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2007;13:6877s-6884s. Clin Cancer Res V. Raman Muthusamy and Kenneth J. Chang Optimal Methods for Staging Rectal Cancer

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Optimal Methods for Staging Rectal CancerV. RamanMuthusamy and KennethJ. Chang

Abstract At present, several modalities exist for the preoperative staging of rectal lesions, includingcomputed tomography (CT), body coil or endorectal coil magnetic resonance imaging (MRI),endoscopic ultrasonography (EUS) done by rigid or flexible probes, and positron emissiontomography (PET). Staging accuracy for CTranges from 53% to 94% forT-stage accuracy andfrom 54% to 70% for N-stage accuracy. Improved CTaccuracy is observed at higher diseasestages. Body coil MRI has shownT- and N-stage accuracy ranging from 59% to 95% and 39%to 95%, respectively. Endorectal coil MRI has shown improved T- and N-stage accuracy,with rates of 66% to 91% and 72% to 79%, respectively.The development of phased-array MRI,combining high spatial resolution with a larger field of view, offers promise to improve on theserates. EUS, considered the current gold standard, has shownT-stage accuracy ranging from75% to 95%, with N-stage accuracy ranging from 65% to 80%. Flexible EUS probes have theadvantage of being able to access and sample iliac nodes. Recent studies also suggest thatthree-dimensional EUS may provide greater accuracy than conventional two-dimensional EUS.Limited studies exist on the use of PET in primary tumor staging. PET may upstage diseasein 8% to 24% of patients and has also been used in posttreatment restaging and surveillance.Postradiation edema, necrosis, and fibrosis seem to decrease restaging accuracy in all modalities.This article reviews the current literature about the staging accuracy of the various modalitiesand suggests a staging algorithm for rectal cancer.

Accurate staging of rectal cancer is necessary to provide theoptimal treatment strategy. Staging information includes extentof tumor involvement of the rectal wall and adjacent structures,presence or absence of adjacent lymphadenopathy, anddetermination of distant metastasis. Preoperative radiationtherapy and total mesorectal excision (TME) are increasinglyused in the treatment of locally advanced rectal cancer to reducetumor recurrence. Recent data have shown that preoperativeradiation therapy can reduce tumor recurrence from 27% to11% (1). In addition, TME (a surgical technique that removesthe rectum and surrounding mesorectal fat and perirectallymph nodes and surrounding mesorectal fascia) has beenshown to reduce postoperative recurrence to 10% withoutradiation therapy (2). A recent randomized controlled trial hasshown that the combination of these techniques may reducerecurrence to 2.4% at 2 years compared with 8.2% with TMEalone (3). Thus, accurate local staging information is para-mount for stratifying patients who would benefit fromneoadjuvant therapy as well as for predicting the surgical

approach. Figure 1 illustrates major decision points that shouldbe addressed in the staging process.At present, several modalities exist for the preoperative

staging of rectal cancer: computed tomography (CT); magneticresonance imaging (MRI) with traditional body, endorectal, orphased-array coils; endorectal ultrasonography (EUS) with rigidor flexible probes; and positron emission tomography (PET)with and without CT fusion. Typically, a combination of thesemodalities is used to provide complete staging information.The choice of modality is often influenced by local expertiseand availability. This article reviews the current literature aboutstaging accuracy, strengths, and limitations of these modalitiesand suggests a staging algorithm for rectal cancer.

CT Imaging

CT imaging allows visualization of the entire abdomen andpelvis. Initial data showed CT T-staging accuracy of 79% to 94%in patients with primarily advanced T-stage disease (4–9).T-staging accuracy fell to 52% to 74% when a broader spectrumof tumor sizes was analyzed (10–17). The decrease in accuracymay have been due in part to the lack of detailed spatial andcontrast resolution offered by standard CT imaging techniques,leading to diminished accuracy for early-stage lesions confinedto the rectal wall. These data suggest that CT T-stage accuracyimproves in more locally advanced tumors. Nodal stagingaccuracy has ranged from 54% to 70% (11, 18). Althoughimprovement in CT imaging (e.g., multidetector row spiral CT)has occurred, data are limited on whether such advances willresult in improved locoregional staging accuracy (19). Yet, CT isused routinely in the staging of rectal cancer, mostly for the

Authors’Affiliation: H.H. Chao Comprehensive Digestive Disease Center, ChaoFamily Comprehensive Cancer Center, Department of Medicine, University ofCalifornia, Irvine Medical Center, Orange, CaliforniaReceived 5/10/07; accepted 8/1/07.Presented at a symposium NewApproaches to Assessing andTreating Early-StageColon and Rectal Cancers heldJanuary12-13, 2007, in SantaMonica, California.Requests for reprints: Kenneth J. Chang, Department of Medicine, University ofCalifornia, Irvine Medical Center, 101The City Drive, Building 23, Route 81, Orange,CA 92868. Phone: 714-456-6187; Fax: 714-456-7520; E-mail: [email protected].

F2007 American Association for Cancer Research.doi:10.1158/1078-0432.CCR-07-1137

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evaluation of distant metastasis. Figure 2 illustrates CT stagingof a rectal cancer.

Magnetic Resonance Imaging

The use of MRI in staging rectal cancer was first reported in1986 (7, 10). Since that time, MRI has gradually surpassed CTfor locoregional rectal cancer staging. The initial studies of MRIin rectal cancer staging were done with a body coil, whichlacked the ability to differentiate the layers of the rectal wall.Consequently, T-staging accuracy of 59% to 88% was reported,which was similar to that reported for CT imaging (7, 10, 14,15, 18, 20, 21). The development of endorectal coils madedetailed imaging of the rectal wall possible, with a corres-ponding improvement in T-staging accuracy of 71% to 91%(22–27). Comparative studies of endorectal coil MRI and EUShave shown similar T-staging accuracy (27–29). However,endorectal coil MRI is hampered by limited availability, highcost, and a diminished field of view due to signal attenuation ata short distance from the coil that can prevent full evaluation ofthe mesorectal fascia and surrounding tissue (9). In addition,positioning the endorectal coil is difficult in patients with

proximal or nearly obstructing tumors, leading to failed coilinsertion in up to 40% of patients (30).The advent of dedicated external coils (e.g., phased-array

coils) allowed for high spatial resolution and an enhancedimaging field. Although initial studies of this multiple-surface coil technique in rectal cancer staging revealed disap-pointing results, compared with standard body coil or CTstaging, recent studies with a new generation of coils haveimproved T-stage accuracy to 65% to 86% (31–39). None-theless, these results are less than initially anticipated, andinterobserver variability with respect to study interpretationhas been substantial. Figure 3 illustrates MR imaging of arectal cancer.As is common with other modalities, the primary staging

inaccuracy of MRI occurs in differentiating T2 from T3 lesions.Because of the desmoplastic reaction seen adjacent to tumors,MRI typically overstages T2 lesions (9), which makes itdifficult to determine whether an irregular outer border of therectal wall represents perirectal fat being invaded by inflam-mation alone or a combination of tumor and peritumoralfibrosis.Nodal staging in rectal cancer is complicated by the fact that

micrometastasis can occur in normal-sized nodes (40–43).Although radiologic imaging may detect nodes as small as 2 to3 mm in size, morphologic criteria alone are poor predictorsof whether a node is reactive or metastatic. Consequently, thenodal staging accuracy of MRI has been highly variable, rangingfrom 39% to 95% (7, 10, 20, 23, 24, 28, 44–48). Recently, MRIwith the use of contrast agents, such as ultrasmall super-paramagnetic iron oxide, has been proposed as a method ofimproving nodal staging (49). Ultrasmall superparamagneticiron oxide undergoes phagocytosis by macrophages in lymphnodes and results in a shortening of the T2 relaxation time anda decrease in signal intensity of normal lymph nodes, whichtheoretically should improve the detection of micrometastaticnodal disease. Although previous studies in patients with headand neck and urologic tumors have been encouraging,published studies using this agent in staging rectal cancer arelacking.As mentioned above, predicting a clear circumferential

margin at the time of TME is becoming the new standard for

Fig. 1. Major decision points that should be addressed in preoperative staging.

Fig. 2. CT images of rectal cancer. A , CT image showing a rectal mass with near circumferential thickening of the rectal wall and posterior rectal lymphadenopathy.B, CT imaging of the liver in the same patient (A) also revealed a single hepatic metastasis (images courtesy of Allen Cohen, MD, University of California, Irvine).

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staging accuracy. A recent European study of 408 patientsundergoing body coil MRI showed 88% accuracy in predictingwhether a clear circumferential margin could be achieved at thetime of operation (50). These results are particularly impres-sive, given that about one fourth of the patients evaluated hadundergone neoadjuvant therapy, which is known to reducestaging accuracy.

Rectal EUS

Intraluminal rectal ultrasound examination of rectal lesionscan be done with a rigid probe or a flexible echoendoscope. Forthe purpose of this discussion, both techniques are consideredEUS.EUS has been used to stage rectal cancer since the early

1980s. A recent publication evaluating all EUS studies from1986 to 2003 in which more than 50 patients were enrolledshowed an overall accuracy of 81.8% (51). Although most ofthe studies had accuracies of 85% to 95%, the compositenumber was influenced by two large studies, each of whichcontained more than 400 patients; in these studies, accuracywas lower (i.e., 63.3% and 69%; refs. 52, 53). As with MRI,most inaccuracy results from overstaging of T2 lesions, asEUS cannot reliably distinguish an irregular outer rectal wallimage as being due to peritumoral inflammation or trans-mural tumor extension. Stenotic lesions may present diffi-culty, as the probe may not be able to traverse the lesion,leading to suboptimal staging. This problem is greater withrigid probes. Catheter probe EUS, which can be done with astandard endoscope, may aid in obtaining accurate tumorstaging in the setting of a malignant stenosis. A well-knownclinical caveat is that obstructing tumors usually represent atleast T3 disease.

EUS nodal staging accuracy is less than that of tumorstaging and ranges from 70% to 75% (47, 54, 55). Flexibleprobes have the ability to evaluate the iliac region foradenopathy, which is clinically important because thesenodes are retained in standard TME resection. In one study,up to 28% of lymph node–positive distal tumors showediliac adenopathy, with 6% of patients having only iliacadenopathy (56). Thus, failure to evaluate this region couldlead to inadequate surgical margins in up to 6% of patientswith low rectal lesions. Morphologic characteristics suggestiveof malignant involvement include hypoechoic appearance,round shape, peritumoral location, and size >5 mm (57). Anearly study showed that lymph nodes >5 mm in size have a50% to 70% chance of being malignant compared with only20% of nodes <4 mm (58). EUS-guided fine-needle aspira-tion (FNA) allows confirmation of malignancy in suspiciousnodes during the same examination, as long as the primarytumor does not lie in the path of the needle. Although initialstudies differed on the role of EUS-guided FNA, a recentstudy of 457 patients showed the value of FNA, particularlyin identifying distant malignant adenopathy (59). Sevenpercent of patients (32 of 457) had iliac adenopathy, with47% of the nodes (15 of 32) having confirmed malignancyby FNA. Of note, only 47% of patients (7 of 15) with malig-nant adenopathy had adenopathy on CT. Figure 4 illustratesEUS imaging and the role of EUS-guided FNA in rectal cancerstaging.Three-dimensional EUS consists of the traditional trans-

verse scan as well as coronal and sagittal scans that allow fora multiplanar display. This procedure has been found to besuperior to CT and two-dimensional EUS in accuratelydetermining tumor margins. The three-dimensional recon-struction is also thought to improve visualization of subtleprotrusions of tumors infiltrating into adjacent tissues andorgans, allowing for improved T and N staging. An initialstudy of 25 patients undergoing three-dimensional EUS, two-dimensional EUS, and endorectal MRI showed no significantdifference in T- or N-stage accuracy, but it was thought thatendorectal MRI and three-dimensional EUS improved under-standing of the spatial relationship of the tumor due to theirability to obtain multiplanar imaging (30). A more recentstudy of 86 patients who underwent three-dimensional EUS,two-dimensional EUS (using a rigid probe), and four-channelmultidetector CT showed T-stage accuracy of 78%, 69%, and57%, respectively; N-stage accuracy was 65%, 56%, and 53%,respectively (60). However, examiner errors in interpretationwere found in 47% of two-dimensional EUS studies and 65%of three-dimensional EUS studies. When these images werecorrectly interpreted, T-stage accuracy improved to 91% forthree-dimensional EUS and 88% for two-dimensional EUSand N-stage accuracy improved to 90% and 76%, respective-ly. This study shows promise for three-dimensional EUSwhile highlighting the highly operator-dependent nature ofEUS data.

Positron Emission Tomography

PET uses the glucose metabolism of malignant cells todiscriminate tumor from benign fibrosis. In rectal cancer, PEThas been used primarily in detecting recurrent disease.Although not used routinely for the staging of primary rectal

Fig. 3. MRI of rectal cancer.This sagittalT2-weighted MRI image reveals a longsegment rectal cancer involving the distal rectum extending above the first valveof Houston. Lymph node metastases are seen high in the posterior mesorectum(image courtesy of Benjamin M.Yeh, MD, University of California, San Francisco).

Staging Rectal Cancer





tumors, PET is increasingly being used in combination withCT to aid in the detection of nodal and distant metastasis.Limited data exist in the preoperative setting, but recentstudies have found preoperative PET to change preoperativemanagement in 17% of patients (61), predict postoperativesurvival (62), and improve staging accuracy in combinationwith CT (63). Figure 5 illustrates PET imaging in rectalcancer.

Staging Accuracy Post-Neoadjuvant Therapy

As neoadjuvant therapy has become more common in thetreatment of rectal cancer, restaging studies before plannedoperative resection are being done with increasing frequency.A recent study comparing EUS staging accuracy in patientsnot receiving neoadjuvant therapy with patients receivingneoadjuvant therapy noted a decrease in T-staging accuracyfrom 86% to 72% and a slight improvement in N-stagingaccuracy from 71% to 80% (64). However, EUS in the post-treatment setting predicted T0N0 disease correctly in only 50%of patients, and similarly, poor results have been observedwith CT and MRI. The reduction in staging accuracy is due topostradiation edema, inflammation, fibrosis, and necrosis. Arecent study of 29 patients undergoing neoadjuvant therapyand pretreatment and posttreatment staging with CT, MRI, andPET showed that PET was 100% sensitive in predicting responseto therapy (compared with 54% for CT and 71% for MRI; ref.65). Corresponding specificity for predicting tumor response totreatment was 60%, 80%, and 67% for PET, CT, and MRI,respectively. The investigators opined that PET was superior toCT and MRI in predicting response to neoadjuvant therapy. Atpresent, staging post-neoadjuvant tumors remains problematicand will likely require improved imaging techniques and acombination of structural (CT, MRI, and EUS) and functional(PET) imaging to achieve improved staging accuracy.

Suggested Algorithm

Based on the currently available literature, EUS or phased-array MRI seem to be appropriate initial studies for local tumor

Fig. 4. EUS imaging of rectal cancer. A , EUS image of asymmetric,anterior (identified by its proximity to the prostate) rectal tumor in a malepatient with extension of the tumor through the muscularis propria,consistent with EUS stageT3 disease.B, EUS imaging of this lesion seenin the 9 to12 o’clock position shows a lesion extending into themuscularis propria but confined to the rectal wall (EUS stageT2).C, careful evaluation of the lesion B, however, revealed a small perirectalnode, which is undergoing EUS-guided FNA in this image. Cytologyobtained was positive for adenocarcinoma. CT-PET imaging previouslydone on this patient was negative for adenopathy.The patient wassubsequently referred for neoadjuvant therapy.This case illustrates theimportant role of EUS and EUS-guided FNA in altering the managementof patients with rectal cancer.

Fig. 5. PET imaging in rectal cancer.This fused PET/CT image illustrates inyellow the 18F-FDGuptake in a left-sided rectal cancer (image courtesy of BenjaminM.Yeh, MD, University of California, San Francisco).





staging. EUS seems to provide more accurate staging for mobileT1 and T2 lesions, whereas MRI seems to be superior for fixed,more locally advanced disease. However, both modalities pro-vide comparable overall T- and N-staging, with EUS currentlybeing the less expensive of the two. Recent studies support thehigh accuracy of MRI in predicting a clear circumferentialresection margin in patients undergoing TME. Both modalitiesare limited by issues of availability and operator dependence.In contrast, CT scanning cannot be considered appropriate

for local tumor staging at present, although additional studieswith multidetector CT are warranted. CT is the current standardfor distant staging, but the combination of CT and PET offersthe promise of both anatomic and functional imaging over awide area and is rapidly gaining acceptance.

Conclusion

Accurate staging of rectal lesions is critical in determiningboth the need for preoperative therapy and when a local ormore radical excision is needed. Currently, a combination oflocoregional staging with EUS and/or MRI with CT or CT-PETfor evaluation of distant metastasis seems to be the bestapproach for obtaining accurate clinical staging. Posttreatmentstaging before operation continues to be suboptimal, andenhancements to current techniques and the use of PET willhopefully improve these results. Future improvements shouldbe pursued that will allow for a single test, such as phased-arrayMRI or multidetector CT in combination with PET, to providecomplete and accurate staging information.

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Discussion: Diagnostic Issues in Early-StageDisease

Dr. Carolyn Compton: Is node suspiciousness based on sizealone?Dr. Kenneth Chang: Yes, but on endoscopic ultrasonography

(EUS), size, shape, and echo texture are used to determine criteriafor malignancy.Dr. Al Benson: Do you report tumor volume as a moment in

time or a continuum? How would you actually calculatevolume in terms of the entire tumor volume?Dr. Chang: Work is being done on three-dimensional EUS

where you can recreate the entire tumor in 3-D and calculate atrue volume. Currently, we are taking two-dimensional, real-time images in cross-section.Dr. Benson: So, you only have a moment in time?Dr. Chang: Yes, we pull back and forth multiple times from

one end of the tumor to the other and determine the largestarea of involvement. We freeze that picture and highlight thecircumference of the tumor using a tracer. The surface area iscalculated in centimeters squared and is called T max. Studieshave shown that reducing T max by 50% after neoadjuvanttherapy is a predictor of favorable outcome and surgicalresponse. Furthermore, it’s far better than merely comparingat pre- and post-T stage.Dr. Daniel Haller: Studies on operator dependency of EUS

and magnetic resonance imaging (MRI) come from experts atone institution. However, in real life, we know from theGerman trial that 20% of patients were treated because of EUSresults and did not need such treatment (i.e., the groupassigned to receive surgery first did not have the disease thatthey were thought to have). It’s my understanding that peopleare more likely to be over- than understaged by EUS or MRI,especially with regard to T stage.Dr. Chang: Operator dependency is definitely a major

consideration in EUS. However, even with CT or MRI, thereis some degree of operator dependency with interpretation.Dr. Haller: Is overstaging from the T standpoint more likely

when patients undergo surgery?Dr. Chang: With a true T2, there tends to be more of a

chance to overstage, whereas with T3, there is more of a chanceto understage. CT can sometimes be confusing if you are tryingto determine lymph node status. This is improved somewhatwith CT/PET fusion. CT is probably the most commonly usedstaging modality. However, the literature suggests that CT is notas accurate for local staging, compared with MRI or EUS. CT isobviously still useful for assessing distant metastasis, but MRImay be just as good for distant staging, as well as local staging,and assessing the circumferential resection margin. EUS is stillthe best modality for T staging. CT/PET may have a role inassessing response to neoadjuvant therapy. We have manyoptions, and the question becomes: which modality orcombination is the most efficient and effective? Currently, inour center, we are relying on the combination of CT and EUSfor preoperative staging.Dr. Patrick Lynch: Could you comment further on the

factors that conspire to the overstaging of T2 tumors?Dr. Chang: If you have a tumor that is deep into the

submucosa, but not obviously going into the muscularispropria, you may be inclined to say that it is a T3 because theouter border of the muscularis propria is somewhat irregular:

This irregularity could be an inflammatory or desmoplasticreaction to the tumor. If I don’t see contiguous, hypoechoicinfiltration through the submucosa into the muscle layer,despite an irregular outer border of the muscularis propria,I would still interpret it as a T1 lesion. However, if I seecontiguous infiltration into the muscle plus irregularity on anyother side with some break away lesions, I feel very comfortablecalling it a T3.Dr. Haller: Has an endoscopic ultrasound society established

recommendations for what one calls a T2 or T3 tumor or is thiscompletely operator dependent?Dr. Heidi Nelson: It’s completely operator dependent. As a

believer in neoadjuvant and even postoperative adjuvanttherapy, I think that if a tumor is node negative, you get downto the fine points. If it is T2, how much T2? If it is T3, howmuch T3?Dr. Haller: It seems as though every institution and ultra-

sonographer has a different definition of T2 and T3. As imperfectas it is, at least the American Joint Committee on Cancer presentsa common definition. Overtreating with radiation is even moreexpensive and toxic than adjuvant chemotherapy.Dr. Nelson: Again, you are right, so if my ultrasonographer

says it’s node negative and T3, I ask, how much T3? Is it justbarely T3?Dr. Compton: The critical cut point is 5 mm. There is a big

difference in risk between a tumor that is 5 mm beyond themuscle wall.Dr. Nelson: If a tumor is node negative, barely T3, and a few

millimeters outside of the muscularis, I may go ahead withsurgery and not administer neoadjuvant therapy because thereis a 20% chance of overstaging. A patient would then receiveradiation that he or she didn’t need.Dr. Haller: Right, especially if sphincter preservation is not

the issue.Dr. Michael Stamos: The problem is that more of these

patients are likely to be node positive than are over staged byEUS, at least at our institution. The patient will now receivepostoperative radiation, which has more complications thanpreoperative radiation.Dr. Compton: The College of American Pathologists has a

proficiency testing program for many tests whereby the peoplewho are performing the tests are tested for competence. Is therean equivalent test here?Dr. Compton: A pathology report on a resection specimen

that has no report of any lymph node status should never beaccepted. If less than 12 lymph nodes are found, thepathologist should be dissatisfied with the number andreexamine the specimen. If on reexamination, which can beanything from fat clearing to carving off all of the extramural fatand putting all through for microscopic elevation, 12 lymphnodes are still not found, the pathology report must be appro-priately documented, as it is a permanent part of the medicalrecord. It is important for the pathologist to explain why themagic number is not being found. The primary responsibilityshould fall with the pathologist.Dr. Lee Rosen: Let me push further. We have 10 lymph

nodes. The pathologist has done a great job and both thesurgeon and medical oncologist have asked questions. Doesthis suffice to make treatment decisions?Dr. Robert Beart: If all of the lymph nodes in the specimen

have been examined and there was an adequate resection and






no positive lymph nodes, we have adequate information. If forsome reason the resection was inadequate, I don’t think weknow.Dr. Compton: We have all agreed about the fictional flavor

of operative reports and that it’s virtually impossible to deter-mine if the resection is adequate from reading such reports. Ifthe pathology exam of the specimen is a form of quality control,the argument is circular. The very fact of finding fewer thanthe magic number may be an indicator of poor-quality surgery,which is the circular argument and a difficult issue to resolve.Surgeons need to be more meticulous about reporting thesurgical parameters of the resection in the operative report.Dr. Axel Grothey:We are not talking about the completeness

or radicality of the surgery when we talk about lymph nodesonly. If only 10 lymph nodes are found, it’s 10 lymph nodes.But, does this convey information about immune status? It’s aprognostic parameter independent of the resection and is moreof an independent statement on prognosis (i.e., how manylymph nodes a patient is able to produce in response to thetumor). So, if there are 10 lymph nodes, is the prognosis poorfrom all that we know? The answer is ‘‘yes’’. When I see apatient with stage II disease, if there is one high-risk factor froma primitive point of view (obtained from the surgical report,pathology report, patient characteristics, perforation, etc.), Iplace this patient in a high-risk category.Dr. Anton Bilchik: Let’s say that the pathology report comes

back as moderate differentiation in a 63-year-old patient with aT3 lesion and 8 negative lymph nodes. Should you this patientreceive chemotherapy or would you ask the pathologist toreexamine the specimen first?Dr. Grothey: I would definitely ask the pathologist to

reexamine the specimen. The responsibility should rely withthe pathologist in the first place, but we medical oncologistsshould have a gatekeeper function.Dr. Beart: I don’t view the operative report as fiction, but do

think that it often lacks critical information. I think that thesurgeon should dictate where the vessels were ligated.

Dr. Lynch: Saying that the operative report is fictional islike saying that the pathology report is fictional. I think wehave to assume the integrity of the people with whom we aredealing.Dr. Rosen: We are talking about checks and balances.Dr. Compton: If there is no statement in the operative or

pathology report about nodes or ligation levels, the personreading the report has no idea what really happened andwhether the person doing the procedure had any notion of theimportance of their role. At that point, it’s not meaningful, andyou always have to assume the worst.Dr. Rosen: How do we rank the importance of the various

prognostic factors?Dr. Bilchik: At present, lymph node evaluation is the single

most important prognostic factor in colon cancer.Dr. Compton: Given the data overall, I agree. We must

establish some kind of stable yardstick by which to measure thebenefit of using proteomic or genomic approaches and definethe benefits of the comparators. If we don’t have a really well-defined baseline, the ‘‘compared to what’’ question cannot beanswered, and we are in that position right now. We have notyet established any objective criteria.Dr. Rosen: The criteria are not equally weighted, which is a

very important point.Dr. Lynch: In the average pathology department, is the gross

specimen maintained well enough that one could go back andaddress the adequacy of the lymph nodes?Dr. Compton: Yes, the specimen is retained for a certain

amount of time until the final diagnosis has been issued. Thisprocedure is addressed by laboratory accreditation standards.Dr. Bilchik: In what percentage of reevaluated patients are

more lymph nodes found?Dr. Compton: In one study, 21 lymph nodes were found on

average during diligent gross examination. On reexaminationof every specimen, all of the extramural soft tissue was strippedoff. On microscopic examination, the number of lymph nodestripled.





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