Prognostic importance of the standardized uptake value on (18)F-fluoro-2-deoxy-glucose-positron emission tomography scan in non-small-cell lung cancer: An analysis of 125 cases. Leuven Lung Cancer Group.

PURPOSE: The amount of radio-labeled (18)F-fluoro-2-deoxy-glucose (FDG) uptake, a measurement of the increased glucose metabolism of non-small-cell lung cancer (NSCLC) cells, has recently been correlated with proliferation capacity. The Standardized Uptake Value (SUV), a semi-quantitative measurement of FDG uptake on positron emission tomography (PET) scan, could thus be of prognostic significance. PATIENTS AND METHODS: We analyzed the follow-up of 125 potentially operable NSCLC patients, previously included in three of our prospective PET protocols. Performance status, maximal tumor diameter, tumor-cell type, SUV, and final staging were analyzed for their possible association with survival. RESULTS: Sixty-five patients had stage I or II NSCLC, 37 had stage IIIA, and 23 had stage IIIB. Treatment was complete resection in 91 cases. In a univariate analysis, performance status (P =.002), stage (P =.001), tumor diameter (P =.06), tumor-cell type (P =.03), and SUV greater than 7 (P =.001) were correlated with survival. For SUV, group dichotomy with a cut-off SUV of 7 had the best discriminative value for prognosis, both in the total and surgical cohort. A multivariate Cox analysis identified performance status (P =.02), stage (P =.01), and SUV (P =.007) as important for the prognosis. In the surgical group, patients with a resected tumor less than 3 cm had an expected 2-year survival of 86%, if the SUV was below 7, and 60%, if above 7. Nearly all resected tumors larger than 3 cm had SUV's greater than 7 and an expected 2-year survival of 43%. CONCLUSION: We conclude that the FDG uptake in primary NSCLC on PET has an important prognostic value and could be complementary to other well-known factors in the decision on adjuvant treatment protocols.

Lymph node staging in non-small-cell lung cancer with FDG-PET scan: a prospective study on 690 lymph node stations from 68 patients.

PURPOSE: To compare the accuracy of computed tomography-(CT) scan and the radiolabeled glucose analog 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) visually correlated with CT (PET + CT) in the locoregional lymph node (LN) staging of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Sixty-eight patients with potentially operable NSCLC underwent thoracic CT, PET, and invasive surgical staging (ISS). Imaging studies were read prospectively and blinded to the surgical and pathologic data. A five-point visual scale was used for the interpretation of LNs on PET. Afterwards, with knowledge of the pathology, the relationship between standardized uptake values (SUVs) and the presence of metastasis in LNs was explored in a receiver operating characteristic (ROC) analysis, and the likelihood ratios (LRs) for SUVs of LNs were determined. RESULTS: ISS was available for 690 LN stations. CT correctly identified the nodal stage in 40 of 68 patients (59%), with understaging in 12 patients and overstaging in 16 patients. PET + CT was accurate in 59 patients (87%), with understaging in five patients and overstaging in four patients. In the detection of locally advanced disease (N2/N3), the sensitivity, specificity, and accuracy of CT were 75%, 63%, and 68%, respectively. For PET + CT, this was 93%, 95%, and 94% (P = .0004). In the ROC curve, the best SUV threshold to distinguish benign from malignant LNs was 4.40. The analysis with this SUV threshold was not superior to the use of a five-point visual scale. The LR of a SUV less than 3.5 in an LN was 0.152; for a SUV between 3.5 and 4.5, it was 3.157; and for a SUV greater than 4.5, it was 253.096. CONCLUSION: PET + CT is significantly more accurate than CT alone in LN staging of NSCLC. A five-point visual scale is as accurate as the use of an SUV threshold for LNs in the distinction between benign and malignant nodes. The very high negative predictive value of mediastinal PET could reduce the need for mediastinal ISS in NSCLC substantially.

Assessment of myocardial viability in chronic coronary artery disease using technetium-99m sestamibi SPECT. Correlation with histologic and positron emission tomographic studies and functional follow-up.

OBJECTIVES: The value of 99mTc-sestamibi (2-methoxy-isobutyl isonitrile [MIBI]) as a viability tracer was investigated in patients undergoing coronary artery bypass graft surgery. BACKGROUND: Initial studies claim that rest MIBI single-photon emission computed tomographic (SPECT) studies can be used to assess myocardial viability. METHODS: Thirty patients with a severely stenosed left anterior descending coronary artery and wall motion abnormalities were prospectively included. The patients underwent a MIBI rest study, a positron emission tomographic (PET) flow (13NH3) and metabolism (18F-deoxyglucose) study and nuclear angiography before undergoing bypass surgery. A preoperative transmural biopsy specimen was taken from the left ventricular anterior wall. Morphometry was performed to assess percent fibrosis. After 3 months, radionuclide angiography was repeated. RESULTS: Statistically significant higher MIBI values were found in the group with myocardial viability as assessed by PET than in the group with PET-assessed nonviability (p < 0.01). Significantly higher MIBI values were found in the group with enhanced contractility at 3 months (76 +/- 13% vs. 53 +/- 22%, p < 0.01). A linear relation was found between MIBI uptake and percent fibrosis in the biopsy specimen (r = 0.78, p < 0.00001). When maximizing the threshold for assessment of viability with MIBI by using functional improvement as the reference standard, a cutoff value of 50% was found, with positive and negative predictive values of 82% and 78%, respectively. CONCLUSIONS: 99mTc MIBI uptake was significantly higher in PET-assessed viable areas and in regions with enhanced contractility at 3 months. A linear relation was found between percent fibrosis and MIBI uptake. An optimal threshold of 50% was found for prediction of functional recovery.

Mediastinal lymph node staging with FDG-PET scan in patients with potentially operable non-small cell lung cancer: a prospective analysis of 50 cases. Leuven Lung Cancer Group.

STUDY OBJECTIVE: To compare the performance of CT, radio-labeled 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) blinded to CT, and FDG-PET visually correlated with CT, in the detection of N2 metastatic mediastinal lymph nodes (MLN) in patients with non-small cell lung cancer (NSCLC) and to hypothesize how PET could influence our actual mediastinal staging procedures. SETTING: Tertiary university hospital. PATIENTS AND METHODS: In 50 patients with potentially operable NSCLC, thoracic CT, PET, and invasive surgical staging were performed. Blinded prospective interpretation was performed for each test and compared with surgical pathology results. Abnormalities on each of these staging examinations were recorded on a standard MLN map. RESULTS: The sensitivity, specificity, and accuracy in detecting N2 disease of CT was 67%, 59%, and 64%, respectively. Results of PET blinded to CT were significantly better (p=0.004): 67%, 97%, and 88%, respectively. For PET visually correlated with CT, this was 93%, 97%, and 96%, respectively. In 22 patients, both CT and PET were normal, and this was correct in all cases. CONCLUSIONS: PET was significantly more accurate than CT in the MLN staging in NSCLC. Both examinations were complementary, since visual correlation with the anatomic information on CT improved the reader's ability to discriminate between hilar vs subaortic MLN FDG uptake, and between paramediastinal tumor vs tracheobronchial MLN FDG uptake. If the results can be confirmed in larger numbers of patients, PET could reduce the need for invasive surgical staging remarkably.

Diagnostic value of SPECT in a case of lower neck uptake on bone scan.

Lower neck uptake in bone scan is hard to interpret because of superposition of several structures. Single photon emission computerized tomography can be beneficial, as illustrated in this patient with a laryngeal tumor.

Clinical value of gallium-67 scintigraphy in the investigation of fever or inflammation of unknown origin in the ultrasound and computed tomography era.

Gallium scintigraphy was performed in 54 consecutive patients hospitalized for exploration of fever or inflammation of unknown origin, in whom thorough initial exploration did not yield any clue. Only in 28 patients (51.8%) could a definite diagnosis be established. The positive gallium scintigraphy results were clinically rated as valuable, questionable or valueless according to their contribution to the diagnosis. Gallium scintigraphy was positive in 22 patients (40%) and deemed valuable in 13 patients (24%). A final diagnosis could be ascertained in 77% of the cases with a positive scintigram. In contrast a cause of fever or inflammation was found only in 34% of the cases with a negative scintigram. Gallium scintigraphy is valuable as an early localizing investigation rather than a last resort test in patients with fever or inflammation of unknown origin. A positive scintigram increases the chances of establishing a final diagnosis.

Clinical value of gallium-67 scintigraphy in evaluation of fever of unknown origin.

This report describes the diagnostic contribution of gallium-67 scintigraphy in 145 cases of fever of unknown origin (FUO) at University Hospital in Leuven, Belgium, in 1980-1989. A final diagnosis was established in 99 (68%) of the 145 cases. Sixty-three scans (43%) were normal, and 82 (57%) were abnormal; only 42 of the abnormal scans (29% of the total number of scans) were considered helpful in diagnosis. Thus 49% of the abnormal scans were considered noncontributory to the diagnosis. In the same population, 15 (6%) of 266 ultrasonograms and 32 (14%) of 233 computed tomograms were helpful in diagnosis. We conclude that gallium scintigraphy remains a valuable screening tool in the investigation of FUO: it yielded diagnostic information in 29% of cases in which the probability of a definitive diagnosis was only 68%. We suggest the use of gallium scintigraphy as a second-step (as opposed to a last-resort) procedure in the evaluation of FUO.

First evaluation of technetium-99m dimercaptopropionyl albumin as a possible tracer agent for ventriculography in a volunteer.

Technetium-99m labelled red blood cells (99mTc-RBCs) are the standard radiopharmaceutical for radionuclide ventriculography but suffer from some practical disadvantages such as risk of viral contamination and lengthy preparation (in vitro labelling) or poor labelling efficiency due to patient medication interactions (in vivo labelling). 99mTc-labelled human serum albumin (HSA) is not really a valuable alternative as the activity diffuses too rapidly out of the vascular space due to the weak binding of the radionuclide. We have modified HSA by reaction with N-hydroxysuccinimidyl 2,3-di(S-acetylmercapto)propionate (SAMP) to introduce a varying number of 2,3-dimercaptopropionyl (DMP) side chains. The resulting DMP-HSA can be rapidly labelled with 99mTc at room temperature by simple addition of stannous ions and eluate of a 99mTc generator. After evaluation in mice and rabbits, two different 99mTc-DMP-HSA preparations - obtained after reaction of SAMP with albumin in a molar ratio of, respectively, 8:1 and 16:1 - were tested in a volunteer and compared to 99mTc-RBCs. The blood time-activity curves of the three preparations were quite similar but both 99mTc-DMP-HSA preparations were excreted much less into the urine than 99mTc-RBCs. Ventriculography was performed with the three tracer agents, each time with a 1-week interval. In the three studies, the heart was clearly visualized and the left and right ventricle could be easily delineated. The ejection fractions obtained after administration of the three preparations were similar. With both 99mTc-DMP-HSA preparations the low activity in the spleen was a distinct advantage and facilitated delineation of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between different methods for analysing ST segment deviation and infarct size as assessed by positron emission tomography.

OBJECTIVE: To study the relation between resolution of ST segment deviation and infarct size using positron emission tomography. METHODS: 45 patients with ST segment elevation acute myocardial infarction treated with thrombolysis or percutaneous coronary intervention were studied prospectively. An ECG was taken before and at (mean (SD)) 100 (45) min after reperfusion therapy. ECGs were analysed by three methods. Residual ST segment deviation, obtained from the ECG immediately after completion of reperfusion therapy, was defined by summation for each of the three methods. Relative resolution of ST segment deviation was defined as the absolute resolution divided by the ST segment deviation score at baseline x 100 (%). After 29 (14) hours, myocardial blood flow was measured with 13NH3. For each patient, the regions with a myocardial blood flow < 80% of normally perfused myocardium ( = hypoperfusion) and < 50% ( = no reflow) were automatically delineated. RESULTS: Substantial differences were found between different ECG analysis methods. There were moderate correlations between the area with myocardial hypoperfusion and ST segment deviation scores at baseline and after reperfusion therapy. After reperfusion therapy, residual ST segment deviation in the single lead with maximum ST segment deviation was as good at discriminating between tertiles of myocardial damage as summed ST segment elevation. Relative ST segment resolution did not discriminate between different degrees of myocardial damage. CONCLUSIONS: In the individual patient, residual ST segment deviation after reperfusion in the single lead with maximum ST segment deviation is at least as good as summed ST elevation in predicting final myocardial damage.

Effects of 6% hydroxyethyl starch and 3% modified fluid gelatin on intravascular volume and coagulation during intraoperative hemodilution.

In the perioperative period, artificial colloids are most often infused in doses of 500-1000 mL intravenously. This randomized study compared the effects on intravascular volume and coagulation of approximately 2000 mL of two isooncotic artificial colloids: 6% hydroxyethyl starch (HES; MW 200,000; substitution ratio 0.40-0.55) and 3% modified fluid gelatin (GEL). We hypothesized more pronounced hypocoagulation with HES and a weaker intravascular volume effect of GEL. Forty-two patients, scheduled for primary total hip replacement, were allocated randomly to receive HES or GEL during acute normovolemic hemodilution and subsequent further intraoperative hemodilution. Blood samples were taken before and after 500 mL and 1000 mL of acute normovolemic hemodilution; intraoperatively after 20 mL/kg of artificial colloid and at the end of colloid infusion; on arrival in the recovery room; and 3 h later. We quantified: 1) coagulation variables; 2) blood loss; 3) hemodynamic stability; 4) necessary infusion volume; 5) interstitial extravasation, calculated from plasma volunteers measured using albumin marked with technetium-99m and iodine-125, respectively; 6) percentage volume effect at the end of the study as well as hematocrit, total serum protein, and colloid osmotic pressure. Intraoperative volume therapy was guided by radial systolic pressure and systolic pressure variation, mixed venous hemoglobin saturation in the pulmonary artery, and pulmonary capillary occlusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Tomographic and planar quantitation of perfusion defects on technetium 99m-labeled sestamibi scans: evaluation in patients treated with thrombolytic therapy for acute myocardial infarction.

BACKGROUND: Our segmentation algorithm for single-photon emission computed tomographic perfusion studies was tested in 244 patients treated by thrombolysis within 5 hours after onset of symptoms. This algorithm uses radial slices to approximate true three-dimensional gradients, determines the apex and basal plane, and creates a perfusion and volume polar map. METHODS AND RESULTS: Perfusion defect size was compared with enzymatic infarct size and global and regional function. All patients underwent rest planar and tomographic 99mTc-labeled sestamibi scanning, contrast coronary angiography, and ventriculography 10 to 14 days after the start of treatment. Manual correction had to be performed in only 10% of the cases and presented no problems. The correlation coefficients (r) between planar and relative tomographic perfusion defects versus enzymatic infarct size were 0.71 and 0.73. A negative correlation was found with left ventricular ejection fraction: r = -0.65 and r = -0.60. A comparable correlation was also found between regional wall motion and perfusion defect size. Most correlations were higher in the case of anterior infarction. An excellent correlation was found between planar and tomographic defect size (r = 0.83). CONCLUSIONS: In most cases, our segmentation algorithm delineates myocardial edges and basal plane automatically. A good correlation was found between perfusion defect size, enzymatic infarct size, and global and regional ventricular function.