ORIGINAL ARTICLE – PERITONEAL SURFACE MALIGNANCY Crohn’s-Like Lymphoid Reaction is Associated with Oncological Prognosis and Nutritional Status in Patients with Pathological Stage II/III Gastric Cancer Yusuke Omura, MD 1 , Yuji Toiyama, MD, PhD, FACS 1 , Yoshinaga Okugawa, MD, PhD 1 , Akira Yamamoto, MD 1 , Chengzeng Yin, MD 1 , Kurando Kusunoki, MD 1 , Yukina Kusunoki, MD 1 , Tsunehiko Shigemori, MD 1 , Shozo Ide, MD 1 , Takahito Kitajima, MD, PhD 1 , Hiroyuki Fujikawa, MD, PhD 1 , Hiromi Yasuda, MD, PhD 1 , Junichiro Hiro, MD, PhD 1 , Shigeyuki Yoshiyama, MD, PhD 1 , Masaki Ohi, MD, PhD 1 , and Masato Kusunoki, MD, PhD 1 Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Japan ABSTRACT Background. Peritumoral lymphoid aggregates, termed Crohn’s-like lymphoid reaction (CLR), are markers of an antitumor immune response, which is an important pre- dictor of patient outcome. In this study, we investigated the prognostic utility of CLR and its relationship with nutri- tional status in patients with gastric cancer (GC). Methods. The study included 170 patients who underwent curative surgery for pathological stage (pStage) II/III GC. The maximum diameters of peritumoral and normal mucosal CLR aggregates were measured, and the median peritumoral diameter (0.57 mm) was used to stratify patients into two groups (large-CLR and small-CLR). The relationships between CLR size and preoperative nutri- tional status (body mass index, body composition status, Onodera’s prognostic nutritional index), tumor-infiltrating CD8? T-lymphocyte count, and survival were evaluated. Results. Peritumoral CLR aggregates were significantly larger than aggregates in the normal mucosa. Clinico- pathological variables were not significantly different between the two patient groups; however, the large-CLR group had better cancer-specific survival (p= 0.018) and recurrence-free survival (p= 0.03) than the small-CLR group. Multivariate analysis revealed that CLR size was an independent prognostic factor for cancer-specific survival [hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.3–3.56, p= 0.002] and recurrence-free survival (HR 1.96, 95% CI 1.22–3.19, p= 0.005). Nutritional status markers were significantly poorer for the small-CLR group than the large-CLR group. CD8? T-cell tumor infiltration was positively correlated with CLR size but not with patient survival. Conclusions. CLR size correlated with patient nutritional status and prognosis and may be helpful in identifying high-risk populations of pStage II/III GC patients. Gastric cancer (GC) is the third leading cause of cancer- related death worldwide, and is especially common in East Asian countries. 1,2 Although postoperative adjuvant chemotherapy is standard treatment for patients with stage II and III (II/III) GC, 3 the disease recurs in a high pro- portion of patients. Therefore, there is an urgent need for prognostic markers to identify patients at high risk for recurrence. 4 In recent years, immunotherapies such as chimeric antigen receptor-bearing T cells (CAR-T) and immune checkpoint inhibitors have achieved remarkable success in Electronic supplementary material The online version of this article (https://doi.org/10.1245/s10434-019-07709-w) contains supplementary material, which is available to authorized users. Ó Society of Surgical Oncology 2019 First Received: 12 December 2018 Y. Toiyama, MD, PhD, FACS e-mail: ytoi0725@clin.medic.mie-u.ac.jp Y. Okugawa, MD, PhD e-mail: yoshinaga.okugawa@gmail.com; yosinaga@clin.medic.mie-u.ac.jp Ann Surg Oncol https://doi.org/10.1245/s10434-019-07709-w