LETTER TO THE EDITOR Should Adenocarcinoma of the Esophagogastric Junction Be Classified as Esophageal Cancer? Limited to Siewert Type II, Yes To the Editor: e read with great interest the recent article by Suh and colleagues.1 They retrospectively evaluated the adequacy of the newly published seventh TNM staging system by the International Union Against Cancer for adenocarcinoma of the esophagogastric junction (AEJ) using a large cohort. According to this classification, AEJ is defined as the tumor the epicenter of which is within 5 cm of the esophagogastric junction (EGJ) and also extends into the esophagus.2 Accordingly, AEJ is classified and staged using the esophageal scheme whereas a tumor without esophageal invasion, even located just beneath the junction, is treated as gastric cancer. The most distinctive difference between the esophageal and gastric staging systems is the value of nodal involvement in the esophageal scheme, in which N1 status even with T1 tumor is classified as stage IIB. In contrast, it is stage IB in the gastric scheme. Their findings support our previous study that showed the distribution of metastatic lymph nodes in 225 Siewert type II carcinomas.3 They showed that paracardial, lesser curve and suprapancreatic nodes (nos. 1, 2, 3, 7, 8, 9) are the major stations involved and there are no metastases in the greater curve and parapyloric nodes in AEJ II whereas metastatic nodes are widely distributed in AEJ III. Therefore, AEJ III seems to be much more “gastric” than AEJ II according to the involved nodes. As the authors described, Ivor-Lewis operation is oncologically feasible and total gastrectomy would not be always needed for AEJ. In fact, the greater curve and parapyloric nodes provide marginal survival benefit by their dissection.3 In their series, they uniquely defined tumors as AEJ when their epicenters were located within 5 cm from the EGJ irrespective of esophageal invasion. “AEJs” with or without esophageal invasion were subclassified as AEJe and AEJg, respectively. Meanwhile, they also classified their series into AEJ II and AEJ III by the tumor epicenter irrespective
W
Disclosure: The authors declare no conflicts of interest. C 2014 Wolters Kluwer Health, Inc. All Copyright rights reserved. ISSN: 0003-4932/14/26103-e0067 DOI: 10.1097/SLA.0000000000000589
FIGURE 1. Overall survival after resection of type II EGJ adenocarcinoma, according to the esophageal (A) and gastric (B) schemes of seventh TNM classification. OS indicates overall survival. of esophageal invasion; therefore, the population in their study heterogeneously consisted of AEJe II, AEJg II, AEJe III, and AEJg III. They concluded that AEJ should be considered a part of gastric cancer irrespective of EGJ involvement. Because AEJg II and AEJg III are classified using the gastric scheme in the current staging system, their conclusion seems to justify the ongoing classification. However, AEJg is not classified as AEJ according to Siewert classification that showed that AEJ III is the subcardial gastric carcinoma that infiltrates the gastroesophageal junction and distal esophagus from below.4 Therefore, Siewert classification can be applied for the tumor with EGJ involvement at least and AEJg in their article is proximal gastric adenocarcinoma and not true AEJ. Their conclusion should be revised according to the data limited to AEJe. In a 221 cohort of AEJe II among 225 Siewert type II carcinoma in our previous study,3 the esophageal staging system demarcated the clinical outcome more clearly than the gastric scheme as shown in Figure 1. Because nodal staging, not depth of the tumor, is the predictor for worse clinical outcome in Siewert type II carcinomas,3 the esophageal scheme that put the emphasis on the nodal involvement seems likely to be valid in this tumor entity. In contrast, pT and pN categories equally reflect the stage in the gastric scheme that decrease the stage number in most parts as compared with the esophageal scheme, which is deemed not to be well suited. There is a possibility that AEJe II patients comprise a small population in their series and do not represent AEJ in their article. In fact, 72% and 70% of the patients are AEJ III and without esophageal invasion, respectively. Therefore, tumor mass seems to be located mainly at the stomach in most of the patients in their series. Taken together with our findings, their results might highlight the difference between AEJe II and AEJe III and
Annals of Surgery r Volume 261, Number 3, March 2015
support the idea that AEJe III, not AEJe II, should be considered a part of gastric cancer. Hiroharu Yamashita, MD Hitoshi Katai, MD Gastric Surgery Division National Cancer Center Hospital Tokyo, Japan [email protected]
REFERENCES 1. Suh YS, Han DS, Kong SH, et al. Should adenocarcinoma of the esophagogastric junction be classified as esophageal cancer? A comparative analysis according to the seventh AJCC TNM classification. Ann Surg. 2012;255:908–915. 2. Sobin LH, Gospodarowicz MK, Wittekind CH. TNM Classification of Malignant Tumours. 7th ed. West Sussex, UK: Wiley-Blackwell; 2009. 3. Yamashita H, Katai H, Morita S, et al. Optimal extent of lymph node dissection for Siewert type II esophagogastric junction carcinoma. Ann Surg. 2011;254:274–280. 4. Siewert JR, Stein HJ. Carcinoma of the gastroesophageal junction—classification, pathology and extent of resection. Dis Esophagus. 1996;9:173– 182.
Reply:
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e appreciate the interest of Drs Hiroharu Yamashita and Hitoshi Katai in our study, “Should Adenocarcinoma of the Esophagogastric Junction (AEJ) Be Classified As Esophageal Cancer? A Comparative Analysis According to the Seventh AJCC TNM Classification.”1 The seventh AJCC TNM classification proposed new a classification system for esophageal adenocarcinoma (eTNM) located at the arbitrary 10-cm segment encompassing the distal 5 cm of the esophagus and proximal Disclosure: The authors declare no conflicts of interest. DOI: 10.1097/SLA.0000000000000587
www.annalsofsurgery.com | e67
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Letters to the Editor
Annals of Surgery r Volume 261, Number 3, March 2015
FIGURE 1. Prognostic grouping based on the AJCC seventh TNM classification for gastric and esophageal adenocarcinomas. Stage II cancers in eTNM consist of stage Ib and IIa cancers in gTNM. The box formed by the dotted line indicates stage II in esophageal TNM classification. The light gray box indicates stage I in gastric TNM classification. The dark gray box indicates stage IIa in gastric TNM classification. The black box indicates stage IIb in gastric TNM classification. 5 cm of the stomach.2 Two separate criteria of this new classification system, “the involvement of esophagogastric junction (EGJ)” and “the distance from EGJ,” are similar but not identical to criteria of the Siewert classification. Our study mainly focused on the prognostic validation of the seventh AJCC TNM classification, especially for the significance of “the involvement of EGJ.” Because Siewert and his colleagues have traditionally used “AEG” for their classification, we selected a different abbreviation, namely, “AEJ,” to prevent confusion. Our study defined AEJ as tumors whose epicenters are within 5 cm proximal and distal to the EGJ, which is the same as the area of contention in the current TNM classification. Because we intended to reveal that the involvement of the EGJ itself is not a reasonable criteria for the application of eTNM by showing similar prognosis, regard-
less of the involvement of EGJ, the analysis including AEJ was inevitable. The basic concept of the seventh TNM classification is harmonization among the esophagus, stomach, and other intestines in terms of each T and N category. Therefore, eTNM and gTNM share the same definition of all N stages and T1/T2 stage, but the prognostic grouping differs between the 2 classification systems. At stage I or II, the prognostic grouping of eTNM has a tendency of “overstaging” compared with the classification of gastric adenocarcinoma (gTNM) (Fig. 1). If the prognoses were compared using the same patients, theoretically, prognoses using eTNM would have a tendency to show better survival than those using gTNM at each stage. For example, stage II of eTNM (the box formed by the dotted line) corresponds to mostly stage IIa and Ib gTNM (Fig. 1). Therefore, after re-
FIGURE 2. Postoperative survival analysis for AEJ IIe depending on eTNM (A) and gTNM (B). gTNM shows more distinctive separation than eTNM. e68 | www.annalsofsurgery.com
grouping based on TNM classification using the same population, stage II eTNM should show better prognosis than stage II gTNM, which may cause loss of distinctiveness between stage I and II eTNMs. Our subgroup analysis for AEJ IIe revealed that gTNMs still showed more distinctive separation than eTNMs, although the total number of AEJ IIe (n = 96) is limited (Fig. 2).Other recent comparative studies revealed results similar to our data.3,4 However, Yamashita and Katai’s data regarding the superiority of the esophageal scheme show poorer stage II prognosis based on the esophageal scheme than that using the gastric scheme. As we mentioned earlier, poorer stage II prognosis using the esophageal scheme cannot be understood theoretically. Even Yamashita and Katai’s data showed that the prognoses of stage I and III cancers, but not stage II cancers, are better in the esophageal scheme than in the gastric scheme. A possible reason for the difference may be the homogeneity of gTNM stage Ib or IIa cancers, which are composed of eTNM stage II cancers. To explain the poorer prognosis of eTNM stage II cancers than that of gTNM stage II cancers in Yamashita and Katai’s data, some patients with gTNM stage Ib cancers may have worse prognosis than those with gTNM stage IIb cancers. It is possible that scrutinizing the characteristics of those specific patients with poor prognosis may help define criteria for eTNM, instead of the involvement of EGJ. Considering the homogeneity of gTNM stage IIa cancers, the comparison of T3 stage between eTNM and gTNM is not clear sometimes. Because of the absence of serosa in certain areas of AEJ, it is sometimes difficult to reclassify tumors that have invaded the adjacent serosa definitely below the diaphragm but have not infiltrated the diaphragm or pleura itself. The printed version of the current seventh AJCC classification system does not have detailed guidelines for such cases, which has already been reported to be a weak point.5 If Yamashita and Katai staged all those cases as T3 in eTNM (downstage from gTNM T4; Fig. 1), stage II eTNM may have shown poorer prognosis than gTNM, unlike our results (Fig. 2). On the contrary, the seventh edition of UICC TNM classification offers addendum information that those AEJs invading the visceral peritoneum are also classified as T4a in eTNM, and we adopted this definition.6 Finally, Yamashita and Katai’s data showed 69.3% differentiated cancers and 28.9% undifferentiated cancers, which differed from ours (54.0% for differentiated and 39.6% for undifferentiated). Their data including a different histological proportion and a larger number of AEJ II patients seem to resemble those of Western institutes more than ours.
C 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Annals of Surgery r Volume 261, Number 3, March 2015
In conclusion, our data emphasize that the criteria of “the involvement of EGJ” and “the distance from EGJ” in the seventh AJCC TNM classification are not appropriate for the prognostic classification of AEJ. On the basis of theoretical reasoning regarding prognostic grouping and our practical data, gTNM can provide better prognostic grouping than eTNM, not only for AEJ III but also for AEJ II, irrespective of the involvement of EGJ. To overcome the difficulties in classifying AEJs, we propose the active collaboration of Eastern and Western institutes. Yun-Suhk Suh, MD Seong-Ho Kong, MD Department of Surgery Seoul National University College of Medicine
Letters to the Editor
Seoul, Korea [email protected] Hyuk-Joon Lee, MD Han-Kwang Yang, MD Department of Surgery and Cancer Research Institute Seoul National University College of Medicine Seoul, Korea
REFERENCES 1. Suh YS, Han DS, Kong SH, et al. Should adenocarcinoma of the esophagogastric junction be classified as esophageal cancer? A comparative analysis according to the seventh AJCC TNM classification. Ann Surg. 2012;255:908– 915.
C 2014 Wolters Kluwer Health, Inc. All rights reserved.
2. Edge SB, Byrd DR, Compton CC. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010. 3. Kim HI, Cheong JH, Song KJ, et al. Staging of adenocarcinoma of the esophagogastric junction: comparison of AJCC 6th and 7th gastric and 7th esophageal staging systems. Ann Surg Oncol. 2013;20:2713–2720. 4. Hasegawa S, Aoyama T, Hayashi T, et al. Esophagus or stomach? The seventh TNM classification for Siewert type II/III junctional adenocarcinoma. Ann Surg Oncol. 2013;20: 773–779. 5. Warneke VS, Behrens HM, Hartmann JT, et al. Cohort study based on the seventh edition of the TNM classification for gastric cancer: proposal of a new staging system. J Clin Oncol. 2011;29: 2364–2371. 6. Sobin LH, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours. Chichester, England: Wiley; 2011.
www.annalsofsurgery.com | e69
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
W
Disclosure: The authors declare no conflicts of interest. C 2014 Wolters Kluwer Health, Inc. All Copyright rights reserved. ISSN: 0003-4932/14/26103-e0067 DOI: 10.1097/SLA.0000000000000589
FIGURE 1. Overall survival after resection of type II EGJ adenocarcinoma, according to the esophageal (A) and gastric (B) schemes of seventh TNM classification. OS indicates overall survival. of esophageal invasion; therefore, the population in their study heterogeneously consisted of AEJe II, AEJg II, AEJe III, and AEJg III. They concluded that AEJ should be considered a part of gastric cancer irrespective of EGJ involvement. Because AEJg II and AEJg III are classified using the gastric scheme in the current staging system, their conclusion seems to justify the ongoing classification. However, AEJg is not classified as AEJ according to Siewert classification that showed that AEJ III is the subcardial gastric carcinoma that infiltrates the gastroesophageal junction and distal esophagus from below.4 Therefore, Siewert classification can be applied for the tumor with EGJ involvement at least and AEJg in their article is proximal gastric adenocarcinoma and not true AEJ. Their conclusion should be revised according to the data limited to AEJe. In a 221 cohort of AEJe II among 225 Siewert type II carcinoma in our previous study,3 the esophageal staging system demarcated the clinical outcome more clearly than the gastric scheme as shown in Figure 1. Because nodal staging, not depth of the tumor, is the predictor for worse clinical outcome in Siewert type II carcinomas,3 the esophageal scheme that put the emphasis on the nodal involvement seems likely to be valid in this tumor entity. In contrast, pT and pN categories equally reflect the stage in the gastric scheme that decrease the stage number in most parts as compared with the esophageal scheme, which is deemed not to be well suited. There is a possibility that AEJe II patients comprise a small population in their series and do not represent AEJ in their article. In fact, 72% and 70% of the patients are AEJ III and without esophageal invasion, respectively. Therefore, tumor mass seems to be located mainly at the stomach in most of the patients in their series. Taken together with our findings, their results might highlight the difference between AEJe II and AEJe III and
Annals of Surgery r Volume 261, Number 3, March 2015
support the idea that AEJe III, not AEJe II, should be considered a part of gastric cancer. Hiroharu Yamashita, MD Hitoshi Katai, MD Gastric Surgery Division National Cancer Center Hospital Tokyo, Japan [email protected]
REFERENCES 1. Suh YS, Han DS, Kong SH, et al. Should adenocarcinoma of the esophagogastric junction be classified as esophageal cancer? A comparative analysis according to the seventh AJCC TNM classification. Ann Surg. 2012;255:908–915. 2. Sobin LH, Gospodarowicz MK, Wittekind CH. TNM Classification of Malignant Tumours. 7th ed. West Sussex, UK: Wiley-Blackwell; 2009. 3. Yamashita H, Katai H, Morita S, et al. Optimal extent of lymph node dissection for Siewert type II esophagogastric junction carcinoma. Ann Surg. 2011;254:274–280. 4. Siewert JR, Stein HJ. Carcinoma of the gastroesophageal junction—classification, pathology and extent of resection. Dis Esophagus. 1996;9:173– 182.
Reply:
W
e appreciate the interest of Drs Hiroharu Yamashita and Hitoshi Katai in our study, “Should Adenocarcinoma of the Esophagogastric Junction (AEJ) Be Classified As Esophageal Cancer? A Comparative Analysis According to the Seventh AJCC TNM Classification.”1 The seventh AJCC TNM classification proposed new a classification system for esophageal adenocarcinoma (eTNM) located at the arbitrary 10-cm segment encompassing the distal 5 cm of the esophagus and proximal Disclosure: The authors declare no conflicts of interest. DOI: 10.1097/SLA.0000000000000587
www.annalsofsurgery.com | e67
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Letters to the Editor
Annals of Surgery r Volume 261, Number 3, March 2015
FIGURE 1. Prognostic grouping based on the AJCC seventh TNM classification for gastric and esophageal adenocarcinomas. Stage II cancers in eTNM consist of stage Ib and IIa cancers in gTNM. The box formed by the dotted line indicates stage II in esophageal TNM classification. The light gray box indicates stage I in gastric TNM classification. The dark gray box indicates stage IIa in gastric TNM classification. The black box indicates stage IIb in gastric TNM classification. 5 cm of the stomach.2 Two separate criteria of this new classification system, “the involvement of esophagogastric junction (EGJ)” and “the distance from EGJ,” are similar but not identical to criteria of the Siewert classification. Our study mainly focused on the prognostic validation of the seventh AJCC TNM classification, especially for the significance of “the involvement of EGJ.” Because Siewert and his colleagues have traditionally used “AEG” for their classification, we selected a different abbreviation, namely, “AEJ,” to prevent confusion. Our study defined AEJ as tumors whose epicenters are within 5 cm proximal and distal to the EGJ, which is the same as the area of contention in the current TNM classification. Because we intended to reveal that the involvement of the EGJ itself is not a reasonable criteria for the application of eTNM by showing similar prognosis, regard-
less of the involvement of EGJ, the analysis including AEJ was inevitable. The basic concept of the seventh TNM classification is harmonization among the esophagus, stomach, and other intestines in terms of each T and N category. Therefore, eTNM and gTNM share the same definition of all N stages and T1/T2 stage, but the prognostic grouping differs between the 2 classification systems. At stage I or II, the prognostic grouping of eTNM has a tendency of “overstaging” compared with the classification of gastric adenocarcinoma (gTNM) (Fig. 1). If the prognoses were compared using the same patients, theoretically, prognoses using eTNM would have a tendency to show better survival than those using gTNM at each stage. For example, stage II of eTNM (the box formed by the dotted line) corresponds to mostly stage IIa and Ib gTNM (Fig. 1). Therefore, after re-
FIGURE 2. Postoperative survival analysis for AEJ IIe depending on eTNM (A) and gTNM (B). gTNM shows more distinctive separation than eTNM. e68 | www.annalsofsurgery.com
grouping based on TNM classification using the same population, stage II eTNM should show better prognosis than stage II gTNM, which may cause loss of distinctiveness between stage I and II eTNMs. Our subgroup analysis for AEJ IIe revealed that gTNMs still showed more distinctive separation than eTNMs, although the total number of AEJ IIe (n = 96) is limited (Fig. 2).Other recent comparative studies revealed results similar to our data.3,4 However, Yamashita and Katai’s data regarding the superiority of the esophageal scheme show poorer stage II prognosis based on the esophageal scheme than that using the gastric scheme. As we mentioned earlier, poorer stage II prognosis using the esophageal scheme cannot be understood theoretically. Even Yamashita and Katai’s data showed that the prognoses of stage I and III cancers, but not stage II cancers, are better in the esophageal scheme than in the gastric scheme. A possible reason for the difference may be the homogeneity of gTNM stage Ib or IIa cancers, which are composed of eTNM stage II cancers. To explain the poorer prognosis of eTNM stage II cancers than that of gTNM stage II cancers in Yamashita and Katai’s data, some patients with gTNM stage Ib cancers may have worse prognosis than those with gTNM stage IIb cancers. It is possible that scrutinizing the characteristics of those specific patients with poor prognosis may help define criteria for eTNM, instead of the involvement of EGJ. Considering the homogeneity of gTNM stage IIa cancers, the comparison of T3 stage between eTNM and gTNM is not clear sometimes. Because of the absence of serosa in certain areas of AEJ, it is sometimes difficult to reclassify tumors that have invaded the adjacent serosa definitely below the diaphragm but have not infiltrated the diaphragm or pleura itself. The printed version of the current seventh AJCC classification system does not have detailed guidelines for such cases, which has already been reported to be a weak point.5 If Yamashita and Katai staged all those cases as T3 in eTNM (downstage from gTNM T4; Fig. 1), stage II eTNM may have shown poorer prognosis than gTNM, unlike our results (Fig. 2). On the contrary, the seventh edition of UICC TNM classification offers addendum information that those AEJs invading the visceral peritoneum are also classified as T4a in eTNM, and we adopted this definition.6 Finally, Yamashita and Katai’s data showed 69.3% differentiated cancers and 28.9% undifferentiated cancers, which differed from ours (54.0% for differentiated and 39.6% for undifferentiated). Their data including a different histological proportion and a larger number of AEJ II patients seem to resemble those of Western institutes more than ours.
C 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Annals of Surgery r Volume 261, Number 3, March 2015
In conclusion, our data emphasize that the criteria of “the involvement of EGJ” and “the distance from EGJ” in the seventh AJCC TNM classification are not appropriate for the prognostic classification of AEJ. On the basis of theoretical reasoning regarding prognostic grouping and our practical data, gTNM can provide better prognostic grouping than eTNM, not only for AEJ III but also for AEJ II, irrespective of the involvement of EGJ. To overcome the difficulties in classifying AEJs, we propose the active collaboration of Eastern and Western institutes. Yun-Suhk Suh, MD Seong-Ho Kong, MD Department of Surgery Seoul National University College of Medicine
Letters to the Editor
Seoul, Korea [email protected] Hyuk-Joon Lee, MD Han-Kwang Yang, MD Department of Surgery and Cancer Research Institute Seoul National University College of Medicine Seoul, Korea
REFERENCES 1. Suh YS, Han DS, Kong SH, et al. Should adenocarcinoma of the esophagogastric junction be classified as esophageal cancer? A comparative analysis according to the seventh AJCC TNM classification. Ann Surg. 2012;255:908– 915.
C 2014 Wolters Kluwer Health, Inc. All rights reserved.
2. Edge SB, Byrd DR, Compton CC. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010. 3. Kim HI, Cheong JH, Song KJ, et al. Staging of adenocarcinoma of the esophagogastric junction: comparison of AJCC 6th and 7th gastric and 7th esophageal staging systems. Ann Surg Oncol. 2013;20:2713–2720. 4. Hasegawa S, Aoyama T, Hayashi T, et al. Esophagus or stomach? The seventh TNM classification for Siewert type II/III junctional adenocarcinoma. Ann Surg Oncol. 2013;20: 773–779. 5. Warneke VS, Behrens HM, Hartmann JT, et al. Cohort study based on the seventh edition of the TNM classification for gastric cancer: proposal of a new staging system. J Clin Oncol. 2011;29: 2364–2371. 6. Sobin LH, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours. Chichester, England: Wiley; 2011.
www.annalsofsurgery.com | e69
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
