Background: Mediastinal lymph node metastases occasionally occur in patients of advanced gastric cancer of the cardia with esophageal invasion, but they rarely occur in patients with gastric cancer of other sites. This report describes a case of a solitary metastasis to t a superior mediastinal lymph node after distal gastrectomy for gastric cancer of the antrum. Case presentation: A 70-year-old man underwent curative distal gastrectomy for advanced gastric cancer of the antrum (pT2pN2M0, stage IIB). Postoperatively, he underwent adjuvant chemotherapy with S-1 (100 mg/day). Although the serum levels of his tumor markers increased after surgery, computed tomography scans did not detect evidence of early recurrence in the superior mediastinum. However, a F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan showed accumulation of fluorodeoxyglucose in the upper mediastinum with no evidence of recurrence elsewhere. Therefore, a solitary superior mediastinal lymph node was suspected to have a metastatic lesion derived from the gastric cancer. The patient underwent tumor resection right mini-thoracotomy two years and three months following gastrectomy. A pathological examination demonstrated moderately differentiated adenocarcinoma, confirming that it was a metastatic adenocarcinoma from the gastric cancer. The patient developed recurrences in the superior mediastinum and several right costa six months following the second surgery. He was treated with chemotherapy, but he died 18 months after the second operation. Conclusion: We present a rare case of a solitary metastasis to a superior mediastinal lymph node after distal gastrectomy for gastric cancer. An FDG-PET scan is useful for the diagnosis of mediastinal lymph node metastasis in gastric cancer. Metastasis to the superior mediastinal lymph nodes from gastric cancer in sites other than the cardia suggests systemic expansion of gastric cancer, and therefore, even a solitary metastasis may be related to a poor prognosis. Keywords: Gastric cancer, Mediastinum, Lymph node metastasis, Gastrectomy, Adenocarcinoma * Correspondence: firstname.lastname@example.org Department of Surgery, North Alps Medical Center Azumi Hospital, 3207-1, Ikeda, Ikeda-cho, Kitaazumi-gun, Nagano 399-8695, Japan © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Kubo et al. BMC Cancer (2018) 18:627 Page 2 of 6 Background (85 mm) (Fig. 1c). The pathological findings of the Mediastinal lymph node metastases in advanced gastric resected primary gastric carcinoma, expressed according cancer of the cardia with esophageal invasion occur oc- to the Japanese Classification of Gastric Carcinoma, were casionally, but metastases from sites other than the car- moderately differentiated adenocarcinoma, mp, INFb, dia are rare. Furthermore, upper mediastinal lymph intermediate, ly1, v0. Additionally, 5 of the 29 resected re- node metastases from gastric cancer are often accom- gional lymph nodes were positive in only the No. 6 (sub- panied by multiple metastases to other sites (e.g., Virch- pyloric) region according to the Japanese Classification of ow’s lymph node); therefore, cases in which a single Gastric Carcinoma (Fig. 1d). The pathological stage was mediastinal metastasis of gastric cancer is resected are classified as IIB based on the American Joint Committee very rare. We report a case in which a solitary metastasis on Cancer TNM staging classification for carcinoma of to a superior mediastinal lymph node occurred after dis- the stomach (7th edition, 2012). The patient’ postoperative tal gastrectomy for gastric cancer of the antrum. course was uneventful; his high preoperative CA19–9 level normalized (26.3 U/ml), and he was discharged. Case presentation Postoperatively, the patient underwent adjuvant A 70-year-old man with anemia was admitted to our hos- chemotherapy with S-1 (100 mg/day). However, his car- pital. A barium meal examination and upper gastrointes- cinoembryonic antigen (CEA) levels ranged from 5 to tinal endoscopy revealed type III advanced gastric cancer 6 U/mL, and his CA 19–9 levels ranged from 40 to in the antrum (Fig. 1a. b). Biopsy specimens from the 120 U/mL beginning at six months after surgery. We tumor demonstrated a moderately differentiated adeno- monitored the patient via CT scans every 6 months and carcinoma. Laboratory examinations revealed a high level observed no evidence of recurrence. His tumor markers of serum tumor markers, including carbohydrate antigen remained in that same range for several months, and (CA) 19–9 (578.5 U/mL). A computed tomography (CT) therefore adjuvant chemotherapy with S-1 was contin- scan showed regional lymph node metastases; however, ued. However, two years and two months after surgery, distant metastases and direct invasion to the surrounding his CEA (12.7 U/mL) and CA 19–9 (714.0 U/mL) levels tissues were not observed. The patient underwent curative increased dramatically, and an F- fluorodeoxyglucose distal gastrectomy with D2 lymphadenectomy. Resected positron emission tomography (FDG-PET) scan was per- specimens demonstrated a flat, elevated, type 5 advanced formed, which revealed an accumulation of FDG in the gastric. tumor that was 6.0 cm in diameter, located in the upper mediastinum but no other evidence of recurrence greater curvature of the antrum. The proximal margin of (Fig. 2). Based on these results, a repeat CT scan was the resected specimen was free of residual cancer cells performed, which revealed an enlargement of a solitary Fig. 1 a, b A barium meal examination and upper gastrointestinal endoscopy revealed type III advanced gastric cancer in the antrum. c Resected specimens demonstrate a flat, elevated type5 advanced gastric cancer, 6.0 cm in diameter, located in the greater curvature of the antrum. d Histological findings of the primary tumor show moderately differentiated adenocarcinoma (hematoxylin and eosin staining, magnification, × 400) Kubo et al. BMC Cancer (2018) 18:627 Page 3 of 6 (Fig. 5a), and histological examination demonstrated a moderately differentiated adenocarcinoma (Fig. 5b). Both the primary tumor and the mediastinal node exhibited partially positive immunohistochemical staining for CK7, positive immunohistochemical staining for CK20 (Fig. 5c, d), and negative staining for Her2, indicating that it was a metastatic adenocarcinoma from the gastric cancer. While the patient received adjuvant chemotherapy with S-1 (100 mg/day) following the initial surgery and because he developed recurrence, he subsequently received adjuvant chemotherapy with docetaxel (40 mg/m on days 1, 8 and 15) in a 28-day cycle after the second operation. Unfortu- nately, he developed recurrences in the superior mediasti- num and some right costa at six months after reoperation. Therefore, he received combination chemotherapy with 2 2 irinotecan (60 mg/m ) and cisplatin (40 mg/m ) every two Fig. 2 F-fluorodeoxyglucose positron emission tomography shows weeks; although he had not previously received this regi- accumulation of fluorodeoxyglucose in the superior mediastinum but men, he developed multiple mediastinal and bone metas- no evidence of recurrence except for that in the mediastinal lymph node (arrow) tases and died 18 months after the second operation. Discussion and conclusions superior mediastinal lymph node (Fig. 3). The enlarged This case revealed two important clinical issues. First, lymph node was suspected to be a metastatic lesion de- this is a rare case of solitary metastasis to a superior me- rived from the gastric cancer. diastinal lymph node after distal gastrectomy for gastric The patient underwent tumor resection by right cancer. Second, an FDG-PET scan was useful for the mini-thoracotomy two years and three months following diagnosis of mediastinal lymph node metastasis of gas- the initial gastrectomy. The metastasized lymph node ex- tric cancer. Thus, even when solitary, the presence of su- hibited strong adhesion to the right brachiocephalic vein; perior mediastinal gastric cnacer metastases, except however, it was on the periphery of the superior vena cava those from gastric cancer of the esophagogastric junc- and therefore could be excised with the right brachioce- tion, may imply systemic expansion of gastric cancer phalic vein (Fig. 4). The patient’s postoperative course was and indicate poor prognosis. uneventful, and he was discharged on postoperative day Gastric cancer cases with esophageal invasions and 17. The resected specimen was 1.5 cm in diameter gastroesophageal junction adenocarcinomas are associ- ated with high rates of mediastinal metastasis, ranging from 16.8 to 18.1% [1, 2]. However, upper mediastinal metastasis in gastric cancer, regardless of the presence of esophageal invasion, are rare [3, 4]. Thus, superior medi- astinal metastasis in gastric cancer, except for those oc- curring in the cardia, are rare. To our knowledge, only two documented case of superior mediastinal metastases of gastric cancer after distal gastrectomy have been re- ported in the Medline and Japana Centra Revuo Medi- cina databases; both are in patients who received chemotherapy but not surgery for superior mediastinal metastasis and multiple organ metastasis [5, 6]. Metastatic pathways include lymphangitic spread of the tumor that reaches the lungs by vascular spread  and a route from the para-aortic lymph node and thor- acic ducts to the mediastinum [8, 9]. The mechanism of mediastinal lymph node metastasis from the abdomen involves retrograde flow into the bronchomediastinal Fig. 3 Computed tomography shows enlargement of the solitary trunk from the thoracic duct . We assumed that this superior mediastinal lymph node, and invasion to the right was also the mechanism of the mediastinal lymph node brachiocephalic vein was suspected (arrow) metastasis in our case because the case involved gastric Kubo et al. BMC Cancer (2018) 18:627 Page 4 of 6 Fig. 4 Intraoperative photography. a The metastasized lymph node was located in the upper mediastinum and was in contact with the right brachiocephalic vein (arrow). b, c, d The metastasized lymph node showed strong adhesion to the right brachiocephalic vein, but it could be excised with the right brachiocephalic vein Fig. 5 a The resected specimen was 1.5 cm in diameter. b Histological findings of the metastatic mediastinal lymph node demonstrate moderately differentiated adenocarcinoma, indicating that it was a metastasis of gastric cancer (hematoxylin and eosin staining, magnification, × 400). c, d Both the primary tumor and the mediastinal node exhibited partially positive immunohistochemical staining for CK7 (data not shown) and positive immunohistochemical staining for CK20 (c: primary tumor, d: mediastinal node, magnification, × 5) Kubo et al. BMC Cancer (2018) 18:627 Page 5 of 6 cancer in a site other than the cardia without lung recurrent para-aortic lymph node metastases in gas- metastasis and with a solitary superior mediastinal tric cancer has also been reported . metastasis. In our case, CT and PET scans did not clearly show An FDG-PET scan has been reported as a useful diag- any metastasis other than that in the solitary superior nostic modality for advanced metastatic or recurrent lymph node. The patient received oral S-1 as adjuvant gastric cancer, but not for detecting gastric cancer in sig- chemotherapy but experienced recurrence and increased net ring cell and poorly differentiated adenocarcinoma, tumour markers. We predicted that tumor control with bone metastasis, peritonitis, or pleuritic carcinomatosis chemotherapy would be difficult; Hence, resection was [11, 12]. Mediastinal lymph node metastases in advanced recommended. The metastasized lymph node showed gastric cancer of the cardia without esophageal invasion strong adhesion to the right brachiocephalic vein, but it occur occasionally, and those from sites other than the was peripheral of the superior vena cava; therefore, it cardia are rare. A solitary superior mediastinal lymph could be excised with the right brachiocephalic vein. We node metastasis after distal gastrectomy is extremely initially thought that the excision of the metastasized rare; therefor, a PET scan is useful for the diagnosis of lymph node was curative because the tumor markers the lesion, which in this case, was not detected by CT. normalized postoperatively, however, the patient devel- In contrast, this patient eventually developed multiple oped recurrence in the superior mediastinum and sev- mediastinal metastasis, which is suggests that it is diffi- eral right costa six months following reoperation. cult for PET scan to detect small lesions (e.g. micro- In conclusion, we present a rare case of solitary metasta- scopic metastasis or peritoneal dissemination). sis to a superior mediastinal lymph node after distal gas- We found only two report of a solitary mediastinal trectomy for gastric cancer. A PET scan was useful for the metastasis in gastric cancer after gastrectomy in the diagnosis of mediastinal lymph node metastasis of gastric Medline and Japana Centra Revuo Medicina databases cancer. Metastasis of gastric cancer to a superior medias- [13, 14]. In first case, total gastrectomy with resection of tinal lymph node implies systemic expansion of gastric the lower esophagus was performed for advanced gastric cancer from sites other than the cardia; therefore, even if cancer of the cardia with slight invasion of the esopha- solitary, metastasis suggests a poor prognosis. gus. Nine months later, a solitary middle mediastinal Abbreviations metastasis was detected and resected. The patient has CA: Carbohydrate antigen; CEA: Carcinoembryonic antigen; CT: Computed been well and without recurrence for 4 years after resec- tomography; FDG-PET: F- fluorodeoxyglucose positron emission tomography tion of the metastatic tumor. In another case, distal gas- trectomy was performed for advanced gastric cancer of New software the lower third of the stomach, five years later, a solitary The authors declare that no new software has been used. thymic metastasis in the anterior mediastinum was de- Authors’ contributions tected and resected. The prognosis of the patient cur- NK and TH performed the surgery in this case. NK and JY treated the patient rently remains unclear. after surgery. NK drafted the manuscript and all authors read and approved the final manuscript. Mediastinal lymph node metastasis from an adeno- carcinoma in the gastroesophageal junction has been Ethics approval and consent to participate suggested as a prognostic factor . An upper medi- Not applicable. astinal lymph node metastasis in patients with gastric Consent for publication cancer often accompanies multiple metastases to Written informed consent was obtained from the patient for publication of other sites (e.g., Virchows lymph node); cases of a this case report and any accompanying images. single mediastinal metastasis of gastric cancer after Competing interests gastrectomy are rare. The two previously documented The authors declare that they have no competing interests. patients with superior mediastinal metastasis of gas- tric cancer that did not occur in the cardia received Publisher’sNote chemotherapy without surgery for superior medias- Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. tinal metastasis and were found to have multiple organ metastasis [5, 6]. 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Published: Jun 4, 2018