Surg Endose Table2 Accuracy of endoscopic ultrasonography(EUS)tumor depth(T)staging Pathologic stage Sensitivity(候) Specificity (% PPV (% NPV ( Accuracy (% T3 T4 EUS T stage 30 0 0 1 86 91 T2 8 8 9 0 5 82 78 T3 2 32 4 8 80 71 86 80 T4 0 0 0 0 N staging additional information was given by EUS about distan metastasis,including one case of celiac nodal metastasis In N staging.EUS had a sensitivity of 42,a specificity of Although the sensitivity of PET and CT for metastasis was 1and an accuracy of%The sensitivity,specificity. unacceptably low,these edictive value was 82 and the dictive value was 60%.Combining the use of these tech niques improved sensitivity (65%)and accurately predicted Discussion N stage for 72%of the patients (Table 3). Metastatic disease Of the 109 patients.5 (4.6)had distant metastases at ageal wal cervical (n=3)celiac (n=1)and retropancreatic layers with histologie correlates [12.A metaanalysis of 49 (n=1)lymph node sites.Whereas EUS could not detect studies that evaluated the accuracy of EUS in detecting any suspicious metastatic foci,CT or PET detected distant esophageal cancer reported that its pooled sensitivity for taging was 81- false in one uracy o 899%14 strated the opic ul raphy(EUS). pos graphy (PET） and Pathologic stage PPV ( NPV ( Accuracy ( NO NI EUS 3 0 66 47 28 40 NI 7 27 CT NO 50 36 93 58 63 NI 19 bined 3 methods 19 65 69 72 30 PPV positive predictive value.NPV negative predictive value Springer
N staging In N staging, EUS had a sensitivity of 42%, a specificity of 91%, and an accuracy of 66%. The sensitivity, specificity, and accuracy did not differ significantly across the three tests (p = 0.30, 0.62, and 0.77, respectively). For EUS, the positive predictive value was 82%, and the negative predictive value was 60%. Combining the use of these techniques improved sensitivity (65%) and accurately predicted N stage for 72% of the patients (Table 3). Metastatic disease Of the 109 patients, 5 (4.6%) had distant metastases at cervical (n = 3), celiac (n = 1), and retropancreatic (n = 1) lymph node sites. Whereas EUS could not detect any suspicious metastatic foci, CT or PET detected distant metastasis in two (16%) of five patients. However, PET showed a false-positive adrenal metastasis, and CT showed a false-positive lung metastasis in one patient. No additional information was given by EUS about distant metastasis, including one case of celiac nodal metastasis. Although the sensitivity of PET and CT for metastasis was unacceptably low, these two methods showed both high specificity and accuracy. Combined use of PET and CT did not improve sensitivity (Table 4). Discussion Our study aimed to investigate the impact of EUS for staging esophageal cancer by comparing it with PET and CT staging. For T staging, EUS is the most accurate technique because it can delineate the esophageal wall layers with histologic correlates [12]. A metaanalysis of 49 studies that evaluated the accuracy of EUS in detecting esophageal cancer reported that its pooled sensitivity for T staging was 81–90% and its specificity was 99% [13]. Another metaanalysis of 27 studies demonstrated the accuracy of EUS for T staging to be 89% [14]. Table 2 Accuracy of endoscopic ultrasonography (EUS) tumor depth (T) staging Pathologic stage Sensitivity (%) Specificity (%) PPV (%) NPV (%) Accuracy (%) T1 T2 T3 T4 EUS T stage T1 39 0 0 0 80 100 100 86 91 T2 8 8 9 0 53 82 32 91 78 T3 2 7 32 4 78 80 71 86 80 T4 0 0 0 0 PPV positive predictive value, NPV negative predictive value Table 3 Comparison of endoscopic ultrasonography (EUS), positron emission tomography (PET), and computed tomography (CT) for lymph nodal (N) staging Pathologic stage Sensitivity (%) Specificity (%) PPV (%) NPV (%) Accuracy (%) N0 N1 EUS N0 49 32 42 91 82 60 66 N1 5 23 PET N0 47 28 49 87 79 63 68 N1 7 27 CT N0 50 36 35 93 83 58 63 N1 4 19 Combined 3 methods N0 43 19 65 80 77 69 72 N1 11 36 PPV positive predictive value, NPV negative predictive value Surg Endosc 123
Surg Endose Table Comparison of (PETand computed (CT or metastasis (M)san Pathologic stage Sensitivity (% Specificity ( PPV ( NPV (% MO PET MO 103 40 96 MI 103 20 99 96 95 ned m 102 40 97 MI PPV positive predictive value,NPV negative predictive value In our study.the of FUS for T sta shown to be n s did no urativ dance with Shimpi et al.[6],who had similar study set- gery,and thus pathologic staging as a gold standard was tings.Our results could be explained by patient selection not completely determined.A major advantage of our study bias because we included only patients who were potential was that a large number of patients with esophageal cancer andida ere there re enrolle All of th the complete slear Ta cases In addition the d tion of T2 stage had the least accuracy.and equal numbers of lesions were under-and overstaged,which may be associated with tion of celiac nodal involvement,which indicates distant microscopic tumor invasion or peritumoral inflammatory cancer.Regardless of echo tea change r factor that nay affe eofuracy in s dy than 1 er .Up to one-third of patients metaanalysis of 25 studies.EUS for celiac node metastasis with esophageal cancer present with marked luminal ste- showed a sensitivity of 67 and a specificity of9%19] nosis that does not permit passage of EUS [15]and We performed EUS for surgically resectable patients at therefore prohibits complete staging by EUS An EUS hac node a position proxim e tumor has pmeeTrairesthene.andoo8eientNhag met was not identified by EUS due to agndy 18 of PET's ability to st had malignant stricture.for which we did no form a dilation procedure before EUS.An earlier study has shown a sensit vity of 88.a s pecificity of93%and an accuracy Our findings showed that the ion was dminis verall accuracy of P lete ng dis tant metasta EUS than the ed in s in its vield of detected celiac i h n [15 171 However perforations during the dilation can In our study.the ability of PET to predict N stage occur occasionally.and the patient must be individually remained unsatisfactory.For detecting N stage.PET had a determined for assessment of the risk-benefit relation sensitivity of 42%and a specificity of 91%.Recent data before the dilation procedure have shown that for N staging.PET has a sensitivity of studies evalu nd Cr mg2.4.781H weve udi (51% reported in Springer
In our study, the accuracy of EUS for T staging was shown to be no greater than 72%, which was in concordance with Shimpi et al. [6], who had similar study settings. Our results could be explained by patient selection bias because we included only patients who were potential candidates for curative surgery. All our cases were therefore pathologic T1 to T3 stages except for four cases, which were more difficult to distinguish from another than clear T4 cases. In addition, the designation of T2 stage had the least accuracy, and equal numbers of lesions were under- and overstaged, which may be associated with microscopic tumor invasion or peritumoral inflammatory change. Another factor that may affect accuracy in staging of esophageal cancer is the presence of strictures that limit passage of an echoendoscope. Up to one-third of patients with esophageal cancer present with marked luminal stenosis that does not permit passage of EUS [15] and therefore prohibits complete staging by EUS. An EUS examination from a position proximal to the tumor has been shown to result in inaccurate T staging and inadequate evaluation of the celiac axis. In our study, 18 patients (16%) had malignant stricture, for which we did not perform a dilation procedure before EUS. An earlier study reported an unacceptably high perforation rate when dilation was administered before EUS [16]. Several studies have recently reported that dilation was safe as long as the rules of sequential dilation were followed. Thus, EUS gained increases in its yield of detected celiac lymph nodes [15, 17]. However, perforations during the dilation can occur occasionally, and the patient must be individually determined for assessment of the risk-benefit relation before the dilation procedure. Previous studies evaluated the comparative accuracy of esophageal cancer staging by EUS, PET, and CT with pathologic staging [2, 4, 7, 8]. However, these studies were somewhat limited by their relatively small size. Furthermore, some of the patients did not undergo curative surgery, and thus pathologic staging as a gold standard was not completely determined. A major advantage of our study was that a large number of patients with esophageal cancer were enrolled. All of these patients provided the complete information regarding pathologic staging, and the accuracy of EUS, CT, and PET was concomitantly evaluated for locoregional staging of esophageal cancer. Endoscopic ultrasonography plays a role in the evaluation of celiac nodal involvement, which indicates distant metastasis in esophageal cancer. Regardless of echo features and size, 90% of all detected celiac lymph nodes were proved to be malignant in one study [18]. Moreover, 100% of celiac nodes larger than 1 cm were malignant. In a metaanalysis of 25 studies, EUS for celiac node metastasis showed a sensitivity of 67% and a specificity of 98% [19]. We performed EUS for surgically resectable patients at preoperative staging, and only one patient had celiac node metastasis, which was not identified by EUS due to malignant stricture. Promising reports of PET’s ability to stage esophageal cancer have been published. For distant metastasis, PET has shown a sensitivity of 88%, a specificity of 93%, and an accuracy of 91% [20]. Our findings showed that the overall accuracy of PET in detecting distant metastasis was not any better than the ability of CT. This was mostly due to the lack of sensitivity in detecting distant lymph node metastases. In our study, the ability of PET to predict N stage remained unsatisfactory. For detecting N stage, PET had a sensitivity of 42% and a specificity of 91%. Recent data have shown that for N staging, PET has a sensitivity of only 57%, a specificity of only 83%, and an accuracy of only 71% [21]. Our result was comparable with the pooled sensitivity (51%) and specificity (84%) reported in a Table 4 Comparison of positron emission tomography (PET) and computed tomography (CT) for metastasis (M) staging Pathologic stage Sensitivity (%) Specificity (%) PPV (%) NPV (%) Accuracy (%) M0 M1 PET M0 103 3 40 99 66 97 96 M1 1 2 CT M0 103 4 20 99 50 96 95 M1 1 1 Combined 2 methods M0 102 3 40 98 50 97 95 M1 2 2 PPV positive predictive value, NPV negative predictive value Surg Endosc 123
Surg Endose tumor with PET In addition PeT may not detect 4.Pfau PR.Perlman SB Sta o P.Frick TJ.Gopal DV.Said A microscopic metastasis of lymph nodes due to its limited resolution effects. In a metaanalysis of the EUS.PET,and CT results for not perfo d and nostic accuracy for N staging did not differ significantly and was in lin e with our results. o E1.Knuuti MJ.Minn HR.Luostarinen ME Regarding the relati vely ow accuracy and sensitivity of stagi EUS-gu dne-needle aspira- method.T use of EUS-FNA preope bo sensitivity and accuracy for the detection of nonperitu- moral lymph node metastases [23].However,lymph nodes Med cause the need would have to traverse 0 This 46 ymp e可A (2002)AJCC Our data are limited by the inclusion of patients with a 11.Dw somewhat narrowed clinical spectrum of disease because 12 330 only surgically re sectable patients were enrolled in this opic u our study shows good diag racy for EUS T staging of esophageal cancer.and our ol14:1479-1490 findings show that the diagnostic accuracy of N staging by Rosch T US is fore,EUS could ncer.esp 15.wa lace MB.Hawes RH.Sahai AV.Van Velse A.Hoffman B 16.Van Dam J.Rice TW.Catalano MF.Kirby T.Sivak MV References 17.Pfaw PR.C nt 1.Mayer RJ(0)cancer. l95281285 18.E ve VI B aE.Fletcher JG.Nathan M.Jensen E.Mullan B Allen MS.Levy M.)Compa d EU on o meta ancern-center 场一的 3 Dullemen HM,van der Jag 2 e na combined Springer
metaanalysis [13]. Not surprisingly, lymph nodes adjacent to the primary tumor are difficult to differentiate from the primary tumor with PET. In addition, PET may not detect microscopic metastasis of lymph nodes due to its limited resolution effects. In a metaanalysis of the EUS, PET, and CT results for esophageal cancer staging, the pooled sensitivities for N stage were 0.80 for EUS, 0.57 for PET, and 0.50 for CT, although these three methods were not performed and analyzed concomitantly [22]. However, the overall diagnostic accuracy for N staging did not differ significantly and was in line with our results. Regarding the relatively low accuracy and sensitivity of these tests for N staging, EUS-guided fine-needle aspiration (EUS-FNA) may be considered for preoperative staging method. The use of EUS-FNA increases both sensitivity and accuracy for the detection of nonperitumoral lymph node metastases [23]. However, lymph nodes at the level of the primary tumor often are not accessible to EUS-FNA because the needle would have to traverse the tumor to obtain a specimen. This carries the potential risk of cancer cells spreading into lymph nodes that may not be malignant. Our data are limited by the inclusion of patients with a somewhat narrowed clinical spectrum of disease because only surgically resectable patients were enrolled in this study. Patients with advanced disease stages were excluded, which may be related to underestimation of both sensitivity and accuracy in the detection of metastasis to lymph nodes. In conclusion, our study shows good diagnostic accuracy for EUS T staging of esophageal cancer, and our findings show that the diagnostic accuracy of N staging by EUS is as good as that of PET or CT. Therefore, EUS could be useful for determining a therapeutic strategy for esophageal cancer, especially for resectable diseases. Disclosures Jeongmin Choi, Sang Gyun Kim, Joo Sung Kim, Hyun Chae Jung, and In Sung Song have no conflicts of interest or financial ties to diclose. References 1. Enzinger PC, Mayer RJ (2003) Esophageal cancer. N Engl J Med 349:2241–2252 2. Lowe VJ, Booya F, Fletcher JG, Nathan M, Jensen E, Mullan B, Rohren E, Wiersema MJ, Vazquez-Sequeiros E, Murray JA, Allen MS, Levy MJ, Clain JE (2005) Comparison of positron emission tomography, computed tomography, and endoscopic ultrasound in the initial staging of patients with esophageal cancer. Mol Imaging Biol 7:422–430 3. van Westreenen HL, Heeren PA, van Dullemen HM, van der Jagt EJ, Jager PL, Groen H, Plukker JT (2005) Positron emission tomography with F-18-fluorodeoxyglucose in a combined staging strategy of esophageal cancer prevents unnecessary surgical explorations. J Gastrointest Surg 9:54–61 4. Pfau PR, Perlman SB, Stanko P, Frick TJ, Gopal DV, Said A, Zhang Z, Weigel T (2007) The role and clinical value of EUS in a multimodality esophageal carcinoma staging program with CT and positron emission tomography. Gastrointest Endosc 65:377– 384 5. Liberale G, Van Laethem JL, Gay F, Goldman S, Nagy N, Coppens E, Gelin M, El Nakadi I (2004) The role of PET scan in the preoperative management of oesophageal cancer. Eur J Surg Oncol 30:942–947 6. Shimpi RA, George J, Jowell P, Gress FG (2007) Staging of esophageal cancer by EUS: staging accuracy revisited. Gastrointest Endosc 66:475–482 7. Rasanen JV, Sihvo EI, Knuuti MJ, Minn HR, Luostarinen ME, Laippala P, Viljanen T, Salo JA (2003) Prospective analysis of accuracy of positron emission tomography, computed tomography, and endoscopic ultrasonography in staging of adenocarcinoma of the esophagus and the esophagogastric junction. Ann Surg Oncol 10:954–960 8. Choi JY, Lee KH, Shim YM, Lee KS, Kim JJ, Kim SE, Kim BT (2000) Improved detection of individual nodal involvement in squamous cell carcinoma of the esophagus by FDG PET. J Nucl Med 41:808–815 9. Catalano MF, Sivak MV Jr, Rice T, Gragg LA, Van Dam J (1994) Endosonographic features predictive of lymph node metastasis. Gastrointest Endosc 40:442–446 10. Greene FL, American Joint Committee on Cancer (2002) AJCC cancer staging manual, 6th edn. Springer, New York 11. Dwyer AJ (1991) Matchmaking and McNemar in the comparison of diagnostic modalities. Radiology 178:328–330 12. Salminen JT, Farkkila MA, Ramo OJ, Toikkanen V, Simpanen J, Nuutinen H, Salo JA (1999) Endoscopic ultrasonography in the preoperative staging of adenocarcinoma of the distal oesophagus and oesophagogastric junction. Scand J Gastroenterol 34:1178– 1182 13. Puli SR, Reddy JB, Bechtold ML, Antillon D, Ibdah JA, Antillon MR (2008) Staging accuracy of esophageal cancer by endoscopic ultrasound: a meta-analysis and systematic review. World J Gastroenterol 14:1479–1490 14. Rosch T (1995) Endosonographic staging of esophageal cancer: a review of literature results. Gastrointest Endosc Clin North Am 5:537–547 15. Wallace MB, Hawes RH, Sahai AV, Van Velse A, Hoffman BJ (2000) Dilation of malignant esophageal stenosis to allow EUSguided fine-needle aspiration: safety and effect on patient management. Gastrointest Endosc 51:309–313 16. Van Dam J, Rice TW, Catalano MF, Kirby T, Sivak MV Jr (1993) High-grade malignant stricture is predictive of esophageal tumor stage: risks of endosonographic evaluation. Cancer 71:2910–2917 17. Pfau PR, Ginsberg GG, Lew RJ, Faigel DO, Smith DB, Kochman ML (2000) Esophageal dilation for endosonographic evaluation of malignant esophageal strictures is safe and effective. Am J Gastroenterol 95:2813–2815 18. Eloubeidi MA, Wallace MB, Reed CE, Hadzijahic N, Lewin DN, Van Velse A, Leveen MB, Etemad B, Matsuda K, Patel RS, Hawes RH, Hoffman BJ (2001) The utility of EUS and EUSguided fine-needle aspiration in detecting celiac lymph node metastasis in patients with esophageal cancer: a single-center experience. Gastrointest Endosc 54:714–719 19. Puli SR, Reddy JB, Bechtold ML, Antillon MR, Ibdah JA (2008) Accuracy of endoscopic ultrasound in the diagnosis of distal and celiac axis lymph node metastasis in esophageal cancer: a metaanalysis and systematic review. Dig Dis Sci 53:2405–2414 Surg Endosc 123
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20. Luketich JD, Schauer PR, Meltzer CC, Landreneau RJ, Urso GK, Townsend DW, Ferson PF, Keenan RJ, Belani CP (1997) Role of positron emission tomography in staging esophageal cancer. Ann Thorac Surg 64:765–769 21. Hsu WH, Hsu PK, Wang SJ, Lin KH, Huang CS, Hsieh CC, Wu YC (2009) Positron emission tomography-computed tomography in predicting locoregional invasion in esophageal squamous cell carcinoma. Ann Thorac Surg 87:1564–1568 22. van Vliet EP, Heijenbrok-Kal MH, Hunink MG, Kuipers EJ, Siersema PD (2008) Staging investigations for oesophageal cancer: a meta-analysis. Br J Cancer 98:547–557 23. Vazquez-Sequeiros E, Norton ID, Clain JE, Wang KK, Affi A, Allen M, Deschamps C, Miller D, Salomao D, Wiersema MJ (2001) Impact of EUS-guided fine-needle aspiration on lymph node staging in patients with esophageal carcinoma. Gastrointest Endosc 53:751–757 Surg Endosc 123
The neW eNGLAND JOURNAL of MEDICINE ESTABLISHED IN 1812 JULY26,2012 voL367N0.4 Coronary CT Angiography versus Standard Evaluation in Acute Chest Pain la k Wo MD T er.M.D.M.P.H Charles S.White.M.D.Scott G.Weiner.M.D.M.P.H.Shant Kalanjian.M.D.Michael E.Mullins,M.D. Issam Mikati,M.D.W.Frank Peacock,M.D.Pearl Zakroysky,B.ADouglas Hayden,Ph.D. .D.,Stephen D.Wiviott,M.D.. ABSTRACT It is unclear whether an evaluation incorporating coronary computed tomographic The auth 2 sted in th angiography (CCTA)is more effective than standard evaluation in the emergency ess reprin department in patients with symptoms suggestive of acute coronary syndromes. al.Cardiac MR PET CT Program.169 METHODS n this multicenter trial,we randomly assigned patients 40 to 74 years of age with N EnglJ Med2012367:299-308 a April 2010 and January 2012.The primary end point was length of stay in the hospi tal.Secondary end points included rates of disch harge from the emergency depart- cardi as cular events at 28 days,and cumulative costs.Safety acute coronary syndromes. evaluation,the mean length of stay in the hospital was reduced by 7.6 hours (001)and more patients were discharged directly from the emergency depart ment (47%vs.12%, erences snmajor adverse card The cumulative mean cost of care was similar in the CCTA group and the standard- evaluation group ($4,8 and$060,respectively;P=0.65). CONCLUSIONS In patients in the emergency department with symptoms suggestive of acute d the eff coronary syndromes,noringCAsategy mpro ciency of clin making, compare de National Heart.Lung.and Blood Institute:ROMICAT-I.gov number. NCT01084239) N ENGLJ MED 367:4 NJM.ORG JULY 26,2012 299
n engl j med 367;4 nejm.org july 26, 2012 299 The new england journal of medicine established in 1812 july 26, 2012 vol. 367 no. 4 Coronary CT Angiography versus Standard Evaluation in Acute Chest Pain Udo Hoffmann, M.D., M.P.H., Quynh A. Truong, M.D., M.P.H., David A. Schoenfeld, Ph.D., Eric T. Chou, M.D., Pamela K. Woodard, M.D., John T. Nagurney, M.D., M.P.H., J. Hector Pope, M.D., Thomas H. Hauser, M.D., M.P.H., Charles S. White, M.D., Scott G. Weiner, M.D., M.P.H., Shant Kalanjian, M.D., Michael E. Mullins, M.D., Issam Mikati, M.D., W. Frank Peacock, M.D., Pearl Zakroysky, B.A., Douglas Hayden, Ph.D., Alexander Goehler, M.D., Ph.D., Hang Lee, Ph.D., G. Scott Gazelle, M.D., M.P.H., Ph.D., Stephen D. Wiviott, M.D., Jerome L. Fleg, M.D., and James E. Udelson, M.D., for the ROMICAT-II Investigators A BS TR AC T The authors’ affiliations are listed in the Appendix. Address reprint requests to Dr. Hoffmann at Massachusetts General Hospital, Cardiac MR PET CT Program, 165 Cambridge St., Suite 400, Boston, MA 02114, or at uhoffmann@partners.org. N Engl J Med 2012;367:299-308. DOI: 10.1056/NEJMoa1201161 Copyright © 2012 Massachusetts Medical Society. Background It is unclear whether an evaluation incorporating coronary computed tomographic angiography (CCTA) is more effective than standard evaluation in the emergency department in patients with symptoms suggestive of acute coronary syndromes. Methods In this multicenter trial, we randomly assigned patients 40 to 74 years of age with symptoms suggestive of acute coronary syndromes but without ischemic electrocardiographic changes or an initial positive troponin test to early CCTA or to standard evaluation in the emergency department on weekdays during daylight hours between April 2010 and January 2012. The primary end point was length of stay in the hospital. Secondary end points included rates of discharge from the emergency department, major adverse cardiovascular events at 28 days, and cumulative costs. Safety end points were undetected acute coronary syndromes. Results The rate of acute coronary syndromes among 1000 patients with a mean (±SD) age of 54±8 years (47% women) was 8%. After early CCTA, as compared with standard evaluation, the mean length of stay in the hospital was reduced by 7.6 hours (P<0.001) and more patients were discharged directly from the emergency department (47% vs. 12%, P<0.001). There were no undetected acute coronary syndromes and no significant differences in major adverse cardiovascular events at 28 days. After CCTA, there was more downstream testing and higher radiation exposure. The cumulative mean cost of care was similar in the CCTA group and the standardevaluation group ($4,289 and $4,060, respectively; P=0.65). Conclusions In patients in the emergency department with symptoms suggestive of acute coronary syndromes, incorporating CCTA into a triage strategy improved the efficiency of clinical decision making, as compared with a standard evaluation in the emergency department, but it resulted in an increase in downstream testing and radiation exposure with no decrease in the overall costs of care. (Funded by the National Heart, Lung, and Blood Institute; ROMICAT-II ClinicalTrials.gov number, NCT01084239.)