Abstract
The incidence of adenocarcinoma of the esophagogastric junction (AEG) has been rising. There is no standard treatment strategy for locally advanced AEG. The standard surgical treatment of Siewert type I AEG is Ivor-Lewis esophagectomy with mediastinal lymph node dissection. The optimal extent of mediastinal lymph node dissection for Siewert type II or III AEG with esophageal invasion of >3 cm remains unclear. Adjuvant chemotherapy should be added to the treatment of AEG. Many trials have demonstrated the beneficial effect of adjuvant chemotherapy. However, the combinations of chemotherapeutic agents and timing of administration of the drugs remains undefined. Adjuvant chemoradiotherapy has been investigated especially in Western countries. The INT-0116 revealed that adjuvant chemoradiotherapy with surgery is effective for AEG, and the CROSS trial showed that neoadjuvant chemoradiotherapy with surgery is effective for AEG. However, notice should be given to the relatively higher rate of distant metastasis after curative resection of AEG. Several molecular targeted agents have been investigated for the treatment of unresectable advanced AEG. Trastuzumab exhibited a beneficial effect for unresectable advanced AEG with overexpression of HER2. Whether the same effect is true in the adjuvant setting is being investigated. Systemic chemotherapy and surgical resection with adequate lymph node dissection may be more effective than localized treatment of chemoradiotherapy and surgical resection with limited lymph node dissection for locally advanced AEG. Molecular targeted agents may be beneficial for the treatment of locally advanced AEG.
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References
DeMeester SR. Adenocarcinoma of the esophagus and cardia: a review of the disease and its treatment. Ann Surg Oncol. 2006;13:12–30.
Devesa SS, Blot WJ, Fraumeni JF Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer. 1998;83:2049–53.
Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005;97:142–6.
Deans C, Yeo MS, Soe MY, Shabbir A, Ti TK, So JB. Cancer of the gastric cardia is rising in incidence in an Asian population and is associated with adverse outcome. World J Surg. 2011;35:617–24.
Kusano C, Gotoda T, Khor CJ, Katai H, Kato H, Taniguchi H, et al. Changing trends in the proportion of adenocarcinoma of the esophagogastric junction in a large tertiary referral center in Japan. J Gastroenterol Hepatol. 2008;23:1662–5.
Yamashita K, Sakuramoto S, Nemoto M, Shibata T, Mieno H, Katada N, et al. Trend in gastric cancer: 35 years of surgical experience in Japan. World J Gastroenterol. 2011;17:3390–7.
Siewert JR, Stein HJ. Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg. 1998;85:1457–9.
Siewert JR, Feith M, Werner M, Stein HJ. Adenocarcinoma of the esophagogastric junction: results of surgical therapy based on anatomical/topographic classification in 1,002 consecutive patients. Ann Surg. 2000;232:353–61.
Siewert JR, Stein HJ, Feith M. Adenocarcinoma of the esophago-gastric junction. Scand J Surg. 2006;95:260–9.
Hulscher JB, van Sandick JW, de Boer AG, Wijnhoven BP, Tijssen JG, Fockens P, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med. 2002;347:1662–9.
Omloo JM, Lagarde SM, Hulscher JB, Reitsma JB, Fockens P, van Dekken H, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized clinical trial. Ann Surg. 2007;246:992–1000 (discussion 1).
Ott K, Bader FG, Lordick F, Feith M, Bartels H, Siewert JR. Surgical factors influence the outcome after Ivor-Lewis esophagectomy with intrathoracic anastomosis for adenocarcinoma of the esophagogastric junction: a consecutive series of 240 patients at an experienced center. Ann Surg Oncol. 2009;16:1017–25.
Altorki N, Kent M, Ferrara C, Port J. Three-field lymph node dissection for squamous cell and adenocarcinoma of the esophagus. Ann Surg. 2002;236:177–83.
Lerut T, Nafteux P, Moons J, Coosemans W, Decker G, De Leyn P, et al. Three-field lymphadenectomy for carcinoma of the esophagus and gastroesophageal junction in 174 R0 resections: impact on staging, disease-free survival, and outcome: a plea for adaptation of TNM classification in upper-half esophageal carcinoma. Ann Surg. 2004;240:962–72 (discussion 72-4).
Sasako M, Sano T, Yamamoto S, Sairenji M, Arai K, Kinoshita T, et al. Left thoracoabdominal approach versus abdominal-transhiatal approach for gastric cancer of the cardia or subcardia: a randomised controlled trial. Lancet Oncol. 2006;7:644–51.
Yamashita H, Katai H, Morita S, Saka M, Taniguchi H, Fukagawa T. Optimal extent of lymph node dissection for Siewert type II esophagogastric junction carcinoma. Ann Surg. 2011;254:274–80.
Hosokawa Y, Kinoshita T, Konishi M, Takahashi S, Gotohda N, Kato Y, et al. Clinicopathological features and prognostic factors of adenocarcinoma of the esophagogastric junction according to Siewert classification: experiences at a single institution in Japan. Ann Surg Oncol. 2012;19:677–83.
Fujitani K, Miyashiro I, Mikata S, Tamura S, Imamura H, Hara J, et al. Pattern of abdominal nodal spread and optimal abdominal lymphadenectomy for advanced Siewert type II adenocarcinoma of the cardia: results of a multicenter study. Gastric Cancer. 2013;16:301–8.
Goto H, Tokunaga M, Miki Y, Makuuchi R, Sugisawa N, Tanizawa Y, et al. The optimal extent of lymph node dissection for adenocarcinoma of the esophagogastric junction differs between Siewert type II and Siewert type III patients. Gastric Cancer. 2015;18:375–81.
Hosoda K, Yamashita K, Katada N, Moriya H, Mieno H, Sakuramoto S, et al. Impact of lower mediastinal lymphadenectomy for the treatment of esophagogastric junction carcinoma. Anticancer Res. 2015;35:445–56.
Kurokawa Y, Hiki N, Yoshikawa T, Kishi K, Ito Y, Ohi M, et al. Mediastinal lymph node metastasis and recurrence in adenocarcinoma of the esophagogastric junction. Surgery. 2015;157:551–5.
Aikou T, Shimazu H. Difference in main lymphatic pathways from the lower esophagus and gastric cardia. Jpn J Surg. 1989;19:290–5.
Cense HA, Sloof GW, Klaase JM, Bergman JJ, van Hemert FJ, Fockens P, et al. Lymphatic drainage routes of the gastric cardia visualized by lymphoscintigraphy. J Nucl Med. 2004;45:247–52.
Mine S, Sano T, Hiki N, Yamada K, Nunobe S, Yamaguchi T. Lymphadenectomy around the left renal vein in Siewert type II adenocarcinoma of the oesophagogastric junction. Br J Surg. 2013;100:261–6.
Wayman J, Bennett MK, Raimes SA, Griffin SM. The pattern of recurrence of adenocarcinoma of the oesophago-gastric junction. Br J Cancer. 2002;86:1223–9.
Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.
Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29:4387–93.
Bang Y-J, Kim Y-W, Yang H-K, Chung HC, Park Y-K, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379:315–21.
Hosoda K, Yamashita K, Katada N, Moriya H, Mieno H, Sakuramoto S, et al. Benefit of neoadjuvant chemotherapy for siewert type II Esophagogastric junction adenocarcinoma. Anticancer Res. 2015;35:419–25.
Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.
Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715–21.
Park I, Ryu MH, Choi YH, Kang HJ, Yook JH, Park YS, et al. A phase II study of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy followed by surgery and adjuvant S-1 chemotherapy in potentially resectable gastric or gastroesophageal junction adenocarcinoma. Cancer Chemother Pharmacol. 2013;72:815–23.
Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725–30.
Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, et al. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012;30:2327–33.
Lee J, Lim do H, Kim S, Park SH, Park JO, Park YS, et al. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012;30:268–73.
Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, et al. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008;26:1086–92.
van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.
Fiorica F, Di Bona D, Schepis F, Licata A, Shahied L, Venturi A, et al. Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis. Gut. 2004;53:925–30.
Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J, Simes J. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007;8:226–34.
Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.
Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, et al. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009;27:851–6.
Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S, Soini Y, et al. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005;16:273–8.
Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19:1523–9.
Hofmann M, Stoss O, Shi D, Buttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52:797–805.
Van Cutsem E, Bang YJ, Feng-Yi F, Xu JM, Lee KW, Jiao SC, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18:476–84.
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.
Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–9.
Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–35.
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Hosoda, K., Yamashita, K., Katada, N. et al. Overview of multimodal therapy for adenocarcinoma of the esophagogastric junction. Gen Thorac Cardiovasc Surg 63, 549–556 (2015). https://doi.org/10.1007/s11748-015-0575-2
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DOI: https://doi.org/10.1007/s11748-015-0575-2