Diagnostic accuracy of contrast-enhanced FDG-PET/CT in primary staging of cutaneous malignant melanoma.

PURPOSE: To evaluate the diagnostic accuracy of contrast-enhanced FDG-PET/CT (ce-PET/CT), PET-only, and CT-only in patients with newly diagnosed and resected cutaneous malignant melanoma. METHODS: A final group of 56 patients (mean age 62 years, range 23-86 years; 29 women, 27 men) were staged with ce-PET/CT after resection of the primary tumour. Histopathology as well as clinical follow-up (mean 780 days, range 102-1,390 days) served as the standards of reference. Differences between the staging modalities were tested for statistical significance with McNemar's test. RESULTS: All imaging procedures provided low sensitivities in the detection of lymph nodes (sensitivity N-stage: PET/CT and PET-only 38.5%; CT-only 23.1%) and distant metastases (sensitivity M-stage: PET/CT 41.7%, PET-only 33.3%, CT-only 25.0%) in initial staging after resection of the primary tumour. No statistically significant differences were detected between the imaging procedures (p > 0.05). PET/CT resulted in an alteration in further treatment in two patients compared to PET-only and in four patients compared to CT-only. CONCLUSION: All imaging modalities had a low sensitivity on initial staging of patients with malignant melanoma. Thus, close patient follow-up must be considered mandatory.

Detailed technical analysis of urine RNA-based tumor diagnostics reveals ETS2/urokinase plasminogen activator to be a novel marker for bladder cancer.

BACKGROUND: The noninvasive detection of RNA tumor markers in body fluids represents an attractive diagnostic option, but diagnostic performance of tissue-derived markers is often poorer when measured in body fluids rather than in tumors. We aimed to develop a procedure for measurement of tumor RNA in urine that would minimize donor-dependent influences on the results. METHODS: RNA isolated from urinary cell pellet, cell-depleted fraction, and whole urine was quantified by reverse transcription quantitative-PCR. The donor-dependent influence of urine background on individual steps of the standardized procedure was analyzed using an external RNA standard. Using a test set of samples from 61 patients with bladder cancer and 37 healthy donors, we compared 4 putative RNA tumor markers identified in whole urine with 5 established, tissue-derived RNA tumor markers for the detection of bladder cancer. RESULTS: Of the markers analyzed by this system, the RNA ratio of v-ets erythroblastosis virus E26 oncogene homolog 2 (avian; ETS2) to urokinase plasminogen activator (uPA) enabled the most specific (100%) and sensitive (75.4%) detection of bladder cancer from whole urine, with an area under the curve of 0.929 (95% CI 0.882-0.976). CONCLUSIONS: The described methodology for RNA marker detection in urine appears to be clinically applicable. The ratio of ETS2 mRNA to uPA mRNA in urine is a potential marker for bladder cancer.

TNM staging with FDG-PET/CT in patients with primary head and neck cancer.

PURPOSE: PET/CT, PET+CT, and CT were compared concerning accuracies in TNM staging and malignancy detection in head and neck cancer. The impact of PET/CT compared to the other imaging modalities on therapy management was assessed. MATERIALS AND METHODS: Fifty-five patients with suspected head and neck primary cancer underwent whole-body FDG-PET/CT. PET/CT and PET+CT were evaluated by a nuclear medicine physician and a radiologist; CT was evaluated by two radiologists, PET by two nuclear physicians. Histopathology served as the standard of reference. Differences between the staging modalities were tested for statistical significance by McNemar's test. RESULTS: Overall TNM-staging and T-staging with PET/CT were more accurate than PET+CT and CT alone (p < 0.05). PET/CT was marginally more accurate than CT alone in N-staging (p = 0.04); no statistically significant difference was found when compared to PET+CT for N-staging. PET/CT altered further treatment in 13 patients compared to CT only and in 7 patients compared to PET+CT. CONCLUSION: Combined PET/CT proved to be partly more accurate in assessing the overall TNM-stage than CT and PET+CT. These results were based on a higher accuracy concerning the T-stage, mainly in patients with metallic implants and marginally the N-stage. Therapy decisions have been influenced in a substantial number of patients. PET/CT might be considered as a first line diagnostic tool in patients with suspected primary head and neck cancer.

Internal limiting membrane peeling with indocyanine green or trypan blue in macular hole surgery: a randomized trial.

OBJECTIVE: To report on anatomical and visual outcomes after vitrectomy and internal limiting membrane peeling for idiopathic macular hole repair. METHODS: Forty patients with stage II to IV idiopathic macular holes were randomly assigned (1:1) in a 2-arm, single-center, randomized controlled . Internal limiting membrane delamination was performed using indocyanine green (ICG) solution (n = 20) or trypan blue (TB) (n = 20). Two patients did not complete the study, for a total of 19 in each group. Follow-up examinations included Early Treatment of Diabetic Retinopathy Study visual acuity, scanning laser ophthalmoscope microperimetry, optical coherence tomography, and fluorescein angiography. Main Outcome Measure Visual acuity 3 months after surgery. RESULTS: Visual acuity did not show a significant difference between study groups (95% confidence interval [CI], -2 to 1 lines). The rate of macular hole closures was identical (84%; 95% CI, 60% to 97%). Within-group visual recovery was significant only in the TB group. Central scotomata despite hole closure persisted in 8 patients (42%) in the ICG group and in 5 (26%) in the TB group. CONCLUSION: Although no statistically significant difference was detected for the primary end point, the better visual recovery in the TB group and the higher rate of persistent central scotomata in the ICG group justify a larger clinical trial. Application to Clinical Practice No statistically significant difference in visual acuity between ICG and TB in the used concentrations and application method could be proved in macular hole surgery.

Pulmonary homograft muscle reduction to reduce the risk of homograft stenosis in the Ross procedure.

OBJECTIVE: The Ross procedure has gained increasing interest as an attractive alternative for aortic valve replacement. Despite its advantages, there is a certain risk of structural valve deterioration, especially of the pulmonary homograft as a result of shrinkage and subsequent stenosis predominantly at the muscular annulus. Theoretically, reduction of homograft muscle tissue could reduce this risk. METHODS: From February 1996 through December 2002, a total of 238 patients (mean age 44 +/- 13.2 years) underwent the Ross procedure with the subcoronary technique with follow-up investigations before discharge and after 12 and 24 months. To estimate the importance of homograft muscle reduction within our institution-specific risk factor scale for change of transhomograft pressure gradient with time, we performed a generalized estimating equation approach, which identified homograft muscle reduction, higher body surface area in male patients, younger patient age, smaller homograft diameter, blood transfusions, and follow-up time as independent risk factors demonstrating a high beta value (-2.8638) for muscle reduction. To find out whether muscle reduction influences transhomograft pressure gradient, we compared patients with (group A, n = 39) and without (group B, n = 199) muscle reduction. The other mentioned independent risk factors were not different between groups, except for blood transfusions (group A greater than B, P < .01), indicating a negative bias for group A. RESULTS: The maximum pressure gradient across the homograft was lower in patients with muscle reduction before discharge (4.5 +/- 2.8 mm Hg group A vs 6.2 +/- 3.8 mm Hg group B, P = .004) and after 1 (9.3 +/- 5.8 vs 13.1 +/- 8.4 mm Hg, P = .028) and 2 years (10.8 +/- 7.6 vs 13.7 +/- 7.5 mm Hg, P = .013). No significant differences were found concerning homograft insufficiency. CONCLUSIONS: We provide some evidence that transhomograft pressure gradient can be reduced significantly within the first 2 years after operation by homograft muscle reduction. Longer term follow-up is necessary to evaluate this promising operative technique further.

Subcoronary Ross procedure in patients with active endocarditis.

BACKGROUND: The Ross procedure has gained increasing interest as an attractive alternative to a prosthetic aortic valve substitute within the last decade. Because of a probably better resistance to infection as one of its advantages, the pulmonary autograft is theoretically preferable for active endocarditis. METHODS: Between June 1994 and July 2003, the Ross procedure was performed using the subcoronary and inclusion technique in 296 patients (231 male, 65 female). Twenty patients had an active endocarditis of the aortic valve at the time of operation. A bicuspid valve was present in 10 patients. One patient had previous aortic valve surgery. Clinical and echocardiographic follow-up was complete. RESULTS: Early mortality was 1, late mortality was 0. There were no recurrence of endocarditis and no neurologic events during the mean follow-up of 47.3 +/- 28.6 months. All patients were in New York Heart Association class I. Mean and maximum pressure gradient across the autograft was 3.5 +/- 2.0 and 6.5 +/- 3.4, respectively, with no autograft insufficiency in 15, 1+ in 4. Comparing postoperative with the last investigations, there were no significant changes of pressure gradients or grade of regurgitation. Mean and maximum homograft pressure gradients were 7.9 +/- 3.7 and 16.2 +/- 8.1 mm Hg, respectively, at last investigation; most patients had no or mild homograft regurgitation (0+, n = 13; 1+, n = 5; 2+, n = 1). CONCLUSIONS: Native valve endocarditis can be treated with excellent results using the Ross procedure with the subcoronary and inclusion technique, with low mortality and morbidity rates and a very low recurrence rate of endocarditis.

Diagnostic accuracy of colorectal cancer staging with whole-body PET/CT colonography.

CONTEXT: Staging of patients with colorectal cancer often requires a multimodality, multistep imaging approach. Colonography composed of a combined modality of positron emission tomography (PET) and computed tomography (CT) provides whole-body tumor staging in a single session. OBJECTIVES: To determine the staging accuracy of whole-body PET/CT colonography compared with the staging accuracies of CT followed by PET (CT + PET) and CT alone and to evaluate the effect of PET/CT colonography on therapy planning compared with conventional staging (CT of the abdomen and thorax and optical colonoscopy). DESIGN, SETTING, AND PATIENTS: Prospective study of 47 patients enrolled between May 2004 and June 2006 with clinical findings and optical colonoscopy that suggested primary colorectal cancer (mean [SD] age, 71 [11] years; range, 47-92 years). Patients underwent whole-body PET/CT colonography 1 day after colonoscopy. The study was conducted at a university hospital with a mean (SD) follow-up of 447 (140) days (range, 232-653 days). MAIN OUTCOME MEASURES: Correct classification of overall TNM stage using PET/CT colonography compared with CT + PET and CT alone. Secondary outcome measures were the accurate assessment of T-stage, N-stage, and M-stage by PET/CT colonography compared with CT + PET and CT alone and the effect of PET/CT colonography on therapy planning. RESULTS: Of the 47 patients with a total of 50 lesions, the overall TNM stage was correctly determined for 37 lesions with PET/CT colonography (74%; 95% confidence interval [CI], 60%-85%), 32 lesions with CT + PET (64%; 95% CI, 49%-77%), and 26 lesions with CT alone with a 0.7-cm node threshold (52%; 95% CI, 37%-66%). Compared with optimized abdominal CT staging alone, PET/CT colonography was significantly more accurate in defining TNM stage (difference, 22%; 95% CI, 9%-36%; P=.003), which was mainly based on a more accurate definition of the T-stage. Differences were not detected for defining N-stage between PET/CT colonography and CT alone with a threshold of 0.7 cm for malignant nodes but were detected with a threshold of 1 cm. Differences were not detected in defining M-stage separately or when comparing the accuracies of PET/CT colonography with CT + PET. PET/CT colonography affected consecutive therapy decisions in 4 patients (9%; 95% CI, 2.4%-20.4%) compared with conventional staging (CT alone and colonoscopy). CONCLUSIONS: In this preliminary study, PET/CT colonography is at least equivalent to CT + PET for tumor staging in patients with colorectal cancer. Thus, PET/CT colonography in conjunction with optical colonoscopy may be a suitable concept of tumor staging for patients with colorectal cancer.

Anterior chamber angle measurement with optical coherence tomography: intraobserver and interobserver variability.

PURPOSE: To assess intraobserver and interobserver variability of anterior segment optical coherence tomography (AS-OCT) as an objective diagnostic tool to quantify the anterior chamber angle and opening width. SETTING: University Eye Clinic, Lübeck, Germany. METHODS: The anterior chamber angle and opening width were assessed in 18 eyes of 9 healthy volunteers by 2 observers. Intraobserver reproducibility was evaluated by calculating an intraclass correlation coefficient (ICC) in a mixed model. Each observer had a separate model using information from 5 scans. Interobserver variability was determined by Bland-Altman analysis. The ICC was calculated in a mixed model using a residual maximum likelihood method. The results of 3 and 5 repeated scans were evaluated to indicate the change to 1 measurement application. RESULTS: The mean anterior chamber angle measurement was 35.9 degrees +/- 5.7 (SD) for observer A and 36.2 +/- 5.7 degrees for observer B. The ICC was 0.94 and 0.91, respectively. The mean opening width was 315 +/- 62 microm for observer A and 317 +/- 60 microm for observer B. The ICC was 0.97 and 0.93, respectively. Interobserver comparisons showed a mean difference between anterior chamber angle measurements of -0.27 +/- 1.6 degrees, a limit of agreement (LOA) interval from -3.52 to 2.98 degrees, and an ICC estimate of 0.96. The mean difference in opening width measurements was 2.40 +/- 12.40 microm, the LOA from -27.20 to 22.40 microm, and the estimated ICC 0.96. Using 1 instead of the mean of 5 measurements, the LOA range increased by 3.46 degrees for the anterior chamber angle and 30.0 microm for the opening width. CONCLUSION: Anterior chamber angle and opening width measurements by OCT showed low intraobserver and interobserver variability, indicating OCT is a valuable technique for quantitative assessment that provides reproducible measurements and objective documentation by different examiners.

Accuracy of whole-body dual-modality fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT) for tumor staging in solid tumors: comparison with CT and PET.

PURPOSE: To assess the accuracy of positron emission tomography/computed tomography (PET/CT) when staging different malignant diseases. PATIENTS AND METHODS: This was a retrospective, blinded, investigator-initiated study of 260 patients with various oncological diseases who underwent fluorine-18-2-fluoro-2-deoxy-d-glucose PET/CT for tumor staging. CT images alone, PET images alone, PET + CT data viewed side by side, and fused PET/CT images were evaluated separately according to the tumor-node-metastasis system. One hundred forty patients with tumors not staged according to the tumor-node-metastasis system or a lack of reference standard were excluded from data analysis; 260 patients were included. Diagnostic accuracies were determined for each of the four image sets. Histopathology and a clinical follow-up of 311 (+/- 125) days served as standards of reference. RESULTS: PET/CT proved significantly more accurate in assessing tumor-node-metastasis system stage compared with CT alone, PET alone, and side-by-side PET + CT (P < .0001). Of 260 patients, 218 (84%; 95% CI, 79% to 88%) were correctly staged with PET/CT, 197 (76%; 95% CI, 70% to 81%) with side-by-side PET + CT, 163 (63%; 95% CI, 57% to 69%) with CT alone, and 166 (64%; 95% CI, 58% to 70%) with PET alone. Combined PET/CT had an impact on the treatment plan in 16, 39, and 43 patients when compared with PET + CT, CT alone, and PET alone, respectively. CONCLUSION: Tumor staging with PET/CT is significantly more accurate than CT alone, PET alone, and side-by-side PET + CT. This diagnostic advantage translates into treatment plan changes in a substantial number of patients.

Effects of verteporfin therapy on central visual field function.

PURPOSE: To evaluate the effect of photodynamic therapy with verteporfin on the maintenance of central visual field function. DESIGN: Randomized controlled clinical trial. PARTICIPANTS: Forty-six consecutive patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration including a classic component were randomly assigned. Thirty-three participants received standard verteporfin therapy, and 13 received placebo and laser treatment. METHODS: The trial was performed as a single-center, double-masked study. Patients were examined before therapy and continuously in 3-month intervals during 2 years of follow-up. A scanning laser ophthalmoscope (SLO) was used to perform macular microperimetry. Absolute and relative scotomas were documented at each visit, and size was measured in square millimeters. MAIN OUTCOME MEASURES: The change in size of central scotoma in the verteporfin group compared with the placebo group. RESULTS: An absolute scotoma was seen in 88%, and a relative scotoma was seen in 100% of eyes before therapy. Absolute defects were associated with the classic CNV component localized angiographically. In the verteporfin group, the absolute scotoma grew from 2.5 mm(2) at baseline to a final size of 7.3 mm(2) at month 24. In the placebo group, the mean lesion size of the absolute scotoma enlarged from an initial size of 2.7 mm(2) to 31.5 mm(2) after 24 months. The relative scotoma increased from 7.9 mm(2) at baseline to 20.8 mm(2) at month 24 in the verteporfin group, whereas a progression from 8.5 mm(2) initially to 48.3 mm(2) at the final presentation was measured in the placebo group. Statistical analysis showed that both the mean absolute and relative scotoma sizes were significantly smaller in the verteporfin group than the placebo group for all intervals from 6 to 24 months (P<0.001). CONCLUSIONS: Documentation of macular function with SLO perimetry demonstrated a significant benefit of verteporfin therapy for the preservation of the central visual field. Absolute and relative scotoma sizes remained smaller after therapy. This may influence reading ability and visual rehabilitation.

Whole-body dual-modality PET/CT and whole-body MRI for tumor staging in oncology.

CONTEXT: Deciding on the appropriate therapy for patients with malignant diseases mandates accurate tumor staging with whole-body coverage. Magnetic resonance imaging (MRI) and a combined modality including positron emission tomography (PET) and computed tomography (CT) provide whole-body tumor staging in a single session. OBJECTIVE: To determine the staging accuracies of both whole-body PET/CT and whole-body MRI for different malignant diseases. DESIGN, SETTING, AND PATIENTS: Prospective, blinded, investigator-initiated study of 98 patients (mean age, 58 years; range, 27-94 years) with various oncological diseases who underwent back-to-back whole-body glucose analog [18F]-fluorodeoxyglucose-PET/CT and whole-body MRI for tumor staging. The study was conducted at a university hospital from December 2001 through October 2002 and had a mean follow-up of 273 days (range, 75-515 days). The images were evaluated by 2 different, blinded reader teams. The diagnostic accuracies of the 2 imaging procedures were compared. MAIN OUTCOME MEASURES: Correct classification of the primary tumor, regional lymph nodes, and distant metastasis (overall TNM stage) using whole-body PET/CT and whole-body MRI. Secondary outcome measures were accurate assessment of T-stage, N-stage, and M-stage by the 2 imaging procedures. RESULTS: Of 98 patients, the overall TNM stage was correctly determined in 75 with PET/CT (77%; 95% confidence interval [CI], 67%-85%) and in 53 with MRI (54%; 95% CI, 44%-64%) (P<.001). Compared with MRI, PET/CT had a direct impact on patient management in 12 patients. Results from MRI changed the therapy regimen in 2 patients compared with PET/CT. Separate assessment of T-stage (with pathological verification) in 46 patients revealed PET/CT to be accurate in 37 (80%; 95% CI, 66%-91%) and MRI to be accurate in 24 (52%; 95% CI, 37%-67%) (P<.001). Of 98 patients, N-stage was correctly determined in 91 patients with PET/CT (93%; 95% CI, 86%-97%) and in 77 patients with MRI (79%; 95% CI, 69%-86%) (P =.001). Both imaging procedures showed a similar performance in detecting distant metastases. CONCLUSIONS: The feasibility and diagnostic accuracy of the whole-body staging strategies of PET/CT and MRI are established. Superior performance in overall TNM staging suggests the use of [18F]-fluorodeoxyglucose-PET/CT as a possible first-line modality for whole-body tumor staging.

Effects of covariates: a summary of Group 5 contributions.

This report summarizes the contributions of Genetic Analysis Workshop 13 (GAW13) related to the use of covariates in genetic analysis. Seven papers are summarized, five of which analyzed the Framingham Heart Study Data, and two the simulated data. Five papers examined the role of covariates in linkage analysis, using a variety of statistical approaches including affected sibling pair analysis, conditional logistic regression, and variance components methods. One paper examined the impact of covariates on family-based association analysis. In each of these papers, the detection of genetic effects could be influenced by the incorporation of covariates. The final paper examined the role of transmission ratio distortion in the analysis of complex traits and the role of covariates in the variability in transmission ratio distortion. While each paper takes a different approach to the genetic analysis of complex traits, a common thread running through each is that the inclusion of covariates can have a substantial impact on the results of the analysis. Care must be taken to understand how the covariates are being used in each analysis, what assumptions are being made, and how these assumptions might affect the results and their interpretation. Finally, the results of Group 5 studies show that inclusion of covariates can increase the power to detect genes for complex traits, and has the potential to advance an understanding of the role of genes in these complex traits.

Midterm results of the Ross procedure preserving the patient's aortic root.

BACKGROUND: Since the early 1990s, the pulmonary autograft is predominantly implanted as a freestanding root for less aortic valve regurgitation is reported. However, there is a certain risk of dilatation of the root over time potentially impairing valve function. We favor since 8 years the original subcoronary or inclusion technique to preserve the root of the patient as a restrain to dilatation. METHODS AND RESULTS: Between June 1994 and May 2002 the subcoronary (n=228) and inclusion technique (n=17) were performed in 245 patients (191 male, 54 female), mean age 45.7+/-13.4 (15-70) years. The underlying aortic valve disease was an aortic insufficiency in n=83, stenosis in n=48, a combined aortic valve disease in n=111 and an acute endocarditis in n=19 patients. Previous aortic valve surgery was performed in n=23. Last follow-up investigations (within last year) including echocardiography was performed at a mean follow-up of 29.4+/-24.7 months (553.7 patient years). Hospital mortality was n=2, late mortality n=4 (all noncardiac). Two patients were lost to follow-up (99% complete clinical follow-up). Reoperations were necessary in n=7 valves (autograft: endocarditis n=1, malpositioning n=1, leaflet prolapse n=1; homograft: stenosis n=2, insufficiency n=2). Autograft insufficiency (AI) was AI 0 in n=154, AI I n=66, AI II n=8. The maximum/mean pressure gradient across the autograft was 6.6+/-3.4 (2.1 to 25.9)/3.6+/-1.8 (1.2 to 13.2) mm Hg, respectively. Homograft insufficiency was 0 in n=167, I in n=54, II in n=9, and III in n=1. Maximum and mean transhomograft pressure gradients were 11.7+/-6.8 (2.2 to 42.6)/6.2+/-3.8 (1.2 to 24.5) mm Hg. Most patients were NYHA class I (n=214), class II (n=19), class III (n=2). Significant aortic root dilatation was not observed. CONCLUSIONS: Aortic valve replacement with a pulmonary autograft in the subcoronary or inclusion technique provides excellent hemodynamics with no root dilatation at least in a mid term postoperative period. Transhomograft pressure gradients are slightly increased. Longer term results with special emphasis on the pulmonary homograft are necessary.