULTS: The prevalence of the observed popliteal lymph nodes was significantly different between all the OA groups or between the grade III OA group and the RA group (p < 0.0001, 0.0001, respectively). The popliteal lymph node was observed in 32 out of 73 OA cases, whereas it was visible in all of the 21 RA cases. The number (mean+/-standard deviation) of lymph nodes in the grade I OA group, the grade II OA group, the grade III OA group and the RA group was 1.2+/-0.4, 1.2+/-0.4, 1.3+/-0.5, and 2.7+/-1.1, respectively. The mean size (mean+/-standard deviation) of the lymph nodes was 3.8+/-1.0 mm, 3.6+/-1.1 mm, 4.1+/-0.8 mm, and 5.4+/-1.3 mm, respectively. The incidence of central fatty changes was significantly lower in the RA group than in all the OA groups and the grade III OA group. When differentiating RA from OA, and when the differentiation was confined to the RA group and grade III OA group, respectively, the criteria of the number of lymph nodes, their size, their central fatty change and a combination of all these three criteria showed statistical significance (Az values for the former were 0.869, 0.847, 0.776, and 0.942; Az values for the latter were 0.855, 0.799, 0.712, and 0.916). The number and mean size of the lymph nodes correlated with the ISVs (r = 0.49, p < 0.001; 0.50, 0.001, respectively). CONCLUSION: The number, size and central fatty changes in the popliteal lymph nodes observed on the MR images might serve as simple and useful markers in differentiating RA disease from OA disease. These markers would be particular helpful in cases of severe synovial enhancement where the ISVs of both RA and OA overlap. The number and mean size of the lymph nodes also correlated well with the ISV.

MR Findings of Peripheral Nerve Entrapment and Compression Syndrome

No abstract available.

Development of PC-based Software to Analyze Dynamic Cerebral Perfusion CT Quantitatively and to Reformat Perfusion Maps

PURPOSE: The purpose of this study was to develop PC-based perfusion software using Microsoft Windows. This software was developed to reformat perfusion maps including CBV (Cerebral Blood Volume), MTT (Mean Transit Time), and CBF (Cerebral Blood Flow) maps and to analyze perfusion quantitatively. MATERIALS AND METHODS: Windows-based perfusion software was developed using IDL (Interactive Data Language) as the development tool. The perfusion software was written to load the source image from dynamic first-pass cerebral perfusion CT and to reformat perfusion maps. Mean perfusion values in gray matter and white matter were calculated and compared to previously calculated data reported in literature. RESULTS: This software reformatted first pass perfusion maps in a user-friendly PC and calculated CBV, MTT, and CBF values. The values were within the normal range of the mean values when compared to previous studies. CONCLUSION: CT perfusion maps and perfusion values can be obtained by using the newly developed PC-based perfusion software. Further study is needed to achieve more precise values. However, we believe that in the future, this program may be used in various clinical settings.

Pharmacokinetic Modeling of Phagocytic Activity of the Liver Using Superparamagnetic Iron Oxide Nanoparticles in Dynamic MR Imaging

The purpose of this study was to determine whether phagocytic activity is measurable by dynamic superparamagnetic iron oxide-enhanced MR imaging. For these experiments on New Zealand White rabbits, which were randomly allocated to normal and silica treated groups, we performed a dynamic MR study and radioisotope study with Tc99m-phytate. In this dynamic MR study, the ratio (Rv) of the distribution volumes of iron oxide (Vm/Ve) could be obtained by applying three- compartment model to the data obtained from the kidney and liver simultaneously. Changes in Rv caused by silica injection and by dosing superparamagnetic iron oxide, AMI-25, were evaluated. In the dynamic MR study using a Beagle dog model the input function could be calculated from data obtained from the hepatic artery and portal vein. Rv's reached maximum values at around 80 minutes after the AMI-25 injection. The Rv of the normal group was 5.06 +/- 1.53 whereas the Rv of the silica treated group was 2.13 +/- 1.20. The results were similar to tissue count data obtained by radioisope study. The Rv value was not dependent on the injected dose of AMI-25. The rate of transport constants (k1, k2, k3) could not be estimated using the 3 compartment model regardless of obtaining the input function. We conclude that Rv may be an quantitative index of decreased phagocytic activity in the liver as determined by dynamic superparamagnetic iron oxide- enhanced MRI.

Visceral Pleural Invasion And Bronchovascular Bundle Thickening To The Same Lobe In NSCLC: Diagnostic Usefulness And Clinical Significance Using HRCT / 결핵

BACKGROUND: To assess the utility of HRCT in the evaluation of visceral pleural invasion and to determine whether visceral pleural invasion and bronchovascular bundle thickening on the same lobe could be related to the recurrence and survival in non-small cell lung cancer (NSCLC). METHOD: Eighty one patients, which were fulfilled long-term follow-up at least 18 months (maximum 103 months) among which 434 patients had underwent curative surgical resection for NSCLC from 1986 to 1995, were studied. They were analyzed to evaluate whether the prognostic factors such as the recurrence and survival depend on visceral pleural invasion and bronchovascular bundle thickening to the same lobe. Thirty two patients adjacent to a chest wall or a fissure were evaluated for visceral pleural invasion by HRCT. CT criteria included abutting pleura along the chest wall, abutting and/or compressing fissure, crossing fissure, and pleural tail. RESULTS: The positive predictive value and the negative predictive value of crossing fissure were 100% and 100%, respectively. Two patients showing spiculated interface between a mass and abutting fissure were confirmed to have visceral pleural invasion at surgery. Visceral pleural invasion confirmed at surgery was significant to local recurrence and survival (p.05). CONCLUSION: Visceral pleural invasion and bronchovascular bundle thickening to the same lobe have a role in predicting prognosis such as recurrence and survival in NSCLC. Therefore, the analysis of visceral pleural invasion on CT scan and the pathological analysis of bronchovascular bundle thickening to the same lobe may be necessary to predict the prognosis in NSCLC.

Benign and Malignant Musculoskeletal Tumors Evaluated with the Aid of Pa rametric Maximum Slope and Blood Volume Images

PURPOSE: To assess the values of parametric "maximum slope(MS) and blood volume(BV)" images as indicators of tissue vascularization and perfusion in distinguishing benign from malignant musculoskeletal tumors. MATERIAL AND METHODS: Dynamic inversion recovery spin-echo echo-planar imaging (TR/TE/TI/NEX: 1 5 0 0 / 2 4 / 5 00 ms/1; matrix 128 x 128; slice thickeness 5 mm, interleaved) at 1.5-second intervals(200 phases) was performed after intravenous bolus injection of Gd-DTPA. A total of 32 pathologically proven muscu-loskeletal masses(benign 9, malignant 23) were included in this study. MS was derived by fitting a time-intensity curve using a polynomial model. BV was determined by integration until maximum slope was reached. On a pixel-by-pixel basis, MS and BV images were generated and displayed by gray-scale. We selected a region of interest(ROI, more than 6 x 6 pixels) including the highest value of the tumors and calculated mean values of MS and BV. Wilcoxon's signed rank test was used to compare benign tumors with malignant pre- and postchemotherapy tumors. RESULT: The mean values of ROIs selected on MS images were significantly different (p=.008) between benign (mean 3.33, range 0.01 -16.47 ) and prechemotherapy malignant(mean 8.54, range 1.61 -16.90) tumors, as were the mean values of ROIs on BV images(p=.005; benign tumors: mean 162.17, range 91.17 -2 8 3 . 7 ; prechemotherapy malignant tumors: mean 330.18, range 117.5 -845.1). MS and BV values of benign and malignant tumors overlapped but tended to be separated. CONCLUSION: BV and MS images may help distinguish benign from malignant musculoskeletal tumors.

Benign and Malignant Musculoskeletal Tumors Evaluated with the Aid of Pa rametric Maximum Slope and Blood Volume Images

PURPOSE: To assess the values of parametric "maximum slope(MS) and blood volume(BV)" images as indicators of tissue vascularization and perfusion in distinguishing benign from malignant musculoskeletal tumors. MATERIAL AND METHODS: Dynamic inversion recovery spin-echo echo-planar imaging (TR/TE/TI/NEX: 1 5 0 0 / 2 4 / 5 00 ms/1; matrix 128 x 128; slice thickeness 5 mm, interleaved) at 1.5-second intervals(200 phases) was performed after intravenous bolus injection of Gd-DTPA. A total of 32 pathologically proven muscu-loskeletal masses(benign 9, malignant 23) were included in this study. MS was derived by fitting a time-intensity curve using a polynomial model. BV was determined by integration until maximum slope was reached. On a pixel-by-pixel basis, MS and BV images were generated and displayed by gray-scale. We selected a region of interest(ROI, more than 6 x 6 pixels) including the highest value of the tumors and calculated mean values of MS and BV. Wilcoxon's signed rank test was used to compare benign tumors with malignant pre- and postchemotherapy tumors. RESULT: The mean values of ROIs selected on MS images were significantly different (p=.008) between benign (mean 3.33, range 0.01 -16.47 ) and prechemotherapy malignant(mean 8.54, range 1.61 -16.90) tumors, as were the mean values of ROIs on BV images(p=.005; benign tumors: mean 162.17, range 91.17 -2 8 3 . 7 ; prechemotherapy malignant tumors: mean 330.18, range 117.5 -845.1). MS and BV values of benign and malignant tumors overlapped but tended to be separated. CONCLUSION: BV and MS images may help distinguish benign from malignant musculoskeletal tumors.

Usefulness of Mammography of Mastectomy Site for Breast Cancer

PURPOSE: To evaluate the usefulness of routine mammography in the detection of local recurrence of breast cancer after mastectomy. MATERIALS AND METHODS: The clinical and mammographic records of 45 patients whounderwent modified mastectomy due to breast cancer were prospectively reviewed. The methods of mastectomy wereAuchincloss (n=36), Patey (n=8) and simple resection (n=1). RESULTS:s Among the 45 patients, five palpable lesionswere detected on physical examination: two of the five were confirmed as tumor recurrence; on mammography, anodule with microcalcifications and low-density lesion was seen, but the other three were benign. In 40 patientsthe results of palpation were negative and during follow-up (mean, 10.9 months ) no newly developed lesions wereseen. On mammography, ten of 45(22.2%) patients showed abnormalities, namely local skin thickening(n=4,40%),increased density in subcutaneous tissue(n=2,20%), nodules(n=2,20%), benign calcification(n=1,10%) and focallow-density lesion(n=1,10%), but only one case with a nodule was confirmed to be recurrence. CONCLUSION: Routinemammography of a mastectomy site was not useful for the differentiation of palpable lesions.

Cerebral Blood Volume and Relative Perfusion Rate Mapping with Contrast Enhanced Gradient Echo Echo PlanarImaging

PURPOSE: To assess regional cerebral blood volume and perfusion rate by MR imaging. MATERIALS AND METHODS:Eight normal volunteers and one patient underwent MR imaging after bolus injection of a double dose ofgadoinium(0.2mMol/kg). Gradient-echo EPI pulse sequencing was used, with TR/TE 1500/40msec, flip angle 90o, matrixsize 256X128. One hundred sequential images at the same level were obtained. The time-signal intensity curve wasplotted and converted to a time-concentration ( R2) curve. Relative cerebral blood volume was determined, withintegration of time-concentration curve pixel by pixel. Perfusion rate was determined by calculating maximal slopeof the R2 curve and the time taken to attain this. RESULTS: On volume maps, clear differentiation of gray matter,white matter and major vessels was established. The mean gray and white matter ratio of blood volume was2.78+/-0.43. Slope and volume maps were similar, but in one patient perfusion was apparently greater on the ratemap than on the volume map. CONCLUSION: Cerebral blood volvme and slope map images reflect changes in cerebralhemodynamics. It is thought that these findings can be clinically applied to the determination of vascularity inbrain tumors and acute cerebral ischemia

Volumetric measurement of the inflamed synovium of rheumatoid wrist joint for the evaluation of synovitis and remission

PURPOSE: To evaluate the changes and remission of disease activity with changes in inflamed synivial volumes of rheumatoid joints after therapy. MATERIALS AND METHODS: Seven rheumatoid arthritis patients who had been treated with antiinflammatory drugs were followed up. Using NIH imaging and a segmentation technique, pre- and post-enhanced images were measured in subtracted images. Intra- and interobserver variation were evaluated by two radiologists(A and B), using two independent measurements. For comparison, the cases were assigned to one of two groups : remission and non-remission. Changes in ESR and total joint counts(TJC) after therapy were compared with inflamed synovial volumes. RESULTS: Intraobserver variations were 3.2% and 2.7% in A and B, respectively, interobserver variation between A and B was 7.1%. Changes in inflamed synovial volumes correlated well with those in ESR (r=0.88, p<0.009) and TJC (r=0.78, p<0.037) after therapy. Changes between the remission and non-remission group were insignificant, however. CONCLUSION: Changes in inflamed synovial volumes reflect those in the activity of rheumatoid arthritis between pre- and post- treatment. This technique may be used as a tool for predicting therapeutic response in rheumatoid arthritis cases. Changes in inflamed synovial volumes are of limited value, however, in predicting the remission of rheumatoid arthritis after therapy.

Volumetric measurement of the inflamed synovium of rheumatoid wrist joint for the evaluation of synovitis and remission

PURPOSE: To evaluate the changes and remission of disease activity with changes in inflamed synivial volumes of rheumatoid joints after therapy. MATERIALS AND METHODS: Seven rheumatoid arthritis patients who had been treated with antiinflammatory drugs were followed up. Using NIH imaging and a segmentation technique, pre- and post-enhanced images were measured in subtracted images. Intra- and interobserver variation were evaluated by two radiologists(A and B), using two independent measurements. For comparison, the cases were assigned to one of two groups : remission and non-remission. Changes in ESR and total joint counts(TJC) after therapy were compared with inflamed synovial volumes. RESULTS: Intraobserver variations were 3.2% and 2.7% in A and B, respectively, interobserver variation between A and B was 7.1%. Changes in inflamed synovial volumes correlated well with those in ESR (r=0.88, p<0.009) and TJC (r=0.78, p<0.037) after therapy. Changes between the remission and non-remission group were insignificant, however. CONCLUSION: Changes in inflamed synovial volumes reflect those in the activity of rheumatoid arthritis between pre- and post- treatment. This technique may be used as a tool for predicting therapeutic response in rheumatoid arthritis cases. Changes in inflamed synovial volumes are of limited value, however, in predicting the remission of rheumatoid arthritis after therapy.