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Status and Prognosis of Lymph Node Metastasis in Patients with Cardia Cancer E a Systematic Review

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Status and Prognosis of Lymph Node Metastasis in Patients with Cardia Cancer E a Systematic Review Surgical Oncology 23 (2014) 140e146 Contents lists available at ScienceDirect Surgical Oncology journal homepage: www.elsevier.com/locate/suronc Review Status and prognosis of lymph node metastasis in patients with cardia cancer e A systematic review * Cecilie Okholm , Lars Bo Svendsen, Michael P. Achiam Department of Surgical Gastroenterology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 København Ø, Denmark article info abstract Article history: Background: Adenocarcinoma of the gastroesophageal junction (GEJ) has a poor prognosis and survival Accepted 1 June 2014 rates significantly decreases if lymph node metastasis is present. An extensive lymphadenectomy may increase chances of cure, but may also lead to further postoperative morbidity and mortality. Therefore, Keywords: the optimal treatment of cardia cancer remains controversial. A systematic review of English publications Adenocarcinoma dealing with adenocarcinoma of the cardia was conducted to elucidate patterns of nodal spread and Cardia cancer prognostic implications. Gastroesophageal junction Methods: A systematic literature search based on PRISMA guidelines identifying relevant studies Lymphadenectomy fi Lymph node metastasis describing lymph node metastasis and the associated prognosis. Lymph node stations were classi ed Prognosis according to the Japanese Gastric Cancer Association guidelines. Results: The highest incidence of metastasis is seen in the nearest regional lymph nodes, station no. 1e3 and additionally in no. 7, 9 and 11. Correspondingly the best survival is seen when metastasis remain in the most locoregional nodes and survival equally tends to decrease as the metastasis become more distant. Furthermore, the presence of lymph node metastasis significantly correlates to the TNM-stage. Incidences of metastasis in mediastinal lymph nodes are associated with poor survival. Conclusion: The best survival rates is seen when lymph node metastasis remains locoregional and sur- vival rates decreases when distant lymph node metastasis is present. The dissection of locoregional lymph nodes offers significantly therapeutic benefit, but larger and prospective studies are needed to evaluate the effect of dissecting distant and mediastinal lymph nodes. © 2014 Elsevier Ltd. All rights reserved. Contents Introduction................................................................ ............................... ....................... 141 Materials and methods . ....................... 141 Search strategy . ..................................................141 Eligibility criteria . ..................................................141 Classifications of cardia cancer . ....................... 141 Siewert's classification . ..........................................141 Classifications of lymph node stations . ..........................................142 The Japanese Gastric Cancer Association . ......................................142 Results.................................................................. ................................. ....................... 142 Pattern of nodal spread in cardia cancer . ..........................................142 Five-year survival related to each lymph node station . ...........................143 Additional findings . ..................................................143 Discussion ................................................................ ................................ ....................... 144 Morbidity and mortality related to D1/D2 dissection . .....................................144 Number of lymph nodes removed . .. ..........................................144 * Corresponding author. Tel.: þ45 25114720. E-mail address: [email protected] (C. Okholm). http://dx.doi.org/10.1016/j.suronc.2014.06.001 0960-7404/© 2014 Elsevier Ltd. All rights reserved. C. Okholm et al. / Surgical Oncology 23 (2014) 140e146 141 Future perspectives . ................................................ 145 Sentinel node for gastric cardia cancer . .......................145 Limitations . ................................................ 145 Conclusion . ................................................ 145 Conflict of interest statement . ............................................... 145 Acknowledgments . .......................145 Authorship statement . ................................................ 145 References................................................................. ................................ .......................145 Introduction study design, since no RCT's has been made to date to our knowledge. Adenocarcinoma of the gastroesophageal junction (GEJ) is an important clinical entity due to the increasing incidence in the Participants: Patients with cardia cancer undergoing surgery West [1,2]. Arising from the gastric cardia, the cancer has a poor primarily focused on Siewert's type II or junctional adenocar- prognosis with five-year survival rates of 24e36% after curative cinomas. If the article was based on several gastric or esophageal resection [3,4]. Located in the borderline between the stomach and cancers, the results for cardia cancer patients had to be pre- esophagus it shares many similarities with both regions, although sented separately. the optimal characterization and treatment of cardia cancer re- Interventions: Patients undergoing lymphadenectomy with mains controversial. retrieval of involved lymph nodes and estimation of lymph node Studies have shown, that lymph node involvement is a strong status. Additionally, records of the incidences of node metastasis prognostic predictor of survival [5], and five-year survival rates to each Japanese Gastric Cancer Association (JGCA) lymph node significantly decreases from 53% to 11% when lymph node metas- station for node positive patients. Of particular interest were tasis is present [6]. Lymphadenectomy is considered essential in articles estimating the associated five-year survival (5-Y-S) to addition to the surgical treatment, since lymph node involvement each lymph node station. is a major determinant of locoregional recurrence [7,8]. Outcome: Incidence of lymph node metastasis to JGCA lymph The standard treatment in Asia for gastric cancer is surgical node stations. In cases where studies presented data from all resection combined with the extensive D2 lymph node dissection, three Siewert's types combined, we still included the studies whereas most of the European countries perform a less extensive since no difference between the three types has been observed. D1þ dissection [5]. The extended lymph node dissection has been Data extraction: Lymph node metastasis in percent associated to associated with an increased chance for cure in some studies, but each lymph node station and median and range of the corre- may also lead to a higher incidence of postoperative morbidity and lated 5-Y-S to each station if presented. Additionally, the prog- mortality [9e11]. Given the different clinicopathological charac- nosis and correlation to the TNM-stage was extracted. Only teristics in patients with cardia cancer, the need and extent of available lymph node stations relevant to the different classifi- lymphadenectomy remain controversial in the West. cations for D1, D2 and D3 dissections were analyzed. Thus, We conducted a systematic review of English publications distant lymph node stations and some upper thoracic and cer- dealing with adenocarcinoma of the cardia to elucidate patterns of vical stations were not included in this review. nodal spread and prognostic implications. Exclusion: Exclusion criteria were articles with non-cardia can- cer, esophagus cancer, subcardia or gastric cancer, and articles Materials and methods with results not distinguished from esophagus or gastric cancer. Additionally gastric carcinosarcoma, stromal tumors and squa- Search strategy mous cell tumors were excluded. Furthermore, articles focusing on biological markers for lymph node retrieval, patients The databases PubMed and EMBASE were searched strategically receiving neoadjuvant chemotherapy and studies without link- for terms according to the PRISMA guidelines on the 15th of April age to lymph node stations were considered irrelevant. If the 2014 [12]. The search was limited to English language. The identi- results were combined for squamous cell and adenocarcinoma fied titles and abstracts were scanned for relevant topics, and the they were excluded in addition. full texts of the potentially relevant articles were obtained. In addition, review articles were scanned for missed articles. Poten- tially relevant studies were identified through hand searching of Classifications of cardia cancer the reference lists of the acquired studies. There were no re- strictions on the year of publication. Siewert's classification The search string used was: ((Gastric cardia cancer OR gastric cardia carcinoma OR gastric cardia adenocarcinoma OR esoph- In 1998 Siewert et al. [13] introduced a classification for ade- agogastric junction cancer OR esophageal cancer OR siewert type II nocarcinomas of the GEJ, defining them as tumors having their OR siewert type 2 OR siewerts type II OR siewerts type 2)) AND epicenter within five cm proximal or distal of the anatomical cardia. (lymphatic metastasis OR nodal spread). Three distinct tumors were differentiated: Type I: Adenocarcinoma Siewert's classification will be presented below. of the distal esophagus which usually arises from an area with The results from the search are presented in Fig. 1. specialized intestinal metaplasia
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