Datos comparativos del ecosistema agroalimentario catalán con el sector

Gianfranco Gualdi, MD

Department of Imaging CT and MR University “La Sapienza”

Rome, Italy

The recent development of three-dimensional (3D) MR spectroscopic imaging expand the diagnostic assessment of prostate cancer beyond the morphologic information provided by Magnetic Resonance (MR) imaging. As with MRI, 3D MR spectroscopic imaging uses a strong magnetic field and radio waves to noninvasively obtain metabolic spectra (peaks) for the citrate, choline, creatine, and various polyamines from contiguous small volumes throughout the gland are observed. The peaks for these different chemicals occur at distinct frequencies or positions in the MRSI spectrum. The areas under these peaks are related to the concentration of the respective metabolites, and changes in these concentrations can be used to identify cancer with reasonably high specificity. The decrease in citrate with prostate cancer is due to both changes in cellular function and changes in the organization of the tissue, which loses its characteristic ductal morphology. The elevation of the choline peak in prostate cancer is associated with changes in cell membrane synthesis and degradation that occur with the evolution of human cancer.

Prostate tumor individuation

Transrectal US is widely used for guidance of prostate gland biopsy, but sensitivity and specificity are low in the localization of prostate cancer. MR imaging has a significantly higher sensitivity for tumor detection than does tran- srectal US but, like transrectal US, has low specificity (1-6). The addition of metabolic information from 3D MR spectroscopic imaging to morphologic data from MR imaging may allow more specific diagnosis and localization of prostate cancer. MR spectroscopy has been used to obtain metabolic data from tumors in situ (7,8). Recent techni- cal developments have allowed the application of localized three-dimensional proton 3D MR spectroscopic imaging to the in vivo evaluation of the human prostate (9). With use of 3D MR spectroscopic imaging, significantly higher choline levels and significantly lower citrate levels were observed in regions of cancer compared with areas of benign prostatic hypertrophy and normal prostatic tissue. The ratio of these metabolites (choline to citrate) in regions of cancer appears not to overlap with ratios in the normal peripheral zone, which suggests that 3D MR spectroscopic imaging combined with MR imaging may improve tumor detection and localization compared to those with MR imaging alone (9). Scheidler et al (10) have performed MR imaging and 3D MR spectroscopic ima- ging examinations in 53 patients with biopsy-proved prostate cancer and subsequent radical prostatectomy with

improved tumor localization for both readers when 3D MR spectroscopic imaging was added to MR imaging. High specificity (up to 91%) was obtained when combined MR imaging and 3D MR spectroscopic imaging indicated cancer, whereas high sensitivity (up to 95%) was obtained when either test alone indicated a positive result. Spermine, spermidine, and other polyamines (11,12) are also listed as diagnostic. To establish the additional value of 3D MR spectroscopy to endorectal MR in the diagnosis and grading of prostate cancer we studied 53 Patients with suspicion of prostatic cancer on the basis of endorectal exploration and/or on transrectal ultrasound and/or on the PSA levels (13). All the examinations were performed with 1,5 T scan. We acquired axial and coronal FSE T2-weighted sequences, axial T1 weighted SE and spectroscopic sequences PRESS 3D CSI (Point Resolved Spectroscopy 3D Chemical Shift Imaging) localized on the axial T2 images so as to include the prostatic gland while excluding the periprostatic fat. MR examinations have been evaluated from two Radiologist unaware of the clini- cal data, of the transrectal ultrasound findings, of the PSA levels and of the histologic findings. MR and MRS 3D CSI findings were compared with biopsy findings in 22 cases and with material obtained from laparoscopic prostatectomy in 31 cases. The histologic examination revealed adenocarcinoma in 35 cases, prostatitis in 2 cases and no alterations in the remaining 13 cases. With morphologic MR exam we reported a sensibility of 76%, a specificity of 53%, an accuracy of 70%, a PPV of 81% and a NPV of 47%. With the combination of MR and MRS 3D CSI we obtained a sensibility of 95%, a specificity of 81%, an accuracy of 91%, a PPV of 92% and a NPV of 87%. In our experience, the MRS 3D CSI has improved the reliability of the endorectal MR in the diagnosis and localization of prostatic cancer.

Prostate tumor local staging

Accurate local staging is needed to optimize treatment decision making in patients with clinically localized prostate cancer. The presence of extracapsular extension (ECE) has been correlated with treatment failure after radical prostatectomy, particularly if nerve-sparing surgical techniques are used (14). Transrectal ultrasonography is the most widely used imaging modality for local staging of prostate cancer; however, transrectal US is not very accurate in the prediction of ECE (15). Endorectal MR imaging shows the most promise for local staging but has not yet realized its potential owing to problems with interobserver variability and variable diagnostic accuracy (16-19). Differences in reader experience and lack of accepted diagnostic criteria have resulted in a wide range of results reported for MR imaging in the detection of ECE. The fact that histopathologic studies have demonstrated a strong correlation between the volume of prostate cancer and the presence of ECE suggests the possibility that 3D MR spectroscopic imaging estimates of tumor volume may be used to assist the diagnosis of ECE, similar to the way in which serum prostate-specific antigen levels are used to assess the risk of ECE. Yu K et Al. (20) have evaluated 3D MR spectroscopic imaging as a potential predictor of ECE but did not determine a specific tumor volume threshold because variations in 3D MR spectroscopic imaging technique during the course of the study prevented determination of absolute tumor volume. A specific volume threshold would be determined best in a prospective study with use of current state-of-the-art 3D MR spectroscopic imaging technique to provide complete gland coverage. Patients with the least extensive tumor at 3D MR spectroscopic imaging (<1 cancer voxel per section) were found to have only a 6% risk of ECE, whereas patients with the most extensive tumor (>4 cancer voxels per section) had an 80% risk of ECE.

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A preliminary MR imaging and MR spectroscopic imaging study of 26 biopsy proven patients prior to radical prostatectomy and step-section pathologic examination has demonstrated a strong linear correlation between cancer aggressiveness (Gleason grade) and tumor metabolic parameters (decrease in citrate and elevation of choline) (21): a statistically significant difference in the ratio of cancer choline to normal choline was observed when comparing high-grade (Gleason score of 7 or more) to moderate-grade (Gleason score 5 or 6). High cancer grade also was significantly correlated with the elevation of choline, the ratio of choline plus creatine to citrate, and reduction in citrate. Patient management can be critically dependent on the Gleason score, so that the potential of MRSI to provide additional information about biologic behaviour is very exciting. In our experience (13) on 35 biopsy-proved prostate cancer (low grade Gleason in 16 and high grade in 19 patients) an elevation of the concentration of choline was found either in the tumors with low Gleason score (5-6) and in the tumors with high Gleason score (7-8-9); instead we found marked reduction (n=9) or absence (n=4) of the concentration of citrate only in the tumors with high Gleason score, while we found normal citrate levels in the 16 tumors with low Gleason score. MRS 3D CSI has demonstrated a linear correlation with cancer grade.

Prostate tumor in patients undergoing hormone deprivation therapy

Mueller-Lisse et al (22) reported a significant time-dependent loss of prostatic choline, creatine, and citrate during hormone deprivation therapy. This loss resulted in the complete loss of all MR spectroscopically observable metabolites (ie, total metabolic atrophy) in 25% of patients who had received more than 16 weeks of therapy. In addition, it was observed that citrate levels decreased faster than did choline and creatine levels during therapy. This faster citrate level decrease resulted in an increase in the mean creatine+choline/ citrate ratio in both normal and malignant tissue with increasing therapy duration and in a loss of all MR spectroscopically detectable citrate in 69% of the patients who had received more than 16 weeks of therapy. Results of this matched case–controlled study (22) demonstrate that MR imaging combined with 3D proton MR spectroscopy of the prostate performed within the first 4 months after hormone deprivation therapy for localized prostate cancer is as accurate, reliable, and likely to help reach a diagnostic decision as that performed prior to therapy. This study (22) demonstrates the potential usefulness of combined MR imaging/3D MR spectroscopic imaging for monitoring the efficacy of hormone deprivation therapy in patients with localized prostate cancer.

References

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2. Jager GJ, Ruijter ET, van de Kaa CA, et al. Local staging of prostate cancer with endorectal MR imaging: cor- relation with histopathology. AJR 1996; 166:845-852.

3. Presti JC, Jr, Hricak H, Narayan PA, Shinohara K, White S, Carroll PR. Local staging of prostatic carcinoma: comparison of transrectal sonography and endorectal MR imaging. AJR 1996; 166:103-108.

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8. Bruhn H, Frahm J, Gyngell ML, et al. Noninvasive differentiation of tumors with use of localized H-1 MR spec- troscopy in vivo: initial experiments in patients with cerebral tumors. Radiology 1989; 172:541-548.

9. Kurhanewicz J, Vigneron DB, Hricak H, Narayan P, Carroll P, Nelson SJ. Three-dimensional H-1 MR spectrosco- pic imaging of the in situ human prostate with high (0.24–0.7-cm3) spatial resolution. Radiology 1996; 198:795-805. 10. Scheidler J, Hricak H, Vigneron DB, et al. Prostate Cancer: Localization with three-dimensional proton MR spectroscopic imaging-clinicopathologic study. Radiology 1999; 213: 473-480.

11. Lynch MJ, Nicholson JK. Proton MRS of human prostatic fluid: correlations between citrate, spermine, and myo-inositol levels and changes with disease. Prostate 1997; 30:248-255.

12. van der Graff M, Schipper RG. 1H MRS of prostatic tissue focussed on the detection of spermine, a possible biomarker of malignant behaviour in prostate cancer (abstr) In: Book of abstracts: Society of Magnetic Resonance in Medicine 1998. Berkeley, Calif: Society of Magnetic Resonance in Medicine, 1998; 613.

13. Casciani E, Polettini E, Bertini L, Emiliozzi P, Amini M, Pansadoro V e Gualdi GF. Prostate cancer: evaluation with endorectal MR imaging and three-dimensional proton MR Spectroscopic imaging. In Press

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