- Email: [email protected]
New Technologies in Rectal Cancer Management
New Technologies in Rectal Cancer Management John R. Warmath, PhD* and Alan J. Herline, MD*,† There are approximately 40,000 rectal cancers diagnosed each year. Transrectal ultrasound has become a standard in the evaluation and staging of these primary tumors. In addition, between 25-35% of patients undergoing traditional operative procedures will develop local recurrence and these recurrences are difficult to detect. While endorectal ultrasound (ERUS) currently provides the preferred method of staging rectal cancers, it remains user dependent and for those surgeons without the ability to perform ERUS often difficult to interpret still images. Image-guided surgery (IGS) is a field of technologies that use localized or tracked instruments (e.g. probes, endoscopes, or RF ablators) and preoperative images (CT, MRI, US, PET) to actively guide the therapy delivered to a patient. This is accomplished by finding the relationship between the space of the patient and the space of an image (registration). A mathematical formula accomplishes this goal and the results are displayed on a computer with real-time updates. The surgeon visualizes the instrumentation overlaid onto the appropriate tomographic slice. This article presents a review of the status of ERUS and the principles to develop a practical interactive image-guided system for use in endorectal ultrasound. The long term goal of this research plan is to develop a tracked ERUS system that will allow for the reconstruction and display of tomographic slices from ultrasound data and inter exam and inter modality (TRUS to CT, MRI, PET) comparison with TRUS. Semin Colon Rectal Surg 16:91-95 © 2005 Elsevier Inc. All rights reserved. KEYWORDS rectal cancer, endorectal ultrasound, image guided surgery
T
he current gold standard for the staging of rectal cancer is conventional two-dimensional endorectal ultrasound (ERUS). However, because of the many technological advances in the field of medical imaging, it is feasible that some other imaging method will be shown to be more appropriate. Threedimensional ERUS may very well be that modality.
Staging of Rectal Cancer The rectal wall is made up of six layers, and the amount of growth of a tumor into these layers helps to classify it into its proper stage. The mucosal layers are hyperechoic, and the muscular layers are hypoechoic, thereby making it feasible to use endorectal ultrasound in T-staging.1 Staging was historically performed clinically and evaluated postoperatively using the pathology specimen. In the early 1980s clinicians realized the
importance of ERUS in rectal cancer staging, and in 1985 the accepted staging methods were revised to include ERUS.2 It should be noted that currently there is not an accurate method to stage lymph nodes associated with rectal cancer. CT and MRI both have reported accuracies between 60 and 65%, while ERUS has reported accuracies ranging from 58 to 81%.3 Improved N-staging techniques should improve benign and malignant lymph node detection in the future. However, a malignant lymph node does not mean that there is spread of the cancer to other sites, and metastatic spread can occur without involved lymph nodes. Therefore, improved lymph node staging does not assure an improvement in the outcome of rectal cancer. While new technologies may improve N-staging in the future, this article is focused on the T-staging of rectal cancer with endorectal ultrasound.
Endorectal Ultrasound *Department of Biomedical Engineering, Vanderbilt University Medical Center, Nashville, TN. †Department of Surgery, Division of General Surgery, Colon and Rectal Surgery, Vanderbilt University Medical Center, Nashville, TN. This work was supported by a Career Development Award from the ASCRS Research Foundation. Address reprint requests to: Vanderbilt University Medical Center, D5220 MCN, Nashville, TN 37232-2543. E-mail: [email protected]
1043-1489/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1053/j.scrs.2005.08.005
Endorectal ultrasound has emerged as the imaging modality of choice for staging rectal cancer and has been shown to be especially accurate for early stage tumors (T1, T2) and tumors that penetrate the rectal wall (T3).1,4-7 Some of the problems using ERUS arise from (1) interuser variability (including T2 versus T3 discrepancies); (2) user to user portability; (3) adjuvant therapy; 91
92 and (4) stenosis. Interuser variability and the wide range in reported staging accuracies are due to the inflammation of some tumors as well as the nontomographic nature of ERUS. Another problem encountered with the use of ERUS is that adjuvant, preoperative radiotherapy can increase the echogenicity of the rectal wall thereby reducing its accuracy in T-staging.1 ERUS is also less accurate in the lower rectum because changes in anatomy cause the examination to be more difficult, although the position of the tumor with respect to the circumference of the rectum does not decrease the accuracy in T-staging.5 There have been problems with overstaging and understaging of midstage tumors for the following two reasons: (1) Overstaging is caused by the lack of differentiation between tumor and inflammation. This is a problem associated with T2 tumors.8 (2) Understaging is caused by a lack of specific, cellular information at the microscopic level.1 With ultrasound, the resolution of the image can be improved by increasing the frequency. However, there is a trade-off for increased frequency, which is decreased imaging depth due to greater tissue absorption at higher frequencies. Therefore a useful balance of imaging resolution and depth must be found. Frequencies from 5 to 10 MHz have been shown to provide acceptable results. ERUS is limited in the visualization of stenotic tumors of the rectum. Approximately 17% of stenotic tumors are impossible to stage with ERUS.1 In women this problem is currently being solved with the use of transvaginal ultrasound (TVUS) because of the improved visualization with this technique.6,9 However, this problem will not be solved in men unless improvements are made in the ERUS systems, or another imaging modality is shown to image stenotic tumors well. Despite the many limitations discussed here, ERUS is a very valuable technique used in the T-staging of rectal cancer. It is inexpensive, relatively easy to use, and identifies early stage and T3 tumors extremely well. It is important for the clinician to understand these benefits but also to recognize its limitations when using it to stage rectal neoplasms.
ERUS Development Needed ERUS image interpretation is associated with a significant learning curve. One group described ERUS as a “relatively simple procedure to learn, and once a moderate degree of experience is gained, should be routinely incorporated into the evaluation of rectal neoplasms.” However, they also say that after 15 ERUS exams have been performed that the examiners interpretative skills would stay at a high level of accuracy. 10 This is in direct conflict with another report that defines a moderate number of exams as 30 per year, and if less than 30 are performed annually, it should be expected that the results would not be as accurate as possible.11 It is also thought that interobserver accuracy may be dependent on stage. Several reports have demonstrated interobserver agreement to be low for T2 tumors, and high for T3 tumors, and that accurate interpretation of T1 and T2 tumors requires a very experienced clinician. Garcia-Aguilar and coworkers concluded that image interpretation explains some differences in reported accuracies among studies.12,13 Marusch and coworkers conclude that the “centralization of transrectal ultrasonography ser-
J.R. Warmath and A.J. Herline vice is mandatory if a high level of quality is to be achieved with this method.”11 In its current form, the centralization of ERUS services seems like a rather daunting task, but the image portability that the proposed 3D freehand ERUS system provides makes this idea more feasible. The accurate staging of rectal tumors is necessary because understaging may lead to undertreatment and overstaging results in potentially more invasive operations and subsequent increased morbidity and mortality.14
Treatment of Rectal Cancer Once a rectal tumor has been accurately staged, the next decision is the appropriate treatment for the patient. This decision is very important because the extent and invasiveness of resection or other therapies used will determine local control, cure, need for adjuvant therapy, sphincter preservation, and preservation or loss of sexual and urinary functions. Surgery has been shown to be the optimal cure for most cases of rectal cancer, and there is agreement that a 1-cm distal surgical margin and a tumor-free circumferential margin are appropriate for most resections.15 Local excision provides many benefits to patients undergoing treatment for rectal cancer, but currently radical excision is the standard procedure. It should again be noted that the correct staging of the tumor is of the utmost importance in the success of the treatment. Improvements in tumor staging have the potential to change the standard of care by moving toward local excision for more patients.
Restaging After Preoperative Radiotherapy Preoperative radiotherapy for the purpose of tumor downstaging has become a common part of the treatment for rectal cancer. However, because of the residual fibrotic tissue caused by the radiation, there has not been a conclusion as to the appropriate method of restaging the tumor after therapy. One study showed that in 28 of 29 cases, fibrosis was the major component of irradiated tumors.16 There is increased echogenicity of the ultrasound as a result of the fibrosis.17 This causes some concern when using ERUS because it is therefore not the tumor that is being staged, but rather the fibrotic tissue, although it has been shown that any residual tumor will be contained within the fibrosis thereby allowing it to be used to stage the maximum extent of the tumor boundary.16 Studies have concluded that ERUS staging accuracy is decreased after the use of radiotherapy; however, it is still more accurate than CT and MRI for this purpose.18-20 Changes due to radiation and the resultant downstaging of the tumor have been shown to be positively associated with patient outcomes.21,22 Tumor restaging following this treatment is being evaluated. Currently the reported accuracies range from 29%22 to 92.8%23 with a large range of values in between (⬃50%,24 66%,25 and 91%18). Some of the accuracy discrepancy could be based on the length of time between radiation and re-evaluation of the tumor. ERUS staging accuracy is reduced because of: (1) postradiation
New technologies in rectal cancer management
93
Figure 1 ERUS probe with attached rigid object for optical tracking. (Color version of figure is available online.)
edema; (2) inflammation; (3) necrosis; and (4) fibrosis.24 The edema and inflammation will decrease over time, so the ERUS staging accuracy should increase over the same time period. Standardization of the waiting period would allow future work to be consistent and would allow a direct comparison of the results of many different studies.
Image-Guided Procedures (IGP) and ERUS In the review article, “The Process and Development of ImagedGuided Procedures,” Galloway sums up the motivation of IGPs: “One of the most fundamental forces in the development of surgery and other forms of directed therapy is the need to increase the information available to physicians and to place that information in both spatial and temporal contexts.”26 This idea also holds true for the area of rectal tumor staging, and therefore, the combination of the fields of IGP and ERUS is a logical one. With this union comes not only the ability to provide more information to the clinician, but also more accurate information in both space and time. The idea has been proposed that this new information will help the surgeon more accurately diagnose, stage, and treat rectal cancer.
3D ERUS Current research is showing the potential widespread use of 3D ultrasound within the medical community. The validity of rectal cancer diagnosis with 3D as compared with 2D ultrasound is being tested, and the reported conclusions to date show 3D to be superior.27 Reported techniques to collect 3D data from 2D ERUS probes include optical tracking, magnetic tracking, the timed pullout method, and a rotating stepper motor for a stationary, side-firing probe.27-32 For the 360-degree rotating BK 1850 ERUS probe, only magnetic tracking, optical tracking, and the timed pullout method are viable options. Magnetic localization systems are currently not as accurate as optical localization systems. A large amount of data has been reported using magnetic tracking for 3D ultrasound acquisition using the Stradx system,29 although they have not reported a quantitative validation of the system. Interestingly, they are proposing to change to an optically tracked system.33
The timed pullout method is also known as linear scanning. Traditional linear scanning devices can provide visually pleasing results but require a bulky device to hold the ERUS probe and must be placed close to the patient. This device contains the stepper motor and controls the linear movement of the probe.31,34 The pullout method is currently being used clinically and can be purchased as an accessory from BK Medical (Herlev, Denmark) with an ERUS system. Improvements to the linear scanning device have been made and BK Medical’s 2050 Ultrasound transducer contains the rotating crystal and linear scanning device within the shaft. While the timed pullout devices allow for reconstruction of 3D volumes, the position and orientation of these volumes is dependent on the rigid fixation of the device. Therefore, any accidental movement of the device would cause invalid data. Also, there is currently not a valid registration method used to align these volumes to other data sets of the same anatomy. An optically tracked ERUS device requires no such fixation thus allowing more freedom of motion and provides a standard coordinate system with which to register the data. Figure 1 shows an ERUS probe with an attached rigid body for optical tracking. Figure 2 shows three parts of an optically tracked ultrasound system, as follows: (1) a computer; (2) an ultrasound machine; and (3) an Optotrak 3020 localization system. Besides ease of use, optical tracking has another advantage over linear scanning. This advantage is a result of coordinate integrated imaging. When using a tracked ultrasonic device, the exact location and orientation of the probe are known. Through the process of calibration, the location and orientation of the ultrasound beam are also known in an external coordinate space. This allows each pixel in the ultrasound data set to be assigned a 3D coordinate value in a physical space that is related to the ultrasound space through a specific transformation matrix. This method of assigning coordinate values to the ultrasound data in physical space has two advantages. First it allows the direct comparison of two imaging modalities. This is achieved by transforming a data set, such as CT, into the same physical space as the ultrasound data, making an accurate comparison possible. Second this method allows localization of multiple tools and image sets into the same physical space. The user then has the ability to guide a tracked instrument, such as a biopsy needle or surgical blade, to a specific location in physical
J.R. Warmath and A.J. Herline
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Figure 2 Optically tracked ERUS system.
space while at the same time viewing the progress in all imaging modalities (ie, ultrasound and CT). These coregistration and guidance techniques are not possible using the mechanical 3D volume reconstruction methods because multiple image sets and surgical tools cannot be localized in the same physical space. The mechanical-based methods are appropriate for 3D volume reconstruction of ultrasound data, but without an accurate registration technique, are not valid for anything beyond visual enhancement of the rectum. Therefore image guidance using tracked ultrasound (3D freehand ultrasound) is the best choice for an improvement in current ERUS techniques. Gee and coworkers reported a few issues with 3-day freehand ultrasound systems that need to be addressed before they will have everyday use in clinics. These include the following: (1) high cost; (2) restricted volumes; and (3) restricted use caused by attached localization devices.35 For the freehand ERUS system we have already solved the problem addressed in number 3, and we believe that the cost and restricted volume size are two issues that can be overcome before
taking this work out of the world of research and placing it into the clinical setting as a medical device intended for daily use.
Clinical Evaluation of 3D ERUS Three-dimensional imaging with ultrasound has become more common over the past 10 years because of major technological advances in the field. The use of 3D ERUS was reported as early as 1992, and in 1997 a clinical study was performed that reported a full 3D tumor reconstruction on 15 patients.36,37 However, it was not until recently that a study reported using 3D ERUS to actually stage rectal tumors. This study compared the staging accuracy of 2D versus 3D ERUS. This study showed a 6.1 and 9% increase in accuracy for tumors staged by pathology as T2 and T3, respectively. However, these results did not show a significant enough improvement to conclusively say that 3D ERUS is better than 2D ERUS for the staging of rectal cancer.38 This work shows great potential
New technologies in rectal cancer management for 3D ERUS; however, more research needs to be conducted to thoroughly evaluate its perceived benefit.
Conclusion As stated earlier, rectal cancer is a disease that is a major problem within the United States. More research and improved screening and treatment standards are needed to reduce the surprisingly high mortality rates. With universal screening, rectal cancer can be found earlier and the patient has a better chance of cure. Improved treatment of rectal cancer greatly depends on the accurate staging of the disease, and amid the ever changing treatment practices, the best options for total cure with the least amount of morbidity and mortality need to be used. ERUS has become accepted as the most reliable and accurate staging technique currently available, although it has difficulties. The incorporation of new technologies, such as those used in imageguided therapy, to the preoperative preadjuvant staging, preoperative postadjuvant staging, and interoperative visualization of rectal cancer with ERUS can potentially help to improve the accuracy of staging, reduce the overall morbidity and mortality rates, and help clinicians to detect and follow rectal cancer over time.
References 1. Heriot AG, Grundy A, Kumar D: Preoperative staging of rectal carcinoma. Br J Surg 86(1):17-28, 1999 2. Hildebrandt U, Feifel G: Preoperative staging of rectal-cancer by intrarectal ultrasound. Dis Colon Rectum 28(1):42-46, 1985 3. McArdle CS, et al: Colorectal Cancer. Oxford, Isis Medical Media Ltd., 2000 4. Boyce GA, et al: Endoscopic ultrasound in the preoperative staging of rectal carcinoma. Gastrointest Endosc 38(4):468-471, 1992 5. Sailer M, et al: Influence of tumor position on accuracy of endorectal ultrasound staging. Dis Colon Rectum 40(10):1180-1186, 1997 6. Scialpi M, et al: Rectal carcinoma—preoperative staging and detection of postoperative local recurrence with transrectal and transvaginal ultrasound. Abdom Imaging 18(4):381-389, 1993 7. Sailer M, et al: The value of endorectal ultrasound in the assessment of adenomas, T1- and T2-carcinomas. Int J Colorec Dis 12a(4):214-219, 1997 8. Hulsmans F, et al: Assessment of tumor infiltration depth in rectal cancer with transrectal sonography— caution is necessary. Radiology 190(3):715-720, 1994 9. Fedyaev EB, Volkova EA, Kuznetsova EE: Transrectal and transvaginal ultrasonography in the preoperative staging of rectal-carcinoma. Eur J Radiol 20(1):35-38, 1995 10. Carmody BJ, Otchy DP: Learning curve of transrectal ultrasound. Dis Colon Rectum 43(2):193-197, 2000 11. Marusch F, et al: Routine use of transrectal ultrasound in rectal carcinoma: results of a prospective multicenter study. Endoscopy 34(5): 385-390, 2002 12. Burtin P, et al: Interobserver agreement in the staging of rectal cancer using endoscopic ultrasonography. Endoscopy 29(7):620-625, 1997 13. Garcia-Aguilar J, et al: Accuracy of endorectal ultrasonography in preoperative staging of rectal tumors. Dis Colon Rectum 45(1):10-15, 2002 14. Kim JC, et al: Source of errors in the evaluation of early rectal cancer by endoluminal ultrasonography. Dis Colon Rectum 44(9):1302-1309, 2001 15. Cohen AM, et al (eds): Cancer of the Colon, Rectum, and Anus. New York, NY, McGraw-Hill, Inc., 1995, pp 1154
95 16. Gavioli M, Bagni A, Piccagli I, et al: Usefulness of endorectal Ultrasound after preoperative radiotherapy in rectal cancer comparison between sonographic and histopathologic changes. Dis Colon Rectum 43(8): 1075-1083, 2000 17. Kuntz C, et al: Endosonographic diagnosis in preoperative radiotherapy of locally advanced rectal carcinoma. Chirurgie 68(1):57-62, 1997 18. Langer C, et al: Endosonography in epithelial rectal tumors. Value of a differentiated therapy concept. Chirurgie 72(3):266-271, 2001 19. Pessaux P, Burtin P, Arnaud JP: Staging for locoregional extension of rectal adenocarcinoma. Ann Chirurg 126(1):10-17, 2001 20. Hoffmann KT, et al: Restaging of locally advanced carcinoma of the rectum with MR imaging after preoperative radio-chemotherapy plus regional hyperthermia. Strahlenther Onkol 178(7):386-392, 2002 21. Valentini V, et al: Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. Int J Radiat Oncol Biol Phys 53(3):664-674, 2002 22. Rau B, et al: Accuracy of endorectal ultrasound after preoperative radiochemotherapy in locally advanced rectal cancer. Surg Endosc 13(10):980-984, 1999 23. Barbaro B, et al: The accuracy of transrectal ultrasound in predicting the pathological stage of low-lying rectal cancer after preoperative chemoradiation therapy. Int J Radiat Oncol Biol Phys 43(5):1043-1047, 1999 24. Savides TJ, Master ss: EUS in rectal cancer. Gastrointest Endosc 56:S12S18, 2002 (suppl 4) 25. Liersch T, et al: Preoperative diagnostic procedures in locally advanced rectal carcinoma (⬎ or ⫽T3 or N⫹). What does endoluminal ultrasound achieve at staging and restaging (after neoadjuvant radiochemotherapy) in contrast to computed tomography?. Chirurgie 74(3):224234, 2003 26. Galloway RL: The process and development of image-guided procedures. Ann Rev Biomed Eng 3:83-108, 2001 27. Tong SD, et al: Intra- and inter-observer variability and reliability of prostate volume measurement via two-dimensional and three-dimensional ultrasound imaging. Ultrasound Med Biol 24(5):673-681, 1998 28. Warmath JR, Bao P, Herline AJ, et al: Ultrasound 3D volume reconstruction from an optically tracked endorectal ultrasound (TERUS) probe. Medical Imaging 2004: Visualization, Image-Guided Procedures, and Display, 2004. 5367: pp 228-236 29. Prager R, et al: Freehand 3D ultrasound without voxels: volume measurement and visualisation using the Stradx system. Ultrasonics 40(18):109-115, 2002 30. Ivanov KD, Diacov CD: Three-dimensional endoluminal ultrasound— new staging technique in patients with rectal cancer. Dis Colon Rectum 40(1):47-50, 1997 31. Blake CC, et al: Variability and accuracy of measurements of prostate brachytherapy seed position in vitro using three-dimensional ultrasound: an intra- and inter-observer study. Med Phys 27(12):27882795, 2000 32. Tong S, et al: A three-dimensional ultrasound prostate imaging system. Ultrasound Med Biol 22(6):735-746, 1996 33. Treece G: High Definition Three-Dimensional Ultrasound EPSRC Grant GR/N21062 http://svr-www.eng.cam.ac.uk/⬃gmt11/hd3dus/ index.html accessed 2/13/03 34. Fenster A, Downey DB, Cardinal HN: Three-dimensional ultrasound imaging. Phys Med Biol 46(5):R67-R99, 2001 35. Gee A, et al: Engineering a freehand 3D ultrasound system. Pattern Recogn Lett 24(4-5):757-777, 2003 36. Mueller, M.P., et al: Three-dimensional transrectal ultrasound: preliminary patient evaluation. J Laparoendosc Surg 2(5):223-227, 1992 37. Ivanov KD, Diavoc CD: Three-dimensional endoluminal ultrasound: new staging technique in patients with rectal cancer. Dis Colon Rectum 40(1):47-50, 1997 38. Kim JC, et al: Comparative study of three-dimensional and conventional endorectal ultrasonography used in rectal cancer staging. Surg Endosc 16(9):1280-1285, 2002
T
he current gold standard for the staging of rectal cancer is conventional two-dimensional endorectal ultrasound (ERUS). However, because of the many technological advances in the field of medical imaging, it is feasible that some other imaging method will be shown to be more appropriate. Threedimensional ERUS may very well be that modality.
Staging of Rectal Cancer The rectal wall is made up of six layers, and the amount of growth of a tumor into these layers helps to classify it into its proper stage. The mucosal layers are hyperechoic, and the muscular layers are hypoechoic, thereby making it feasible to use endorectal ultrasound in T-staging.1 Staging was historically performed clinically and evaluated postoperatively using the pathology specimen. In the early 1980s clinicians realized the
importance of ERUS in rectal cancer staging, and in 1985 the accepted staging methods were revised to include ERUS.2 It should be noted that currently there is not an accurate method to stage lymph nodes associated with rectal cancer. CT and MRI both have reported accuracies between 60 and 65%, while ERUS has reported accuracies ranging from 58 to 81%.3 Improved N-staging techniques should improve benign and malignant lymph node detection in the future. However, a malignant lymph node does not mean that there is spread of the cancer to other sites, and metastatic spread can occur without involved lymph nodes. Therefore, improved lymph node staging does not assure an improvement in the outcome of rectal cancer. While new technologies may improve N-staging in the future, this article is focused on the T-staging of rectal cancer with endorectal ultrasound.
Endorectal Ultrasound *Department of Biomedical Engineering, Vanderbilt University Medical Center, Nashville, TN. †Department of Surgery, Division of General Surgery, Colon and Rectal Surgery, Vanderbilt University Medical Center, Nashville, TN. This work was supported by a Career Development Award from the ASCRS Research Foundation. Address reprint requests to: Vanderbilt University Medical Center, D5220 MCN, Nashville, TN 37232-2543. E-mail: [email protected]
1043-1489/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1053/j.scrs.2005.08.005
Endorectal ultrasound has emerged as the imaging modality of choice for staging rectal cancer and has been shown to be especially accurate for early stage tumors (T1, T2) and tumors that penetrate the rectal wall (T3).1,4-7 Some of the problems using ERUS arise from (1) interuser variability (including T2 versus T3 discrepancies); (2) user to user portability; (3) adjuvant therapy; 91
92 and (4) stenosis. Interuser variability and the wide range in reported staging accuracies are due to the inflammation of some tumors as well as the nontomographic nature of ERUS. Another problem encountered with the use of ERUS is that adjuvant, preoperative radiotherapy can increase the echogenicity of the rectal wall thereby reducing its accuracy in T-staging.1 ERUS is also less accurate in the lower rectum because changes in anatomy cause the examination to be more difficult, although the position of the tumor with respect to the circumference of the rectum does not decrease the accuracy in T-staging.5 There have been problems with overstaging and understaging of midstage tumors for the following two reasons: (1) Overstaging is caused by the lack of differentiation between tumor and inflammation. This is a problem associated with T2 tumors.8 (2) Understaging is caused by a lack of specific, cellular information at the microscopic level.1 With ultrasound, the resolution of the image can be improved by increasing the frequency. However, there is a trade-off for increased frequency, which is decreased imaging depth due to greater tissue absorption at higher frequencies. Therefore a useful balance of imaging resolution and depth must be found. Frequencies from 5 to 10 MHz have been shown to provide acceptable results. ERUS is limited in the visualization of stenotic tumors of the rectum. Approximately 17% of stenotic tumors are impossible to stage with ERUS.1 In women this problem is currently being solved with the use of transvaginal ultrasound (TVUS) because of the improved visualization with this technique.6,9 However, this problem will not be solved in men unless improvements are made in the ERUS systems, or another imaging modality is shown to image stenotic tumors well. Despite the many limitations discussed here, ERUS is a very valuable technique used in the T-staging of rectal cancer. It is inexpensive, relatively easy to use, and identifies early stage and T3 tumors extremely well. It is important for the clinician to understand these benefits but also to recognize its limitations when using it to stage rectal neoplasms.
ERUS Development Needed ERUS image interpretation is associated with a significant learning curve. One group described ERUS as a “relatively simple procedure to learn, and once a moderate degree of experience is gained, should be routinely incorporated into the evaluation of rectal neoplasms.” However, they also say that after 15 ERUS exams have been performed that the examiners interpretative skills would stay at a high level of accuracy. 10 This is in direct conflict with another report that defines a moderate number of exams as 30 per year, and if less than 30 are performed annually, it should be expected that the results would not be as accurate as possible.11 It is also thought that interobserver accuracy may be dependent on stage. Several reports have demonstrated interobserver agreement to be low for T2 tumors, and high for T3 tumors, and that accurate interpretation of T1 and T2 tumors requires a very experienced clinician. Garcia-Aguilar and coworkers concluded that image interpretation explains some differences in reported accuracies among studies.12,13 Marusch and coworkers conclude that the “centralization of transrectal ultrasonography ser-
J.R. Warmath and A.J. Herline vice is mandatory if a high level of quality is to be achieved with this method.”11 In its current form, the centralization of ERUS services seems like a rather daunting task, but the image portability that the proposed 3D freehand ERUS system provides makes this idea more feasible. The accurate staging of rectal tumors is necessary because understaging may lead to undertreatment and overstaging results in potentially more invasive operations and subsequent increased morbidity and mortality.14
Treatment of Rectal Cancer Once a rectal tumor has been accurately staged, the next decision is the appropriate treatment for the patient. This decision is very important because the extent and invasiveness of resection or other therapies used will determine local control, cure, need for adjuvant therapy, sphincter preservation, and preservation or loss of sexual and urinary functions. Surgery has been shown to be the optimal cure for most cases of rectal cancer, and there is agreement that a 1-cm distal surgical margin and a tumor-free circumferential margin are appropriate for most resections.15 Local excision provides many benefits to patients undergoing treatment for rectal cancer, but currently radical excision is the standard procedure. It should again be noted that the correct staging of the tumor is of the utmost importance in the success of the treatment. Improvements in tumor staging have the potential to change the standard of care by moving toward local excision for more patients.
Restaging After Preoperative Radiotherapy Preoperative radiotherapy for the purpose of tumor downstaging has become a common part of the treatment for rectal cancer. However, because of the residual fibrotic tissue caused by the radiation, there has not been a conclusion as to the appropriate method of restaging the tumor after therapy. One study showed that in 28 of 29 cases, fibrosis was the major component of irradiated tumors.16 There is increased echogenicity of the ultrasound as a result of the fibrosis.17 This causes some concern when using ERUS because it is therefore not the tumor that is being staged, but rather the fibrotic tissue, although it has been shown that any residual tumor will be contained within the fibrosis thereby allowing it to be used to stage the maximum extent of the tumor boundary.16 Studies have concluded that ERUS staging accuracy is decreased after the use of radiotherapy; however, it is still more accurate than CT and MRI for this purpose.18-20 Changes due to radiation and the resultant downstaging of the tumor have been shown to be positively associated with patient outcomes.21,22 Tumor restaging following this treatment is being evaluated. Currently the reported accuracies range from 29%22 to 92.8%23 with a large range of values in between (⬃50%,24 66%,25 and 91%18). Some of the accuracy discrepancy could be based on the length of time between radiation and re-evaluation of the tumor. ERUS staging accuracy is reduced because of: (1) postradiation
New technologies in rectal cancer management
93
Figure 1 ERUS probe with attached rigid object for optical tracking. (Color version of figure is available online.)
edema; (2) inflammation; (3) necrosis; and (4) fibrosis.24 The edema and inflammation will decrease over time, so the ERUS staging accuracy should increase over the same time period. Standardization of the waiting period would allow future work to be consistent and would allow a direct comparison of the results of many different studies.
Image-Guided Procedures (IGP) and ERUS In the review article, “The Process and Development of ImagedGuided Procedures,” Galloway sums up the motivation of IGPs: “One of the most fundamental forces in the development of surgery and other forms of directed therapy is the need to increase the information available to physicians and to place that information in both spatial and temporal contexts.”26 This idea also holds true for the area of rectal tumor staging, and therefore, the combination of the fields of IGP and ERUS is a logical one. With this union comes not only the ability to provide more information to the clinician, but also more accurate information in both space and time. The idea has been proposed that this new information will help the surgeon more accurately diagnose, stage, and treat rectal cancer.
3D ERUS Current research is showing the potential widespread use of 3D ultrasound within the medical community. The validity of rectal cancer diagnosis with 3D as compared with 2D ultrasound is being tested, and the reported conclusions to date show 3D to be superior.27 Reported techniques to collect 3D data from 2D ERUS probes include optical tracking, magnetic tracking, the timed pullout method, and a rotating stepper motor for a stationary, side-firing probe.27-32 For the 360-degree rotating BK 1850 ERUS probe, only magnetic tracking, optical tracking, and the timed pullout method are viable options. Magnetic localization systems are currently not as accurate as optical localization systems. A large amount of data has been reported using magnetic tracking for 3D ultrasound acquisition using the Stradx system,29 although they have not reported a quantitative validation of the system. Interestingly, they are proposing to change to an optically tracked system.33
The timed pullout method is also known as linear scanning. Traditional linear scanning devices can provide visually pleasing results but require a bulky device to hold the ERUS probe and must be placed close to the patient. This device contains the stepper motor and controls the linear movement of the probe.31,34 The pullout method is currently being used clinically and can be purchased as an accessory from BK Medical (Herlev, Denmark) with an ERUS system. Improvements to the linear scanning device have been made and BK Medical’s 2050 Ultrasound transducer contains the rotating crystal and linear scanning device within the shaft. While the timed pullout devices allow for reconstruction of 3D volumes, the position and orientation of these volumes is dependent on the rigid fixation of the device. Therefore, any accidental movement of the device would cause invalid data. Also, there is currently not a valid registration method used to align these volumes to other data sets of the same anatomy. An optically tracked ERUS device requires no such fixation thus allowing more freedom of motion and provides a standard coordinate system with which to register the data. Figure 1 shows an ERUS probe with an attached rigid body for optical tracking. Figure 2 shows three parts of an optically tracked ultrasound system, as follows: (1) a computer; (2) an ultrasound machine; and (3) an Optotrak 3020 localization system. Besides ease of use, optical tracking has another advantage over linear scanning. This advantage is a result of coordinate integrated imaging. When using a tracked ultrasonic device, the exact location and orientation of the probe are known. Through the process of calibration, the location and orientation of the ultrasound beam are also known in an external coordinate space. This allows each pixel in the ultrasound data set to be assigned a 3D coordinate value in a physical space that is related to the ultrasound space through a specific transformation matrix. This method of assigning coordinate values to the ultrasound data in physical space has two advantages. First it allows the direct comparison of two imaging modalities. This is achieved by transforming a data set, such as CT, into the same physical space as the ultrasound data, making an accurate comparison possible. Second this method allows localization of multiple tools and image sets into the same physical space. The user then has the ability to guide a tracked instrument, such as a biopsy needle or surgical blade, to a specific location in physical
J.R. Warmath and A.J. Herline
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Figure 2 Optically tracked ERUS system.
space while at the same time viewing the progress in all imaging modalities (ie, ultrasound and CT). These coregistration and guidance techniques are not possible using the mechanical 3D volume reconstruction methods because multiple image sets and surgical tools cannot be localized in the same physical space. The mechanical-based methods are appropriate for 3D volume reconstruction of ultrasound data, but without an accurate registration technique, are not valid for anything beyond visual enhancement of the rectum. Therefore image guidance using tracked ultrasound (3D freehand ultrasound) is the best choice for an improvement in current ERUS techniques. Gee and coworkers reported a few issues with 3-day freehand ultrasound systems that need to be addressed before they will have everyday use in clinics. These include the following: (1) high cost; (2) restricted volumes; and (3) restricted use caused by attached localization devices.35 For the freehand ERUS system we have already solved the problem addressed in number 3, and we believe that the cost and restricted volume size are two issues that can be overcome before
taking this work out of the world of research and placing it into the clinical setting as a medical device intended for daily use.
Clinical Evaluation of 3D ERUS Three-dimensional imaging with ultrasound has become more common over the past 10 years because of major technological advances in the field. The use of 3D ERUS was reported as early as 1992, and in 1997 a clinical study was performed that reported a full 3D tumor reconstruction on 15 patients.36,37 However, it was not until recently that a study reported using 3D ERUS to actually stage rectal tumors. This study compared the staging accuracy of 2D versus 3D ERUS. This study showed a 6.1 and 9% increase in accuracy for tumors staged by pathology as T2 and T3, respectively. However, these results did not show a significant enough improvement to conclusively say that 3D ERUS is better than 2D ERUS for the staging of rectal cancer.38 This work shows great potential
New technologies in rectal cancer management for 3D ERUS; however, more research needs to be conducted to thoroughly evaluate its perceived benefit.
Conclusion As stated earlier, rectal cancer is a disease that is a major problem within the United States. More research and improved screening and treatment standards are needed to reduce the surprisingly high mortality rates. With universal screening, rectal cancer can be found earlier and the patient has a better chance of cure. Improved treatment of rectal cancer greatly depends on the accurate staging of the disease, and amid the ever changing treatment practices, the best options for total cure with the least amount of morbidity and mortality need to be used. ERUS has become accepted as the most reliable and accurate staging technique currently available, although it has difficulties. The incorporation of new technologies, such as those used in imageguided therapy, to the preoperative preadjuvant staging, preoperative postadjuvant staging, and interoperative visualization of rectal cancer with ERUS can potentially help to improve the accuracy of staging, reduce the overall morbidity and mortality rates, and help clinicians to detect and follow rectal cancer over time.
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